A Mendelian randomization analysis reveals the role of the skin microbiota in systemic lupus erythematosus.

Background: Systemic lupus erythematosus (SLE) is influenced by a complex array of factors, encompassing genetic, hormonal, and microbial components. This study seeks to investigate the causal relationships between specific skin microbiotas and SLE using a Mendelian randomization (MR) analysis and a Bayesian weighted Mendelian randomization (BWMR) analysis.

Methods: We utilized genome-wide association study (GWAS) data to investigate the role of skin microbiota in SLE.

The Therapeutic Effects of Acorus Tatarinowii Volatile Oil and Electroacupuncture in Post-Stroke Cognitive Impairment Patients: A Clinical Trial Protocol.

Background: Post-stroke cognitive impairment (PSCI) is a common complication following stroke, with limited effective treatments. This randomized controlled trial aims to evaluate the efficacy of two non-pharmacological interventions-electroacupuncture therapy (EA) and herbal olfactory therapy (HOT)-in improving cognitive function in PSCI patients, both as standalone treatments and in combination.

Methods: This parallel-group, assessor-blinded, randomized controlled trial will recruit 210 PSCI patients, randomly assigned to one of six groups: control, EA, HOT, combination therapy, sham therapy, or the healthy (ratio 1:1:1:1:1:1).

TRPM2 channels mediate ROS-induced actin remodeling and cell migration of prostate cancer cells.

Background: Actin remodeling plays important roles in pathophysiological processes such as cancer metastasis and angiogenesis. Reactive oxygen species (ROS) are signaling molecules thought to regulate cell migration by remodeling actin cytoskeleton. Earlier, we demonstrated that Transient receptor potential melastatin 2 (TRPM2) channels mediates HO-induced actin remodeling and cell migration in HeLa cells by manipulating Ca and Zn.

Hematoporphyrin monomethyl ether sonodynamic therapy (HMME-SDT) mitigates keloid scarring via the PI3K-AKT signaling pathway.

Background: This study investigates the effects and underlying molecular mechanisms of Hematoporphyrin Monomethyl Ether Sonodynamic Therapy (HMME-SDT) on keloid fibroblasts (KFs) in vitro and in vivo, utilizing animal models.

Methods: The activation effect of ultrasound on HMME was ascertained using UV-visible light absorption spectroscopy. The influence of HMME-SDT on KFs was assessed in terms of cell proliferation, migration, reactive oxygen species (ROS) generation, mitochondrial membrane potential, and apoptosis.

Association between osteoarthritis and cognitive function: results from the NHANES 2011-2014 and Mendelian randomization study.

Background: Previous meta-analyses have demonstrated osteoarthritis (OA) is associated with an increased risk of dementia, but these studies were prone to bias based on residual confounding factors and reverse causality.

Objectives: We aimed to investigate associations between OA and cognitive function using data from the National Health and Nutrition Examination Survey (NHANES) and to investigate the causality using Mendelian randomization (MR).

Design: This is a cross-sectional study and MR study.

Dysregulation of parvalbumin expression and neurotransmitter imbalance in the auditory cortex of the BTBR mouse model of autism spectrum disorder.

Individuals diagnosed with autism spectrum disorder (ASD) frequently exhibit abnormalities in auditory perception, a phenomenon potentially attributed to alterations in the excitatory and inhibitory cells constituting cortical circuits. However, the exact genetic factors and cell types affected by ASD remain unclear. The present study investigated the balance of excitatory and inhibitory activity in the auditory cortex using BTBR T Itpr3/J (BTBR) mice, a well-established model for autism research.

Novel needle-type electrocoagulation and combination pharmacotherapy: Basic and clinical studies on efficacy and safety in treating keloids.

Background And Aim: Keloids cannot be effectively treated using monotherapy regimens. This study aimed to evaluate the efficacy and safety of ablation (a novel needle-assisted electrocoagulation technique) combined with pharmacotherapy (corticosteroid and 5-fluorouracil [5-FU] injections) in removing keloids and to investigate the underlying biological mechanisms.

Methods: The effects of energy consumption and duration of needle-assisted electrocoagulation on the ablation zone were tested in porcine liver tissue, which simulates human skin.

Protective autophagy enhances antistress ability through AMPK/ULK1 signaling pathway in human immortalized keratinocytes.

Keratinocytes, located in the outermost layer of human skin, are pivotal cells to resist environmental damage. Cellular autophagy plays a critical role in eliminating damaged organelles and maintaining skin cell homeostasis. Low-dose 5-Aminolevulinic acid photodynamic therapy (ALA-PDT) has been demonstrated to enhance skin's antistress ability; however, the regulatory mechanisms of autophagy in keratinocytes remain unclear.

Cognitive impairment in Alzheimer's disease FAD mouse model: Synaptic loss facilitated by activated microglia via C1qA.

Alzheimer's disease (AD) is a chronic and progressive neurodegenerative disorder characterized by cognitive dysfunction. The connection between neuroinflammation and abnormal synaptic function in AD is recognized, but the underlying mechanisms remain unclear. In this study, we utilized a mouse model of AD, FAD mice aged 6-7 months, to investigate the molecular changes affecting cognitive impairment.

P2Y12 receptor mediates apoptosis and demyelination to affect functional recovery in mice with spinal cord injury.

Among diseases of the central nervous system (CNS), spinal cord injury (SCI) has a high fatality rate. It has been proven that P2Y G protein-coupled purinergic receptors have a neuroprotective role in apoptosis and regeneration inside the damaged spinal cord. The P2Y12 receptor (P2Y12R) has recently been linked to peripheral neuropathy and stroke.

Upregulation of SLC12A3 and SLC12A9 Mediated by the HCP5/miR-140-5p Axis Confers Aggressiveness and Unfavorable Prognosis in Uveal Melanoma.

Perturbation of solute carriers (SLCs) has been implicated in metabolic disorders and cancer, highlighting the potential for drug discovery and therapeutic opportunities. However, there is relatively little exploration of the clinical relevance and potential molecular mechanisms underlying the role of the SLC12 family in uveal melanoma (UVM). Here, we performed an integrative multiomics analysis of the SLC12 family in multicenter UVM datasets and found that high expression of SLC12A3 and SLC12A9 was associated with unfavorable prognosis.

Integrated immunogenomic analysis of single-cell and bulk tissue transcriptome profiling unravels a macrophage activation paradigm associated with immunologically and clinically distinct behaviors in ovarian cancer.

Introduction: Increasing evidence demonstrates that the activation states and diverse spectrum of macrophage subtypes display dynamic heterogeneity in the tumor microenvironment, which plays a critical role in a variety of cancer types.

Objectives: To investigate the heterogeneity and the homeostasis of different macrophage subtypes, as well as their effect on biological and clinical manifestations of ovarian cancer (OV).

Method: Integrated immunogenomic analysis of single-cell and bulk tissuetranscriptome profiling was performed to systematically investigate the association between macrophage activation and prognostic and therapeutic efficacy.

Pan-cancer landscape of T-cell exhaustion heterogeneity within the tumor microenvironment revealed a progressive roadmap of hierarchical dysfunction associated with prognosis and therapeutic efficacy.

Background: T cells form the major component of anti-tumor immunity. A deeper understanding of T cell exhaustion (TEX) heterogeneity within the tumor microenvironment (TME) is key to overcoming TEX and improving checkpoint blockade immunotherapies in the clinical setting.

Methods: We conducted a comprehensive pan-cancer analysis of TEX subsets from 9564 tumor samples across 30 bulk solid cancer types.

A multi-omics deep learning model for hypoxia phenotype to predict tumor aggressiveness and prognosis in uveal melanoma for rationalized hypoxia-targeted therapy.

Uveal melanoma (UM) represents the most common primary intraocular malignancy in adults and is characterized by aggressive behaviors and a lack of targeted therapies. Hypoxia-targeted therapy has become a promising new therapeutic strategy in tumors. Therefore, a better understanding of the tumor hypoxia microenvironment is critical to improve the treatment efficacy of UM.

iUMRG: multi-layered network-guided propagation modeling for the inference of susceptibility genes and potential drugs against uveal melanoma.

Uveal melanoma (UM) is the most common primary malignant intraocular tumor. The use of precision medicine for UM to enable personalized diagnosis, prognosis, and treatment require the development of computer-aided strategies and predictive tools that can identify novel high-confidence susceptibility genes (HSGs) and potential therapeutic drugs. In the present study, a computational framework via propagation modeling on integrated multi-layered molecular networks (abbreviated as iUMRG) was proposed for the systematic inference of HSGs in UM.

Transcriptional landscape of circulating platelets from patients with COVID-19 reveals key subnetworks and regulators underlying SARS-CoV-2 infection: implications for immunothrombosis.

Background: Thrombosis and coagulopathy are pervasive pathological features of coronavirus disease 2019 (COVID-19), and thrombotic complications are a sign of severe COVID-19 disease and are associated with multiple organ failure and increased mortality. Platelets are essential cells that regulate hemostasis, thrombus formation and inflammation; however, the mechanism underlying the interaction between platelets and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains unclear.

Results: The present study performed RNA sequencing on the RNA isolated from platelets obtained from 10 COVID-19 patients and eight healthy donors, and discovered that SARS-CoV-2 not only significantly altered the coding and non-coding transcriptional landscape, but also altered the function of the platelets, promoted thrombus formation and affected energy metabolism of platelets.

Computational elucidation of spatial gene expression variation from spatially resolved transcriptomics data.

Recent advances in spatially resolved transcriptomics (SRT) have revolutionized biological and medical research and enabled unprecedented insight into the functional organization and cell communication of tissues and organs i. Identifying and elucidating gene spatial expression variation (SE analysis) is fundamental to elucidate the SRT landscape. There is an urgent need for public repositories and computational techniques of SRT data in SE analysis alongside technological breakthroughs and large-scale data generation.

Cell-free DNA 5-hydroxymethylcytosine profiles of long non-coding RNA genes enable early detection and progression monitoring of human cancers.

Background: 5-Hydroxymethylcytosine (5hmC) is a significant DNA epigenetic modification. However, the 5hmC modification alterations in genomic regions encoding long non-coding RNA (lncRNA) and their clinical significance remain poorly characterized.

Results: A three-phase discovery-modeling-validation study was conducted to explore the potential of the plasma-derived 5hmC modification level in genomic regions encoding lncRNAs as a superior alternative biomarker for cancer diagnosis and surveillance.

Pan-cancer characterization of lncRNA modifiers of immune microenvironment reveals clinically distinct de novo tumor subtypes.

The emerging field of long noncoding RNA (lncRNA)-immunity has provided a new perspective on cancer immunity and immunotherapies. The lncRNA modifiers of infiltrating immune cells in the tumor immune microenvironment (TIME) and their impact on tumor behavior and disease prognosis remain largely uncharacterized. In the present study, a systems immunology framework integrating the noncoding transcriptome and immunogenomics profiles of 9549 tumor samples across 30 solid cancer types was used, and 36 lncRNAs were identified as modifier candidates underlying immune cell infiltration in the TIME at the pan-cancer level.

Treatment and management of adrenal cancer in a specialized Australian endocrine surgical unit: approaches, outcomes and lessons learnt.

Background: Adrenocortical carcinoma is a rare and heterogeneous malignancy with poor outcomes. Recent research has suggested that outcomes may be improved by centralization of care in specialist centres. We review our evolving 21-year experience in managing adrenocortical carcinoma with a view towards outcomes and lessons learnt.