Articles Listed in PubMed

Lymphangioleiomyomatosis (LAM) is a rare, female-dominated pulmonary cystic disease. Cysts that develop in LAM are characterized by the presence of smooth muscle-like (LAMCore) cells in the periphery. These cells harbor mutations in Tuberous Sclerosis Complex 1 or 2 (TSC1/2), driving uncontrolled proliferation through the mTORC1 pathway. LAMCore cells originate from an extrapulmonary source. Published data supports the uterine origin of LAMCore cells that metastasize from the uterus to precipitate pulmonary function destruction. Immune evasion is hypothesized to occur to allow seeding of the lungs from the uterus. This evasion specifically involves dysfunctional NK cells to allow aberrant proliferation and migration from the tissue.

Congenital neutropenia is characterized by a reduced neutrophil count, decreased innate immunity and increased susceptibility to recurrent infections. While congenital neutropenia has various genetic causes, recent studies have linked TCIRG1 mutations to this condition. TCIRG1, a key component of the vacuolar ATPase (V-ATPase) complex, is essential for osteoclast function, but its role in hematopoiesis remains unclear. We previously identified heterozygous TCIRG1 mutations, including R736S, R736C, R736P, and E722D, in individuals with congenital neutropenia.

Understanding the development of the auditory system is crucial for uncovering the molecular origins of hearing and its related disorders. During this development, spiral ganglion neurons extend peripheral fibers to cochlear hair cells and central projections to the cochlear nuclei, setting up a tonotopic map that connects the ear to the brainstem, enabling frequency-specific sound perception. This sensory information is then integrated bilaterally through a relay involving the superior olivary complex, lateral lemniscus, inferior colliculus, medial geniculate body, and the auditory cortex.

Background: Frailty is increasingly recognized in older people living with HIV (PLWH), but optimal diagnostics are yet to be determined. Frailty indices (FI) represent an accumulation of health deficits shown to correlate better with mortality and adverse effects of aging than the frailty phenotype or chronological age. Methods: This is a retrospective cohort study of frailty assessments in PLWH aged ≥ 50 years in a multidisciplinary urban HIV clinic. Frailty was assessed using Frailty Phenotype (FP) and a new 40-variable clinical composite FI derived from routine clinical and laboratory data (CCFI). 

Most malignantly transformed cells are metabolically rewired to promote their survival and progression, even under conditions that would be unfavorable for normal counterparts. Arguably the most impactful metabolic transformation and recognized cancer hallmark is the reprogrammed lipid metabolism. Lipids are not only primary constituents of cell membranes but essential participants in fundamental cellular functions including cell signaling, protein regulation, energy provision, inflammation, and cell-cell interaction. Engagement of lipids in critical physiological functions in cells is additionally accentuated upon malignant transformation. Pivotal roles of lipids as influential inter- and intracellular signaling molecules, particularly under conditions of hyper oxidative stress, are delineated.

An increase in the temperature of lakes and ponds facilitates the over-growth of photosynthetic cyanobacteria that produce a class of toxins called cyanotoxins. The abundance of cyanobacteria poses a significant threat to drinking and irrigation water supplies, and therefore, cyanotoxins have become a major class of environmental pollutants. Microcystins, the most common cyanotoxins, are cyclic peptides produced by cyanobacteria through non-ribosomal peptide synthases, and currently, approximately 279 microcystins have been identified to date.

This study aimed to investigate the role of the renin-angiotensin system (RAS) in COVID-19, particularly focusing on key components such as ACE, ACE2, and their related peptides, angiotensin-(1-7) and angiotensin-(1-9). Using serum samples from healthy controls and both non-severe and severe COVID-19 patients, ELISA assays revealed no significant differences in these RAS components between the groups.

Chikungunya virus (CHIKV) is an alphavirus spread by mosquitos, primarily Aedes aegypti and Aedes albopictus, that causes a debilitating febrile illness called chikungunya fever (CHIKF). CHIKF usually presents in two phases, starting as an acute illness, characterized by high fever, polyarthralgia and polyarthritis, headache, maculopapular skin rash, sometimes pruritic, and severe fatigue, commonly accompanied by anorexia, nausea, vomiting and diarrhea. This first phase usually resolves within 5-14 days.

Protein citrullination (PC) is a posttranslational modification (PTM) that converts a peptidyl arginine into a peptidyl citrulline. Aberrant PC is a hallmark of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), Alzheimer’s disease, Parkinson’s disease, prion disease, and multiple sclerosis. Common among these diseases is a dramatic increase of PC in reactive astrocytes. Some citrullinated proteins have been identified. 

Neutrophil elastase (ELANE) mutations are the most common cause of cyclic (CyN) and congenital neutropenia (SCN), two autosomal dominant disorders causing recurrent infections due to impaired neutrophil production. Granulocyte colony-stimulating factor (G-CSF) corrects neutropenia but has adverse effects, including bone pain and in some cases, an increased risk of myelodysplasia (MDS) and acute myeloid leukemia (AML). Hematopoietic stem cell transplantation is an alternative but is limited by its complications and donor availability. Alternative therapies are needed, particularly for patients with poor responses to G-CSF and those at higher risk of MDS/AML.

Polyamines are small organic molecules ubiquitously present in all living organisms and function as crucial regulators of biological processes ranging from fundamental cellular metabolism to immune regulation. Dysregulation of polyamine metabolism has been implicated in numerous diseases, including neurodegenerative disorders, inflammatory conditions, autoimmune diseases, and cancer. This review provides an overview of pathophysiology of these conditions, highlighting polyamines’ role in immunometabolic alterations in the context of immune regulation.

It is impossible for a person to begin to learn what he thinks he already knows. That's what Epictetus, the Greek Stoic philosopher, taught us two millennia ago. Yet somehow that lesson never made it to some of us – myself included. Rather, we have to learn it on our own and pay the appropriate price

Tumor-induced immune suppression has been recognized as one of the major barriers for cancer immune therapies, including checkpoint inhibitors. Immunosuppressive mechanisms that tumors utilize to silence anti-tumor immune cells are numerous and differ between tumor types. 

Pancreatic Ductal Adenocarcinoma (PDAC) remains one of the most lethal solid tumor diagnoses given its limited treatment options and dismal prognosis. Its complex tumor microenvironment (TME), heterogeneity, and high propensity for drug resistance are major obstacles in developing effective therapies. Here, we highlight the critical role of Redox effector 1 (Ref-1) in PDAC progression and drug resistance, focusing on its redox regulation of key transcription factors (TFs) such as STAT3, HIF1α, and NF-κB, which are pivotal for tumor survival, proliferation, and immune evasion.

Pancreatic ductal adenocarcinoma (PDAC) is the third most common cause of cancer-related deaths in the United States. Modeling studies project PDAC to be the second leading cause of cancer-related mortality by 2040. Poor survival rates are attributed to the overwhelming majority (>80%) of patients presenting with locally advanced or metastatic disease, which precludes surgical resection and possibility of a long-term cure. 

Protein post-translational modifications play a vital role in various cellular events essential for maintaining cellular physiology and homeostasis. In cancer cells, aberrant post-translational modifications such as glycosylation, acetylation, and phosphorylation on proteins can result in the generation of antigenic peptide variants presented in complex with MHC molecules. These modified peptides add to the class of tumor-specific antigens and offer promising avenues for targeted anti- cancer therapies. In this review, we focus on the role of phosphorylated peptides (p-peptides) in cancer immunity.

In the evolving landscape of bladder cancer (BCa) immunotherapy, this commentary offers a critical and timely reflection on a recent review that we published previously on targeting innate lymphoid cells (ILCs) in BCa. Even though BCa immunotherapy has traditionally focused on enhancing T-cell responses, the review explores the promising but underappreciated role of ILCs in BCa. From natural killer cells to the diverse ILC subtypes, these cells offer a dualistic impact on tumor progression and immune surveillance.

Pro-angiogenic paracrine/autocrine signaling impacts myocardial repair in cell-based therapies. Activin A receptor-like type 1 (ACVRL1, ALK1) signaling plays a pivotal role in cardiovascular development and maintenance, but its importance in human-derived therapeutic cardiac cells is not well understood. Here, we isolated a subpopulation of human highly proliferative cells (hHiPCs) from adult epicardial tissue and found that they express ALK1, a high affinity receptor for bone morphogenetic protein-9 (BMP9), which signals via SMAD1/5 to regulate paracrine/autocrine signaling and angiogenesis.

Renal Cell Carcinoma (RCC) is among the most frequently diagnosed malignancies in both genders with over 81,000 estimated cases in 2024. Despite increasing incidence of renal cell carcinomas <4 cm, up to 1/3 of patients diagnosed with RCC exhibit metastatic disease (mRCC) at time of diagnosis. Cytoreductive nephrectomy (CN), a procedure which encompasses the surgical removal of the primary tumor in patients with metastatic disease

Phosphoinositide (PIP_n) signaling plays pivotal roles in myriad biological processes and is altered in many diseases including cancer. Canonical PIP_n signaling involves membrane-associated PIP_n lipid second messengers that modulate protein recruitment and activity at membrane focal points. In the nucleus, PIP_n signaling operates separately from membranous compartments defining the paradigm of non-canonical PIP_n signaling.

Cutaneous melanoma, a malignancy originating from melanocytes in the skin, is challenging to treat due to its aggressive nature and propensity to metastasize. Despite the advancement of multifaceted treatment interventions, including targeted therapy, immunotherapy, and cellular therapy, the five-year-survival for patients with stage IV melanoma is only ~30% [1-3]. BRAF activating mutations are the most common genetic alteration in melanoma, comprising ~50% of all cutaneous melanoma cases [4,5]. 

KRAS is a commonly mutated gene in advanced colorectal cancer (CRC). Recently, inhibitors of KRAS G12C were developed and have shown promising efficacy for KRAS G12C mutated non-small cell lung cancer. However, KRAS G12C inhibitor monotherapy has not demonstrated excellent efficacy for KRAS G12C mutated advanced CRC due to multiple resistance mechanisms, especially receptor tyrosine kinase (RTK) signaling activation.

Support for stem cell self-renewal and differentiation hinges upon the intricate microenvironment termed the stem cell 'niche'. Within the adipose tissue stem cell niche, diverse cell types, such as endothelial cells, immune cells, mural cells, and adipocytes, intricately regulate the function of adipocyte precursors. These interactions, whether direct or indirect, play a pivotal role in governing the balance between self-renewal and differentiation of adipocyte precursors into adipocytes. 

Early-stage NSCLC, encompassing resectable stage I-III  are curable, and represents 25% of all lung cancers. The management of non-metastatic NSCLC is a rapidly changing area of clinical oncology, where utilization of molecular biomarkers has become a cornerstone in informing appropriate management. In current clinical practice, adjuvant chemotherapy is recommended after surgical resection for tumors ≥ 4 cms in size (AJCC 7th stage IB, AJCC 8th stage IIA, and higher stage groups thereafter).

Background: Chikungunya virus (CHIKV) is an alphavirus spread by mosquitos that causes arthralgias and arthritis that may last for years. The objective of this study was to describe the arthritis progression and T cell immunology over a two-year period. Methods: A cohort of 40 cases of serologically confirmed CHIKV from Magdalena and Atlántico, Colombia were followed in 2019 and again in 2021. Arthritis disease severity, disability, pain, stiffness, physical function, mobility, fatigue, anxiety, sleep disturbances and depression were assessed. 

The NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome, crucial in the innate immune response, is linked to various human diseases. However, the effect of endogenous metabolites, like 4-hydroxynonenal (HNE), on NLRP3 inflammasome activity remains underexplored. Recent research highlights HNE's inhibitory role in NLRP3 inflammasome activation, shedding light on its potential as an endogenous regulator of inflammatory responses.

Checkpoint inhibitors offer promise in treating muscle-invasive and metastatic bladder cancer, but the optimal timing of their administration—neoadjuvant or adjuvant—remains unclear. To determine the efficacy of combining checkpoint inhibition with standard cisplatin-based chemotherapy, we conducted a phase II trial of neoadjuvant anti-PD-1 (αPD-1) and anti-CTLA-4 (αCTLA-4), in combination with cisplatin-gemcitabine, for patients with muscle-invasive bladder cancer prior to radical cystectomy. 

Chimeric antigen receptor (CAR)-T cell therapy has shown potential in improving outcomes for individuals with hematological malignancies. However, achieving long-term full remission for blood cancer remains challenging due to severe life-threatening toxicities such as limited anti-tumor efficacy, antigen escape, trafficking restrictions, and limited tumor invasion. Furthermore, the interactions between CAR-T cells and their host tumor microenvironments have a significant impact on CAR-T function.

The emergence of chimeric antigen receptor T cell (CAR-T cell) therapy has revolutionized cancer treatment, particularly for hematologic malignancies. This commentary discusses developments in CAR-T cell therapy, focusing on the molecular mechanisms governing T cell fate and differentiation. Transcriptional and epigenetic factors play a pivotal role in determining the specificity, effectiveness, and durability of CAR-T cell therapy.

In the quest for improving the clinical outcome of patients with metastatic genitourinary cancers, including metastatic renal cell carcinoma (mRCC), the emphasis often is on finding new targeted therapies. However, two studies by Jordan et al. (Oncogenesis 2020) and Wang et al. (Cancer Cell Int 2022) demonstrate the feasibility of improving the efficacy of a modestly effective drug Sorafenib against mRCC by attacking a mechanism hijacked by RCC cells for inactivating Sorafenib.

This review underscores the important role of nutrition in enhancing the management of Human Immunodeficiency Virus type 1 (HIV-1). Highlighting the efficacy of dietary interventions, including, the importance of omega-3 fatty acids, vitamins D and B-12, and the Mediterranean diet, we delineate how these beneficial nutritional strategies can improve the effectiveness of combined antiretroviral therapy (cART), mitigate its side effects, and ameliorate metabolic disorders in people living with HIV-1 (PLWH). 

The role of the microbiome in the development and treatment of genitourinary malignancies is just starting to be appreciated. Accumulating evidence suggests that the microbiome can modulate immunotherapy through signaling in the highly dynamic tumor microenvironment. Nevertheless, much is still unknown about the immuno-oncology-microbiome axis, especially in urologic oncology. The objective of this review is to synthesize our current understanding of the microbiome’s role in modulating and predicting immunotherapy response to genitourinary malignancies.

The role of inflammation has been accepted as a factor in the complications of diabetic retinopathy. Discovery of the upstream regulation of these inflammatory factors has remained a challenge. In this study, we explored the actions of ephrin B1 in retinal Müller cells and their actions on inflammatory proteins. We used diabetic human and mouse samples, as well as Müller cells in culture to measure ephrin B1 in Müller cells.

Alzheimer’s Disease (AD) and Alzheimer’s Disease-Related Dementia (ADRD) are the primary causes of dementia that has a devastating effect on the quality of life and is a tremendous economic burden on the healthcare system. The accumulation of extracellular beta-amyloid (Aβ) plaques and intracellular hyperphosphorylated tau-containing neurofibrillary tangles (NFTs) in the brain are the hallmarks of AD.

Metabolic alterations induced by unhealthy lifestyles, including obesity and insulin resistance are often associated with increased innate immune response and chronic inflammation. Cholesterol has been identified as a key metabolite driving the activation of the inflammasome and the “epigenetic memory” in long-term living hematopoietic stem cells.  

Thirty percent of ischemic stroke patients develop vascular cognitive impairment and dementia (VCID) within 1 year of stroke onset. The expression of C-C motif chemokine receptor 3 (CCR3) is associated with endothelial dysfunction and memory impairment. CCR3 has been reported to increase after experimental stroke and in human stroke patients. Using an in vivo model of stroke, our study aims to link CCR3 expression with endothelial dysfunction in this rodent stroke model.

α6-containing GABA_A receptors (α6GABA_ARs) are strongly expressed in cerebellar granule cells, where they mediate a correctly timed and precise coordination of all muscle groups that execute behavior and protect the brain from information overflow. Recently, it was demonstrated that positive modulators with a high selectivity for α6GABA_ARs (α6-modulators) can reduce the symptoms of multiple neuropsychiatric disorders in respective animal models to an extent comparable with established clinical therapeutics.

Type 1 diabetes has historically been described as an endocrine (β-cell) specific autoimmune disease. However, a substantial reduction (20-50%) in pancreas organ size and subclinical to symptomatic exocrine pancreatic insufficiency are present at diagnosis and may begin even prior to the development of islet autoimmunity. The mechanisms of exocrine loss in type 1 diabetes are not well understood, but leading hypotheses include developmental defects, β-cell loss resulting in exocrine atrophy, or autoimmune or inflammatory destruction of exocrine cells.

This retrospective chart review study aims to identify patients in an HIV clinical setting in an area of high HIV prevalence in Atlanta, Georgia, USA who have chronic pain, analgesic prescriptions, and/or mental health diagnoses.

Mitochondrial dysfunction underlines neurodegenerative diseases which are mostly characterized by progressive degeneration of neurons. We previously reported that Cellular retinoic acid Binding protein 1 (Crabp1) knockout (CKO) mice spontaneously developed age-dependent motor degeneration, with defects accumulated in spinal motor neurons (MNs), the only cell type in spinal cord that expresses CRABP1.

Excessive food intake leads to lipid accumulation in white adipose tissue, triggering inflammation, cellular stress, insulin resistance, and metabolic syndrome. In contrast, the dynamic energy expenditure and heat generation of brown and beige adipose tissue, driven by specialized mitochondria, render it an appealing candidate for therapeutic strategies aimed at addressing metabolic disorders.

Vaccines are among the most effective tools for combatting the impact and spread of infectious diseases. However, the effectiveness of a vaccine can be diminished by vaccine inequality, particularly during severe outbreaks of infectious diseases in resource-poor areas. As seen in many developing countries that lack adequate healthcare infrastructure and economic resources, the acquisition and distribution of potentially life-saving vaccines may be limited, leading to prolonged suffering and increased deaths.

Introduction: During the past two decades, new therapeutic agents have greatly improved the treatment landscape in multiple myeloma (MM). Treatments such as proteasome inhibitors, immunomodulatory agents, targeted monoclonal antibody therapy, and chimeric antigen receptor (CAR) T-cell therapy have improved outcomes with less toxicity. Advances in laboratory testing have accompanied this change,

Stroke is a debilitating neurologic condition characterized by an interruption or complete blockage of blood flow to certain areas of the brain. While the primary injury occurs at the time of the initial ischemic event or hemorrhage, secondary injury mechanisms contribute to neuroinflammation, disruption of the blood-brain barrier (BBB), excitotoxicity, and cerebral edema in the days and hours after stroke.

Heparin is a highly sulfated, hence highly polyanionic, glycosaminoglycan with a repeating disaccharide that contains a hexuronic acid, and it has been used as an anticoagulant clinically for more than half a century. Daily IP injections of small amounts of heparin in the STZ diabetic rat prevented these pathological responses even though the animals sustained hyperglycemic levels of glucose throughout.

A major obstacle to fulfilling the therapeutic promise of gene therapies for hereditary brain diseases, such as Huntington’ Disease (HD), is the requirement for viral vectors and/or an invasive delivery system (stereotaxic injection into brain or infusion into the intrathecal space). HD is an autosomal dominant neurodegenerative disease for which several clinical trials have demonstrated gene-lowering effects following intrathecal administration.

Neuromyelitis Optica (NMO) is a serious condition associated with inflammation. Early diagnosis and detection are critical for early intervention. In this systematic review, we investigate the role of the neutrophil to lymphocyte ratio (NLR) as an important biomarker for NMO.

Ocular surface complications occur in more than 50% of individuals diagnosed with diabetes. The financial and health-related burden of diabetes is increasing annually. Several major ocular complications associated with diabetes involve the limbus. The vascular limbus, adjacent to the avascular cornea, is the source of circulating growth factors, elevated glucose, and cytokines for the cornea.

Palliative care (PC) aims to prioritize the quality of life and comfort of those with complex and terminal illnesses through the physical, psychological, social, and spiritual needs of the individual. Palliative care can support individuals from the day of their cancer diagnosis through end-of-life and bereavement

The dissemination of the extended spectrum β-lactamases (ESBL) producing E. coli poses a significant public health problem. Understanding the efficiency and frequency of horizontal gene transfer via conjugation of ESBL producing E. coli is imperative towards devising prevention and control measures. This study compared the frequencies and efficiencies of horizontal bla_CTX-M gene transfer via conjugation among Escherichia coli isolates from urine and gastrointestinal tract (GIT) of patients with urinary tract infection (UTI), their animals and environment.

Abdominal Aortic Aneurysms (AAA) remain a clinically devastating disease with no effective medical treatment therapy. AAAs are characterized by immune cell infiltration, smooth muscle cell apoptosis, and extracellular matrix degradation. Interleukin-1 (IL-1) has been shown to play role in AAA associated inflammation through immune cell recruitment and activation,

Venetoclax, a small-molecule B-cell lymphoma 2 (BCL-2) inhibitor, selectively eradicates leukemic stem cells (LSCs). While venetoclax has revolutionized the treatment of acute myeloid leukemia (AML), treatment failure and disease relapse are common. Mechanisms underlying venetoclax resistance are surprisingly heterogeneous.

While medications for opioid use disorder (MOUD) reduce overdose risk, inconsistent use can lead to substance use recurrence and compromise achieving optimal opioid use disorder (OUD) treatment outcomes. Research is limited on patient-reported perspectives on consistency of MOUD self-administration at home and its related social factors.

Inorganic microparticles are ubiquitous in the modern Western diet present as food additives and are actively scavenged by microfold (M) cells overlying human intestinal lymphoid aggregates. In Crohn’s disease (CD), inflammation is caused by the inability of the intestinal mucosa to sustain tolerance to gut luminal factors including bacteria and their by-products.

Oxidative stress (OS) in the airway epithelium is associated with inflammation, cell damage, and mitochondrial dysfunction that may initiate or worsen respiratory disease. Redox regulation maintains the equilibrium of pro-oxidant/antioxidant reactions but can be disturbed by environmental exposures. The mechanism(s) underlying the induction and impact of OS on airway epithelium and how these influences on respiratory disease is poorly understood.

Oxidative stress (OS) in the airway epithelium is associated with cell damage, inflammation, and mitochondrial dysfunction that may initiate or worsen respiratory disease. However, it is unclear whether exogenous antioxidants can provide protection to the airway epithelium from OS. Resveratrol and astaxanthin are nutritional compounds that have shown diverse benefits including protection against OS and inflammation in various situations.

Autism spectrum disorder (ASD) prevalence has increased year on year for the past two decades and currently affects 1 in 44 individuals in the US. An increasing number of studies have pointed to increased immune activation as both an etiological agent and also involved in the ongoing pathological process of ASD. Both adaptive and innate immune responses have been implicated. Evidence of innate dysregulation has so far included increased production of innate inflammatory cytokines, increased cell numbers, and altered activation in monocytes in the blood and microglia in the brain.

Calcitonin gene related peptide (CGRP) is a potent vasodilator and neurotransmitter that has been extensively studied in the context of migraine pathophysiology. Recently, studies have explored its role in the treatment of traumatic brain injury (TBI) and subarachnoid hemorrhage (SAH). Although a multitude of therapies exist for migraine, there has been little study on the management of migraine following neurologic injury.

The adoptive transfer of T cells expressing chimeric antigen receptors (CAR-T cells) has revolutionized the treatment of hematological malignancies, providing unmatched clinical responses in adults and children with relapsed or refractory B cell malignancies.

Diabetes is a chronic disorder that affects more than 500 million individuals worldwide. It is a life-long disease with complications that attack nearly all other systems within the body. Although there is a slight increase in the prevalence of diabetes in males, ocular surface complications are equally present in males and females.

Endovascular stenting has continued to evolve given the new trials. Several new stents have recently been developed to address specific purposes. In this focused review, we discuss the concepts of neurointerventional stents and address the clinical implications.

A role for oxidative stress in the etiology of myriad neuropathologies is well accepted. However, the specific effects of oxidative DNA damage in the onset or promotion of neuronal dysfunction have been less studied. In our recent publication by Behrouzi et al. (Oxidative DNA Damage and Cisplatin Neurotoxicity Is Exacerbated by Inhibition of OGG1 Glycosylase Activity and APE1 Endonuclease Activity in Sensory Neurons), inhibition of enzymes that play a role in repairing oxidative DNA damage exacerbated neurotoxic effects of the chemotherapeutic agent, cisplatin. 

Idiopathic pulmonary fibrosis (IPF) is an incurable disease that affects approximately 3 million people worldwide. Although two drugs (nintedanib and pirfenidone) have been approved for treatment of IPF, currently there is a lack of effective pharmacotherapy that could stop the progression or offer a cure for this devasting disease.

Bladder cancer is the sixth most common malignancy in the United States and 70% of cases are non-muscle invasive at the time of diagnosis. Effective treatment is crucial to prevent progression, which occurs in about 30% of patients. The American Urological Association (AUA) guidelines recommend treatment of non-muscle invasive bladder cancer (NMIBC) with intravesical Bacille Calmette-Guerin (BCG) and chemotherapy.

HIV infection in pregnancy continues to be of significant clinical and public health importance [1,2]. The current statistics published by the World Health Organization (WHO) demonstrate that 38 million people are living with HIV in 2019, and 1.1 million (85%) pregnant women living with HIV received antiretroviral therapy (ARVs) during pregnancy and postpartum.

The study “Experimental Mouse Models of Disseminated Candida auris Infection” provides the first insight into the critical role of C5 in the host antimicrobial defense to disseminated candidiasis caused by C. auris. This study also establishes an inbred A/J mouse model of systemic C. auris infection without drug-induced immunosuppression. C. auris has become the first fungal pathogen causing global public health threat due to its multidrug resistance (MDR) and persistence in hospital and nursing home settings.

Mild traumatic brain injury (mTBI) has been shown to acutely alter the gut microbiome diversity and composition, known as dysbiosis, which can further exacerbate metabolic and vascular changes in the brain in both humans and rodents. However, it remains unknown how mTBI affects the gut microbiome in the chronic phase recovery (past one week post injury). It is also unknown if injury recovery can be improved by mitigating dysbiosis. The goal of the study is to fill the knowledge gap.

All cellular RNAs are synthesized by evolutionary related DNAdependent multisubunit RNA polymerases (Pols). Bacteria and archaea each use a single Pol to synthesize all their RNAs whereas a hallmark of eukaryotes is three homologous Pols, I, II and III and the associated Pol-specific transcription factors (TFs) to regulate synthesis of different class RNAs. The Pol III system produces high molar amounts of tRNAs and other small ncRNAs by the efficient reuse of its stable transcription complexes after formation on the promoters of its target genes, and the recycling of Pol III itself.

Plant virus nanoparticles (PVNPs) are increasingly recognized and studied for use in biomedical applications. PVNPs include plant virions with self-assembled capsid protein coats (PC) that encapsulate the virus genome, and virus-like particles (VLPs), a capsid without the viral genome.

Heterozygous mutations in ELANE, the gene for neutrophil elastase, cause cyclic and congenital neutropenia through the programed cell death of neutrophil progenitors in the bone marrow. Granulocyte colony-stimulating factor is an effective therapy for these diseases, but alternative therapies are needed, especially for patients who do not respond well or are at high risk of developing myeloid malignancies. We developed an HL60 cell model for ELANE neutropenia and previously demonstrated that transient and regulated expression of mutant ELANE causes cell death by accelerated apoptosis.

Bacterial communication via quorum sensing (QS) molecules, as well as toxin-antitoxin (TA) gene modules located on bacterial chromosomes are well-studied mechanisms. Escherichia coli mazEF is a stress-induced TA system mediating cell death requiring a QS extracellular death factor (EDF), the pentapeptide NNWNN. MazF is an endoribonuclease specific for ACA sites. During adverse conditions, the activated MazF generates a stress induced translation machinery, composed of MazF-processed mRNAs and selective ribosomes that specifically translate these processed mRNAs.

Polycystic kidney disease is an inherited degenerative disease in which the uriniferous tubules are replaced by expanding fluid-filled cysts that ultimately destroy organ function. Autosomal dominant polycystic kidney disease (ADPKD) is the most common form, afflicting approximately 1 in 1,000 people and is caused by mutations in the transmembrane proteins polycystin-1 (Pkd1) and polycystin-2 (Pkd2).

Alzheimer’s disease (AD) research has long been dominated with communications regarding the amyloid hypothesis and targeting amyloid clearance through pharmacological therapies from the brain. Unfortunately, this research strategy has yielded only one new FDA-accelerated approved therapeutic for early AD, and its clinical benefit still needs to be verified. It may be time to employ a new strategy in AD therapeutics research. Hammond et al. reported that diminished uptake of glucose in the brain is a better marker for classifying AD than beta-amyloid (Aβ) or phosphorylated tau deposition.

The Randomized intervention for Vesicoureteral Reflux (RiVUR) study was an effort by the National Institute of Health to identify the most significant question on the management of vesicoureteral reflux (VUR), i.e. Did antibiotic prophylaxis reduce the incidence of recurrent urinary tract infections (UTI) in children with VUR? During the initial phases of the RiVUR study, several similar studies were performed that seemed to indicate lack of benefit of antibiotic prophylaxis in VUR.

Alzheimer’s disease (AD) is the most common form of dementia with hallmarks of ß-amyloid (Aß) plaques, tau tangles, and neurodegeneration. Studies have shown that neurodegeneration components, especially brain metabolic deficits, are more predictable for AD severity than Aß and tau. However, detailed knowledge of the biochemical composition of AD brain tissue vs. normal brain tissue remains unclear.

The prevalence of many musculoskeletal and cardiovascular diseases that cause limitations in physical functioning has increased globally [1] with age-adjusted rates of incidence rising for many of these diseases [2-5]. In the United States alone, chronic health conditions that limit physical function have an estimated economic impact of $200

Inflammation drives prostate cancer (PCa) progression. While inflammation is a cancer hallmark, the underlying mechanisms mediating inflammation-induced PCa are still under investigation. Interleukin-1 (IL-1) is an inflammatory cytokine that promotes cancer progression, including PCa metastasis and castration resistance. We previously found that acute IL-1 exposure represses PCa androgen receptor (AR) expression concomitant with the upregulation of pro-survival proteins, causing de novo accumulation of castration-resistant PCa cells.

In 1989, researchers proposed an intricate strategy in the field of adoptive cell therapy (ACT). Using the T-cell receptor (TCR) as a template, they replaced the coding sequence for the Vα and Vβ chains with the antigen- recognition domains from an antibody (VH and VL chains).

Interleukin (IL)-2 was first identified as a potent T cell growth factor in 1976 and cloned in 1983. In the late 1990s, IL-2 gained further attention as the first immunotherapy demonstrating clinical efficacy against metastatic cancer, as high dose IL-2 was approved by the United States Food & Drug Administration (FDA) for the treatment of metastatic renal cell carcinoma in 1992 and metastatic melanoma in 1998.

Diffuse intrinsic pontine glioma (DIPG) is an aggressive brain tumor that arises in the ventral pons during middle childhood. 

The multi-ligand binding protein megalin (LRP2) is ubiquitously expressed and facilitates cell uptake of hormones, nutrients and vitamins. We have recently shown megalin is present in the mitochondria of cultured epithelial and mesenchymal cells, as well as many organs and tissues. Mitochondrial megalin associates with stanniocalcin-1 and SIRT3; two proteins that promote anti-oxidant defenses.

Inflammatory Bowel Disease (IBD), which includes Crohn’s Disease (CD) and Ulcerative Colitis (UC), has a heterogeneous pathogenesis underlined by genetic predisposition, intestinal barrier dysfunction, impaired immune response, and microbiota imbalance. This proceeds to aberrant immune cells presence and function in the affected tissue, activation of signaling pathways, and expression of regulators that subsequently drive inflammation.

Alzheimer’s Disease (AD) and Alzheimer’s Disease-Related Dementias (ADRD) are debilitating conditions that are highly associated with aging populations, especially those with comorbidities such as diabetes and hypertension.

Cancer is a worldwide public health issue that affects millions of people every year. In 2018 there were 17 million newly documented cases of cancer globally (8.8 million in men and 8.2 million in women), leading to 9.6 million deaths. Cancer is a vastly heterogeneous disease, with over 100 different types of cancer currently identified in humans; the most common types of cancer are lung, female breast, bowel and prostate, these four types account for more than 40% of all new cancer case

Previously characterized as a purely immune mediated disease, sepsis is now recognized as a dysregulated multisystem response against a pathogen. Recognition of the infectious agent by pathogen recognition receptors (PRRs) can initiate activation of the NF-κB signaling pathway and promote the secretion of proinflammatory cytokines. During sepsis, the activation of NF-κB is dysregulated and results in cytokine storm, or the pathologic release of cytokines.

The replication of viruses requires host cell functions, specifically for protein synthesis, as viruses lack their own translational machinery. Failure to translate viral mRNAs and generate viral proteins would affect the propagation and evolution of a virus. Thus, independently of their size, complexity, and genomes, viruses evolved sophisticated molecular mechanisms to hijack the translational apparatus of a host in order to recruit ribosomes for efficient protein production. 

Neuroblastoma is derived from the developing sympathetic nervous system and is the most common extracranial solid tumor of childhood.

 Inhaled budesonide benefits patients with COVID-19. ProLung™-budesonide enables the sustained, low dose administration of budesonide within a delivery vehicle similar to lung surfactant. ProLung™-budesonide may offer anti-inflammatory and protective effects to the lung in COVID-19, yet it’s effect on SARS-CoV-2 replication is unknown.

Hepatocellular carcinoma (HCC) is a significant cause of cancer mortality worldwide. Chronic hepatic inflammation and fibrosis play a critical role in the development of HCC. Liver fibrosis develops as a result of response to injury such that a persistent and excessive wound healing response induces extracellular matrix (ECM) deposition leading to HCC.

The electron-dense spherical granules found in the perinuclear region of atrial myocytes store and release both proatrial and probrain natriuretic peptides (proANP and proBNP, respectively). Mature ANP and BNP produce vasodilation and natriuresis and inhibit the renin-angiotensin and sympathetic nervous systems.

Hydrogen peroxide (H₂O₂) is an important intra- and extra-cellular signaling molecule that can determine cell fate. At low concentrations, H₂O₂ plays roles in proliferation, immunity, and metabolism. Cellular exposure to higher non-physiologic concentrations of H₂O₂ can result in oxidative stress.

Cullin-RING E₃ ubiquitin ligase 4 (CRL₄) plays an essential role in cell cycle progression. Recent efforts using high throughput screening and follow up hit-to-lead studies have led to identification of small molecules 33-11 and KH-4-43 that inhibit E₃ CRL₄’s core ligase complex and exhibit anticancer potential.

The survival probability of early human conceptions is very low. At least 73% of natural single conceptions have no real chance of surviving six weeks of gestation. After six weeks, survival rates improve rapidly as 90% of the remainder will survive to term. This low fetal loss rate is close to the low rates of 1% - 2.9% for different methods of artificial reproduction. From 16 weeks the rate of loss reduces further, to around 1%.

The western diet and overuse of anti-inflammatory medication have caused a great deal of stress on the liver. Obesity and the associated inflammatory state in insulin-responsive tissues result in the release of pro-inflammatory cytokine that activates the stress-responsive MAPKs, p38 MAPK, and JNK. These MAPKs have figured prominently as critical effectors in physiological and pathophysiological hepatic inflammation.

Cardiac sarcomeres express a variant of troponin I (cTnI) that contains a unique N-terminal extension of ~30 amino acids with regulatory phosphorylation sites. The extension is important in the control of myofilament response to Ca²⁺, which contributes to the neuro-humoral regulation of the dynamics of cardiac contraction and relaxation.

Health intelligence on the frequency of cardiovascular disease (CVD) and its risk factors identifies targets and populations for preventative strategies and allows evaluation of health outcomes, behaviors and interventions in populations and health care settings.

In the realm of DNA repair, base excision repair (BER) protein, APE1/Ref-1 (Apurinic/Apyrimidinic Endonuclease 1/Redox Effector - 1, also called APE1) has been studied for decades. However, over the past decade, APE1 has been established as a key player in reduction-oxidation (redox) signaling. In the review by Caston et al. (The multifunctional APE1 DNA repair-redox signaling protein as a drug target in human disease), multiple roles of APE1 in cancer and other diseases are summarized. 

The expression of small non-coding RNA MicroRNAs (miRNAs) during respiratory viral infections is of critical importance as they are implicated in the viral replication, immune responses and severity of disease pathogenesis. Respiratory viral infections have an extensive impact on human health across the globe. For that is essential to understand the factors that regulate the host response against infections.

Environmental enrichment produces beneficial effects in the brain at genetic, molecular, cellular and behavior levels, and has long been studied as a therapeutic intervention for a wide variety of neurological disorders. However, the complexity of applying a robust environmental enrichment paradigm makes clinical use difficult. Accordingly, there has been increased interest in developing environmental enrichment mimetics, also known as enviromimetics.

Traumatic brain injury (TBI) has a bimodal age distribution with peak incidence at age 24 and age 65 with worse outcomes developing in aged populations

Experimental and hereditary defects in the ubiquitous scaffolding proteins of the spectrin gene family cause an array of neuropathologies

Diabetes is a major healthcare concern worldwide. In addition to the financial burden estimated at $760 billion, the human suffering related to complications of diabetes as well as the disease itself are immense. Complications associated with diabetes affect both men and women, but there is a higher incidence reported in the aging population, women, and people of color.

Dementia and hypertension are highly prevalent, epidemiologically related chronic conditions disproportionately affecting older persons; approximately 97% of persons with dementia and 66% with hypertension are over the age of 65.

In 2019, approximately 38 million people were infected with HIV worldwide [1]. Although there is still no cure that successfully eradicates the disease, combination antiretroviral therapy (cART) has improved to a point where undetectable viral loads have become achievable and HIV carriers often live almost normal lives with very substantially increased average life expectancies compared to historical data.

Chemokines and their receptors are the communication mechanism used by cells of the immune system, allowing them to identify and eliminate pathogens and cancerous cells. However, it is becoming clear that chemokines and their receptors are also playing a role in tumor progression and metastasis. An example of such coopting is the CCL2-CCR2 axis.

APE1/Ref-1 (also called Ref-1) has been extensively studied for its role in DNA repair and reduction-oxidation (redox) signaling. The review titled: “The multifunctional APE1 DNA repair-redox signaling protein as a drug target in human disease” by Caston et. al. summarizes the molecular functions of Ref-1 and the role it plays in a number of diseases, with a specific focus on various types of cancer.

Extracellular matrix (ECM) surrounding cells in solid tissue provides mechanical support and communicates with cells through cell adhesion molecules (CAMs) at the cell surface. Integrin is a major group of CAMs represented by a family of αβ heterodimeric single transmembrane receptors. 

Exosomes are nanosized, organelle-like membranous vesicles secreted from various cell types, including normal cells and cancer cells. Exosomes contain abundant bioactive molecules, including nucleic acids, lipids, and proteins and dynamically participate in intercellular communications. By shuttling the functional molecules into the recipient cells, exosomes secreted by cancerous cells can alter the cellular environment to favor tumor growth and metastasis.

Bladder cancer is one of the most common and expensive cancers in the United States, with an expected 81,400 new cases and 17,980 deaths in 2020 alone. The incidence is increased among white men and diagnoses often occur in the 7th decade of life.

Improving our knowledge regarding the cellular and molecular mechanisms underlying murine models of alcoholic liver injury should enhance the management and therapies of alcoholic liver disease (ALD) seen in humans [1]. Although none of the animal models available reproduce all main aspects of human ALD, they still provide very

Bacillus anthracis (Ba) is a gram-positive, rod-shaped, spore- and toxin-forming bacterium. While mainly an herbivore pathogen, human infection with Ba spores can occur through a number of routes including cutaneous, gastrointestinal, injectional, or inhalational. The deadliest form of anthrax exposure is through inhalation of Ba spores, leading to systemic dissemination of the bacteria, with mortality ranging from 45% to 90%. 

Ca²⁺/ calmodulin (CaM) signaling is important for a wide range of cellular functions. It is not surprised the role of this signaling has been recognized in tumor progressions, such as proliferation, invasion, and migration. However, its role in leukemia has not been well appreciated. The multifunctional Ca²⁺/CaM-dependent protein kinases (CaMKs) are critical intermediates of this signaling and play key roles in cancer development.

The current COVID-19 pandemic has brought to public attention the conceptual difference between a test for COVID-19 derived RNA or proteins indicating the presence of an active infection, versus COVID-19 serology testing indicating pathogen infection. Only the former test for molecules derived from COVID-19 provides reliable evidence of a current active infection.

Extracellular vesicles (EVs) are emerging as a key mediator of intercellular communication as well as a major mechanism of functional reprogramming of cells in disease. All cells produce EVs, which freely circulate and are found in all body fluids. EVs are heterogenous, consisting of subsets of vesicles with different sizes, distinct origins, and various functions (Figure 1). They mediate a broad variety of biological events ranging from cellular activation, inflammation, blood coagulation, angiogenesis, cellular transport, and others.

Flavopiridol (FVP; alvocidib), an FDA-approved orphan drug, has been studied in clinical trials under both single treatment and combination scenarios; several singleagent Phase I and Phase II clinical trials against leukemia, lymphomas, and solid tumors are active. To date, there have been more than 50 clinical trials involving FVP in the United States. Unfortunately, almost half of patients on FVP clinical trials showed serious adverse effects, implicating appropriate dosages need to be found and an alternative way to circumvent the toxicity of FVP with synergistic agents.

Objective: To evaluate demographics and outcomes of maternal-fetal pairs in early onset fetal growth restriction (FGR) requiring delivery prior to 34 weeks’ gestation based on ultrasound indication leading to diagnosis. Study Design: This is a descriptive study of maternal-fetal pairs with early FGR diagnosed prior to 30 weeks’ gestation and delivering between 22w0d and 34w0d under the care of Wake Forest University Perinatology 01/2012-12/2016. 

Neuroinflammation is closely associated with various diseases including neuropathic pain. Microglia are immune cells in the central nervous system which are the main players of immunity and inflammation. Since microglia are activated by nerve injury, and they produce proinflammatory mediators to cause neuropathic pain, targeting activated microglia is considered to be a strategy for treating neuropathic pain.

New globally circulating SARS-CoV-2 strains are causing concern about evolution of virus transmissibility, fitness and immune evasion mechanisms. A variant emerging from the United Kingdom called SARS-CoV-2 VUI 202012/01, or B.1.1.7, is thought to exhibit increased transmissibility that results from replication 4-10 times faster than the original Wuhan virus (Wuhan-Hu-1).

HIV is a known risk factor for both ischemic and hemorrhagic stroke. Even with the widespread use of antiretroviral therapy, stroke incidence is higher in patients with HIV compared to non-HIV control subjects.

The ongoing pandemic of the novel coronavirus of 2019 (COVID-19) has resulted in over 1 million deaths, primarily affecting older patients with chronic ailments. Multiple sclerosis (MS) patients have been deemed particularly vulnerable given their high rates of disability and increased susceptibility to infections. There have also been concerns regarding disease-modifying therapy (DMT) during the pandemic as many DMTs may increase the risk of infection due to some of their immunosuppressive properties.

Myocardial infarction (MI) due to coronary artery stenosis compromises vascular endothelial integrity and increases vascular permeability. Concurrently, ensuing myocardial tissue death and necrosis results in the release of danger associated molecular patterns (DAMPs), cytokines, chemokines, bioactive lipids, as well as activation of the complement cascade. 

Since the declaration of COVID-19 as a pandemic in March 2020, there have been more than 100 million reported cases of COVID-19 worldwide and more than 2.1 million deaths. The purpose of this editorial is to review recent updates regarding COVID-19 disease and SARS-CoV-2 vaccination in cancer patients.

The positive prognostic role of the immune environment in colorectal cancer is widely accepted. However, there are few data about the prognostic significance of interleukin-22 in human colorectal cancer which is still debated.

Among women living with HIV (WLWH), increases in body weight and body mass index (BMI, kg/m2) have been observed after switching to the antiretroviral therapies (ART) - Integrase Inhibitors (INSTI) and/or Tenofovir Alafenamide (TAF).

Cell Death has long been considered to be an inevitable part of the life cycle of a cell and hence, considered a familiar consequence of cellular life.

The present Commentary is a critical follow-up of a previous review about “Extracellular vesicles, news about their role in immune cells: physiology, pathology and diseases”, appeared in Clinical and Experimental Immunology last June 2019 [1].

The Wnt signaling is classified as two distinct pathways of canonical Wnt/β-catenin signaling, and the non-canonical pathways of planar cell polarity and Wnt/Ca²⁺ pathways. However, the scientific discoveries in recent years have shown that canonical and noncanonical Wnts pathways are intertwined and have complex interaction with other major signaling pathways such as hedgehog, Hippo and TOR signaling.

The outbreak of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has led to coronavirus disease-19 (COVID-19); a pandemic disease that has resulted in devastating social, economic, morbidity and mortality burdens. SARS-CoV-2 infects cells following receptor-mediated endocytosis and priming by cellular proteases.

In 2019, approximately 56,770 new cases of pancreatic cancer were diagnosed in the United States, resulting in an estimated 45,750 deaths. Pancreatic cancer is one of the leading causes of cancer-related death, with a fiveyear survival rate of 9%. Based on the eighth edition of the American Joint Committee on Cancer (AJCC) staging system for pancreatic adenocarcinoma, multi-center analyses have validated that poorer prognosis is associated with node-positive disease (N1 and N2).

Macrophages play a crucial role in host innate immune defense against infection and tissue injury. Although macrophage activation and polarization has been well studied, we know less regarding the role of macrophage activation/polarization in inflammationassociated necrotic cell death. By using bone marrow-derived macrophages, we have recently demonstrated that M1 macrophages are much more susceptible than M0 and M2 subtypes of macrophages to necrotic cell death.

The concept of immunotherapy has been traced as far back to third century BC Qin dynasty in China through the purposeful inoculation of Variola minor to prevent smallpox. 

Currently, there is a growing need for culturing hematopoietic stem/progenitor cells (HSPCs) ex vivo for various clinical applications such as HSPC transplantation and gene therapy. For many patients with hematologic, genetic, and immune diseases, HSPC transplants can be a life-saving treatment. There are over 20,000 patients in the US receiving HSPC transplantation yearly.

Until recently, oral glucocorticoid (GC) therapies were the mainstay of treatment for uncontrolled inflammatory disease across many body systems. The last 30 years, however, have witnessed a transformation in the management of many diseases due to the development of targeted biological agents leading to a reduction, albeit not a removal, of the dependence on oral GCs.

Recent progress in the therapies used for patients with Non- Hodgkin’s lymphoma (NHL) has improved survival. In 2020, 77,240 people were diagnosed with NHL. Although it accounts for 4% of all cancers, the incidence has been reported to be decreasing in the last few years. About 26% of people will expire from NHL (15% males and 11% females).Non-Hodgkin lymphoma arises from the clonal expansion of B, T, and natural killer (NK) cells. There is a significant degree of heterogeneity in NHL and this is likely related to different degrees of differentiation and maturation of these cells. These hematological malignancies exhibit different tumor behavior and are responsive to different chemotherapy agents which impacts clinical outcomes. There are patients who can be cured with current regimens; however, subtypes such as indolent and some aggressive lymphomas remain incurable necessitating treatment with new therapies including immunotherapy, targeted therapy, CAR T cells, and hematopoietic stem cell transplant.

Acute respiratory distress syndrome (ARDS) is the major cause of mortality among hospitalized acute lung injury (ALI) patients. Lung macrophages play an important role in maintaining the tissue-fluid homeostasis following injury. We recently showed that circulating monocytes recruited into the alveolar space suppressed the stimulator of type 1 interferon genes (STING) signaling in alveolar macrophages through sphingosine-1-phosphate (S1P). 

Chronic pain, defined as pain lasting longer than three months, is a significant public health burden and has been associated with depression, anxiety, poor quality of life and opioid use disorder (OUD).

We recently reviewed the scientific literature linking dopamine agonist pharmacotherapy for neurological disorders to the development of impulsive and compulsive spectrum disorders (ICSDs). 

The neuropeptide Calcitonin Gene-Related Peptide (CGRP) is a 37-amino acid peptide, with a wide-range of biological activities including vasodilation, neurogenic inflammation, immune function and hypertension. In addition to these various roles, it has also been heavily implicated in metabolic disease, with roles in feeding, energy dissipation processes and pancreatic β-cell insulin secretion.

Deoxyribonucleic acid (DNA) methylation is a critical type of epigenetic modification that typically occurs in a specialized region of DNA, CpG-rich regions in the mammalian genome and is associated with regulating gene expression. Previous studies have revealed a strong association of change in DNA methylation with various diseases such as cancer, obesity and posttraumatic stress disorder (PTSD).

Forkhead transcription factors (TFs) often dimerize outside their extensive family, whereas bHLH transcription factors typically dimerize with E12/E47. Based on structural similarities, we predicted that a member of the former, Forkhead Box P1 (FOXP1), might heterodimerize with a member of the latter, MYOD1 (MyoD).

The renewed interest in understanding how activated T cells alter their metabolism to support their growth and differentiation has led to several innovative advances in synthetic biology; culminating in a number of genetic and pharmacologic approaches aimed at improving the antitumor function of adoptively transferred T cells. Indeed, the growing field of immunometabolism has accelerated rapidly giving rise to exciting discoveries and exploratory studies revealing how T cells balance metabolic adaptations in response to intrinsic and extrinsic regulatory cues. Central to this body of work, we showed how chimeric antigen receptors (CAR)-induced metabolic reprogramming is an important determinant of efficacy and clinical outcome in blood-based malignancies.

Epigenetic processes provide a mechanism for integrating metabolic inputs and translating them into various phenotypic outputs [1,2]. Indeed, epigenetic modifiers often require or are inhibited by key citric acid cycle (CAC) metabolites (e.g. succinate,

Due to use as human vaccines and therapies, the clostridial neurotoxins (CNTs) have been subjected to decades of scientific investigation using biophysical, electrophysiological, and pharmacological approaches to establish mechanisms of toxin action. 

Caspase-6 was discovered decades ago, but its roles in biological processes remain largely unknown. Recently, we have demonstrated that caspase-6 plays a critical role in influenza A virus (IAV)-induced cell death and innate immune responses. During IAV infection, Z-DNA binding protein 1 (ZBP₁) initiates ZBP₁-PANoptosome assembly to drive inflammasome activation and cell death, and we showed that caspase-6 interacts with RIPK₃ to enhance the interaction between RIPK₃ and ZBP₁, thus promoting PANoptosome assembly.

We review here the evidence for participation of mitochondrial autoimmunity in BC inception and progression and propose a new paradigm that may challenge the prevailing thinking in oncogenesis by suggesting that mitochondrial autoimmunity is a major contributor to breast carcinogenesis and probably to the inception and progression of other solid tumors. It has been shown that MNRR1 mediated mitochondrial-nuclear function promotes BC cell growth and migration and the development of metastasis and constitutes a proof of concept supporting the participation of mitochondrial autoimmunity in breast carcinogenesis. 

Chronic, non-healing, or slow to heal wounds present a significant and growing health problem in the United States, with an estimated 6.5 million people affected, at an annual cost of US $20 billion, with the highest risk groups represented by the elderly and the increasing prevalence of lifestyle diseases such as diabetes and obesity.

In our recent publication, we have explored at the molecular level the consequences of reovirus administration to patients with KRAS mutated colorectal cancer (CRC). This was the first reported study where transcriptome assay was performed on KRAS mutated CRC patients receiving reovirus (pelareorep) therapy. Using peripheral mononuclear cells as a tumor surrogate, we have identified several hundred genes that were significantly altered in a transcriptome assay of patients receiving pelareorep serving as their own controls (pre and post reovirus administration) and compared to untreated controls.

Obesity has reached a global epidemic and it predisposes to the development of insulin resistance, type 2 diabetes and related metabolic diseases. Current interventions against obesity and/or type 2 diabetes such as calorie restriction, exercise, genetic manipulations or established pharmacological treatments have not been successful for many patients with obesity and/or type 2 diabetes.

Nausea and vomiting are protective defense mechanisms by which vomit competent species avoid ingestion of potentially toxic substances. More specifically, vomiting is the act of forceful expulsion of gastrointestinal contents through the mouth, whereas nausea is an unpleasant painless subjective feeling that one will imminently vomit.

Nonalcoholic fatty liver disease (NAFLD), a spectrum of pathologies ranging from simple steatosis to fibrosis and cirrhosis, is the most common cause of chronic liver disease, affecting over 80% of adults with obesity, one third of obese children ages 3-18 in North America [2] and ~10% of the general pediatric population.

The symptoms of the COVID-19 range from asymptomatic or mild disease to severe disease that results in acute respiratory distress syndrome (ARDS) and eventually death. Understanding the molecular mechanisms responsible for the progression from mild to severe disease is the key to decreasing the mortality of COVID-19. Compared to mild cases, severe cases of the COVID-19 have decreased interferon (IFN) a, ß, λ production. Type I (IFN a/ß) and III IFNs (λ) work coordinately to induce inhibition of viral reproduction through the stimulation of interferon stimulated genes (ISGs).

At the end of 2019, a novel coronavirus was identified as the cause of a cluster of pneumonia cases in Wuhan, a city in the Hubei Province of China.

Background: We have recently published SL-BioDP, a web resource for querying, exploration and visualization of potential synthetic lethal targets and possible synergistic drug combinations for 18 cancer types. Methods: From our predictive synthetic lethality model used in SL-BioDP, we inferred TP53 mutation lead to potential synergistic drug combination of Bortezomib and Vorinostat. Here we show, how to extrapolate the drug combination results by combining drug screening data from cancer cell lines and showed the potential synergy of the drug targets, proteasome, and histone deacetylase (HDAC) pathways respectively, for patient survival advantage.

The failure to eradicate minimal residual disease often located at metastatic sites and/or the bone marrow niche continues to be a clinical barrier for successful treatments in cancer.

Competent human DNA mismatch repair (MMR) corrects DNA polymerase mistakes made during cell replication to maintain complete DNA fidelity in daughter cells; faulty DNA MMR occurs in the setting of inflammation and neoplasia, creating base substitutions (e.g. point mutations) and frameshift mutations at DNA microsatellite sequences in progeny cells. Frameshift mutations at DNA microsatellite sequences are a detected biomarker termed microsatellite instability (MSI) for human disease, as this marker can prognosticate and determine therapeutic approaches for patients with cancer.

Fatty acid oxidation disorders unfortunately can result in the sudden unexplained death of infants. Mitochondrial trifunctional protein (MTP) deficiency is one such disease where long-chain fatty acids cannot be fully oxidized through beta-oxidation which, can lead to cardiac arrythmias in an infant.

ICAM-1 is a transmembrane, cell surface glycoprotein expressed by a variety of cells, but has been best-studied in vascular endothelium. Structurally, ICAM-1 is composed of five extracellular IgG- like domains to help facilitate cell-cell interactions and has a short cytoplasmic tail anchored to the cytoskeleton to facilitate intracellular signal transduction.

Fluoropyrimidines have been extensively used for almost 6 decades to treat a variety of solid cancers, especially colon, gastric, anal, rectal, head & neck and breast. However, 31–34% of patients encountered grade 3–4 adverse events (AEs) with 0.5% mortality oftennecessitating dose reduction or discontinuation. A significant proportion of these AEs are likely to be the result of inter-individual genetic variation, in particularly such as dihydropyrimidine dehydrogenase (DPYD). DPYD gene encodes DPD, the rate-limiting enzyme responsible for catabolism of 5-FU and is responsible for >85% of 5-FU elimination.

Vinpocetine is a derivative of vincamine. It has been used to prevent and treat cerebrovascular disorders such as stoke and dementia, and remains widely available in dietary supplements that often marketed as nootropics. Due to its excellent safety profile at therapeutic dose regimen, vinpocetine has raised research interest in its new applications in various experimental disease models.

The immunomodulatory drug lenalidomide is used for the treatment of certain hematologic malignancies, including myelodysplastic syndromes (MDS). Lenalidomide interacts with cereblon (CRBN), a component of the CRL₄^CRBN E₃ ubiquitin ligase complex, leading to ubiquitination and subsequent degradation of substrates, such as transcription factor Ikaros (Ikaros family zinc finger 1, IKZF1).

Being a sophisticated and highly organized living system, mammals harbor a large number of biomolecular machineries which represent a dynamic and complex network of interconnections responsible for the effective operation, development and survivability of their body cells. Sphingolipids are a special class of lipids in eukaryotic cells, which have recently gained the attention of researchers because of their involvement in several fundamental processes of living cells, including proliferation

Men who have sex with other men (MSM) comprise the single largest group of individuals contracting HIV in the United States, accounting for more than one-half of all new HIV diagnoses.

Fluoropyrimidines compose the backbone of regimens to treat many common solid tumors, including gastrointestinal (GI), breast and head/neck. As we continue to use these agents routinely, recognition of rare but real toxicities, such as cardiotoxicity, has also improved. The treatment options for patients who have encountered fluoropyrimidine-induced cardiotoxicity are limited as many anti-angiogenic drugs also pose a cardiac risk.

Malignant mesothelioma is a relatively rare malignancy arising in the body’s serosal surfaces, with malignant pleural mesothelioma (MPM) being the most common type. It is characterized by local spread within the thorax, poor prognosis and resistance to treatment. The development of various immunotherapeutic options has provided a new way- and hope- in treating cancer patients. Chimeric antigen receptor (CAR) T cell therapy has been proven very successful in treating hematological cancers, like leukemias and lymphomas, and its use is now being tested in solid tumors.

Five months into the COVID-19 pandemic, the U.S. death toll from the virus has now surpassed 100,000 people. Many more cases remain nationwide, while an unknown number of patients currently harbor the virus asymptomatically. While health officials are now optimistic regarding the decline in prevalence and number of deaths due to COVID-19 and the possibility of a vaccine by the fall, we cannot lose sight of the bigger picture: the next pandemic.

In a recent paper, we introduced a variant of the classical Simeoni tumor growth model, and illustrated its value in assessing tumor growth in a reproducible mouse model for mammary tumors. Our modification consisted of incorporating delay differential equations in the mathematical formulation of the Simeoni model, to represent the delay in drug action often observed under chemotherapeutic or immunotherapeutic regimens.

Glucocorticoids (GCs) are defined by their role in maintaining glucose homeostasis and natural GCs are a class of corticosteroids secreted by the adrenal cortex. Cortisol is the most important natural GC in humans. Cellular cortisol levels are regulated by the tissue-specific metabolic enzymes 11β-hydroxysteroid dehydrogenase 1 and 2 (11β-HSD 1 and 2); 11β-HSD 1 converts inactive cortisone to active cortisol, while 11β-HSD 2 has the opposite function.

Observational studies have demonstrated association of metformin with reduced cancer incidence and mortality in multiple cancer types, including gastrointestinal (GI) malignancies. Anti-neoplastic effects of metformin are believed through many mechanisms including activation of AMP-activated protein kinase, which controls mammalian target of rapamycin (mTOR) growth regulatory pathway.

Damage to the nervous system can have direct and indirect impact on the lower urinary tract. Broadly speaking, damage can be grouped into three categories: problems with bladder storage, stress incontinence, and problems with bladder emptying [1]. 

While the global COVID-19 pandemic has challenged the entire humanity and health systems, it also triggered researchers to urgently perform clinical trials to assess the safety and efficacy of many agents and modalities to combat COVID-19. As of April 22, over 650 clinical studies have been registered both in USA and internationally. Results from these studies are also coming at a brisk pace in this unprecedented emergency.

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease characterized by an accumulation of scar tissue within the lungs and the common presence of usual interstitial pneumonia. Unfortunately, only a few FDA-approved therapeutic options are currently available for the treatment of IPF and IPF remains associated with poor prognosis. Therefore, the identification of new pharmacological targets and strategies are critical for the treatment of IPF.

CRISPR (clustered regularly interspaced short palindromic repeats) technology has dramatically simplified genome editing and is widely applicable in both basic research and therapeutic areas. The basic principle of CRISPR relies on the use of guide RNA which is designed to bind to the DNA sequence of interest along with a CRISPR-associated (Cas) endonuclease which introduces a double-stranded DNA break (DSB) at that site.

Breast implant-associated anaplastic large cell lymphoma is a recently recognized complication of textured breast implants. It typically presents as unilateral peri-implant swelling approximately 7-10 years after implantation. While the course is usually indolent, breast implant-associated anaplastic large cell lymphoma may form a locally invasive mass and metastasize to regional lymph nodes or beyond to distant sites.

Human monocytic ehrlichiosis (HME) is an emerging life-threatening tick-borne disease caused by the obligate intracellular bacterium Ehrlichia chaffeensis. HME is often presented as a nonspecific flu-like illness characterized by presence of fever, headache, malaise, and myalgia. However, in some cases the disease can evolve to a severe form, which is commonly marked by acute liver injury followed by multi-organ failure and toxic shock-like syndrome.

Low back pain (LBP) is one of the most prevalent conditions that will affect 70-85% of individuals at some point in their life [1]. LBP accounts for 2.3% of all visits to the physician, and is the most common area of the body to experience pain [2]. Exercise has been a mainstay for managing persons with chronic low back pain for almost 40

It is now well accepted that the ionizing radiation-generated reactive oxygen species (ROS), that constitute ~2/3 of the effects of external beam radiation, do not only produce direct tumor cell death, but also affect the surrounding microenvironment. Moreover, this indirect effect of radiation may result in systemic effects, specifically the initiation of an inflammatory response.

Hypothesis-driven research has dominated biomedical science for at least the past century. There are many papers and grant applications that will have been rejected because they are not hypothesis-driven. For example, Haufe reports that the NIH guidelines for RO1 grants states that “A strong grant application is driven by a strong, solid hypothesis with clear research objectives”.

Diabetes is a widespread autoimmune disorder that affects nearly 10% of the adult population in the United States. In addition to the primary disease, there are numerous complications associated with inflammation including abnormalities of the heart, visual system, and peripheral nervous system. More than half of the individuals with diabetes will have one or more ocular related complications such as dry eye disease (DED), keratopathy, or retinopathy.

Ovarian cancer stands as the most lethal gynecologic malignancy and remains the fifth most common gynecologic cancer. Poor prognosis and low five-year survival rate are attributed to nonspecific symptoms at early phases along with a lack of effective treatment at advanced stages. It is thus paramount, that ovarian carcinoma be viewed through several lenses in order to gain a thorough comprehension of its molecular pathogenesis, epidemiology, histological subtypes, hereditary factors, diagnostic approaches, and methods of treatment.

With increasing rates of obesity, rates of type 2 diabetes and diabetic complications are expected to rise exponentially over the next few decades (American Diabetic Association). A key feature of type 2 diabetes is a resistance to insulin. Insulin signaling is key to a number of physiological processes, including glucose metabolism, cell growth, general gene expression, and apoptosis.

Different humanized mouse models have been introduced to enable HIV-1 research in vivo, which has been made possible by the development of immunodeficient mouse strains.

Autophagy was originally viewed as a widely conserved multistep lysosomal degradation pathway in eukaryotes. It includes the formation of autophagosomes, doublemembrane structures engulfing cytoplasm with damaged organelles during the degradation process.

The human induced pluripotent stem cell (iPSC) technology was developed more than ten years ago and has provided important tools for the mechanistic and cellular interrogation of many diseases [1]. To generate iPSC lines, somatic cells are reprogrammed into cells resembling embryonic stem cells by the overexpression of key transcription factors.

Necroptosis is a form of programed necrosis mediated by receptor-interacting serine/threonine-protein kinase 1 (RIP1) and RIP3 and the subsequent phosphorylation of mixed lineage kinase domain-like protein (MLKL). Necroptosis has been implicated in multiple human diseases such as myocardial infarction, atherosclerosis, and abdominal aortic aneurysms (AAAs). Levels of RIP3 are elevated in the human tissues affected by these diseases.

Systemic Lupus Erythematosus (SLE) is a devastating autoimmune disease that affects women to men at a ratio of 9:1 and is predominant in those of African ancestry. In SLE, the presence of autoantigens results in aberrant immune activation leading to systemic inflammation that predominantly affects the brain, kidneys, blood, and skin. Current guidelines recommend treatment with immunosuppressive drugs like prednisone, cyclophosphamide, azathioprine, and even some antimalarial drugs

Antibiotics can treat the acute phase of a disease, but often do not completely clear the etiologic agent, allowing the pathogen to establish persistent infection that can revive the disease in a frustrating recurrence of infection. The mechanisms that control chronic bacterial infections are complex and involve pathogen adaptations that favor survival from both host immune responses and antibiotic bactericidal activity.

Worldwide, obesity is a public health concern and a metabolic ailment characterized by excessive adipose tissue accumulation resulting from an imbalance of energy expenditure and energy intake [1]. This disorder is a known risk factor for cardiovascular disease, type 2 diabetes mellitus, dyslipidemia, hypertension, and metabolic

Type 2 diabetes (T2D) remains undiagnosed for many years in large number of persons living in developing countries. The cost of diagnostic tests and the invasive procedures involved in conventional screening methods remain a major setback to timely testing

HIV/AIDS continues to be a major public health disease accounting for 35 million deaths across the world. In 2016 alone, there were 1.8 million new HIV infections and 1 million deaths worldwide.

Inflammation can be caused by various environmental factors, including microbial infection and toxic chemical exposure. In response to inflammation, immune cells like macrophages, B and T lymphocytes, fibroblasts, endothelial cells, and various stromal cells secrete soluble polypeptide cytokine Tumor Necrosis Factor Alpha (TNF?)

The recently published manuscript entitled “Epigenetically Altered T Cells Contribute to Lupus Flares” summarizes recent advances in our understanding of how the environment alters the immune system to cause flares of systemic lupus erythematosus (SLE) in genetically predisposed people, and why it affects women approximately 9 times more often than men

Diabetes mellitus (DM) is an age-related metabolic disorder affecting 347 million people in modern society. Expanding its prevalence beyond developed countries, DM has emerged as a global public health issue associated with a high morbidity and mortality.

Cellular components are attractive targets for antiviral therapy because they do not mutate as readily as do viral proteins do [1-3]. The identification of CCR₅ as an HIV-1 coreceptor [4-7], facilitated by the discovery of the antiviral activities of CCR₅ ligand ?-chemokines [8], resulted in the development of new viral entry inhibitors to block CCR₅ binding, including both- small molecules and CCR₅ antibodies

The primary objective of this research was to explore the link between sleep and flare pain associated with chikungunya virus (CHIKV) infection. The secondary objective was to investigate if cytokines and T regulatory (Treg) cells have an influence on this relationship.

Human embryogenesis and the development of its most unique product, the human brain, are believed to be precisely regulated by factors adopted during human
evolution that differentiate us from other species.

Alzheimer disease (AD) is a debilitating neurodegenerative disorder characterized by extracellular deposition of the amyloid β-protein (Aβ) and intraneuronal accumulation of the microtubule-associated protein, tau

Anorexia nervosa (AN) is an eating disorder characterized by a fear of gaining weight and self-starvation, leading to life-threatening weight loss [1]. It occurs predominately in women and frequently begins during adolescence.

Uromodulin (UMOD) is a glycoprotein expressed by the epithelial cells of the thick ascending limb of Henle’s loop in the kidney. Research has shown that increased uromodulin expression may be associated with lower risk of cardiovascular disease in adults.

Dravet syndrome (DS) is an intractable childhood epilepsy disorder affecting one in 15,000 to 20,000 births [1]. It is caused by de novo heterozygous lossof- function mutations in the SCN1A gene encoding the brain type-I voltage-gated sodium channel Na_v1.1

Using four core genotypes (FCG) mice, we have previously shown a larger number of CD4⁺ and CD8⁺ T cells in the spleens of female mice, a sex difference that develops by postnatal day 7 and is retained through adulthood. This difference in splenic T cell number is a consequence of reduced thymic egress and reduced splenic seeding in male mice, caused in part by the male-specific perinatal surge of testosterone, and in part by Sry, which is overexpressed in this model.