Perturbation of mammary epithelial cell apicobasal polarity by RHBDF1-facilitated nuclear translocation of PKCζ.

Background: The establishment of apicobasal polarity in epithelial cells is of critical importance in morphogenesis of mammary gland and other secretive gland tissues. The demise of the polarity is a critical step in early stages of tumorigenesis such as in breast ductal carcinoma in situ. The underlying molecular mechanism thus warrants in-depth investigations.

Depletion of regulatory T cells enhances the T cell response induced by the neoantigen vaccine with weak immunogenicity.

Background: The neoantigen vaccine has remarkable potential in treating advanced cancer due to its tumor specificity and ability to bypass central tolerance mechanisms. However, numerous neoantigens show poor immunogenicity, and the immune inhibitory factors of present in both tumors and tumor-draining lymph nodes impair the efficacy of cancer neoantigen vaccine. Eliminating immunosuppressive cells will improve the priming and expansion of anti-tumor immune cells induced by the vaccine.

Sodium-glucose co-transporter-2 inhibitors in patients with chronic kidney disease with or without type 2 diabetes: systematic review and meta-analysis.

Objective: To examine cardiovascular and kidney benefits and harms of sodium-glucose co-transporter-2 (SGLT-2) inhibitors stratified by risk in adults with chronic kidney disease regardless of diabetes status.

Design: Systematic review and meta-analysis.

Data Sources: Ovid Medline, Embase, and Cochrane Central from database inception to 15 June 2024.

UGT708S6 from Dendrobium catenatum, catalyzes the formation of flavonoid C-glycosides.

Background: Dendrobium catenatum is a perennial herb of the genus Dendrobium orchidaceae. It has been known as "Golden Grass, Soft Gold" since ancient times with effects of strengthening the body, benefiting the stomach, generating body fluid, nourishing Yin and clearing internal heat. The flowers of D.

Precise HER2 Protein Degradation via Peptide-Conjugated Photodynamic Therapy for Enhanced Breast Cancer Immunotherapy.

Breast cancer, the most prevalent malignancy among women, frequently exhibits high HER2 expression, making HER2 a critical therapeutic target. Traditional treatments combining the anti-HER2 antibody trastuzumab with immunotherapy face limitations due to toxicity and tumor microenvironment immunosuppression. This study introduces an innovative strategy combining HER2-targeting peptides with the photosensitizer (PSs) pyropheophorbide-a (Pha) via a gelatinase-cleavable linker, forming self-assembling nanoparticles.

STING signaling contributes to methotrexate-induced liver injury by regulating ferroptosis in mice.

Methotrexate (MTX), an anti-metabolite agent, is a widely used chemotherapeutic anticancer drug, but its hepatotoxicity severely limits its clinical application. Nevertheless, the precise mechanisms of MTX-caused liver damage are extremely intricate and still need to be fully clarified. In the current study, we investigated the role of the STING-ERS-ferroptosis axis in MTX-triggered hepatic toxicity in vivo and in vitro models.

Novel perspectives on the link between obesity and cancer risk: from mechanisms to clinical implications.

Existing epidemiologic and clinical studies have demonstrated that obesity is associated with the risk of a variety of cancers. In recent years, an increasing number of experimental and clinical studies have unraveled the complex relationship between obesity and cancer risk and the underlying mechanisms. Obesity-induced abnormalities in immunity and biochemical metabolism, including chronic inflammation, hormonal disorders, dysregulation of adipokines, and microbial dysbiosis, may be important contributors to cancer development and progression.

Discovery of new fungal jumonji H3K27 demethylase inhibitors for the treatment of Cryptococcus neoformans and Candida auris infections.

Invasive fungal infections have become a serious public health problem. To tackle the challenges of limited efficacy in antifungal therapy and severe drug resistance, antifungal drugs with new mechanisms of action are urgently needed. Our previous study identified JIB-04 to be an inhibitor of fungal histone demethylase (HDM).

The Scalp Nerve Block Combined with Intercostal Nerve Block Improves Recovery After Deep Brain Stimulation in Patients with Parkinson's Disease: A Prospective, Randomized Controlled Trial.

Objective: To explore the effect of scalp nerve block (SNB) combined with intercostal nerve block (ICNB) on quality of recovery (QoR) after deep brain stimulation (DBS) in patients with Parkinson's disease (PD).

Methods: We conducted a prospective randomized controlled trial in which 88 patients with PD were randomly assigned to undergo SNB combined with ICNB (SNB group) or not (control group) before surgery. The primary outcome was the 15-item QoR (QoR-15) score 24 h after surgery.

Research progress of the Hippo signaling pathway in renal cell carcinoma.

Objective: This review aimed to summarize the role of the Hippo signaling pathway in renal cell carcinoma (RCC), a urologic malignancy with subtle initial symptoms and high mortality rates due to metastatic RCC. The Hippo signaling pathway, which regulates tissue and organ sizes, plays a crucial role in RCC progression and metastasis. Understanding the involvement of the Hippo signaling pathway in RCC provides valuable insights for the development of targeted therapies and improved patient outcomes.

Demethylzeylasteral induces PD-L1 ubiquitin-proteasome degradation and promotes antitumor immunity targeting USP22.

Programmed cell death ligand-1 (PD-L1) is a T cell inhibitory immune checkpoint molecule that interacts with programmed cell death-1 (PD-1) to promote immune escape of tumor cells. Compared with antibody therapies, small molecule drugs show better prospects due to their advantages such as higher bioavailability, better tissue penetration, and reduced risk of immunogenicity. Here, we found that the small molecule demethylzeylasteral (Dem) can significantly downregulate the expression of PD-L1 in colorectal cancer cells and enhance the killing effect of T cells on tumor cells.

Does snake-eye appearance affect the clinical outcome of ACDF in treating cervical myelopathy.

Purpose: To explore the impact of the snake-eye appearance (SEA) on the efficacy of anterior cervical discectomy and fusion (ACDF) in treating Degenerative Cervical Myelopathy (DCM).

Methods: A total of 316 Patients were divided into three groups, those with SEA were in the SEA group, and those with the absence of SEA were in the non-SEA group. Meanwhile, in the non-SEA group, patients with grade 1 or 2 increased signal intensity (ISI) on T2-weighted MRI were in the ISI group, and the remaining patients without ISI were in the non-ISI group.

METTL14 Induced N-Methyladenosine Modification of FOXP4 mRNA in HBV-HCC.

Chronic hepatitis B virus infections are a significant cause of liver cirrhosis and cancer. Our research reveals that HBV infection leads to a marked increase in m6A modification of Foxp4 mRNA, resulting in enhanced stability of the mRNA and a subsequent increase in Foxp4 mRNA levels. Analysis of biopsy samples from chronic HBV patients demonstrated consistent upregulation of m6A-modified Foxp4 mRNA levels alongside increased Foxp4 mRNA levels.

Immune Checkpoints in B Cells: Unlocking New Potentials in Cancer Treatment.

B cells are crucial component of humoral immunity, and their role in the tumor immune microenvironment (TME) has garnered significant attention in recent years. These cells hold great potential and application prospects in the field of tumor immunotherapy. Research has demonstrated that the TME can remodel various B cell functions, including proliferation, differentiation, antigen presentation, and antibody production, thereby invalidating the anti-tumor effects of B cells.

Comparative Proteomic and Phosphoproteomic Analyses Reveal Molecular Signatures of Myocardial Infarction and Transverse Aortic Constriction in Aged Mouse Models.

In the elderly population, coronary heart disease (CHD) often coexists with hypertension. However, excessive blood pressure reduction can paradoxically increase the incidence of adverse events. Understanding the molecular mechanisms underlying hypertension and CHD in aged populations is crucial for developing targeted therapies and improving clinical outcomes.

Integrative analyses of genetic mechanisms responsible for bone-fat imbalance in osteoporosis.

Osteoporosis manifests through adipocyte accrual and osteoblast diminution within bone marrow. However, the precise mechanisms driving the shift from osteogenesis to adipogenesis in bone marrow mesenchymal stem cells (BMSCs) remain largely undefined. In this study, we harnessed the power of bioinformatic tools to analyze gene expression patterns of BMSCs during adipogenic differentiation and osteoporosis using the data from Gene Expression Omnibus (GEO) repositories (GSE113253 and GSE35956), complemented by in vitro and in vivo experiments to validate the findings.

Role of glycogen in cardiac metabolic stress.

Metabolic stress in the myocardium arises from a diverse array of acute and chronic pathophysiological contexts. Glycogen mishandling is a key feature of metabolic stress, while maladaptation in energy-stress situations confers functional deficits. Cardiac glycogen serves as a pivotal reserve for myocardial energy, which is classically described as an energy source and contributes to glucose homeostasis during hypoxia or ischemia.

Network Medicine-Based Strategy Identifies Maprotiline as a Repurposable Drug by Inhibiting PD-L1 Expression via Targeting SPOP in Cancer.

Immune checkpoint inhibitors (ICIs) are drugs that inhibit immune checkpoint (ICP) molecules to restore the antitumor activity of immune cells and eliminate tumor cells. Due to the limitations and certain side effects of current ICIs, such as programmed death protein-1, programmed cell death-ligand 1, and cytotoxic T lymphocyte-associated antigen 4 (CTLA4) antibodies, there is an urgent need to find new drugs with ICP inhibitory effects. In this study, a network-based computational framework called multi-network algorithm-driven drug repositioning targeting ICP (Mnet-DRI) is developed to accurately repurpose novel ICIs from ≈3000 Food and Drug Administration-approved or investigational drugs.