Long-term efficacy and safety of tirzepatide in participants with type 2 diabetes with inadequate glycaemic control on metformin and/or sulfonylurea: Post-hoc analysis of SURPASS-4.

Aim: To evaluate the long-term efficacy and safety data at 104 weeks in tirzepatide-treated participants with type 2 diabetes who had inadequate glycaemic control on metformin and/or sulfonylurea.

Materials And Methods: This post-hoc analysis was based on the SURPASS-4 data (NCT03730662), a multicenter, Phase III trial. Participants were randomised to receive tirzepatide (5, 10, or 15 mg) or insulin glargine.

Alleviating effects of polyphenol extract from rapeseed meal on type 2 diabetes in mice via modulation of gut microbiota and AMPK/mTOR signaling pathways.

Type 2 diabetes mellitus (T2DM) is a a complex metabolic disorder that poses a serious threat to human health. Although polyphenol extract from rapeseed meal (RMP) has demonstrated inhibitory activity against α-glucosidase, the alleviating effects on T2DM and the underlying molecular mechanisms remain largely unexplored in T2DM. In this study, the antidiabetic effects of RMP were investigated using a T2DM mouse model induced by a high-fat diet (HFD) combined with streptozotocin (STZ) administration.

Advances in Research on Monogenic Hereditary Hypertension.

Hypertension is one of the most significant preventable health risk factors globally. Among its various forms, monogenic hypertension, although rare, warrants attention. As awareness of monogenic hypertension grows within both the public and medical communities, research efforts are intensifying.

Assessment of docosahexaenoic acid's preventive efficacy against unconjugated bilirubin neurotoxicity through MRP1 protein expression.

Objective: Jaundice in neonates promotes unconjugated hyperbilirubinemia (UCB), which causes neurological disorders, and its management remains a challenge. This study evaluated the protective effect of docosahexaenoic acid (DHA) against UCB-induced neurotoxicity.

Method: Astrocyte cell lines were prepared and separated into four different groups: SAL group; DHA group treated with 50 µM DHA; UCB group treated with 50 µM UCB; and UCB + DHA group treated with 50 µM UCB along with 50 µM DHA.

Mechanisms of podophyllotoxin-induced enterotoxicity: A multi-omics integration of gut microbiota, short-chain fatty acids, and inflammatory mediators.

Podophyllotoxin (PPT), a lignan extracted from the roots and stems of Podophyllum species, exhibits significant enterotoxicity that limits its clinical application. However, its underlying mechanisms remain unclear. This study aimed to elucidate the mechanisms underlying PPT-induced enterotoxicity.

2-1,4-Benzoxazin-3(4)-one linked 1,2,3-triazole derivatives and their study on inducing DNA damage in tumor cells.

This study explores the anticancer potential of rigid planar compounds capable of intercalating into tumor cell DNA, thereby inducing DNA damage and subsequent cell death. A novel series of compounds () were synthesized using 2-1,4-benzoxazin-3(4)-one as the planar core structure, with 1,2,3-triazole groups introduced at the 7-position. Biological evaluation across multiple human tumor cell lines revealed that several c-series compounds exhibited notable inhibitory activity against Huh-7 liver cancer cells, with IC values of 28.

The key enzyme PYCR1 in proline metabolism: a dual driver of cancer progression and fibrotic remodeling.

Pyrroline-5-Carboxylate Reductase 1 (PYCR1), a member of the PYCR family, is a key enzyme in the proline biosynthesis pathway. Notably, PYCR1 was originally identified via genetic disease research, linking its mutations to the occurrence of cutis laxa. PYCR1 contributes to the pathogenesis of malignancies and fibrotic diseases via mechanisms involving metabolic reprogramming, Extracellular Matrix (ECM) remodelling, and redox homeostasis maintenance.

Pemafibrate treatment produces antidepressant-like effects in CUMS and CRS models through activation of hippocampal PPARa and BDNF signaling.

Background: It is well established that peroxisome proliferator-activated receptor α (PPARα) plays a crucial role in the pathogenesis of depression. Several PPARα agonists, including WY14643, fenofibrate, and gemfibrozil, have been reported to produce antidepressant-like effects in mouse models through PPARα-mediated enhancement of hippocampal brain-derived neurotrophic factor (BDNF) signaling and neurogenesis. Pemafibrate is a novel and highly selective modulator of PPARα, and therefore, we hypothesised that it might also exhibit antidepressant-like efficacy.

Dysbiosis of gut and urinary microbiota in urolithiasis patients and post-surgical cases.

Background: Research on the microbial roles in urolithiasis primarily focuses on the intestinal microbiota. This study analyzed urine and fecal samples from three cohorts: healthy controls (Control), patients with urinary stones (US), and postoperative patients (PS). We conducted 16S rRNA sequencing analysis to evaluate the variations in microbial communities among these groups during urinary stone production and therapy processes.

Stress hyperglycemia ratio and incident hypertension in chinese middle-aged and older adults: mediating roles of lipids in a prospective cohort.

Background: Although dysglycemia and dyslipidemia contribute to hypertension, the role of stress hyperglycemia ratio (SHR), a dynamic glycemic marker, and its interaction with lipids remain unclear. Currently, the independent and synergistic effects of these factors on hypertension in older adults have not been fully elucidated in a large cohort. This study investigated the SHR-lipid interplay and quantified the mediating pathways, addressing a critical gap in understanding the metabolic drivers of hypertension.

A novel residual network based on multidimensional attention and pinwheel convolution for brain tumor classification.

Early and accurate brain tumor classification is vital for clinical diagnosis and treatment. Although Convolutional Neural Networks (CNNs) are widely used in medical image analysis, they often struggle to focus on critical information adequately and have limited feature extraction capabilities. To address these challenges, this study proposes a novel Residual Network based on Multi-dimensional Attention and Pinwheel Convolution (Res-MAPNet) for Magnetic Resonance Imaging (MRI) based brain tumor classification.

Blood transfusion mediated tumor microenvironment remodeling in breast cancer.

Blood transfusions play a critical role in breast cancer management, particularly in addressing perioperative blood loss and chemotherapy-induced anemia. However, emerging evidence suggests that transfusions may adversely affect oncologic outcomes by inducing transfusion-related immunomodulation (TRIM) and altering the tumor microenvironment (TME). TRIM suppresses cytotoxic immune responses, potentially facilitating tumor progression-especially in aggressive subtypes such as triple-negative breast cancer (TNBC) and HER2-positive cancers.

Antidepressant-like actions of lanifibranor and its related mechanisms in mouse models of depression: Involvement of hippocampal PPARα and BDNF.

Current commercial antidepressants worldwide are mainly developed according to the monoaminergic hypothesis of depression and have various limitations. Thus, exploring new antidepressants with better therapeutic efficacy and fewer adverse effects remain a hot topic in the field of neuropsychiatric research. Peroxisome proliferator-activated receptors (PPARs) have been demonstrated to closely participate in the pathophysiology of depression, and here we assume that lanifibranor, a novel pan-PPAR agonist for α, δ, and γ, may induce antidepressant-like actions by PPARs activation.

Understanding the risk of diabetic retinopathy from glucagon-like peptide-1 receptor agonists: a Mendelian randomization study and systematic review of European populations.

Background: Glucagon-like peptide-1 receptor agonists (GLP-1RA) are extensively prescribed to treat obesity and diabetes. However, previous studies have debated whether GLP-1RA use induces diabetic retinopathy (DR) in diabetic populations, and the relationship between the two is unclear.

Methods: Cis-expressed quantitative trait locus data (Cis-eQTL) in blood tissue were used to extract single nucleotide polymorphisms (SNPs) as a genetic proxy tool.

Composite dietary antioxidant index and HPV infection from single and mixed associations to SHAP-interpreted machine learning predictions.

Background: Some studies have shown that dietary antioxidants may prevent the occurrence of Human Papillomavirus (HPV) infection. However, the relationship between the composite dietary antioxidant index (CDAI) and HPV infection among adult women in the United States remains unknown.

Methods: Participants from the National Health and Nutrition Examination Survey (NHANES) during 2003-2016 were included.

Genetic variants of Toll-like receptor 9 are associated with susceptibility to systemic lupus erythematosus in Han Chinese female patients.

Background: Variations in the TLR9 gene have been associated with several autoimmune disorders, but the relationship between TLR9 polymorphisms and systemic lupus erythematosus (SLE) remains controversial. This study aims to evaluate the potential association between three single-nucleotide polymorphisms (SNPs) within the TLR9 gene and susceptibility to SLE in the Han Chinese female population.

Methods: A total of 150 SLE patients and 151 healthy controls of Han Chinese ethnicity were enrolled.

Case Report: Treatment of delayed tremor episodes in a patient with DPPX antibody encephalitis.

Introduction: Autoimmune encephalitis is a neurological disease caused by abnormal autoimmune mechanisms, characterized by a range of symptoms such as psychiatric and behavioral abnormalities, cognitive impairment, memory decline, and seizures. It is primarily identified by the presence of autoantibodies against neuronal surface antigens in the cerebrospinal fluid. This disease is relatively rare in clinical settings, and its diagnosis remains challenging, with fewer than a hundred cases reported to date.

Salt-inducible kinase 1 and CREB-regulated transcription co-activator 1 in the paraventricular nucleus participate in the antidepressant-like mechanism of (2R, 6R)-hydroxynorketamine and (2S, 6S)-hydroxynorketamine in mice.

Background: Previous studies have demonstrated that ketamine's metabolic conversion to (2S, 6S; 2R, 6R)-HNK is indispensable for its fast-onset and long-lasting antidepressant-like actions, and moreover, both (2R, 6R)-HNK and (2S, 6S)-HNK exert N-methyl-D-aspartate receptor (NMDAR)-independent antidepressant-like activities. Up to date, many pharmacological targets other than NMDAR have been reported for (2R, 6R)-HNK and (2S, 6S)-HNK. We have previously found that salt-inducible kinase 1 (SIK1) and cAMP response element binding protein (CREB)-regulated transcription co-activator 1 (CRTC1) in the paraventricular nucleus (PVN) participate in depression neurobiology by regulating the hypothalamic-pituitary-adrenal (HPA) axis, and here, we assume that (2R, 6R)-HNK and (2S, 6S)-HNK may also produce effects on the two molecules.

Transcriptome Sequencing Reveals ceRNA Networks and Molecular Signatures in Myopic Mouse Retina.

Purpose: Long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) in the retina play crucial roles in myopia; however, their regulatory mechanisms remain unclear. This study aimed to investigate significant genes and related signaling pathways associated with myopia by constructing and analyzing competitive endogenous RNA (ceRNA) networks within the retina.

Materials And Methods: We investigated the expression patterns of lncRNAs, circRNAs, microRNAs (miRNAs), and messenger RNAs (mRNAs) within the retina using a form-deprivation myopia mouse model to elucidate their regulatory mechanisms in myopia.

Ultrasound-Targeted Nanobubbles Codelivering NKP-1339 and miR-142-5p for Synergistic Mitochondrial Immunogenic Cell Death and PD-L1 Inhibition in Cancer Therapy.

The combination of chemical immunotherapy and gene therapy holds great promise for malignant tumor treatment. Here, we developed an ultrasound-targeted liposome nanobubbles system (NKP-1339/miR-142-NBs) for precise codelivery of drugs and genes to treat esophageal squamous cell carcinoma (ESCC) with ultrasound-targeted microbubble destruction (UTMD). This study systematically investigated the system's therapeutic mechanisms-including mitochondrial dysfunction induction, immunogenic cell death (ICD), and antitumor immune activation-alongside its pharmacokinetics and targeting efficiency.

Cyclic Amplified Programmable Allosteric DNA Biosensor for Enzyme-Triggered Spatially Controlled Mitochondrial Molecular Imaging.

The abnormal localization of mitochondrial human apurinic/apyrimidinic endonuclease 1 (APE1) is closely associated with tumor progression, prognosis, and drug resistance. While APE1 can localize to both the cytoplasm and nucleus as well as mitochondria. Consequently, the design of approaches with controllable localization for imaging of mitochondrial APE1 is particularly challenging.

Depression mediates the association between lipid accumulation products and overactive bladder.

The relationship between lipid accumulation products (LAP) and overactive bladder (OAB) has not been explored. This study aims to investigate the relationship between LAP and OAB and the mediating role of depression. Data from seven cycles of the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018 were used to analyze the relationship between LAP and OAB.

Global trends and future predictions of gastrointestinal ulcers in youth.

Background: By analyzing past disease trends and comparing two time series statistical models, we can predict the global burden of gastrointestinal ulcers in specific populations of adolescents and young adults aged 10-24. This prediction can provide important references for optimizing prevention and control strategies in healthcare systems.

Methods: We collected data on prevalence, incidence, disability-adjusted life years (DALYs), and mortality for specific age groups between 10 and 24 years from 1990 to 2019.

Dexmedetomidine attenuates oxaliplatin-induced neuropathic pain by modulating the TLR4/NF-κB pathway to reduce spinal inflammation and oxidative stress.

Purpose: This study aimed to investigate the effects of Dexmedetomidine (Dex) on oxaliplatin-induced neuropathic pain and its underlying mechanisms.

Methods: A murine model of oxaliplatin-induced neuropathic pain was established using intraperitoneal injections of oxaliplatin. Dex was administered at different doses, and behavioral tests were performed to assess pain.