Dual targeting PPARα and NPC1L1 metabolic vulnerabilities blocks tumorigenesis.

Dysregulated lipid metabolism is linked to tumor progression. In this study, we identified Niemann-Pick C1-like 1 (NPC1L1) as a downstream effector of PKM2. In breast cancer cells, PKM2 knockout (KO) enhanced NPC1L1 expression while downregulating peroxisome proliferator-activated receptor α (PPARα) signaling pathway.

Shouhui Tongbian Capsule ameliorates obesity by enhancing energy consumption and promoting lipolysis via cAMP-PKA pathway.

Background: The prevalence of obesity and its associated diseases has sharply increased, becoming a global health issue. White adipose tissue (WAT), responsible for lipid storage via hyperplasia and hypertrophy, and brown adipose tissue (BAT), which facilitates energy dissipation, have increasingly been recognized as critical regulators of weight loss. Shouhui Tongbian Capsule (SHTB) has traditionally been used for detoxification, weight loss, and lipid reduction, and clinical evidence supports its use for relieving constipation.

Simultaneous Induction of Immunogenic Pyroptosis and PD-L1 Downregulation by One Single Photosensitizer for Synergistic Cancer Photoimmunotherapy.

Pyroptosis, an excellent form of immunogenic cell death that can effectively activate antitumor immune responses, is attracting considerable interest as a promising approach for cancer immunotherapy. Immunogenic pyroptosis can recruit and stimulate dendritic cells to provoke further activation and tumor infiltration of T cells by releasing danger-associated molecular patterns, thus improving the tumor response to PD-1/PD-L1 checkpoint blockade immunotherapy. Here, we report the discovery of a bifunctional photosensitizer Nile Violet that can simultaneously trigger caspase-3/GSDME-mediated immunogenic pyroptosis and PD-L1 downregulation for cancer photoimmunotherapy.

Robust and Regular Micronano Binary Texture on the Complex Curved Surface for Enhanced Reendothelialization and Antithrombotic Performance.

Blood-contacting medical devices can easily trigger immune responses, leading to thrombosis and hyperblastosis. Constructing microtexture that provides efficient antithrombotic and rapid reendothelialization performance on complex curved surfaces remains a pressing challenge. In this work, we present a robust and regular micronano binary texture on the titanium surface, characterized by exceptional mechanical strength and precisely controlled wettability to achieve excellent hemocompatibility.

Exploring the Binding Mechanism of ADGRG2 Through Metadynamics and Biochemical Analysis.

G protein-coupled receptors (GPCRs) play essential roles in numerous physiological processes and are key targets for drug development. Among them, adhesion GPCRs (aGPCRs) stand out for their unique domain structures and diverse functions. ADGRG2 is a member of the aGPCR family and is involved in the regulation of various systems in the human body, including reproductive, nervous, cardiovascular, and endocrine systems.

Signature of collagen alpha-1(x) gene expression in human cancers and their therapeutic implications.

Cancers are a class of disorders that entail uncontrollably unwanted cell development with dissemination. One in six fatalities globally is attributed to cancer, a global health issue. The analysis of the entire DNA sequence and how it expresses itself in tumor cells is known as cancer genomics.

Optimal treatment approach for intracranial germinoma: a systematic review and meta-analysis.

Background: To determine the optimal treatment modality for intracranial germinoma (IG).

Materials And Methods: A search of Medline, Embase, Web of Science and Cochrane Library was conducted up to April, 2024. Pooled risk ratio (RR) and 95% confidence interval (CI) were calculated.

Evolutionary study and structural basis of proton sensing by Mus GPR4 and Xenopus GPR4.

Animals have evolved pH-sensing membrane receptors, such as G-protein-coupled receptor 4 (GPR4), to monitor pH changes related to their physiology and generate adaptive reactions. However, the evolutionary trajectory and structural mechanism of proton sensing by GPR4 remain unresolved. Here, we observed a positive correlation between the optimal pH of GPR4 activity and the blood pH range across different species.

Wogonin suppresses proliferation, invasion and migration in gastric cancer cells via targeting the JAK-STAT3 pathway.

Wogonin is a compound extracted from the medicinal plant Scutellaria baicalensis Geogi and has been found to exert antitumor activities in a variety of malignancies. However, the molecular mechanisms involved in the anti-gastric cancer (GC) effects of wogonin remain poorly understood. In the present study, we found that wogonin treatment inhibited the proliferation of GC cells, induced apoptosis and G0/G1 cell arrest, and suppressed the migration and invasion of SGC-7901 and BGC-823 cells in vitro.

Renal Juxtaglomerular Cell Tumors Exhibit Distinct Genomic and Epigenomic Features and Lack Recurrent Gene Fusions: Comprehensive Molecular Analysis of a Multi-institutional Series.

Juxtaglomerular cell tumor (JxGCT) is a rare type of renal neoplasm demonstrating morphologic overlap with some mesenchymal tumors such as glomus tumor (GT) and solitary fibrous tumor (SFT). Its oncogenic drivers remain elusive, and only a few cases have been analyzed with modern molecular techniques. In prior studies, loss of chromosomes 9 and 11 appeared to be recurrent.

Bisphenol S impairs oocyte quality by inducing gut microbiota dysbiosis.

Unlabelled: A good quality egg is essential for a successful pregnancy and early embryo development. Oocyte development is vulnerable to environmental exposures. Bisphenol S (BPS) is widely used as a replacement for its analog bisphenol A, but the reproductive toxicity of BPS has been of great concern.

Causal effects of the RANK-RANKL-OPG system and scoliosis: A bidirectional 2-sample Mendelian randomization study.

Epidemiological studies and a recent Mendelian randomization (MR) study have identified an association between low bone mass and an increased risk of scoliosis. Previous research suggests that bone loss in patients with scoliosis may be related to the RANK-RANKL-OPG system. This study is to investigate whether a causal relationship exists between the RANK-RANKL-OPG system and the development of scoliosis.

Design and synthesis of N-(3-cyanothiophen-2-yl)-2-phenoxyacetamide-based α-glucosidase inhibitors.

This study investigates the design and synthesis of a series of novel selective α-glucosidase inhibitors based on N-(3-cyanothiophen-2-yl)-2-phenoxyacetamide framework, employing a bioisosterism strategy. Among the nineteen newly synthesized analogs, compound 4d9 demonstrated the highest α-glucosidase inhibitory potency (IC = 2.11 μM) when compared to the established inhibitors Acarbose (IC = 327.

Dual-phase SilMA hydrogel: a dynamic scaffold for sequential drug release and enhanced spinal cord repair via neural differentiation and immunomodulation.

Introduction: Spinal cord injury (SCI) is a severe central nervous system disorder that results in significant sensory, motor, and autonomic dysfunctions. Current surgical techniques and high-dose hormone therapies have not achieved satisfactory clinical outcomes, highlighting the need for innovative therapeutic strategies.

Methods: In this study, we developed a Dual-Phase Silk Fibroin Methacryloyl (SilMA) hydrogel scaffold (DPSH) that incorporates PLGA microspheres encapsulating neurotrophin-3 (NT-3) and angiotensin (1-7) (Ang-(1-7)).

Machine learning-based analysis of programmed cell death types and key genes in intervertebral disc degeneration.

Intervertebral disc degeneration (IVDD) is intricately associated with various forms of programmed cell death (PCD). Identifying key PCD types and associated genes is essential for understanding the molecular mechanisms underlying IVDD and discovering potential therapeutic targets. This study aimed to elucidate core PCD types, related genes, and potential drug interactions in IVDD using comprehensive bioinformatic and experimental approaches.

Identification of host proteins that interact with African swine fever virus pE301R.

African swine fever virus (ASFV) infection poses enormous threats and challenges to the global pig industry; however, no effective vaccine is available against ASFV, attributing to the huge viral genome (approximately189 kb) and numerous encoding products (>150 genes) due to the limited understanding on the molecular mechanisms of viral pathogenesis. Elucidating the host-factor/viral-protein interaction network will reveal new targets for developing novel antiviral therapies. Using proteomic analysis, we identified 255 cellular proteins that interact with the ASFV-encoded pE301R protein when transiently expressed in HEK293T cells.

Treatment of constipation with and its compatibility prescriptions.

Constipation is a common and prevalent digestive system disease in clinical practice, which seriously affects human physical and mental health. Currently, chemical drugs have good short-term therapeutic effects. However, because of their adverse reactions, easy recurrence after drug discontinuation, and dependence with long-term use, the long-term efficacy is unsatisfactory.

Discovery of epigenetic modulators targeting HDACs and EZH2 simultaneously for the treatment of hematological malignancies.

Epigenetic-targeted therapy has been applied in the treatment of several types of cancer. Herein, based on the synergistic antitumor effects of co-targeting HDACs and EZH2 in some hematological malignancies, a novel series of tazemetostat-based HDACs/EZH2 dual inhibitors were rationally designed, synthesized, and biologically evaluated. Satisfyingly, compounds 22a and 22b were identified as potent HDACs/EZH2 dual inhibitors with robust antiproliferative activities against one diffuse large-cell B cell lymphomas (DLBCL) cell line harboring EZH2 mutation and multiple acute myeloid leukemia (AML) cell lines.

Probiotics and their metabolite spermidine enhance IFN-γCD4 T cell immunity to inhibit hepatitis B virus.

The therapeutic potential of commensal microbes and their metabolites is promising in the functional cure of chronic hepatitis B virus (HBV) infection, which is defined as hepatitis B surface antigen (HBsAg) loss. Here, using both specific-pathogen-free and germ-free mice, we report that probiotics significantly promote the decline of HBsAg and inhibit HBV replication by enhancing intestinal homeostasis and provoking intrahepatic interferon (IFN)-γCD4 T cell immune response. Depletion of CD4 T cells or blockage of IFN-γ abolishes probiotics-mediated HBV inhibition.

Recent advances in microfluidic chip technologies for applications as preclinical testing devices for the diagnosis and treatment of triple-negative breast cancers.

The leading cause of cancer-related death among female patients is breast cancer. Among all the types of breast cancer, triple-negative breast cancer (TNBC) is the most dangerous molecular subtype of breast cancer characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) expression. Since there is no particular therapeutic strategy for TNBC that has been shown to worsen the disease prognosis, 3D models are superior to 2D models as a predictive tool for drug discovery because they more accurately reflect the in vivo biological components of humans.

Trojan Horse Strategy for Wireless Electrical Stimulation-Induced Zn Release to Regulate Neural Stem Cell Differentiation for Spinal Cord Injury Repair.

Due to the uncertain differentiation of neural stem cells (NSCs), replenishing lost neurons by endogenous neural differentiation to repair spinal cord injury (SCI) remains challenging. The electrical stimulation-induced drug release is a promising approach for the localized and controlled release of drugs to regulate the differentiation of NSCs into neurons. Here, we developed Zn-PDA@BT nanoparticles acted as Trojan Horse to enter cells through endocytosis for Zn-controlled release therapy by the potentials generated by the piezoelectric effect.