Recent ucsdsom_path_oapdeposits items

PrPC-facilitated cell signaling activates phospholipase Cɣ1 and triggers an Arc/Arg3.1 response in mouse and iPSC-derived human neurons

Thu, 4 Jun 2026 00:00:00 +0000

Synapse loss is an early feature of prion disease, yet the underlying drivers are poorly understood. We recently found evidence of neuronal hyperactivity and synaptic loss in prion-infected mice. Herein, we identified increased Arc/Arg3.1 in patients with prion disease, suggesting heightened neuronal activity also occurs in the human prion-affected brain. To determine the signaling events initiated by prion aggregates (PrPSc), we developed a disease model in which human iPSC-derived excitatory neurons are stimulated with a PrPSc-mimetic antibody, POM1, that binds cellular prion protein (PrPC). Within 2 h of POM1 exposure, we detected an Arc/Arg3.1 response together with transcriptomic changes previously reported in prion-infected mice. We identified altered phosphorylation of PLC-γ1, ERK1/2, and EGFR as additional PrPC-triggered cell signaling events. These results suggest that PrPC ligands, including PrPSc, trigger rapid signaling events linked to neuronal hyperactivity in human...

FAK inhibition in ovarian cancer releases omega-3 fatty acids to program CXCL13-producing anti-tumor resident peritoneal macrophages

Fri, 15 May 2026 00:00:00 +0000

High-grade serous ovarian cancer (HGSOC) is a lethal malignancy characterized by therapy resistance. Focal adhesion kinase (FAK) is highly expressed in HGSOC, yet its impact on tumor-immune communication remains incompletely defined. Using three syngeneic ovarian cancer models, we show that FAK inhibition (FAKi) increased macrophage CXCL13 expression and promoted peritoneal B cell infiltration. Combining FAKi with low-dose pegylated doxorubicin and anti-T cell immunoreceptor with Ig and ITIM domains (TIGIT) checkpoint blockade suppressed orthotopic ovarian tumor growth, extended survival, and induced tertiary lymphoid structures. Macrophage lineage factor GATA6 inactivation reduced CXCL13 expression, enhanced FAK-knockout tumor growth, and limited ascites B cell accumulation. Mechanistically, FAKi-treated or FAK-deficient tumor cells release exosomes enriched in omega-3 fatty acids that stimulated macrophage CXCL13 production. Exposure of macrophages to tumor-derived omega-3 lipids...

Recommendations for HLA Genotyping Data Standards and Clinical Laboratory Staffing Considerations.

Thu, 30 Apr 2026 00:00:00 +0000

The rapid advances in HLA genotyping technology and the massive amounts of associated data have created a demand for better and more efficient laboratory data management practices. However, while some standards have been developed, there is a need for comprehensive guidelines that include all laboratory data-related processes such as messaging, storage and retention, documentation, reporting, validation and quality control. An important consideration in developing these recommendations is the feasibility of application in a laboratory setting without posing a substantial staff and cost burden for implementation and long-term maintenance and the availability of publicly available tools. This article presents evidence-based recommendations for multiple laboratory general data practices, focusing on HLA genotyping data and associated meta-data. These recommendations are compiled by experts in the fields of histocompatibility and immunogenetics (H&I) and representation from multiple...

Association of neurogenic orthostatic hypotension with cognitive decline in Parkinson’s disease: a longitudinal cohort study

Thu, 23 Apr 2026 00:00:00 +0000

Neurogenic orthostatic hypotension (nOH), a common non-motor feature of Parkinson’s disease (PD), is defined as a sustained drop in blood pressure (BP) upon standing due to autonomic dysfunction. Although prior studies support an association between nOH and cognitive impairment, its longitudinal impact on cognitive decline in PD remains insufficiently explored. We aimed to determine to what extent baseline nOH is associated with an accelerated decline in global and exploratory domain-specific cognitive functions. A retrospective longitudinal cohort study was conducted using clinical data from patients with PD evaluated at the University of California San Diego movement disorders clinics between 2012 and 2024. Participants were classified as having nOH (nOH+) or without nOH (nOH−) based on initial orthostatic BP measurements (≥20 mmHg systolic BP and/or ≥10 mmHg diastolic BP reduction within 3 minutes of standing, with a blunted heart rate response [ΔHR/ΔSBP] < 0.5 bpm/mmHg)....

Prevalence of Mycoplasma genitalium in a Southern California patient population

Thu, 26 Feb 2026 00:00:00 +0000

Mycoplasma genitalium as a cause of genitourinary sexually transmitted disease symptoms often goes underdiagnosed in many patient populations. We investigated a patient population in Southern California at high risk for Chlamydia trachomatis (CT) and Neisseria gonorrhea (NG) infections to determine whether they also may be at high risk for Mycoplasma genitalium (MG) sexually transmitted infections that may be going untreated. We found that there was a relatively high prevalence of CT (13.9 %) and NG (9.0 %) in our population, but there was also a relatively high prevalence of undiagnosed MG infections (8.7 %). In this same patient population, there were few (0.5 %) subjects diagnosed with Trichomonas vaginalis (TV) infections; however, there were high numbers of coinfections identified for MG with CT and NG. We found high numbers of positive results in both symptomatic and asymptomatic individuals. We also identified that there were high numbers of subjects with genetic markers...

Review: False Positive Urine Drug Screens

Thu, 26 Feb 2026 00:00:00 +0000

Immunoassay-based urine drug screens are widely employed in clinical toxicology due to their speed, low cost, and ease of automation. However, these assays are inherently limited by antibody cross-reactivity, which can result in false-positive findings and incorrect interpretations with major implications for patient care, employment, and legal outcomes. This review updates prior literature by analyzing reported false-positive interferences published between 2013 and 2024 across commonly screened drug classes, including opioids, amphetamines, benzodiazepines, cannabinoids, barbiturates, phencyclidine (PCP), cocaine, ethanol, and ethyl glucuronide. A total of 61 studies met inclusion criteria from 569 unique publications retrieved via PubMed. Each report was categorized by level of evidence, ranging from single case reports to controlled spiking experiments. Despite advances in antibody specificity, immunoassay drug screens remain presumptive and require confirmation by orthogonal...

Milk as a Transmission Vehicle for Highly Pathogenic Avian Influenza A (H5N1).

Thu, 12 Feb 2026 00:00:00 +0000

Highly pathogenic avian influenza A (H5N1) (H5N1 hereafter) is an emerging pathogen in mammals. The recent recognition of H5N1 in dairy cattle increases opportunities for human exposure and infection and may accelerate a trajectory toward sustained human-to-human transmission. Furthermore, the presence of virus at high concentration in unpasteurized milk raises new risks for humans, especially infants and children. Milk has been identified as a vehicle for viral transmission in and between mammalian species, including humans. Sialic acids (SAs) found on cell surfaces are important mediators of species susceptibility to specific influenza strains and play an important role in viral tropism. New data demonstrate that SA receptors with α2,3 linkages capable of binding avian influenza strains are present in human mammary tissue. The presence of SA receptors that can bind avian influenza and a comparative analysis of viral transmission risk of raw and pasteurized milk in several mammalian...

Comparison of six serum analyte workflows using routine liquid chromatography-tandem mass spectrometry methods at multiple laboratories with the Cobas i 601 analyzer, an automated mass spectrometry system

Thu, 12 Feb 2026 00:00:00 +0000

OBJECTIVES: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) offers substantial analytical advantages over traditional immunoassay methods, including greater specificity and robustness. Conventional LC-MS/MS methods are labor-intensive, requiring highly trained, dedicated laboratory staff. The Cobas^® i 601 analyzer (Roche Diagnostics International Ltd., Rotkreuz, Switzerland) is an automated, random-access, mass spectrometry (MS) system designed to improve workflows and reduce turnaround times. This study evaluated turnaround times for analyses with the i 601 analyzer vs. routine LC-MS/MS using batch processing. METHODS: We performed a workflow analysis for six sets of analytes (mycophenolic acid, antibiotics, antiepileptics, voriconazole, testosterone, and 25-hydroxyvitamin D) in seven laboratories across Europe, North America, and Asia. We recorded batch size, result turnaround times, and hands-on times (including quality control) for 93 batches analyzed...

Lung Cancer Cells Secrete Glutamine to Accumulate Tumor‐Associated Macrophages

Fri, 16 Jan 2026 00:00:00 +0000

Tumor-associated macrophages (TAMs) are critical contributors to cancer progression and are often recruited by cancer cells to support a pro-tumorigenic microenvironment. Integrin αvβ3 is a known driver and marker of cancer stem-like properties, including tumor initiation, in various epithelial cancers. We have previously shown a positive correlation between αvβ3 expression and TAM infiltration across multiple tumor types; however, the mechanistic link remains undefined. Here, we demonstrated that integrin αvβ3 expression in non-small cell lung cancer (NSCLC) cells is both necessary and sufficient to drive TAM accumulation. In orthotopic murine and human NSCLC models, ectopic integrin αvβ3 expression increased TAM infiltration independently of T cells, whereas genetic deletion of integrin β3 significantly reduced TAM numbers and tumor burden. Mechanistically, integrin αvβ3 promotes glutamine secretion from NSCLC cells, which enhances the survival and/or differentiation of bone...

A Clinical-Stage Cysteine Protease Inhibitor blocks SARS-CoV‑2 Infection of Human and Monkey Cells

Thu, 15 Jan 2026 00:00:00 +0000

Host-cell cysteine proteases play an essential role in the processing of the viral spike protein of SARS coronaviruses. K777, an irreversible, covalent inactivator of cysteine proteases that has recently completed phase 1 clinical trials, reduced SARS-CoV-2 viral infectivity in several host cells: Vero E6 (EC₅₀< 74 nM), HeLa/ACE2 (4 nM), Caco-2 (EC₉₀ = 4.3 μM), and A549/ACE2 (<80 nM). Infectivity of Calu-3 cells depended on the cell line assayed. If Calu-3/2B4 was used, EC₅₀ was 7 nM, but in the ATCC Calu-3 cell line without ACE2 enrichment, EC₅₀ was >10 μM. There was no toxicity to any of the host cell lines at 10-100 μM K777 concentration. Kinetic analysis confirmed that K777 was a potent inhibitor of human cathepsin L, whereas no inhibition of the SARS-CoV-2 cysteine proteases (papain-like and 3CL-like protease) was observed. Treatment of Vero E6 cells with a propargyl derivative of K777 as an activity-based probe identified...

Per Se Driving Under the Influence of Cannabis Statutes and Blood Delta-9-Tetrahydrocannabinol Concentrations following Short-Term Cannabis Abstinence

Thu, 4 Dec 2025 00:00:00 +0000

BACKGROUND: Several US states have per se laws using 2 or 5 ng/mL of delta-9-tetrahydrocannabinol (THC) as cutpoints for driving under the influence of cannabis, while some have zero-tolerance statutes. These cutpoints are considered prima facia evidence of driving impairment. METHODS: In a cohort of people who regularly use cannabis (N = 190) we measured baseline concentrations of THC after instructing participants to abstain from cannabis for at least 48 hours. Baseline driving performance was evaluated using a driving simulator. We also measured blood THC concentrations serially following a smoking session (placebo or active cannabis). RESULTS: Forty-three percent of the participants exceeded zero-tolerance statutes (≥0.5 ng/mL) at baseline. Twenty-four percent had baseline blood THC concentrations that were ≥2 ng/mL and 5.3% were ≥5 ng/mL. The maximum observed baseline blood concentration was 16.2 ng/mL. Six hours after smoking active cannabis, the median (interquartile range)...

BRD2 bromodomain-mediated regulation of cell state plasticity modulates therapy response in glioblastoma

Thu, 4 Dec 2025 00:00:00 +0000

BACKGROUND: Glioblastoma (GBM) displays remarkable cell state plasticity, a major contributor to therapeutic resistance and tumor progression. While epigenetic mechanisms play a central role in driving this plasticity, the key regulators remain poorly understood, and developing effective therapeutic strategies targeting them has been challenging. METHODS: We investigated the role of BRD2, a key regulator of NF-κB-mediated mesenchymal (MES) transition, using GBM patient-derived xenograft cell lines, CRISPR-mediated knock-in/knockout approaches, RNA-seq, and in vitro and in vivo modeling. BET inhibitors were employed to target MES gene expression and sensitize GBM to radiation therapy. RESULTS: We found that PTEN loss induces RelA chromatin localization and acetylation-mediated recruitment of BRD2 to the MES gene promoters. BRD2 binding is essential for maintaining MES gene expression and phenotype. Genetic ablation or loss-of-function mutation of BRD2 bromodomains reverses MES...

Cannabidiol mitigates alcohol dependence and withdrawal with neuroprotective effects in the basolateral amygdala and striatum

Mon, 1 Dec 2025 00:00:00 +0000

Alcohol use disorder (AUD) remains a pervasive public health issue with limited effective treatments. Cannabidiol (CBD), a non-psychotropic constituent of cannabis, shows promise in modulating addictive behaviors. This study investigated the effects of chronic CBD administration on alcohol dependence, withdrawal symptoms, and neurodegeneration using two complementary rodent models: chronic intermittent ethanol (CIE) exposure, which models established alcohol dependence, and ethanol vapor self-administration (EVSA), which captures the volitional aspects of alcohol intake. In the CIE model, CBD reduced alcohol self-administration during acute withdrawal without affecting alcohol metabolism or locomotor activity. CBD decreased motivation for alcohol, somatic withdrawal signs, withdrawal-induced anxiety-like behaviors, and mechanical sensitivity. During extinction, CBD attenuated alcohol-seeking behavior and stress-induced reinstatement. Electrophysiological recordings revealed that...

Pathologist-like explainable AI for interpretable Gleason grading in prostate cancer

Thu, 23 Oct 2025 00:00:00 +0000

The aggressiveness of prostate cancer is primarily assessed from histopathological data using the Gleason scoring system. Conventional artificial intelligence (AI) approaches can predict Gleason scores, but often lack explainability, which may limit clinical acceptance. Here, we present an alternative, inherently explainable AI that circumvents the need for post-hoc explainability methods. The model was trained on 1,015 tissue microarray core images, annotated with detailed pattern descriptions by 54 international pathologists following standardized guidelines. It uses pathologist-defined terminology and was trained using soft labels to capture data uncertainty. This approach enables robust Gleason pattern segmentation despite high interobserver variability. The model achieved comparable or superior performance to direct Gleason pattern segmentation (Dice score: 0.713±0.003$${0.713}_{\pm 0.003}$$ vs. 0.691±0.010$${0.691}_{\pm 0.010}$$) while providing interpretable outputs. We...

Alveolar Macrophages Mimic Tumor Cells in Lung Tissue: A Diagnostic Pitfall in Cytology FNA and EBUS Specimens

Thu, 25 Sep 2025 00:00:00 +0000

Fine-needle aspiration (FNA) or core needle biopsy via EBUS procedure is commonly used to assess suspicious lung nodules. Alveolar macrophages are commonly seen in these specimens. In cases when hypercellular specimens with large aggregates of alveolar macrophages are encountered, especially when they show epithelioid morphology, vacuolated cytoplasm, and significant cytological atypia, including marked anisonucleosis and intracytoplasmic inclusion, they can be mistakenly interpreted as "lesional cells" during rapid on-site evaluation (ROSE) and cease the EBUS procedure prematurely. It is important to keep in mind that epithelioid alveolar macrophages may mimic lung neuroendocrine tumor (NET), lung adenocarcinoma, or even metastatic process. Cytoplasmic pigmentation and immunohistochemistry analysis can be extremely useful to prevent a false diagnosis of malignancy.

PolyIC as an adjuvant outperforms anti-VEGF in combination with anti-PD-L1 therapy in mouse liver tumor models

Fri, 12 Sep 2025 00:00:00 +0000

BACKGROUND: Immune checkpoint inhibitors combined with antiangiogenic therapy have become the standard of care for advanced HCC, albeit with limited therapeutic benefit. Our previous studies demonstrated the immunomodulatory and antitumor effects of polyIC, a synthetic dsRNA. Here, we compared the efficacy of anti-programmed death ligand 1 (αPD-L1) plus polyIC versus αPD-L1 plus anti-vascular endothelial growth factor (αVEGF) in mouse tumor models. METHODS: We established a primary liver tumor model using hydrodynamic tail vein injection of Ras/Myc oncogenes and a metastasized tumor model via intrasplenic injection of colon cancer cells. Flow cytometry and gene expression analysis were performed to assess immune profiles across treatment groups. Key factors contributing to antitumor efficacy were explored. RESULTS: In both models, αPD-L1 plus polyIC demonstrated superior antitumor effects relative to αPD-L1 plus αVEGF. Unlike αVEGF, polyIC enhanced the immune response to αPD-L1...

Spatial transcriptomics identifies disrupted circadian gene expression in a mouse model of Alzheimer’s disease

Thu, 11 Sep 2025 00:00:00 +0000

Abstract: Background: Disruptions in circadian rhythm are a common symptom of Alzheimer’s disease (AD), which occur early in disease progression and may contribute to the neurodegenerative process. However, the mechanisms that link alterations in rhythmic transcription and disease pathology are poorly understood. Here we used brain‐wide spatial transcriptomics to elucidate progressive disruptions in diurnal transcriptional rhythms in a mouse model of AD. Method: Using Visium spatial transcriptomic technology, we investigated transcriptional changes with spatiotemporal resolution in APP23 transgenic mice, which overexpress human APP with the Swedish mutation. Sagittal brain slices from APP23 and littermate control mice were collected at 4 Zeitgeber times (ZT). We used community detection to cluster the spatial locations according to shared patterns of gene expression, which corresponded to major anatomical brain regions. Pseudobulk profiles were computed for each cluster in...

The Emerging Roles of Metabolic Reprogramming in Non-Small Cell Lung Cancer Progression

Thu, 28 Aug 2025 00:00:00 +0000

Lung cancer remains a leading cause of cancer-related mortality due to its capacity for silent metastasis and the significant challenges in achieving effective treatment. Currently, targeted therapies and chemotherapies are the primary options for advanced or inoperable lung cancer; however, their efficacy is often undermined by the cancer's ability to develop resistance through both genetic and non-genetic mechanisms. This review explores recent advances in understanding metabolic reprogramming in non-small cell lung cancer (NSCLC), focusing on its critical role in cancer progression. NSCLC cells exhibit heterogeneous activation of metabolic pathways influenced by their oncogenic mutations. Notably, their metabolic phenotypes evolve in response to environmental stressors and therapeutic pressures. Moreover, NSCLC cells engage in metabolic crosstalk with their microenvironment to enhance survival, leveraging distinct metabolic adaptations at both primary and metastatic sites....

Surveillance donor-specific antibody and pathologic antibody-mediated rejection testing in heart transplant patients in the contemporary era

Thu, 14 Aug 2025 00:00:00 +0000

BACKGROUND: Surveillance donor-specific antibody (DSA) and pathologic antibody-mediated rejection (pAMR) testing is recommended in the first year after heart transplantation (HTx) in adult patients. Whether pAMR testing adds prognostic information to contemporary DSA testing has not been fully studied. METHODS: This was a single-center study of consecutive endomyocardial biopsies (EMB) performed between November 2010 and February 2023 in adult HTx patients. The primary objective was to evaluate whether pAMR testing contributes additional information to DSA testing to better predict overall survival. Secondary end-points included cardiac survival and allograft dysfunction. RESULTS: A total of 6,033 EMBs from 544 HTx patients were reviewed for the study. The pAMR+/DSA+ patients had significantly lower overall (p_c = 0.013) and cardiac survival (p_c = 0.002), while the pAMR+/DSA- and pAMR-/DSA+ patients showed no difference in either outcome compared...

The Sialome of the Retina, Alteration in Age-Related Macular Degeneration Pathology, and Potential Impacts on Complement Factor H

Thu, 31 Jul 2025 00:00:00 +0000

Purpose: Little is known about sialic acids of the human retina, despite their integral role in self /non-self-discrimination by complement factor H (FH), the alternative complement pathway inhibitor. Methods: A custom sialoglycan microarray was used to characterize the sialic acid-binding specificity of native FH or recombinant molecules where IgG Fc was fused to FH domains 16 to 20 (which contains a sialic acid-binding site), domains 6 and 7 (which contains a glycosaminoglycan-binding site), or the FH-related proteins (FHRs) 1 and 3. We analyzed macular and peripheral retinal tissue from postmortem ocular globes for the amount, type, and presentation (glycosidic linkage type) of sialic acid in individuals with age-related macular degeneration (AMD) and age-matched controls using fluorescent lectins and antibodies to detect sialic acid and endogenous FH. Released sialic acids from neural retina, retinal pigmented epithelium (RPE) cells, and the Bruch's membrane (BrM) were labeled...

Comparative physiological anthropogeny: exploring molecular underpinnings of distinctly human phenotypes

Thu, 31 Jul 2025 00:00:00 +0000

Anthropogeny is a classic term encompassing transdisciplinary investigations of the origins of the human species. Comparative anthropogeny is a systematic comparison of humans and other living nonhuman hominids (so-called "great apes"), aiming to identify distinctly human features in health and disease, with the overall goal of explaining human origins. We begin with a historical perspective, briefly describing how the field progressed from the earliest evolutionary insights to the current emphasis on in-depth molecular and genomic investigations of "human-specific" biology and an increased appreciation for cultural impacts on human biology. While many such genetic differences between humans and other hominids have been revealed over the last two decades, this information remains insufficient to explain the most distinctive phenotypic traits distinguishing humans from other living hominids. Here we undertake a complementary approach of "comparative physiological anthropogeny,"...

Social, microbial, and immune factors linking bacterial vaginosis and infectious diseases

Thu, 31 Jul 2025 00:00:00 +0000

Bacterial vaginosis (BV) is a polymicrobial condition of the vaginal microbiota associated with a variety of sexually transmitted infections, infections of maternal and fetal tissues during pregnancy, and even some infections outside of the reproductive tract, including the urinary tract and mouth. BV has also been associated with conditions in which the body generates prominent inflammatory reactions to microbes, including infections of the cervix and other upper genital tract tissues. For reasons still not understood, BV is a highly recurrent and often difficult-to-treat condition, complicating attempts to prevent these associated infections. An additional layer of complexity arises from the increasing awareness that the presence of BV-associated bacteria in the vagina is not always symptomatic or associated with adverse outcomes. In this concise Review, we summarize and synthesize three groups of factors grounded in the literature that may be fueling the associations between...

Genetic and pharmacological targeting of nicotinic acetylcholine receptor action blocks tumor progression in mouse models of breast cancer

Thu, 31 Jul 2025 00:00:00 +0000

Effective small molecule therapies are a major unmet need in triple-negative breast cancer. Therefore, we examined the mechanism of action of a novel cancer therapeutic target in preclinical mouse models focusing on the α7 nicotinic acetylcholine receptor (CHRNA7). E0771 breast tumor cells were implanted into CHRNA7KO mice to determine the role of CHRNA7, which is expressed in tumor-associated myeloid immune cells. We observed that tumor-bearing CHRNA7KO mice had decreased survival and increased tumor burden linked to a CHRNA7-mediated reduction in immune cell activation. Based on the tumor permissive phenotype of CHRNA7KO mice, we tested the effect of a small molecule agonist of CHRNA7, AR-R17779, in several mouse models of breast cancer. For example, in both the E0771 tumor model and PyMT tumor models, treatment with AR-R17779 increased survival. In the 4T1 breast tumor model, treatment with AR-R17779 also increased survival, with a well-defined reduction in primary tumor burden...

Evolution of Human Susceptibility to Alzheimer's Disease: A Review of Hypotheses and Comparative Evidence

Thu, 31 Jul 2025 00:00:00 +0000

Primates rely on memory to navigate both physical and social environments and in humans, loss of memory function leads to devastating consequences. Alzheimer's disease (AD) is a neurodegenerative disease which begins by impacting memory functioning and is ultimately fatal. AD is common across human populations and its prevalence is predicted to rise with increases in the aging population. Despite this, the full AD phenotype has not been observed in any other nonhuman primate species. While a significant amount of research has been devoted to understanding the immediate mechanisms involved in AD pathogenesis in humans, less research has focused on why humans are particularly vulnerable to neurodegenerative diseases like AD. Here we explore hypotheses on the evolution of distinct human susceptibility to AD and place these in the context of findings from comparative neuroanatomical and molecular studies and discuss recent evidence for evolutionary changes protective against AD in...

Correction: Current Strategies of Modeling Human Trophoblast Using Human Pluripotent Stem Cells in vitro

Thu, 17 Jul 2025 00:00:00 +0000

In the Reagents and Solutions section of the above-referenced article: 1.Matrigel: In the paper, “Corning, cat. no. 356231” has been changed to “Corning, cat. no. 354234”. 2.1-Thioglycerol: In the paper, “MilliporeSigma, cat. no. M1753” has been changed to “MilliporeSigma, cat. no. M6145”. The current version online now includes these corrections and may be considered the authoritative version of record.

Elucidating VEGF Biology: A Journey of Discovery and Clinical Translation

Thu, 19 Jun 2025 00:00:00 +0000

Elucidating VEGF Biology: A Journey of Discovery and Clinical Translation

A dataset of chronic nicotine-induced genes in breast cancer cells

Thu, 22 May 2025 00:00:00 +0000

These data show the differentially expressed genes (DEG) from HCC38 breast cancer cell line chronically exposed to nicotine versus vehicle control. Additional data is also provided from dynamic trajectory analysis, identifying the most dynamic genes due to chronic nicotine treatment. To produce this dataset, we first performed single cell RNA sequencing from HCC38 cells chronically treated with vehicle or nicotine, followed by scanpy analysis to yield 6 discrete cell clusters at conservative resolution. We then evaluated differential gene expression between chronic nicotine and control cells for each individual cluster or in the whole sample using PyDESeq2. For dynamic trajectory analysis, Velocyto (0.6) was used to estimate the spliced and unspliced counts for each gene between chronic nicotine-treated cells and vehicle, allowing computation of gene velocities. These data are useful for analysing the expression of individual genes or gene velocities either in the whole sample...

A case of hypoglossal nerve palsy with evolving cranial nerve involvement in renal cell carcinoma: a case report

Thu, 24 Apr 2025 00:00:00 +0000

BackgroundRenal cell carcinoma is a rare pediatric solid tumor that typically presents with hematuria, abdominal mass, or flank pain. It is uncommon for renal cell carcinoma to manifest with headache and isolated extra-urogenital symptoms. We present, to our knowledge, the first case of renal cell carcinoma with bony metastases, presenting initially as isolated cranial nerve twelve palsy. Although bony metastases can occur in renal cell carcinoma, skull-based metastases and cranial neuropathies are exceedingly rare, especially in the pediatric population.Case presentationWe describe the unusual presentation of renal cell carcinoma with bony skull-based metastases presenting initially as isolated hypoglossal nerve palsy, that progressed to multiple cranial neuropathies in a previously healthy 14-year-old female of Indian descent.ConclusionThe differential for hypoglossal nerve with evolving cranial nerves 9 and 10 involvement can be broad owing to the course of the nerve, the structures...

Zika but not Dengue virus infection limits NF-κB activity in human monocyte-derived dendritic cells and suppresses their ability to activate T cells

Sat, 12 Apr 2025 00:00:00 +0000

Understanding flavivirus immunity is critical for the development of pan-flavivirus vaccines. Dendritic cells (DC) coordinate antiviral innate and adaptive immune responses, and they can be targeted by flaviviruses as a mechanism of immune evasion. Using an unbiased genome-wide approach designed to specifically identify flavivirus-modulated pathways, we found that, while dengue virus (DENV) robustly activates DCs, Zika virus (ZIKV) causes minimal activation of genes involved in DC activation, maturation, and antigen presentation, reducing cytokine secretion and the stimulation of allogeneic and peptide-specific T cell responses. Mechanistically, ZIKV inhibits DC maturation by suppressing NF-κB p65 recruitment and the subsequent transcription of proinflammatory and DC maturation-related genes. Thus, we identify a divergence in the effects of ZIKV and DENV on the host T cell response, highlighting the need to factor such differences into the design of anti-flavivirus vaccines.

Over‐Expression of RNA Processing, Heat Shock, and DNA Repair Proteins in Breast Tumor Compared to Normal Tissue