Advancing Patient Advocacy in Mycology: Cultivating Collaboration in Education, Research, and Policy.

In the healthcare landscape, diseases such as cancer and HIV/AIDS have benefited from the patient's perspective. For fungal diseases, the patient voice remains absent in critical areas such as policy formulation, funding decisions, and research priorities. Patients affected by fungal disease, along with their caregivers and advocacy groups, possess invaluable insights into the challenges and unmet needs they face.

Siah2 antagonism of Pard3/JamC modulates Ntn1-Dcc signaling to regulate cerebellar granule neuron germinal zone exit.

Exiting a germinal zone (GZ) initiates a cascade of events that promote neuronal maturation and circuit assembly. Developing neurons and their progenitors must interpret various niche signals-such as morphogens, guidance molecules, extracellular matrix components, and adhesive cues-to navigate this region. How differentiating neurons in mouse brains integrate and adapt to multiple cell-extrinsic niche cues with their cell-intrinsic machinery in exiting a GZ is unknown.

Albumin-based nanocarriers loaded with novel Zn(II)-thiosemicarbazone compounds chart a new path for precision breast cancer therapy.

This study explores the therapeutic potential of albumin-bound Zn(II)-thiosemicarbazone compounds (Alb-ZnTcA, Alb-ZnTcB) against breast cancer cells. Previous research indicates that these compounds hinder cancer cell proliferation by blocking DNA synthesis, promoting oxidative stress to induce apoptosis, and disrupting the cell cycle to inhibit cellular division. This study focuses on the loading and characterization of these potentially chemically unstable compounds on bovine serum albumin-based nanocarriers.

Sphingosine kinase 2 (SphK2) depletion alters redox metabolism and enhances inflammation in a diet-induced MASH mouse model.

Background: Sphingosine-1 phosphate (S1P) is a bioactive lipid molecule that modulates inflammation and hepatic lipid metabolism in MASLD, which affects 1 in 3 people and increases the risk of liver fibrosis and hepatic cancer. S1P can be generated by 2 isoforms of sphingosine kinase (SphK). SphK1 is well-studied in metabolic diseases.

Somatic copy number deletion of chromosome 22q in papillary thyroid carcinoma.

Deletion of the long q arm of chromosome 22 (22qDEL) is the most frequently identified recurrent somatic copy number alteration (SCNA) observed in papillary thyroid carcinoma (PTC). Since its role in PTC is not fully understood, we conducted a pooled analysis of genomic characteristics and clinical correlates in 1094 primary tumors from four published PTC genomic studies. The majority of PTC with 22qDEL exhibited arm-level loss of heterozygosity (86%); nearly all PTC with 22qDEL had losses in 22q12 and 13, which together constitute 70% of the q arm.

Prediction of protein biophysical traits from limited data: a case study on nanobody thermostability through NanoMelt.

In-silico prediction of protein biophysical traits is often hindered by the limited availability of experimental data and their heterogeneity. Training on limited data can lead to overfitting and poor generalizability to sequences distant from those in the training set. Additionally, inadequate use of scarce and disparate data can introduce biases during evaluation, leading to unreliable model performances being reported.

Targeting the CD74 signaling axis suppresses inflammation and rescues defective hematopoiesis in -familial platelet disorder.

Familial platelet disorder (FPD) is associated with germline mutations, establishing a preleukemic state and increasing the risk of developing leukemia. Currently, there are no intervention strategies to prevent leukemia progression. Single-cell RNA sequencing ( = 10) combined with functional analysis of samples from patients with -FPD ( > 75) revealed that FPD hematopoietic stem and progenitor cells (HSPCs) displayed increased myeloid differentiation and suppressed megakaryopoiesis because of increased activation of prosurvival and inflammatory pathways.

APOBEC3A deaminates CTG hairpin loops to promote fragility and instability of expanded CAG/CTG repeats.

CAG/CTG repeats are prone to expansion, causing several inherited human diseases. The initiating sources of DNA damage which lead to inaccurate repair of the repeat tract to cause expansions are not fully understood. Expansion-prone CAG/CTG repeats are actively transcribed and prone to forming stable R-loops with hairpin structures forming on the displaced single-stranded DNA (S-loops).

NAC regulates metabolism and cell fate in intestinal stem cells.

Intestinal stem cells (ISCs) face the challenge of integrating metabolic demands with unique regenerative functions. Studies have shown an intricate interplay between metabolism and stem cell capacity; however, it is still not understood how this process is regulated. Combining ribosome profiling and CRISPR screening in intestinal organoids, we identify the nascent polypeptide-associated complex (NAC) as a key mediator of this process.

Protocol for generating a pancreatic cancer organoid associated with heterogeneous tumor microenvironment.

Pancreatic ductal adenocarcinoma (PDAC) organoids that simulate the tumor microenvironment (TME) are an effective tool to identify how TME affects PDAC malignancy. We present a protocol for generating a fused pancreatic cancer organoid (FPCO) that partly reproduces the TME, including heterogeneous cancer-associated fibroblasts (CAFs), using patient-derived PDAC cells and human-induced pluripotent cell-derived endothelial and mesenchymal cells. We also describe the procedure for analyzing FPCO characteristics.

Nucleoside Reverse Transcriptase Inhibitor (NRTI)-Induced Neuropathy and Mitochondrial Toxicity: Limitations of the Poly-γ Hypothesis and the Potential Roles of Autophagy and Drug Transport.

Nucleoside reverse transcriptase inhibitors (NRTIs) are the backbone of highly active antiretroviral therapy (HAART)-the current standard of care for treating human immunodeficiency virus (HIV) infection. Despite their efficacy, NRTIs cause numerous treatment-limiting adverse effects, including a distinct peripheral neuropathy, called antiretroviral toxic neuropathy (ATN). ATN primarily affects the extremities with shock-like tingling pain, a pins-and-needles prickling sensation, and numbness.

Curcumin and Its Potential to Target the Glycolytic Behavior of Lactate-Acclimated Prostate Carcinoma Cells with Docetaxel.

Dysregulated cellular metabolism is known to be associated with drug resistance in cancer treatment. In this study, we investigated the impact of cellular adaptation to lactic acidosis on intracellular energy metabolism and sensitivity to docetaxel in prostate carcinoma (PC) cells. The effects of curcumin and the role of hexokinase 2 (HK2) in this process were also examined.

Promotes Antioxidant Gene Expression and Mitochondrial Oxidative Respiration in Experimental Autoimmune Encephalomyelitis.

(L.) Urban (family Apiaceae) () is a traditional botanical medicine used in aging and dementia. Water extracts of (CAW) have been used to treat neuropsychiatric symptoms in related animal models and are associated with increases in antioxidant response element (ARE) genes and improvements in mitochondrial respiratory function and neuronal health.

Visualizing the Tumor Microenvironment: Molecular Imaging Probes Target Extracellular Matrix, Vascular Networks, and Immunosuppressive Cells.

The tumor microenvironment (TME) is a critical factor in cancer progression, driving tumor growth, immune evasion, therapeutic resistance, and metastasis. Understanding the dynamic interactions within the TME is essential for advancing cancer management. Molecular imaging provides a non-invasive, real-time, and longitudinal approach to studying the TME, with techniques such as positron emission tomography (PET), magnetic resonance imaging (MRI), and fluorescence imaging offering complementary strengths, including high sensitivity, spatial resolution, and intraoperative precision.

Expression Levels of MUC5AC and MUC5B in Airway Goblet Cells Are Associated with Traits of COPD and Progression of Chronic Airflow Limitation.

Mucins 5AC (MUC5AC) and 5B (MUC5B) are the major mucins providing the organizing framework for the airway's mucus gel. We retrieved bronchial mucosal biopsies and bronchial wash (BW) samples through bronchoscopy from patients with chronic obstructive pulmonary disease ( = 38), healthy never-smokers ( = 40), and smokers with normal lung function ( = 40). The expression of MUC5AC and MUC5B was assessed immunohistochemically.

Tumorigenesis Caused by Aberrant Expression of GANP, a Central Component in the Mammalian TREX-2 Complex-Lessons from Transcription-Coupled DNA Damages.

DNA is frequently damaged by genotoxic stresses such as ionizing radiation, reactive oxygen species, and nitrogen species. DNA damage is a key contributor to cancer initiation and progression, and thus the precise and timely repair of these harmful lesions is required. Recent studies revealed transcription as a source of genome instability, and transcription-coupled DNA damage has been a focus in cancer research.

Oncogenic Functions of Alternatively Spliced Isoform in Retroperitoneal Liposarcoma.

Retroperitoneal liposarcoma (RPLPS) is one of the most common histologic subtypes of soft tissue sarcoma (STS). Complete surgical resection remains the mainstay treatment, while the high rate of locoregional recurrence constitutes the predominant cause of mortality. Well-differentiated (WDLPS) and dedifferentiated (DDLPS) liposarcoma are the most frequent subtypes of RPLPS and present amplified MDM2 gene as a hallmark.

Cancer Cell's Achilles Heels: Considerations for Design of Anti-Cancer Drug Combinations.

Loss of function screens using shRNA (short hairpin RNA) and CRISPR (clustered regularly interspaced short palindromic repeats) are routinely used to identify genes that modulate responses of tumor cells to anti-cancer drugs. Here, by integrating GSEA (Gene Set Enrichment Analysis) and CMAP (Connectivity Map) analyses of multiple published shRNA screens, we identified a core set of pathways that affect responses to multiple drugs with diverse mechanisms of action. This suggests that these pathways represent "weak points" or "Achilles heels", whose mild disturbance should make cancer cells vulnerable to a variety of treatments.

Oleanolic Acid Modulates DNA Damage Response to Camptothecin Increasing Cancer Cell Death.

Targeting DNA damage response (DDR) pathways represents one of the principal approaches in cancer therapy. However, defects in DDR mechanisms, exhibited by various tumors, can also promote tumor progression and resistance to therapy, negatively impacting patient survival. Therefore, identifying new molecules from natural extracts could provide a powerful source of novel compounds for cancer treatment strategies.

Association of Computed Tomography Scan-Assessed Body Composition with Immune and PI3K/AKT Pathway Proteins in Distinct Breast Cancer Tumor Components.

This hypothesis-generating study aims to examine the extent to which computed tomography-assessed body composition phenotypes are associated with immune and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathways in breast tumors. A total of 52 patients with newly diagnosed breast cancer were classified into four body composition types: adequate (lowest two tertiles of total adipose tissue [TAT]) and highest two tertiles of total skeletal muscle [TSM] areas); high adiposity (highest tertile of TAT and highest two tertiles of TSM); low muscle (lowest tertile of TSM and lowest two tertiles of TAT); and high adiposity with low muscle (highest tertile of TAT and lowest tertile of TSM). Immune and PI3K/AKT pathway proteins were profiled in tumor epithelium and the leukocyte-enriched stromal microenvironment using GeoMx (NanoString).

Whole-Exome Sequencing, Mutational Signature Analysis, and Outcome in Multiple Myeloma-A Pilot Study.

The complex and heterogeneous genomic landscape of multiple myeloma (MM) and many of its clinical and prognostic implications remains to be understood. In other cancers, such as breast cancer, using whole-exome sequencing (WES) and molecular signatures in clinical practice has revolutionized classification, prognostic prediction, and patient management. However, such integration is still in its early stages in MM.