PD15, a steroidal saponin, induces apoptosis of HCT116 colorectal cancer cells via suppressing the Akt/GSK3β pathway.

Objectives: PD15, a novel natural steroidal saponin extracted from the rhizomes of Paris delavayi Franchet, has demonstrated a strong cytotoxic effect against HepG2 and U87MG cells. However, its therapeutic effects on colorectal cancer (CRC) and the underlying molecular mechanisms remain unclear.

Methods: MTT assay, clonogenic assay, Hoechst 33258 staining, flow cytometry, molecular docking, and western blot were used to investigate the mechanism of PD15 in HCT116 cell lines.

Sodium alginate/low methoxyl pectin composite hydrogel beads prepared via gas-shearing technology for enhancing the colon-targeted delivery of probiotics and modulating gut microbiota.

The probiotic encapsulation system has the potential to enhance the prebiotic effects of probiotics. However, challenges arise from the release behavior of this system in vivo and the large size of hydrogel beads. This study aims to address the issues related to the size of previous hydrogel beads and assess the colon-targeted delivery of probiotic polysaccharides composite hydrogel beads (PPHB).

Simulated microgravity predisposes kidney to injury through promoting intrarenal artery remodeling.

Spaceflight-induced multi-organ dysfunction affects the health of astronauts and the safety of in-orbit flight. However, the effect of microgravity on the kidney and the underlying mechanisms are unknown. In the current study, we used a hindlimb unweighting (HU) animal model to simulate microgravity and employed histological analysis, ischemia-reperfusion experiments, renal ultrasonography, bioinformatics analysis, isometric force measurement, and other molecular experimental settings to evaluate the effects of microgravity on the kidneys and the underlying mechanisms involved in this transition.

Research on the function of epigenetic regulation in the inflammation of non-alcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver condition, characterized by a spectrum that progresses from simple hepatic steatosis to nonalcoholic steatohepatitis, which may eventually lead to cirrhosis and hepatocellular carcinoma. The precise pathogenic mechanisms underlying NAFLD and its related metabolic disturbances remain elusive. Epigenetic modifications, which entail stable transcriptional changes without altering the DNA sequence, are increasingly recognized as pivotal.

Mitochondrial transplantation for the treatment of cardiac and noncardiac diseases: mechanisms, prospective, and challenges.

Mitochondrial transplantation (MT) is a promising therapeutic strategy that involves introducing healthy mitochondria into damaged tissues to restore cellular function. This approach has shown promise in treating cardiac diseases, such as ischemia-reperfusion injury, myocardial infarction, and heart failure, where mitochondrial dysfunction plays a crucial role. Transplanting healthy mitochondria into affected cardiac tissue has resulted in improved cardiac function, reduced infract size, and enhanced cell survival in preclinical studies.

Osteoporosis under psychological stress: mechanisms and therapeutics.

Psychological stress has been associated with the onset of several diseases, including osteoporosis. However, the underlying pathogenic mechanism remains unknown, and effective therapeutic strategies are still unavailable. Growing evidence suggests that the sympathetic nervous system regulates bone homeostasis and vascular function under psychological stress, as well as the coupling of osteogenesis and angiogenesis in bone development, remodeling, and regeneration.

A biomarker framework for liver aging: the Aging Biomarker Consortium consensus statement.

In human aging, liver aging per se not only increases susceptibility to liver diseases but also increases vulnerability of other organs given its central role in regulating metabolism. Total liver function tends to be well maintained in the healthy elderly, so liver aging is generally difficult to identify early. In response to this critical challenge, the Aging Biomarker Consortium of China has formulated an expert consensus on biomarkers of liver aging by synthesizing the latest scientific literature, comprising insights from both scientists and clinicians.

Questionnaire survey on the clinical application of Hall technique preformed metal crowns in caries of primary molars in China.

Objective: To analyze the clinical application and limiting factors of the Hall technique (HT) preformed metal crowns in caries of primary molars and to provide reference for its clinical application based on a questionnaire survey.

Materials And Methods: From June to December 2022, a questionnaire was distributed to pediatric dentists through the WeChat platform using "Questionnaire Star" to analyze the clinical application and influencing factors of the HT preformed metal crowns in caries of primary molars.

Results: A total of 700 survey questionnaires were distributed, and 650 valid questionnaires were recovered, with a effectiveness rate of 92.

IDH1 mutation inhibits differentiation of astrocytes and glioma cells with low oxoglutarate dehydrogenase expression by disturbing α-ketoglutarate-related metabolism and epigenetic modification.

Isocitrate dehydrogenase (IDH) mutations frequently occur in lower-grade gliomas and secondary glioblastomas. Mutant IDHs exhibit a gain-of-function activity, leading to the production of D-2-hydroxyglutarate (D-2HG) by reducing α-ketoglutarate (α-KG), a central player in metabolism and epigenetic modifications. However, the role of α-KG homeostasis in IDH-mutated gliomagenesis remains elusive.

Bioaugmented design and functional evaluation of low damage implantable array electrodes.

Implantable neural electrodes are key components of brain-computer interfaces (BCI), but the mismatch in mechanical and biological properties between electrode materials and brain tissue can lead to foreign body reactions and glial scarring, and subsequently compromise the long-term stability of electrical signal transmission. In this study, we proposed a new concept for the design and bioaugmentation of implantable electrodes (bio-array electrodes) featuring a heterogeneous gradient structure. Different composite polyaniline-gelatin-alginate based conductive hydrogel formulations were developed for electrode surface coating.

Evenly Distributed Microporous Structure and E7 Peptide Functionalization Synergistically Accelerate Osteogenesis and Angiogenesis in Engineered Periosteum.

Repairing large bone defects remains a significant clinical challenge. Stem cell is of great importance in bone regeneration, and periosteum is rich in periosteal stem cell, which has a great influence on repairing bone defects. Bioengineered periosteum with excellent biocompatibility and stem cell homing capabilities to promote bone regeneration is of great clinical significance.

Platinum drugs upregulate CXCR4 and PD-L1 expression via ROS-dependent pathways, with implications for novel combined treatment in gastric cancer.

CXC chemokine receptor 4 (CXCR4) and programmed cell death-ligand 1 (PD-L1) are two critical molecules involved in the tumor immune microenvironment. However, the impact of platinum drugs, such as cisplatin, on CXCR4 or PD-L1 expression and the underlying mechanisms in gastric cancer (GC) remain unknown. Moreover, the correlation between their expression levels in GC remains elusive.

Placental mitochondrial metabolic adaptation maintains cellular energy balance in pregnancy complicated by gestational hypoxia.

The mechanisms that drive placental dysfunction in pregnancies complicated by hypoxia and fetal growth restriction remain poorly understood. Changes to mitochondrial respiration contribute to cellular dysfunction in conditions of hypoxia and have been implicated in the pathoaetiology of pregnancy complications, such as pre-eclampsia. We used bespoke isobaric hypoxic chambers and a combination of functional, molecular and imaging techniques to study cellular metabolism and mitochondrial dynamics in sheep undergoing hypoxic pregnancy.

The Role of Aryl Hydrocarbon Receptor in Skin Homeostasis: Implications for Therapeutic Strategies in Skin Disorders.

The aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, is extensively expressed in diverse human organs and plays a pivotal role in mediating the onset, progression, and severity of numerous diseases. Recent research has explored the substantial impact of AhR on skin homeostasis and related pathologies. As a multi-layered organ, the skin comprises multiple cell populations that express AhR.

Overexpression of miR-124 enhances the therapeutic benefit of TMZ treatment in the orthotopic GBM mice model by inhibition of DNA damage repair.

Glioblastoma (GBM) is the most common malignant primary brain cancer with poor prognosis due to the resistant to current treatments, including the first-line drug temozolomide (TMZ). Accordingly, it is urgent to clarify the mechanism of chemotherapeutic resistance to improve the survival rate of patients. In the present study, by integrating comprehensive non-coding RNA-seq data from multiple cohorts of GBM patients, we identified that a series of miRNAs are frequently downregulated in GBM patients compared with the control samples.

Posttranslational modifications in cardiac metabolic remodeling mediated by metabolites: Implications for disease pathology and therapeutic potential.

The nonenergy-producing or biomass-accumulating functions of metabolism are attracting increasing attention, as metabolic changes are gaining importance as discrete signaling pathways in modulating enzyme activity and gene expression. Substantial evidence suggests that myocardial metabolic remodeling occurring during diabetic cardiomyopathy, heart failure, and cardiac pathological stress (e.g.

Duhuo Jisheng Mixture attenuates neuropathic pain by inhibiting S1PR1/P2YR pathway after Chronic Constriction Injury in mice.

Background: The pathogenesis of neuropathic pain is complex and lacks effective clinical treatment strategies. Medical plants and herbal extracts from traditional Chinese medicine with multi-target comprehensive effects have attracted great attention from scientists.

Purpose: To investigate the pharmacological active components and mechanism underlying the anti-neuralgia effect of classic analgesic formulas Duhuo Jisheng Mixture (DJM).

Engineered extracellular vesicles for TGF-β encapsulation as a therapeutic strategy against LPS-induced systemic inflammation.

Inflammation underlies a wide variety of physiological and pathological processes, the Lipopolysaccharide (LPS)-induced inflammation model is widely recognized as a classical inflammatory paradigm, while Transforming growth factor-β (TGF-β) serves as a potent immunosuppressant capable of inhibiting immune responses and mitigating inflammation. However, its in vivo instability and the high cost associated with purification have imposed limitations on its clinical application. Therefore, we propose a therapeutic strategy for genetically modifying extracellular vesicles (HEVs) derived from HEK-293 T cells to incorporate TGF-β which holds potential for mitigating LPS-induced inflammation.

Innovative Strategies in Oncology: Bacterial Membrane Vesicle-Based Drug Delivery Systems for Cancer Diagnosis and Therapy.

Outer membrane vesicles (OMVs) are double-layered structures of nanoscale lipids released by gram-negative bacteria. They have the same membrane composition and characteristics as primitive cells, which enables them to penetrate cells and tissues efficiently. These OMVs exhibit excellent membrane stability, immunogenicity, safety, and permeability (which makes it easier for them to penetrate into tumour tissue), making them suitable for developing cancer vaccines and drug delivery systems.

Astrocytic Acid-Sensing Ion Channel 1a Contributes to the Development of Epileptic Cognitive Impairment.

Reactive astrogliosis and acidosis, common features of epileptogenic lesions, express a high level of astrocytic acid-sensing ion channel-1a (ASIC1a), a proton-gated cation channel and key mediator of responses to neuronal injury. This study investigates the role of astrocytic ASIC1a in cognitive impairment following epilepsy. Status epilepticus (SE) in C57/BL6 mice was induced using lithium-pilocarpine; the impact of ASIC1a on astrocytes was assessed using rAAV-ASIC1a-NC and rAAV-ASIC1a-shRNA, injected in the CA3 region of mice.

Integrated Proteomic and Metabolomic Analysis of Muscle Atrophy Induced by Hindlimb Unloading.

Skeletal muscle atrophy, which is induced by factors such as disuse, spaceflight, certain medications, neurological disorders, and malnutrition, is a global health issue that lacks effective treatment. Hindlimb unloading is a commonly used model of muscle atrophy. However, the underlying mechanism of muscle atrophy induced by hindlimb unloading remains unclear, particularly from the perspective of the myocyte proteome and metabolism.

TLR7: A Key Prognostic Biomarker and Immunotherapeutic Target in Lung Adenocarcinoma.

The tumor microenvironment (TME) plays a crucial role in the progression of lung adenocarcinoma (LUAD). However, understanding its dynamic immune and stromal modulation remains a complex challenge. We utilized the ESTIMATE algorithm to evaluate the immune and stromal components of the LUAD TME from the TCGA database.

The Pathogenic Role of Expanded CD8⁺CD28 Angiogenic T Cells in ANCA-Associated Vasculitis.

Angiogenic T cells (Tang) are crucial in promoting angiogenesis, with the loss of CD28 serving as a marker for highly differentiated and senescent T cells. This study aims to investigate the characteristics and potential roles of CD8CD28 Tang in patients with ANCA-associated vasculitis (AAV). A cohort of AAV patients and matched healthy controls (HCs) were analyzed.

HGF/c-Met Promotes Breast Cancer Tamoxifen Resistance Through the EZH2/HOTAIR-miR-141/200a Feedback Signaling Pathway.

Tamoxifen is one of the most frequently used endocrine medications for the treatment of estrogen receptor-positive (ER + ) breast cancer (BC). Unfortunately, tamoxifen resistance (TR) brings more challenges to the clinical treatment, and the mechanisms of TR have not yet been fully clarified. HGF/c-Met is closely associated with cancer metastasis, but whether it is involved in TR remains unclear.