Lentinan's effect on gut microbiota and inflammatory cytokines in 5-FU-induced mucositis mice.

Chemotherapeutic therapies for cancer are frequently associated with cytotoxic side effects that can be harmful to human health, including the development of intestinal mucositis (IM). It mostly affects the gastrointestinal tract, causing ulceration, inflammation, and the formation of lesions in the colon. Surprisingly, despite the frequency of IM, therapeutic choices remain restricted.

Enhanced antitumor efficacy of nanostructured lipid carrier co-loaded with docetaxel and 5-fluorouracil for targeted gastric cancer therapy.

This study presents nanostructured lipid carrier (NLC) co-loaded with Docetaxel (DCT) and 5-Fluorouracil (5-FU) as a targeted therapeutic approach for gastric cancer (GC). Using nanoprecipitation, NLC-DCT/5-FU were synthesized and exhibited an average particle size of 215.3 ± 10.

Potential roles of cigarette smoking on gut microbiota profile among Chinese men.

Background: Cigarette smoking is posited as a potential factor in disrupting the balance of the human gut microbiota. However, existing studies with limited sample size have yielded inconclusive results.

Methods: Here, we assessed the association between cigarette smoking and gut microbial profile among Chinese males from four independent studies (N total = 3308).

Spatial transcriptomics and single-cell RNA-sequencing revealed dendritic cell-mediated inflammation in keratoconus.

Keratoconus (KC) is a corneal disorder characterized by central corneal protrusion and thinning. In this study, spatial transcriptomics was employed to investigate molecular and cellular variations in KC, revealing a distinct pattern of inflammatory responses across the cornea. Upregulation of inflammatory processes was observed in the central cornea, while downregulation was noted in the periphery, indicating complex regional inflammatory changes in the KC cornea.

Genetic mapping of serum metabolome to chronic diseases among Han Chinese.

Serum metabolites are potential regulators for chronic diseases. To explore the genetic regulation of metabolites and their roles in chronic diseases, we quantified 2,759 serum metabolites and performed genome-wide association studies (GWASs) among Han Chinese individuals. We identified 184 study-wide significant (p < 1.

Biocomputing at the crossroad between emulating artificial intelligence and cellular supremacy.

Biocomputation aims to create sophisticated biological systems capable of addressing important problems in (bio)medicine with a machine-like precision. At present, computational gene networks engineered by single- or multi-layered assembly of DNA-, RNA- and protein-level gene switches have allowed bacterial or mammalian cells to perform various regulation logics of interest, including Boolean calculation or neural network-like computing. This review highlights the molecular building blocks, design principles, and computational tasks demonstrated by current biocomputers, before briefly discussing possible fields where biological computers may ultimately outcompete their electronic counterparts and achieve cellular supremacy.

Exosome miR-199a-5p modulated vascular remodeling and inflammatory infiltration of Takayasu's arteritis.

Background: Advances in treatment have swiftly alleviated systemic inflammation of Takayasu's arteritis (TAK), while subclinical vascular inflammation and the ensuing arterial remodeling continue to present unresolved challenges in TAK. The phenotypic switching of vascular smooth muscle cells (VSMC) is regarded as the first step in vascular pathology and contributes to arterial remodeling. Exosomes facilitate the transfer and exchange of proteins and specific nucleic acids, thereby playing a significant role in intercellular communication.

Lung-specific CRBN knockout attenuates influenza a virus-induced acute lung injury in mice: a potential therapeutic approach.

Influenza-related acute lung injury is a life-threatening condition primarily caused by uncontrolled replication of the influenza virus and intense proinflammatory responses. Cereblon (CRBN) is a protein known for its role in the ubiquitin-proteasome system and as a target of the drug thalidomide. However, the function of CRBN in influenza virus infection remains poorly understood.

Genetic features and pharmacological rescue of novel Kv7.2 variants in patients with epilepsy.

Background: Increasing evidence indicates a robust correlation between epilepsy and variants of the Kv7.2 () channel, which is critically involved in directing M-currents and regulating neuronal excitability within the nervous system. With the advancement of next-generation sequencing, the identification of variants has surged.

β-receptor blocker enhances anti-tumor immunity via inhibiting lactate-induced norepinephrine metabolism of macrophages during malignant pleural effusion.

Introduction: Malignant pleural effusion (MPE) is associated with poor quality of life and mortality in patients with tumors. In clinical practice, we observed that patients with malignant pleural effusion (MPE) and concurrent heart disease exhibited a decrease in MPE volumes following treatment with β-receptor blockers for heart disease. Immunosuppressive tumor microenvironment was found to play a substantial role in the progression of MPE, and mainly attributed to tumor-associated macrophages (TAMs).

Tissue-specific modulation of NADH consumption as an anti-aging intervention in Drosophila.

Aging is characterized by extensive metabolic dysregulation. Redox coenzyme nicotinamide adenine dinucleotide (NAD) can exist in oxidized (NAD) or reduced (NADH) states, which together form a key NADH/NAD redox pair. Total levels of NAD decline with age in a tissue-specific manner, thereby playing a significant role in the aging process.

The rationale, design of the Assisted reproductive technology cohort nested in a pre-pregnancy family cohort (APP-Cohort).

Introduction: Infertility has become a major global issue due to the trend of delaying marriage and advanced maternal age. Family/Birth cohort studies are essential for exploring ways to enhance health outcomes at both the individual and societal levels. However, there is a shortage of cohorts that include families who have utilized assisted reproductive technology (ART), particularly initiated at the early stages before pregnancy.

Computational frameworks transform antagonism to synergy in optimizing combination therapies.

While drug combinations are increasingly important in disease treatment, predicting their therapeutic interactions remains challenging. This review systematically analyzes computational methods for predicting drug combination effects through multi-omics data integration. We comprehensively assess key algorithms including DrugComboRanker and AuDNNsynergy, and evaluate integration approaches encompassing kernel regression and graph networks.

Regional adipose distribution and metabolically unhealthy phenotype in Chinese adults: evidence from China National Health Survey.

Background: The mechanisms distinguishing metabolically healthy from unhealthy phenotypes within the same BMI categories remain unclear. This study aimed to investigate the associations between regional fat distribution and metabolically unhealthy phenotypes in Chinese adults across different BMI categories.

Methods: This cross-sectional study involving 11833 Chinese adults aged 20 years and older.

3D imaging and pathological analysis of microglia in LPS-treated mice with light-sheet fluorescence microscopy.

Although two-dimensional (2D) histology and immunohistochemistry techniques have long been established and successfully applied to obtain structural information from tissues, recent advances in tissue clearing and expansion approaches combined with light sheet microscopy have led to the realization of three-dimensional (3D) nondestructive pathology, which may revolutionize our knowledge of the morphology of an organ or the whole body in its true state. Employing these 3D technologies, we obtained imaging data of microglia in whole hippocampus of mice. We established a simple procedure to analyze the 3D structures of microglia using the commercial software Amira.

A novel dual fixation method for improving the reliable assessment of pulmonary vascular morphology in pulmonary hypertension rats.

This study introduced a novel dual fixation method for the pulmonary vasculature and lung tissue in pulmonary hypertension (PH) rats, addressing the limitations of traditional fixation methods that failed to accurately preserve the in vivo status of pulmonary vascular morphology. The modified method involved a dual fixation process, combining individualized ventilation support and vascular perfusion to simulate the respiratory motion, pulmonary artery pressure and right ventricular output of the rat under in vivo conditions. Utilizing a monocrotaline-induced PH rat model, this study compared the dual fixation with the traditional immersion fixation, focusing on the quantitative assessment of alveolar expansion degree, capillary patency, endothelial cell quantity and wall thickness of pulmonary vein and artery.

Cortisol regulates neonatal lung development via Smoothened.

Background: Neonatal respiratory distress syndrome (NRDS), one of the main causes of neonatal death, is clinically characterized by progressive dyspnea and cyanosis 1 to 2 h after birth. Corticosteroids are commonly used to prevent NRDS in clinical. However, the protective mechanism of the corticosteroids remains largely unclear.

Innovative PBMC-derived humanized mouse model reveals CD8 T cell-intrinsic regulation during antitumor immunity.

The PBMC-derived humanized mouse model (PBMC model) may serve as an excellent tool in the field of immunology for both preclinical research and personalized therapeutic strategy development. However, single transplantation of complete PBMCs without modifications prevents the identification of cell type-specific factors that are potentially involved in modulating cell-intrinsic functions for the immune response. Here, we establish an innovative strategy for PBMC model generation, where two-step transplantations coupled with cell type-specific gene manipulation were conducted to evaluate the potential role of CD8 T cell-intrinsic factors in regulating antitumor immunity toward PDX-based tumors.

Mannose: A game-changer for T cell immunotherapy.

Metabolism influences the behavior of various immune cell types. In a recent Cancer Cell study, Qiu et al. revealed mannose metabolism as a prominent metabolic feature of tumor precursor exhausted T cells (Tpex) that is crucial for maintaining T cell stemness.

From chaos to order: optimizing fecal microbiota transplantation for enhanced immune checkpoint inhibitors efficacy.

The integration of fecal microbiota transplantation (FMT) with immune checkpoint inhibitors (ICIs) presents a promising approach for enhancing cancer treatment efficacy and overcoming therapeutic resistance. This review critically examines the controversial effects of FMT on ICIs outcomes and elucidates the underlying mechanisms. We investigate how FMT modulates gut microbiota composition, microbial metabolite profiles, and the tumor microenvironment, thereby influencing ICIs effectiveness.

Chinese Registry of Rheumatoid Arthritis (CREDIT) VI: Temporal Trends in Patients With Early Rheumatoid Arthritis and Moderate-To-Severe Disease Activity - A Multicenter Cohort Study of Treatment Strategies and Outcomes.

Aim: The continuous update of international guidelines and enhanced availability of biological disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs) have made a significant impact on the diagnosis and treatment of early rheumatoid arthritis (ERA). This study aims to systematically evaluate the current treatment strategies and outcomes within a large-scale cohort of patients with ERA.

Methods: Data from the Chinese Registry of Rheumatoid Arthritis (CREDIT), a large multicenter Chinese registry of RA, were collected to analyze temporal trends in clinical profiles, therapeutic strategies, and treatment outcomes among patients with ERA.

Intercellular TIMP-1-CD63 signaling directs the evolution of immune escape and metastasis in KRAS-mutated pancreatic cancer cells.

Background And Aims: Oncogenic KRAS mutations are present in approximately 90% of pancreatic ductal adenocarcinoma (PDAC). However, Kras mutation alone is insufficient to transform precancerous cells into metastatic PDAC. This study investigates how KRAS-mutated epithelial cells acquire the capacity to escape senescence or even immune clearance, thereby progressing to advanced PDAC.

Melanophilin-induced primary cilia promote pancreatic cancer metastasis.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant tumors because of its high metastatic ability. The glutamine (Gln)-deficient microenvironment contributes to PDAC metastasis; however, the underlying molecular mechanisms remain unclear. Here, we demonstrated that melanophilin (MLPH) promotes PDAC metastasis by inducing the regrowth of primary cilia.

Chemical imaging unveils mitochondria as the major site of medicinal biguanide accumulation within cells.

Metformin (MET), a commonly prescribed medication for managing type 2 diabetes, has demonstrated various beneficial effects beyond its primary anti-diabetic efficacy. However, the mechanism underlying MET activity and its distribution within organelles remain largely unknown. In this study, we integrate multiple technologies, including chemical labeling, immunostaining, and high-resolution microscopy imaging, to visualize the accumulation of MET in organelles of cultured cells.

Nuclear adenine activates hnRNPA2B1 to enhance antibacterial innate immunity.

Bacterial infection reprograms cellular metabolism and epigenetic status, but how the metabolic-epigenetic crosstalk empowers host antibacterial defense remains unclear. Here, we report that heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) is a sensor for metabolite adenine to launch an antimicrobial innate response through increasing Il1b transcription. Myeloid cell-specific Hnrnpa2b1-cKO mice are more susceptible to bacterial infection, while interleukin 1 beta (IL-1β) supplementation rescues the phenotype.