Indole-3-propionic acid alleviates DSS-induced colitis in mice through macrophage glycolipid metabolism.

Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease for which current therapeutic approaches still face many dilemmas, and targeting macrophage polarization and metabolism for the treatment of this disease is a potentially effective strategy. The gut microbial metabolite indole-3-propionic acid (IPA) has favorable anti-inflammatory and antioxidant effects and plays a role in a variety of disease models. IPA is effective in the treatment of UC, but the underlying mechanisms have not been well explored.

Anti-TNF therapy in the treatment of systemic autoinflammatory diseases: the responses of innate immune cells.

Systemic autoinflammatory diseases (SAIDs) are rare conditions resulting from innate immune system dysregulation, culminating in repetitive bouts of systemic inflammation without the presence of external or self-antigens. Most SAIDs are associated with mutations in genes affecting the innate immune response. Tumor necrosis factor (TNF) is a central player in the pathogenesis of numerous chronic inflammatory disorders, and anti-TNF therapy is widely used in the clinical management of SAIDs.

Circulating IL6 is involved in the infiltration of M2 macrophages and CD8+ T cells.

To elucidate the relationship between circulating cytokines and the prognosis of microsatellite-stable(MSS) colorectal cancer (CRC) patients, we examined the correlation between circulating cytokine levels and tumor immune infiltration microenvironment in this patient population. By conducting a preliminary analysis of the GEO database, we identified five core genes associated with colorectal cancer and further analyzed their impact on immune infiltration. We measured serum cytokine levels and validated the immune infiltration results through immunohistochemical staining of common inflammatory cell markers, including CD3, CD4, CD8, CD163, and FOXP3.

The value of peripheral blood inflammation markers in risk assessment and prediction of lung cancer.

Background: Lung cancer has high mortality rates globally, with inflammatory processes playing a pivotal role in NSCLC progression. Peripheral blood inflammation markers offer promise for NSCLC risk assessment and prediction.

Methods: A retrospective case-control study included 50 NSCLC patients and 50 healthy individuals admitted for routine health examinations as controls.

Postpartum hemorrhage emerges as a key outcome of maternal SARS-CoV-2 omicron variant infection surge across pregnancy trimesters.

Background: Despite evidence showing changes in disease severity with the virus's evolution and vaccination efforts, the link between maternal, perinatal, and neonatal outcomes and SARS-CoV-2 infections during different pregnancy trimesters remains unclear, especially with the BA.5 and BF.7 Omicron subvariant surge in China in December 2022.

Modeling Charge Collection in Silicon Pixel Detectors for Proton Therapy Applications.

Monolithic active pixel sensors are used for charged particle tracking in many applications, from medical physics to astrophysics. The Bergen pCT collaboration designed a sampling calorimeter for proton computed tomography, based entirely on the ALICE PIxel DEtector (ALPIDE). The same telescope can be used for in-situ range verification in particle therapy.

Advancing sepsis diagnosis and immunotherapy machine learning-driven identification of stable molecular biomarkers and therapeutic targets.

Sepsis represents a significant global health challenge, necessitating early detection and effective treatment for improved outcomes. While traditional inflammatory markers facilitate the diagnosis of sepsis, the aspect of immune suppression remains poorly addressed. This study aimed to identify critical immune-related genes (IIRGs) associated with sepsis through genomic analysis and machine learning techniques, thereby enhancing diagnostic and treatment response predictions.

Efficacy and Safety of 611 in Chinese Adults with Moderate-to-Severe Atopic Dermatitis: Results from a Phase II Trial.

Introduction: Atopic dermatitis (AD) is a chronic inflammatory skin disease. 611, a humanized monoclonal antibody, selectively targets the interleukin (IL)-4 receptor alpha, thereby inhibiting the signaling of both interleukin (IL)-4 and IL-13. This phase 2 study aimed to evaluate the efficacy and safety of 611 in Chinese adults with moderate-to-severe AD.

Artesunate attenuates skin hypertrophic scar formation by inhibiting fibroblast activation and EndMT of vascular endothelial cells.

Background Hypertrophic scarring is an abnormal condition involving excessive fibroblast activation, aberrant extracellular matrix deposition, and persistent inflammation. Current treatments have limited efficacy and potential adverse effects, necessitating the development of new approaches. Purpose In this study, we investigated the effects of artesunate (ART) on hypertrophic scar (HS) formation and explored the underlying cellular and molecular mechanisms.

The Role of Non-Coding RNA in Systemic Sclerosis: From Mechanism to Translation.

Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by imbalanced immunity, vasculopathy, and excessive fibrosis. The etiology and pathology of this disease remain to be fully elucidated. Genetic predisposition, along with epigenetic modifications are widely considered to significantly affect its development.

Cascade-Type Microglial Pyroptosis Inhibitors for Enhanced Treatment of Cerebral Ischemia-Reperfusion Injury.

Neuroinflammation is a critical factor in the progression of cerebral ischemia-reperfusion injury (CIRI). Pyroptosis, which is an inflammatory form of programmed cell death, greatly amplifies neuroinflammatory processes. It does so by promoting the release of various inflammatory contents that intensify the overall inflammatory response within the central nervous system.

Combination of cadonilimab (PD-1/CTLA-4 bispecific antibody) and apatinib as salvage therapy achieves partial response in MSI-H advanced gastric cancer: a case report.

Microsatellite instability-high (MSI-H) gastric cancer (GC) is recognized as a unique subtype of gastric cancer. While patients with advanced MSI-H gastric cancer may respond favorably to a combination of immune checkpoint inhibitors and chemotherapy in first-line treatment, no definitive recommendations exist regarding the optimal regimen for subsequent therapy. Cadonilimab, a PD-1 and CTLA-4 bispecific antibody, has shown encouraging efficacy and safety in the first-line treatment of advanced gastric cancer.

An overview of Sgc8 aptamer as a potential theranostic agent for cancer with PTK7 oncogenic target.

Aptamers have attracted exceptional attention in medical field due to their intrinsic properties equivalent to antibodies such as high target affinity, low immunogenicity and toxicity, cost-effectiveness and ease of synthesis and modification, and good stability under extreme conditions, thereby providing new avenues for basic research and clinical application. Protein tyrosine kinase 7 (PTK7) has been proved to be closely linked with the progression of many types of cancer. The aberrant expression of PTK7 has positioned it as a potential theranostic biomarker for multiple cancers.

Elbow Interposition Arthroplasty With Meniscal Allograft.

Painful, end-stage elbow arthritis in young, active patients remains a challenging and unsolved problem. Lifetime weight-bearing restrictions make total elbow arthroplasty (TEA) an unrealistic and unsustainable option for most of these patients, and the alternatives for treating a failed TEA are limited and mostly unsatisfactory. Elbow interposition arthroplasty can provide good pain relief and reasonable restoration of motion while avoiding weight-bearing restrictions.

Enhancer reprogramming: critical roles in cancer and promising therapeutic strategies.

Transcriptional dysregulation is a hallmark of cancer initiation and progression, driven by genetic and epigenetic alterations. Enhancer reprogramming has emerged as a pivotal driver of carcinogenesis, with cancer cells often relying on aberrant transcriptional programs. The advent of high-throughput sequencing technologies has provided critical insights into enhancer reprogramming events and their role in malignancy.

STSF: Spiking Time Sparse Feedback Learning for Spiking Neural Networks.

Spiking neural networks (SNNs) are biologically plausible models known for their computational efficiency. A significant advantage of SNNs lies in the binary information transmission through spike trains, eliminating the need for multiplication operations. However, due to the spatio-temporal nature of SNNs, direct application of traditional backpropagation (BP) training still results in significant computational costs.

Reduction of intestinal RIPK1 ameliorates HFD-induced metabolic disorders in female mice.

In modern society, excessive nutrient intake from food is a major factor contributing to the development of a series of metabolic disorders and cardiovascular diseases. Further investigation of the mechanisms underlying nutrient absorption in the intestine will help to better understand and develop preventive or therapeutic strategies. In this study, using receptor-interacting protein kinase 1 () intestine-specific heterozygous knockout mice ( ) and high-fat diet (HFD)-feeding mouse model, we report that HFD-induced shift in the transcriptional profile of the ileum toward that of the jejunum, characterized by increased expression of jejunal feature genes in the ileum, are attenuated in female mice, but not in males.

MIF-ACKR3 causes irreversible fat loss by impairing adipogenesis in cancer cachexia.

Both exercise and cancer can cause adipose tissue shrinkage. However, only cancer-associated weight loss, namely cachexia, is characterized by profound adipose inflammation and fibrosis. Here, we identified tumor-secreted macrophage migration inhibitory factor (MIF) as a major driver that skews the differentiation of adipose stem and progenitor cells (ASPCs) toward a pro-inflammatory and pro-fibrogenic direction, with reduced adipogenic capacity in cancer cachexia.

FJSSZ23M10 modulates gut microbiota and metabolism to alleviate obesity through strain-specific genomic features.

Obesity is a major global public health challenge, affecting billions and serving as a primary risk factor for many chronic diseases. Certain probiotics have shown promise in regulating energy balance and enhancing fat metabolism, offering potential strategies for managing obesity. In this study, we evaluated three strains of and identified FJSSZ23M10 as the most effective in alleviating high-fat diet (HFD)-induced obesity.

FOXO4-DRI induces keloid senescent fibroblast apoptosis by promoting nuclear exclusion of upregulated p53-serine 15 phosphorylation.

Keloids are pathological scars exhibiting tumour-like aggressiveness and high recurrence rate. Here we find increased proportion of pro-inflammatory and mesenchymal fibroblast subpopulations and senescent fibroblasts, and enhanced expression of senescence-associated secretory phenotype genes using single-cell RNA sequencing analysis, as well as elevated p16 protein and more β-galactosidase-positive cells in keloids. The up-regulated p53-serine15 phosphorylation (p53-pS15) in keloids is identified by phosphospecific protein microarray and western blotting.

Mechano-oncogenic cytoskeletal remodeling drives leukemic transformation with mitochondrial vesicle-mediated STING activation.

Mitochondria are integrated within the cytoskeleton for structural integrity and functional regulation, yet the pathological exploitation of these interactions in cell fate decisions remains largely unexplored. Here, we identify a cytoskeleton-mitochondria remodeling mechanism underlying leukemic transformation by the core-binding factor subunit beta and smooth muscle myosin heavy-chain fusion (CBFβ-SMMHC). This chimera reconstructs a cytosolic filamentous cytoskeleton, inducing NMIIA phosphorylation and INF2-dependent filamentous actin (F-actin) assembly, which enhance cellular stiffness and tension, leading to calcium-mediated mitochondrial constriction, termed cytoskeletal co-option of mitochondrial constriction (CCMC).

Recognizing the Evolution of Clinical Syndrome Spectrum Progression in Individuals with Single Large-Scale mitochondrial DNA deletion syndromes (SLSMDS).

Introduction: Single Large-Scale mtDNA Deletions (SLSMD) result in Single Large Scale Deletion Syndromes (SLSMDS). SLSMDS presentations have classically been recognized to encompass at least three distinct clinical phenotypes, Pearson Syndrome (PS), Kearns-Sayre Syndrome (KSS), and Chronic Progressive Ophthalmoplegia (CPEO).

Methods: Facilitated review of electronic medical records, manual charts, and REDCap research databases was performed to complete a retrospective natural history study of 30 SLSMDS participants in a single health system seen between 2002 and 2020.

CpG-Based Nanovaccines Enhance Ovarian Cancer Immune Response by Gbp2-Mediated Remodeling of Tumor-Associated Macrophages.

CpG oligodeoxynucleotides (CpG), as an immunoadjuvant, can facilitate the transformation of tumor-associated macrophages (TAMs)into tumoricidal M1 macrophages. However, the accumulation of free CpG in tumor tissues remains a substantial challenge. To address this, a nanovaccine (PLGA-CpG@ID8-M) is engineered by encapsulating CpG within PLGA using ID8 ovarian cancer cell membranes (ID8-M).

A panel of altered blood oxysterols in patients with mild cognitive impairment: A novel combined diagnostic marker.

Perturbed cholesterol metabolism may play an important role in the development of dementia and its preclinical stage, mild cognitive impairment (MCI). Oxysterols, the metabolites generated during cholesterol oxidation, also appear to be risk factors for MCI. Therefore, we aimed to investigate if the metabolic profile of blood oxysterols could be used to characterize MCI risk.