Metabolic Signaling in the Tumor Microenvironment.

Cancer cells must reprogram their metabolism to sustain rapid growth. This is accomplished in part by switching to aerobic glycolysis, uncoupling glucose from mitochondrial metabolism, and performing anaplerosis via alternative carbon sources to replenish intermediates of the tricarboxylic acid (TCA) cycle and sustain oxidative phosphorylation (OXPHOS). While this metabolic program produces adequate biosynthetic intermediates, reducing agents, ATP, and epigenetic remodeling cofactors necessary to sustain growth, it also produces large amounts of byproducts that can generate a hostile tumor microenvironment (TME) characterized by low pH, redox stress, and poor oxygenation.

Impacts of Diabetes Self-Management Education and Support Programs in Hispanic Church Settings: A Cluster-Randomized Trial Comparing Faith-Based and Faith-Placed Approaches.

This study aimed to adapt evidence-based diabetes self-management education and support (DSMES) into a faith-based (FB) context for Hispanic communities and compare its effectiveness to a faith-placed (FP) approach using the church as a venue for DSMES delivery. A cluster-randomized trial was conducted among adults with type 2 diabetes from predominantly Hispanic churches. The churches were assigned to either the FB Group (nine churches, n = 146) or the FP Group (seven churches, n = 125).

Head-to-Head Comparison of Aptamer- and Antibody-Based Proteomic Platforms in Human Cerebrospinal Fluid Samples from a Real-World Memory Clinic Cohort.

High-throughput proteomic platforms are crucial to identify novel Alzheimer's disease (AD) biomarkers and pathways. In this study, we evaluated the reproducibility and reliability of aptamer-based (SomaScan 7k) and antibody-based (Olink Explore 3k) proteomic platforms in cerebrospinal fluid (CSF) samples from the Ace Alzheimer Center Barcelona real-world cohort. Intra- and inter-platform reproducibility were evaluated through correlations between two independent SomaScan assays analyzing the same samples, and between SomaScan and Olink results.

Molecular basis of interchain disulfide bond formation in BMP-9 and BMP-10.

BMP-9 and BMP-10 are TGF-β family signaling ligands naturally secreted into blood. They act on endothelial cells and are required for proper development and maintenance of the vasculature. In hereditary hemorrhagic telangiectasia, regulation is disrupted due to mutations in the BMP-9/10 pathway, namely in the type I receptor ALK1 or the co-receptor endoglin.

The adiponectin-PPARγ axis in hepatic stellate cells regulates liver fibrosis.

Hepatic stellate cells (HSCs) are key drivers of local fibrosis. Adiponectin, conventionally thought of as an adipokine, is also expressed in quiescent HSCs. However, the impact of its local expression on the progression of liver fibrosis remains unclear.

Targeting N-Myc in neuroblastoma with selective Aurora kinase A degraders.

The N-Myc transcription factor, encoded by MYCN, is a mechanistically validated, yet challenging, target for neuroblastoma (NB) therapy development. In normal neuronal progenitors, N-Myc undergoes rapid degradation, while, in MYCN-amplified NB cells, Aurora kinase A (Aurora-A) binds to and stabilizes N-Myc, resulting in elevated protein levels. Here, we demonstrate that targeted protein degradation of Aurora-A decreases N-Myc levels.

Oral cavity and oropharyngeal cancers in Texas: examining incidence rates in dental health professional shortage areas.

Purpose: Oral cavity (OC) and oropharyngeal (OP) cancer rates have increased annually rising in the U.S. and Texas.

Conventional Cytogenetic Analysis of Solid Tumor Abnormalities: A 25-Year Review of Proficiency Test Results from the College of American Pathologists/American College of Medical Genetics and Genomics Cytogenetics Committee.

The joint College of American Pathologists/American College of Medical Genetics and Genomics Cytogenetics Committee works to ensure the competency and proficiency of clinical cytogenetic testing laboratories through proficiency testing (PT) programs for various clinical tests offered by such laboratories, including the evaluation of cytogenetic abnormalities in solid tumors. Review and analyze 25 years (1999-2023) of solid tumor chromosome analysis PT results, utilizing G-banded karyograms. A retrospective review of results from 1999 to 2023 was performed, identifying the challenges addressing solid tumors.

A Novel Triplet of Alisertib Plus Ibrutinib Plus Rituximab Is Active in Mantle Cell Lymphoma.

: Aurora (AK) A/B are oncogenic mitotic kinases that when over-expressed are poor prognostic markers in mantle cell lymphoma (MCL). : Alisertib, an AK-A inhibitor, has anti-tumor activity in relapsed/refractory (r/r) MCL patients. We evaluated alisertib plus ibrutinib in MCL to abrogate ibrutinib resistance.

Prevalence, patterns, and predictors of prescribing medications for opioid use disorder (MOUD) in the Inpatient setting.

Background: There are many barriers to prescribing medications for opioid use disorder (MOUD). This study evaluates the prevalence, patterns, and predictors of inpatient MOUD prescribing at discharge to patients with a diagnosis of opioid use/opioid use disorder (OUD) that developed opioid withdrawal during their hospital stay.

Methods: This multicenter, retrospective cross-sectional study occurred at three hospitals in Arizona.

Truncated TrkB: The predominant TrkB Isoform in Nociceptors.

Truncated TrkB (TrkBT1), traditionally considered a dominant-negative regulator of full-length TrkB (TrkBTK+), remains poorly understood in peripheral sensory neurons, particularly nociceptors. Furthermore, sensory neuronal TrkB expression and function has been traditionally associated with non-nociceptive neurons, particularly Aδ low-threshold mechanoreceptors. This study challenges prevailing assumptions by demonstrating that TrkBT1 is the predominant TrkB isoform expressed in sensory neurons and plays a functional role in modulating neuronal activity.

MTCH2 controls energy demand and expenditure to fuel anabolism during adipogenesis.

Mitochondrial carrier homolog 2 (MTCH2) is a regulator of apoptosis, mitochondrial dynamics, and metabolism. Loss of MTCH2 results in mitochondrial fragmentation, an increase in whole-body energy utilization, and protection against diet-induced obesity. In this study, we used temporal metabolomics on HeLa cells to show that MTCH2 deletion results in a high ATP demand, an oxidized cellular environment, and elevated utilization of lipids, amino acids, and carbohydrates, accompanied by a decrease in several metabolites.

Deciphering the fate of replication-induced DNA double-strand breaks.

In this issue of Molecular Cell, studies by Xu et al., Kimble et al., and Elango et al.

Factors That Determine Successful Social Housing of African Green Monkeys () in Same-Sex Pairs and Trios.

Social housing provides a high level of enrichment for captive non-human primates, but providing this in research situations can be challenging. We have developed a multifactorial animal selection and introduction process coordinated by veterinary and animal care behavioral teams. This process sought to successfully establish lasting same-sex pairs and trios for African green monkeys () in studies lasting from three months to over a year.

The Maturation of the International Health Crisis Response: The Polish Typhus Epidemic of 1916-1923 Compared to the African Ebola Virus Disease Epidemic of 2013-2016: Part I, the Polish Epidemic.

Poland suffered an epidemic of louse-borne typhus from 1916-1923, with 400,000 cases and more than 130,000 deaths. The causative factors were depressed economic conditions and a refugee crisis that engulfed Poland after World War I. The recognition of the epidemic in 1919 stimulated the creation of the League of Red Cross Societies (LRCS).

Autophosphorylation of the Tousled-like kinases TLK1 and TLK2 regulates recruitment to damaged chromatin via PCNA interaction.

Tousled-like kinases 1 and 2 (TLK1 and 2) are cell cycle-regulated serine/threonine kinases that are involved in multiple biological processes. Mutation of TLK1 and 2 confer neurodegenerative diseases. Recent studies demonstrate that TLK1 and 2 are involved in DNA repair.

Anti-Bacterial and Anti-Dermatophytic Activity of Extracellular Secondary Metabolites of Streptomyces glaucescens NTSB-37 Isolated from Lichen Parmotrema perlatum (Huds.) M. Choisy in Kolli Hills, Tamil Nadu, India.

Lichen-associated endophytic Actinobacteria, particularly Streptomyces species, are recognized for their production of bioactive secondary metabolites with significant pharmaceutical potential. With the escalating prevalence of diseases, Streptomyces species are being investigated for its natural source of antimicrobial compounds for new antibiotics. This study focuses on the bioactive properties of secondary metabolites from lichen-associated endophytic Actinobacteria, focusing on Streptomyces glaucescens NTSB-37 isolated form lichen, Parmotrema perlatum (Huds.

Molecular dissection of laboratory contamination between two schistosome populations.

Background: Genomic analysis has revealed extensive contamination among laboratory-maintained microbes including malaria parasites, Mycobacterium tuberculosis, and Salmonella spp. Here, we provide direct evidence for recent contamination of a laboratory schistosome parasite population, and we investigate its genomic consequences. The Brazilian Schistosoma mansoni population SmBRE has several distinctive phenotypes, showing poor infectivity, reduced sporocyst number, low levels of cercarial shedding and low virulence in the intermediate snail host, and low worm burden and low fecundity in the vertebrate rodent host.

Intra-abdominal Hypertension Is a Strong Predictor of Mortality and Poor Clinical Outcome in Severe Acute Pancreatitis.

Background: Acute pancreatitis is one of the leading causes of mortality and morbidity. Most acute pancreatitis scoring systems have no pathophysiologic basis when evaluating severity. Such a limitation led to an interest in measuring intra-abdominal pressure (IAP) as a method to predict outcomes in patients with acute pancreatitis.

Design and synthesis of JNK1-targeted PROTACs and research on the activity.

Kinase dysregulation is greatly associated with cell growth, proliferation, differentiation and apoptosis, which indicates their great potential as therapeutic targets for treatment of numerous progressive disorders, including inflammatory, metabolic and autoimmune disorders, organ fibrosis and cancer. The c‑Jun N‑Terminal Kinase (JNK), as a member of MAPK family, is proved to be a potential target for the treatment of pulmonary fibrosis, which is the most common progressive and fatal fibrotic lung disease. As a new strategy, small-molecule-mediated targeted protein degradation pathway has the advantages of catalytic properties, overcoming drug resistance and expanding target space, which can circumvent the limitations associated with kinase inhibitors.

Comparing Medical Record Abstraction (MRA) error rates in an observational study to pooled rates identified in the data quality literature.

Background: Medical record abstraction (MRA) is a commonly used method for data collection in clinical research, but is prone to error, and the influence of quality control (QC) measures is seldom and inconsistently assessed during the course of a study. We employed a novel, standardized MRA-QC framework as part of an ongoing observational study in an effort to control MRA error rates. In order to assess the effectiveness of our framework, we compared our error rates against traditional MRA studies that had not reported using formalized MRA-QC methods.

Anti‑proliferative effects of in a model for triple negative breast cancer.

Triple negative breast cancer (TNBC) is characterized by the absence of hormones and growth factor receptors. It is typically responsive to anthracycline/taxol-based conventional chemotherapy. However, major therapeutic limitations include systemic toxicity and acquired resistance to chemotherapeutics.

Measuring Patient-Reported Outcomes Following Traumatic Craniomaxillofacial Injuries: Development of the AO CMF Injury Symptom Battery.

Traumatic craniomaxillofacial (CMF) injuries are associated with various symptoms/concerns that affect patients' quality of life. The assessment of outcomes from the patient perspective has been limited by the absence of patient-reported outcome (PRO) measures tailored to this patient population. To address this need, we employed a mixed methods, multi-step process to first identify the most important symptoms/concerns and then use this information to construct a PRO symptom battery.