CDK8 mediated inflammatory microenvironment aggravates osteoarthritis progression.

Introduction: Cyclin-Dependent Kinase 8 (CDK8), a CDK family member, regulates the development of inflammatory processes through transcriptional activation. The involvement of CDK8 in osteoarthritis (OA) progression is not yet understood.

Objectives: This study aims to investigate whether CDK8, through its transcriptional regulatory functions, collaborates with NF-κB in chondrocytes to regulate the transcription of senescence-associated secretory phenotype (SASP) genes, thereby exacerbating the inflammatory microenvironment in the progression of osteoarthritis (OA), and to explore the specific mechanisms involved.

Deep learning-based lymph node metastasis status predicts prognosis from muscle-invasive bladder cancer histopathology.

Purpose: To develop a deep learning (DL) model based on primary tumor tissue to predict the lymph node metastasis (LNM) status of muscle invasive bladder cancer (MIBC), while validating the prognostic value of the predicted aiN score in MIBC patients.

Methods: A total of 323 patients from The Cancer Genome Atlas (TCGA) were used as the training and internal validation set, with image features extracted using a visual encoder called UNI. We investigated the ability to predict LNM status while assessing the prognostic value of aiN score.

Enzyme-assisted Rosa davurica mitigates UV-induced skin photodamage by modulating apoptosis through Nrf2/ARE and MAPK/NF-κB pathways.

Exposure to UV irradiation results in abnormal, extensive apoptosis of skin cells. This excessive cell death can promote inflammation and alter the microenvironment, increasing the risk of skin cancer. Despite extensive research, few materials are effective at simultaneously protecting against both UVA and UVB irradiation.

Plantaginis Herba attenuates adriamycin-induced nephropathy: Molecular mechanism insights by integrated transcriptomic and experimental validation.

Ethnopharmacological Relevance: The Chinese herbal Plantaginis Herba (PL) is one of the most widely used plants for both medicinal and dietary purposes. Plantaginis Herba is the main medicine used in a traditional Chinese prescription called Cheqiancao decoction, and it is known for its liver and kidney protective properties.

Aim Of The Study: The aim of the present study was to explore the interventions and mechanisms of PL in ADR nephropathy by performing an integrated analysis of in vitro and in vivo experiments.

TAX1BP1 regulates the apoptosis of renal tubular epithelial cells in ischemia/reperfusion injury via the NF-kB/PMAIP1 signaling pathway.

Background: The pathogenesis of acute kidney injury (AKI) is not fully understood. Tax1-binding protein 1 (TAX1BP1) modulates inflammation and apoptosis through the NF-kB signaling pathway, however, its specific role in ischemic AKI remains unclear.

Methods: We injected a TAX1BP1 overexpression plasmid into the tail vein of male C57BL/6 mice, followed by clamping the bilateral renal arteries to induce AKI.

Pathomics-based machine learning models for predicting pathological complete response and prognosis in locally advanced rectal cancer patients post-neoadjuvant chemoradiotherapy: insights from two independent institutional studies.

Background: Accurate prediction of pathological complete response (pCR) and disease-free survival (DFS) in locally advanced rectal cancer (LARC) patients undergoing neoadjuvant chemoradiotherapy (NCRT) is essential for formulating effective treatment plans. This study aimed to construct and validate the machine learning (ML) models to predict pCR and DFS using pathomics.

Method: A retrospective analysis was conducted on 294 patients who received NCRT from two independent institutions.

Vitexin alleviates MNNG-induced chronic atrophic gastritis via inhibiting NLRP3 inflammasome.

Ethnopharmacological Relevance: The dried fruit of Crataegus pinnatifida Bunge (Hawthorn in Chinese) is a traditional medicine used in China, Japan and Korea for thousands of years. Hawthorn is documented in the Chinese Pharmacopoeia, as a folk medicine that is used to eliminate food, strengthen the stomach, move qi and dissipate blood stasis, treat stagnation of meat and food, gastric distention and fullness, and has anti-inflammatory effects. Vitexin, a flavonoid glycoside, is an important biologically active compound derived from Hawthorn, with significant antioxidant and anti-inflammatory properties.

["Shugan Tiaoshen" needling improves depression after ischemic stroke by regulating AMPK-dependent autophagy].

Objectives: To observe the effect of "Shugan Tiaoshen"(soothing the liver and regulating the mental activities) needling on the expressions of AMP-activated protein kinase (AMPK) and autophagy-related proteins in the prefrontal cortex of rats with depression after ischemic stroke (post-stroke depression), in order to explore its mechanisms underlying improvement of post-stroke depression behaviors.

Methods: A total of 60 male SD rats were randomly divided into sham operation (control), stroke, post-stroke depression, inhibitor, acupuncture, and acupuncture + inhibitor groups. The post-stroke depression model was established by occlusion of the middle cerebral artery and reperfusion (MCAO/R), combined with chronic unpredictable mild stimulation (CUMS).

Dextran Sulfate-Modified and pH-Responsive Nanoprobes for Magnetic Resonance/Fluorescence Dual-Modality Imaging of Vulnerable Plaques.

Triggered by the vulnerability to atherosclerotic plaques, cardiovascular diseases (CVDs) have become a main reason for high mortality worldwide. Thus, there is an urgent need to develop functional molecular imaging modalities to improve the detection rate of vulnerable plaques. In this study, polyethyleneimine (PEI) was coated on the surface of mesoporous silica nanoprobes (MSN) loaded with GdO (MSN@GdO), followed by coupling the fluorescent dye carboxylated heptamethine cyanine (IR808), and then the dextran sulfate (DS) was modified on the surface of MSN@GdO@IR808 by electrostatic adsorption, to construct a targeted and pH-responsive magnetic resonance (MR)/near-infrared fluorescence imaging (NIRF) dual-modal nanoprobe (MSN@GdO@IR808@DS nanoparticles).

Effects of chronic cold stress and thermal stress on growth performance, hepatic apoptosis, oxidative stress, immune response and gut microbiota of juvenile hybrid sturgeon (Acipenser baerii ♀ × A. schrenkii ♂).

The current study was conducted to investigate the effects of chronic cold stress and thermal stress on the growth performance, hepatic oxidative status, immune response, apoptosis and gut microbiota in juvenile hybrid sturgeon. The fish (initial mean weight: 21.4 ± 0.

Interpretable multi-modal artificial intelligence model for predicting gastric cancer response to neoadjuvant chemotherapy.

Neoadjuvant chemotherapy assessment is imperative for prognostication and clinical management of locally advanced gastric cancer. We propose an incremental supervised contrastive learning model (iSCLM), an interpretable artificial intelligence framework integrating pretreatment CT scans and H&E-stained biopsy images, for improved decision-making regarding neoadjuvant chemotherapy. We have constructed and tested iSCLM using retrospective data from 2,387 patients across 10 medical centers and evaluated its discriminative ability in a prospective cohort (132 patients; ChiCTR2300068917).

Shanyao regulates the PI3K/AKT/P21 pathway to promote oogonial stem cell proliferation and stemness restoration to alleviate premature ovarian insufficiency.

Ethnopharmacological Relevance: Shanyao (SY, yam, Rhizoma Dioscoreae, the dried rhizome of Dioscorea oppositifolia L.) was recorded in the Chinese pharmacopoeia and was often used in the treatment of premature ovarian insufficiency (POI).

Aim Of Study: To evaluate the efficacy of shanyao in cyclophosphamide (CTX)-induced POI and explore its potential mechanism of action.

Levamisole Ameliorates Rheumatoid Arthritis by Downregulating the PI3K/Akt Pathway in SD Rats.

Rheumatoid arthritis (RA) is a systemic chronic autoimmune disease characterized by a protracted course, high rates of morbidity, and disability yet lacks effective therapeutic modalities. Levamisole (LVM), an immunomodulatory drug, has been clinically reported for its potential in RA treatment, while its therapeutic mechanism toward RA remains to be elucidated. Hence, this study provides theoretical support for the application of LVM in the treatment of RA.

Zuogui pills ameliorate chemotherapy-induced ovarian aging by improving stemness, regulating cell cycle and reducing apoptosis of oogonial stem cells via the Notch1/Nrf2 pathway.

Ethnopharmacological Relevance: Zuogui Pills (ZGP) is a classic traditional Chinese herbal formula originating from the Ming Dynasty. It has been widely used in the treatment of kidney deficiency-related diseases, including ovarian aging.

Aim Of The Study: To investigate the effects and potential mechanisms of ZGP on ovarian aging induced by the chemotherapeutic agent cyclophosphamide (CTX), as well as its impact on the therapeutic target, oogonial stem cells (OSCs), involving the Notch1/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway.

IWR-1 attenuates the promotional effect of IL-36γ in a mouse model of psoriasis.

Background: Psoriasis is a chronic inflammatory skin disease. The Wnt/β-catenin signaling pathway is essential for the regulation of adult stem cells, homeostasis, and tissue regeneration; however, the relationship between this pathway and interleukin (IL)-36γ in the pathogenesis of psoriasis remains unclear.

Methods: In this study, psoriasiform model mice were established using imiquimod (IMQ) induction.

Ampelopsis grossedentata tea alleviating liver fibrosis in BDL-induced mice via gut microbiota and metabolite modulation.

Liver fibrosis (LF) is a common sequela to diverse chronic liver injuries, leading to rising rates of cirrhosis and hepatocellular carcinoma (HCC). As the medicinal and edible homologous material, traditional teas have exhibited promising applications in the clinical management of liver fibrosis. Here, we generated a liver fibrosis mouse model to explore the potent therapeutic ability of Ampelopsis grossedentata (AG) tea on this condition by multi-omics analysis.

Manual Therapy Exerts Local Anti-Inflammatory Effects Through Neutrophil Clearance.

Manual therapy (MT) has been widely used in China to treat local tissue inflammation for a long time. However, there is a lack of scientific evidence for using MT in anti-inflammatory therapy, and its anti-inflammatory mechanism needs further clarification. We utilized MT to treat cardiotoxin (CTX) injury-induced skeletal muscle inflammation in C57BL6/J mice.

HMGB2 promotes smooth muscle cell proliferation through PPAR-γ/PGC-1α pathway-mediated glucose changes in aortic dissection.

Background And Aims: Aortic dissection (AD) is a fatal condition with a complicated pathogenesis. High mobility group protein B2 (HMGB2) is a member of the high mobility group protein family; HMGB2 is involved in innate immunity and inflammatory diseases, but its role in AD remains unclear.

Methods: HMGB2 mice were generated and treated with β-aminopropionitrile and angiotensin II (Ang II) to establish an AD model.

Risperidone accelerates bone loss in mice models of schizophrenia by inhibiting osteoblast autophagy.

Background: Risperidone (RIS) is the first-line drug in the clinical treatment of schizophrenia, and long-term use may lead to bone loss and even osteoporosis. This study investigated whether the mechanism of RIS-induced bone loss is related to autophagy.

Methods: The schizophrenia mice were established with the administration of MK-801.

Safety Evaluation of a Potential Anti-Rheumatoid Arthritis Candidate, Levamisole.

Introduction: Given the limitations and adverse effects of current rheumatoid arthritis (RA) treatments, there is an urgent need for safer and more effective therapeutic options. Levamisole (LVM) is a non-specific immunomodulator with potential for treating skin diseases, tumors, and autoimmune disorders. Recognizing LVM's potential despite its controversial reputation, this study aimed to investigate its safety profile and therapeutic efficacy towards RA.

Integrative multi-omics and network pharmacology reveal the mechanisms of Fangji Huangqi Decoction in treating IgA nephropathy.

Ethnopharmacological Relevance: Fangji Huangqi Decoction (FJHQD), a classical Chinese herbal formulation, has demonstrated significant clinical efficacy in the treatment of IgA nephropathy (IgAN), although its mechanisms remain poorly understood.

Aim Of The Study: This study aims to investigate the renal protective mechanisms of FJHQD using an integrated approach that combines transcriptomics, proteomics, and network pharmacology.

Methods: Renal glomerular structure changes were assessed via hematoxylin and eosin (H&E) and Masson staining.

NRF1-induced mmu_circ_0001388/hsa_circ_0029470 confers ferroptosis resistance in ischemic acute kidney injury via the miR-193b-3p/TCF4/GPX4 axis.

Aims: Circular RNAs (circRNAs) are critical in the progression of ischemic acute kidney injury (AKI). Nevertheless, the specific functions and regulatory pathways of mmu_circ_0001388 and hsa_circ_0029470 remain elusive.

Methods: Real-time quantitative polymerase chain reaction (RT-qPCR) was utilized to assess the expression patterns of mmu_circ_0001388, hsa_circ_0029470, and miR-139b-3p.

Establishment of a dexamethasone-induced zebrafish skeletal muscle atrophy model and exploration of its mechanisms.

Background: Skeletal muscle atrophy is one of the main side effects of high-dose or continuous use of glucocorticoids (such as dexamethasone). However, there are limited studies on dexamethasone-induced skeletal muscle atrophy in zebrafish and even fewer explorations of the underlying molecular mechanisms. This study aimed to construct a model of dexamethasone-induced skeletal muscle atrophy in zebrafish and to investigate the molecular mechanisms.

HDAC6 promotes inflammation in lupus nephritis mice by regulating transcription factors MAFF and KLF5 in renal fibrosis.

Aim: This study explored the effect and mechanism of MAFF and HDAC6 on renal fibrosis and inflammation in lupus nephritis (LN).

Methods: IL-33 treated renal epithelial cells and MRL/lpr mice were respectively used for and experiments. The expressions of HDAC6, MAFF, and KLF5 were measured in cells and renal tissues.