Telmisartan modulates exercise responses in peripheral artery disease: Analyses of skeletal muscle from the TELEX Trial.

Objective: In people with peripheral artery disease (PAD), the Telmisartan Plus Exercise to Improve Functioning in Peripheral Artery Disease (TELEX) randomized clinical trial tested whether telmisartan (TEL), with or without exercise, significantly improved 6-minute walk distance at 6-month follow-up, compared with placebo (PLA). This study investigated the effects of TEL on exploratory muscle biopsy outcomes of muscle cellular characteristics (myofiber size, satellite cell content, capillary density, extracellular matrix, and collagen area) and molecular characteristics (cell-specific transcriptomics) in people undergoing supervised exercise in the TELEX Trial.

Methods: Baseline and 6-month follow-up muscle biopsies were obtained from 13 participants with PAD in the TELEX trial randomized to exercise + TEL (n = 6) or exercise + PLA (n = 7).

Butyrate-producing commensal bacteria mediates the efficacy of herbal medicine JCM-16021 on abdominal pain in diarrhea-predominant irritable bowel syndrome: a randomized clinical trial.

Background: Irritable bowel syndrome with diarrhea (IBS-D) presents significant treatment challenges due to limited therapeutic options that effectively target the underlying pathophysiological mechanisms. In this study, we performed a multi-center, double-blind randomized placebo-controlled trial to investigate the efficacy and safety of herbal medicine JCM-16021 on IBS-D with a focus on its effects on gut microbiota.

Results: Our study assessed the clinical efficacy and safety of JCM-16021 in alleviating abdominal pain in IBS-D patients.

Ferroptosis: Disease Associations and Therapeutic Target Exploration.

Ferroptosis, a distinct form of cell death, is transforming the understanding of complex diseases such as cancer, neurodegenerative disorders. Driven by iron accumulation and lipid peroxidation, ferroptosis offers significant therapeutic potential by selectively targeting diseased cells. Ferroptosis is closely associated with renal impairment, metabolic disease, and neurological disorders.

Subthalamic deep brain stimulation in isolated generalised or segmental dystonia (RELAX Study): a multicentre, randomised, double-blind, controlled trial.

Background: The safety and effectiveness of deep brain stimulation of the subthalamic nucleus (STN-DBS) for the treatment of dystonia lack high-level evidence-based medical support. This study aimed to clarify the efficacy and safety of STN-DBS and perform a post hoc analysis comparing it with DBS of the internal globus pallidus (GPi-DBS).

Methods: This multicentre, randomised, double-blind, controlled trial included 67 patients aged 6-60 years old diagnosed with genetic or idiopathic isolated generalised or segmental dystonia.

Long-term outcome of vagus nerve stimulation therapy in drug-resistant epilepsy: a retrospective single-center study.

Introduction: Vagus nerve stimulation (VNS) has garnered widespread application in patients with drug-resistant epilepsy (DRE), while the efficacy and prognostic factors of VNS in DRE remain elusive. Moreover, clinical determinants associated with rapid response to VNS have never been uncovered. This study aimed to elucidate factors influencing efficacy and rapid response to VNS.

Disulfidoptosis: A New Key to Unlocking Cancer Treatment.

The metabolic properties of disulfidoptosis targeting cancer cells have become a new key to unlocking cancer treatment's lock. Conventional cancer therapies aim to kill tumor cells through apoptosis, but cell death is carried out by a network of cascading enzymes. Malignant cells can evade the death process by downregulating key enzymes or inhibiting death-inducing triggers, leading to cancer persistence and recurrence of cancer cells that are resistant to conventional therapies and immune escape, which has compelled researchers to explore new therapeutic avenues.

Abnormal epigenetic modification of lysosome and lipid regulating genes in Alzheimer's disease.

BackgroundAbnormal lipid metabolism has been identified as a potential pathogenic mechanism of Alzheimer's disease (AD), which might be epigenetically regulated. Lysosomes are critical organelles for lipid metabolism. However, the epigenetic modifications of lysosome and lipid regulating genes remain unclear in AD patients.

Decoding Abdominal Pain in Constipation-predominant Irritable Bowel Syndrome and Functional Constipation: Mechanisms and Managements.

Purpose Of Review: Abdominal pain in constipation-predominant irritable bowel syndrome (IBS-C) and functional constipation (FC) remains a difficult clinical challenge due to unclear pathophysiological mechanisms and limited pain-targeted treatments. This review critically evaluates the evidence on the underlying pain mechanisms in IBS-C and/or FC and explores management strategies, their limitations, and future directions.

Recent Findings: Most research on constipation-related pain is based on IBS-C patients or animal models, with limited studies focusing on FC.

Target inhibition of SPAK in choroid plexus attenuates T cell infiltration and demyelination in experimental autoimmune encephalomyelitis.

Background: Disease-modifying therapies (DMTs) that prevent immune cell infiltration into the brain have demonstrated efficacy in multiple sclerosis (MS) treatment. However, their unpredictable adverse effects necessitate the development of safer therapeutic alternatives. The choroid plexus (ChP) functions as a crucial barrier against immune cell invasion, and previous studies have shown that preventing immune cell infiltration across the ChP reduces brain lesion in MS animal models.

Home-Based Exercise and Patient-Reported Outcome Measures in Peripheral Artery Disease: The LITE Randomized Clinical Trial.

In patients with peripheral artery disease (PAD), we evaluated the effects of 12 months of walking exercise at a pace inducing ischemic leg symptoms (high intensity) on the attainment of meaningful improvement in patient-reported outcome measures (PROMs) and 6-minute walk, compared to walking exercise at a comfortable pace (low intensity) and a nonexercise control. Participants completed the 6-minute walk test (6MWT) to evaluate objective walking ability. PROMs included the Walking Impairment Questionnaire (WIQ) distance and speed scores (range 0 to 100, 100-best, minimal clinically important difference (MCID) = 15 and 11, respectively).

Hepatocyte growth factor for walking performance in peripheral artery disease.

Background: VM202 is a plasmid encoding two isoforms of hepatocyte growth factor. In preclinical studies, hepatocyte growth factor stimulated angiogenesis and muscle regeneration. This preliminary clinical trial tested the hypothesis that VM202 injections in gastrocnemius muscle would improve walking performance in people with mild to moderate and symptomatic lower extremity peripheral artery disease (PAD).

Subthalamic γ Oscillation Underlying Rapid Eye Movement Sleep Abnormality in Parkinsonian Patients.

Background: Abnormal rapid eye movement (REM) sleep, including REM sleep behavior disorder (RBD) and reduced REM sleep, is common in Parkinson's disease (PD), highlighting the importance of further study on REM sleep. However, the biomarkers of REM disturbances remain unknown, leading to the lack of REM-specific neuromodulation interventions.

Objective: This study aims to investigate the neurophysiological biomarkers of REM disturbance in parkinsonian patients.

Progress of research and application of non-pharmacologic intervention in Alzheimer's disease.

Alzheimer's disease (AD) is a common neurodegenerative disease characterized by amyloid-β (Aβ) deposition and neurofibrillary tangles formed by high phosphorylation of tau protein. At present, drug therapy is the main strategy of AD treatment, but its effects are limited to delaying or alleviating AD. Recently, non-pharmacologic intervention has attracted more attention, and more studies have confirmed that non-pharmacologic intervention in AD can improve the patient's cognitive function and quality of life.

Exosomes and Macrophages: Bidirectional Mutual Regulation in the Treatment of Diabetic Complications.

Purpose: The bidirectional regulation of macrophages and exosomes provides a meaningful research direction for the treatment of complications arising from both type 1 and type 2 diabetes mellitus. However, there is currently no comprehensive evaluation of the bidirectional regulatory role of macrophages and exosomes in diabetic complications. In this review, we aim to provide the detailed process of the bidirectional regulation mechanism of macrophages and exosomes, and how macrophage-associated exosomes use this mechanism to make it better applied to clinical practice through biotechnology.

The ankle-brachial index, gastrocnemius mitochondrial respirometry, and walking performance in people with and without peripheral artery disease.

Background: Mitochondrial abnormalities exist in lower-extremity peripheral artery disease (PAD), yet the association of the ankle-brachial index (ABI) with mitochondrial respiration in gastrocnemius muscle is unknown. The association of gastrocnemius mitochondrial respiration with 6-minute walk distance in PAD is unknown. This objective of this study was to describe associations of the ABI with mitochondrial respiratory function in gastrocnemius muscle biopsies and associations of gastrocnemius mitochondrial respirometry with 6-minute walk distance in people with and without PAD.

Curcumin nanopreparations: recent advance in preparation and application.

Curcumin is a natural polyphenolic compound extracted from turmeric with antibacterial, antioxidant, antitumor, preventive and therapeutic neurological disorders and a variety of bioactivities, which is widely used in the field of food and medicine. However, the drawbacks of curcumin such as poor aqueous solubility and stability have limited the practical application of curcumin. To overcome these defects and enhance its functional properties, various nanoscale systems (liposomes, polymer nanoparticles, protein nanoparticles, solid lipid nanoparticles, metal nanoparticles, etc) have been extensively employed for curcumin encapsulation and delivery.

Rhein and hesperidin nanoparticles remodel tumor immune microenvironment by reducing CAFs and CCL2 secreted by CAAs for efficient triple-negative breast cancer therapy.

In triple-negative breast cancer (TNBC), the tumor immune microenvironment (TIME) is a highly heterogeneous ecosystem that exerts indispensable roles in tumorigenesis and tumor progression. Cancer-associated fibroblasts (CAFs) and cancer-associated adipocytes (CAAs) are the main matrix components in the TIME of TNBC. CAFs mediate the edesmoplastic response, which is a major driver of the immunosuppressive microenvironment to promote tumor growth.

Nano-mediated strategy: recent advance in the application of drug delivery systems in melanoma treatment and diagnosis.

Melanoma is a common malignant tumor, with a five-year mortality rate as high as 62% in cases of metastatic melanoma according to cancer statistics (2024). In recent years, the focus of melanoma research has predominantly centered on immunotherapy and targeted therapy, grappling with challenges such as resistance and immunogenicity. The discovery of nanoparticles (NPs) has brought nano-delivery systems to the forefront of melanoma diagnosis and treatment.

Recent progress in artificial intelligence and machine learning for novel diabetes mellitus medications development.

Diabetes mellitus, stemming from either insulin resistance or inadequate insulin secretion, represents a complex ailment that results in prolonged hyperglycemia and severe complications. Patients endure severe ramifications such as kidney disease, vision impairment, cardiovascular disorders, and susceptibility to infections, leading to significant physical suffering and imposing substantial socio-economic burdens. This condition has evolved into an increasingly severe health crisis.

Temporal Variations in Fire Impacts on Characteristics and Composition of Soil-Derived Dissolved Organic Matter at Qipan Mountain, China.

Dissolved organic matter (DOM), the most reactive fraction of forest soil organic matter, is increasingly impacted by wildfires worldwide. However, few studies have quantified the temporal changes in soil DOM quantity and quality after fire. Here, soil samples were collected after the Qipan Mountain Fire (3-36 months) from pairs of burned and unburned sites.

Alterations in Synaptic Connectivity and Synaptic Transmission in Alzheimer's Disease with High Physical Activity.

Background: Alzheimer's disease (AD) is a progressive neurodegeneration disease. Physical activity is one of the most promising modifiable lifestyles that can be effective in slowing down the progression of AD at an early stage.

Objective: Explore the molecular processes impaired in AD that were conversely preserved and enhanced by physical activity.

Neurophysiological features of STN LFP underlying sleep fragmentation in Parkinson's disease.

Background: Sleep fragmentation is a persistent problem throughout the course of Parkinson's disease (PD). However, the related neurophysiological patterns and the underlying mechanisms remained unclear.

Method: We recorded subthalamic nucleus (STN) local field potentials (LFPs) using deep brain stimulation (DBS) with real-time wireless recording capacity from 13 patients with PD undergoing a one-night polysomnography recording, 1 month after DBS surgery before initial programming and when the patients were off-medication.

Rhein potentiates doxorubicin in treating triple negative breast cancer by inhibiting cancer-associated fibroblasts.

Cancer-associated fibroblasts (CAFs), one of the most abundant stromal cells in the tumor microenvironment, mediate desmoplastic responses. CAFs are major drivers for the failure of triple-negative breast cancer (TNBC) chemotherapy. It is well-documented that many traditional Chinese medicines (TCMs) exhibit potent anti-fibrotic effects based on their capacity to suppress the production of ECM proteins.