P2Y12 receptor-independent antiplatelet mechanism of cryptotanshinone: network pharmacology and experimental validation of multi-target signaling pathways.

Ethnopharmacological Relevance: Cryptotanshinone serves as the principal bioactive constituent of Salvia miltiorrhiza Bunge, possesses a wide range of pharmacological activities. Salvia miltiorrhiza Bunge, a long-standing therapeutic agent in traditional Chinese medicine (TCM) practice, is renowned for its efficacy in enhancing blood circulation and alleviating blood stasis and infarction, thereby treating cardiovascular and cerebrovascular diseases.

Aim Of The Study: Platelet activation, when excessive or aberrant, poses a significant risk, catalyzing the onset of various thrombotic disorders.

Fuzheng Jiedu decoction alleviates H1N1 virus-induced acute lung injury in mice by suppressing the NLRP3 inflammasome activation.

Ethnopharmacological Relevance: Severe influenza, marked by excessive cytokine production, is a major contributor to death in hospitalized individuals. Fuzheng Jiedu decoction (FZJDD), an effective traditional Chinese herbal recipe, has demonstrated promising results in combating the COVID-19 pandemic by reducing mortality and improving Symptoms, and has exhibited anti-inflammatory properties in both clinical trials and laboratory research. Given that pneumonia is a common outcome of SARS-CoV-2 and H1N1 virus infections, we hypothesized that FZJDD may also have therapeutic effects on influenza-related pneumonia and acute lung injury (ALI).

Galvanic Cell-Stimulated Mesenchymal Stem Cell Mesh for Enhanced Pelvic Organ Prolapse Treatment.

Implantation of a mesh loaded with mesenchymal stem cells (MSCs) is a common approach for the treatment of pelvic organ prolapse (POP). The mesh provides effective support to pelvic floor, enhancing muscle contraction of pelvic organs while reducing inflammation. In this study, a fully degradable mesh is designed for the treatment of POP, utilizing MSCs stimulated by a galvanic battery-powered electric field.

Novel research model for in vitro immunotherapy: co-culturing tumor organoids with peripheral blood mononuclear cells.

Tumor organoids have emerged as powerful tools for in vitro cancer research due to their ability to retain the structural and genetic characteristics of tumors. Nevertheless, the absence of a complete tumor microenvironment (TME) limits the broader application of organoid models in immunological studies. Given the critical role of immune cells in tumor initiation and progression, the co-culture model of organoids and peripheral blood mononuclear cells (PBMCs) may provide an effective platform for simulating the interactions between immune and tumor cells in vitro.

Potential molecular targets and pathways of a traditional Chinese medicine formula for bovine endometritis identified by network pharmacology.

Bovine endometritis has become a persistent issue in the global dairy business, resulting in huge economic losses. Due to their numerous positive benefits, Chinese herbal medicines (CHMs) have recently demonstrated remarkable pharmacological potential against endometritis. The objective of this study was to investigate the effects and elucidate the underlying mechanisms of the Yimucao formula (YMF) that involves five herbs in lactation cows under endometritis conditions.

Unveiling Key Biomarkers and Mechanisms in Septic Cardiomyopathy: A Comprehensive Transcriptome Analysis.

Purpose: Septic cardiomyopathy (SCM) is a significant global public health concern characterized by substantial morbidity and mortality, which has not been improved for decades due to lack of early diagnosis and effective therapies. This study aimed to identify hub biomarkers in SCM and explore their potential mechanisms.

Methods: We utilized the GSE53007 and GSE207363 datasets for transcriptome analysis of normal and SCM mice.

Application two-dimensional gel electrophoresis coupled with LC-MS/MS to identify candidate serodiagnostic antigens for early detection Psoroptes ovis var. cuniculi infection.

Currently, the 'gold standard' for diagnosis of Psoroptes ovis infections is detecting Psoroptes mites or eggs in skin scrapings under microscopy, but it is prone to be mis-diagnosed for detecting early infection of P. ovis. Hence, seeking a reliable diagnostic technique for detecting early-stage mite infections is extremely desirable.

Gut microbes with the genes determine TMAO production from L-carnitine intake and serve as a biomarker for precision nutrition.

Gut microbial metabolism of L-carnitine, which leads to the production of detrimental trimethylamine N-oxide (TMAO), offers a plausible link between red meat consumption and cardiovascular risks. Several microbial genes, including , the operon, and the recently identified gene cluster, have been implicated in the conversion of dietary L-carnitine into TMA(O). However, the key microbial genes and associated gut microbes involved in this pathway have not been fully explored.

The compound (E)-2-(3,4-dihydroxystyryl)-3-hydroxy-4H-pyran-4-one alleviates neuroinflammation and cognitive impairment in a mouse model of Alzheimer's disease.

JOURNAL/nrgr/04.03/01300535-202511000-00034/figure1/v/2024-12-20T164640Z/r/image-tiff Previous studies have shown that the compound (E)-2-(3,4-dihydroxystyryl)-3-hydroxy-4H-pyran-4-one (D30), a pyromeconic acid derivative, possesses antioxidant and anti-inflammatory properties, inhibits amyloid-β aggregation, and alleviates scopolamine-induced cognitive impairment, similar to the phase III clinical drug resveratrol. In this study, we established a mouse model of Alzheimer's disease via intracerebroventricular injection of fibrillar amyloid-β to investigate the effect of D30 on fibrillar amyloid-β-induced neuropathology.

Modifiable Risk Factors for Breast Cancer: Insights From Systematic Reviews.

Objective: To conduct a comprehensive review of reversible factors associated with breast cancer, with the aim of offering insights for the creation of early intervention strategies for breast cancer prevention.

Methods: The PubMed, EMBASE, and Scopus databases were systematically searched to collect systematic reviews and meta-analyses related to breast cancer risk. Searches were limited to literature published from the inception of each database up to May 1, 2024.

Dura immunity configures leptomeningeal metastasis immunosuppression for cerebrospinal fluid barrier invasion.

The cerebrospinal fluid (CSF) border accommodates diverse immune cells that permit peripheral cell immunosurveillance. However, the intricate interactions between CSF immune cells and infiltrating cancer cells remain poorly understood. Here we use fate mapping, longitudinal time-lapse imaging and multiomics technologies to investigate the precise origin, cellular crosstalk and molecular landscape of macrophages that contribute to leptomeningeal metastasis (LM) progression.

A GSH-responsive oxidative stress nanoamplifier for self-augmented chemo/chemodynamic therapy to reverse cisplatin resistance.

Drug resistance and off-target toxicity of cisplatin (CDDP) pose significant challenges in effectively treating non-small cell lung cancer (NSCLC). Recently, chemodynamic therapy (CDT), an emerging reactive oxygen species (ROS)-mediated tumor-specific therapeutic modality, has shown great potential in sensitizing multidrug resistance tumor cells. Herein, a glutathione (GSH)-responsive Pt(IV) prodrug-based oxidative stress nanoamplifier (CuBSO@Pt) was developed for effective chemo/chemodynamic therapy to reverse CDDP resistance in NSCLC.

Effects of Yersinia pseudotuberculosis outer membrane vesicles on Pseudomonas aeruginosa antigens immune response.

Outer membrane vesicles (OMVs) are immunogenic self-adjuvanting vesicles produced by Gram-negative bacteria such as Pseudomonas aeruginosa and Yersinia pseudotuberculosis. While the effects of OMVs on different antigens immune stimulation are not clear. In this study, we constructed recombinant Yersinia pseudotuberculosis ΔlpxL strain,with pBlue-PcrV and pBlue-OprF/I, and then purified ΔlpxL rOMVPcrV (rOMVyp2P)and ΔlpxL rOMVOprF/I (rOMVyp2F) and analyzed its effect on immune response and protection against Pseudomonas aeruginosa PAO1 infection.

Effectiveness of a Novel PLA2R1 Knock-in Middle Age Rat Model in Repairing Renal Function Damage.

Phospholipase A2 receptor 1 (PLA2R1) exists important role in membranous nephropathy. In this study, we evaluate a PLA2R1 in a middle-aged rat model of renal function repair to further investigate the molecular mechanisms of membranous nephropathy. We analyzed the PLA2R1 knockout (KO) model and PLA2R1 knock in (KI) model in rats, extending the time to 85 weeks of age.

Enhancement of adult liver regeneration in mice through the hepsin-mediated epidermal growth factor receptor signaling pathway.

Given the widespread use of partial hepatectomy for treating various liver pathologies, understanding the mechanisms of liver regeneration is vital for enhancing liver resection and transplantation therapies. Here, we demonstrate the critical role of the serine protease Hepsin in promoting hepatocyte hypertrophy and proliferation. Under steady-state conditions, liver-specific overexpression of Hepsin in adult wild-type mice triggers hepatocyte hypertrophy and proliferation, significantly increasing liver size.

Knockout of hexokinase 2 regulates mitochondrial dysfunction and activates the NLRP3 signal pathway in the rumen epithelial cells of dairy cows.

Hexokinase 2 (HK2) plays a vital role in mitochondrial homeostasis; however, the molecular mechanisms underlying its involvement in high-concentrate diet-induced damage in the ruminal epithelium of dairy cows are poorly understood. This study aimed to explore the regulatory role of HK2 in mitochondrial function and responses to inflammation in the rumen of dairy cows fed a high-concentrate diet. Our results showed that, compared with a low-concentrate (LC) diet, feeding a high-concentrate (HC) diet increased oxidative stress and reduced relative antioxidant gene expression levels and enzyme activities in the ruminal epithelium.

The Role and Research Progress of ACPA in the Diagnosis and Pathological Mechanism of Rheumatoid Arthritis.

An autoimmune condition known as rheumatoid arthritis (RA) is characterized by persistent polyarticular inflammation. Within two years of the disease's onset, irreparable bone and joint deterioration can occur as a result of the inflammatory course of the illness, leading to joint deformity and loss of function. In most patients diagnosed with RA, a range of autoantibodies, particularly anti-citrullinated protein antibodies (ACPA), can be detected months to years before the onset of clinically recognizable disease.

Research progress in tracing technology for extracellular vesicles.

Cells have the capability to discharge extracellular vesicles (EVs) into a range of bodily fluids. Extracellular vesicles (EVs) encapsulate biological molecules such as proteins and nucleic acids, playing a role in facilitating cell-cell communication. They actively engage in a myriad of physiological and pathological processes.

Engineered Bacteria Manipulate Cysteine Metabolism to Boost Ferroptosis-Based Pancreatic Ductal Adenocarcinoma Therapy.

Cysteine metabolism is a key determinant of the defense against ferroptosis in pancreatic ductal adenocarcinoma (PDAC). Blocking cysteine metabolism may trigger potent ferroptosis in PDAC cells by generating lipid peroxides during tumor metabolic processes. However, current methods to limit cysteine availability fall short, failing to efficiently block cysteine metabolism due to inadequate tumor targeting and compensatory cysteine sources.

circPRMT10 regulated by QKI hypermethylation attenuates lung tumorigenesis induced by tobacco carcinogen NNK.

Chronic exposure to environmental carcinogens is a major cause of tumorigenesis. A potent tobacco-specific nitrosamine carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), exhibits high carcinogenicity to induce lung cancer. However, the function and mechanism of circular RNA (circRNA) in chemical carcinogenesis, especially the regulation of circRNA formation upon exposure to environmental chemicals, remain unclear.

Annexin A2: the feasibility of being a therapeutic target associated with cancer metastasis and drug resistance in cancer microenvironment.

At present, there is still a lack of effective treatment strategies for cancer metastasis and drug resistance, so finding effective biomarkers is particularly important. AnnexinA2 (ANXA2), a vital membrane protein, critically influences cancer progression, tumor invasion, and tumor microenvironment modulation. To assess the possible application of ANXA2 as a therapeutic target against cancer cell metastasis and drug resistance to chemotherapeutic drugs in the tumor microenvironment, we elucidated the functionality of ANXA2 in stromal cells, angiogenic vascular cells, and infiltrated immune cells that mediate metastasis and drug resistance, as well as its potential as a therapeutic target.

Item response theory for the color-picture version of Boston naming test in a Chinese sample with neurodegenerative diseases.

Background: Although Boston Naming Test has been thoroughly validated at a global level, there is limited assessment of item-level properties using modern psychometric methods.

Objective: This study aimed to investigate the construct validity and item-level properties of the color-picture version of Boston Naming Test (CP-BNT) in a Chinese cohort with neurodegenerative diseases.

Methods: This retrospective study included 424 participants, consisting of 118 normal controls, 152 with Alzheimer's disease, 101 with primary progressive aphasia, and 53 with other neurodegenerative diseases.

Association between mitophagy and inflammasome in uric acid nephropathy.

Objective: This study was recruited to investigate the role of mitophagy in activating NLRP3 inflammasome in the kidney of uric acid (UA) nephropathy (UAN) rats.

Methods: This study developed a uric acid nephropathy (UAN) rat model divided into five groups: Negative control (NC), UAN model (M), UAN + autophagy inhibitor (3-MA), UAN + lysosome inhibitor (CQ), and ROS scavenger (N-acetylcysteine, N). H&E staining assessed renal structure, ROS levels were measured with 2, 7dichlorofluorescin diacetate, and ELISA measured serum markers (, , cystatin , , , ).

Deciphering the hepatitis E virus ORF1: Functional domains, protein processing, and patient-derived mutations.

Hepatitis E virus (HEV) is a major cause of acute and chronic hepatitis in humans. The HEV open reading frames (ORF1) encodes a large non-structural protein essential for viral replication, which contains several functional domains, including helicase and RNA-dependent RNA polymerase. A confusing aspect is that, while RNA viruses typically encode large polyproteins that rely on their enzymatic activity for processing into functional units, the processing of the ORF1 protein and the mechanisms involved remain unclear.