Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonists are increasingly used in the management of type 2 diabetes mellitus and obesity due to their ability to stimulate insulin secretion, delay gastric emptying, and suppress appetite. The combination of GLP-1 and GIP agonists improves glycemic control and promotes weight loss. However, the introduction of these novel therapies has raised safety concerns, including the risk of cholestatic hepatitis. We report a case of a patient with obesity who was prescribed a GLP-1/GIP dual-receptor agonist as part of his treatment regimen. Importantly, both before the initiation of this therapy and during the course of treatment, the patient was not taking any other medications. Shortly after receiving four doses of the therapy, the patient developed symptoms of severe cholestatic hepatitis, including jaundice and elevated liver enzyme levels. During hospitalization, no alternative causes for the condition were identified, and a liver biopsy confirmed the diagnosis of drug-induced cholestatic hepatitis. This is the first recorded case of cholestatic hepatitis induced by a GLP-1/GIP dual agonist, and it aimed to raise global awareness of this potential side effect.

Chlorella vulgaris is a green, photosynthetic microalga in the phylum Chlorophyta. The goal of our study was to perform a bioinformatics analysis of Photosystem I P700 chlorophyll a apoprotein A2, one of its photosynthesis-related proteins, and to hunt for potent bioactive peptides.

To generate peptides and estimate the safety and efficacy of each bioactive peptide, we employed the tools BIOPEP-UWM™, PeptideRanker, DBAASP, and ToxinPred. PepDraw was used to understand the physicochemical properties and primary chemical structures of the selected bioactive peptides.

The liberated peptides exhibit up to 17 distinct bioactivities, as shown by the in silico digestion of the protein using several proteolytic enzymes. The peptides with bioactivities are listed as angiotensin-converting enzyme inhibitor, dipeptidyl peptidase IV inhibitor, dipeptidyl peptidase III inhibitor, antioxidative, renin inhibitor, glucose uptake stimulator, neuropeptide regulator (regulating stomach mucosal membrane activity and ion flow), antithrombotic, anti-amnestic, CaMPDE inhibitor, activators of ubiquitin-mediated proteolysis, alpha-glucosidase inhibitor, immunomodulating, calcium-binding, antibacterial, anti-inflammatory, and hypotensive agent. Using the Database of Antimicrobial Activity and Structure of Peptides (DBAASP) prediction method, the antibacterial activity of the released peptides was predicted, highlighting the existence of potent antibacterial peptides. An examination of their physicochemical properties revealed that most peptides are low molecular weight, mildly acidic, and moderately water-soluble. To further establish the non-toxicity profile of the released peptides (sequence length > 3), a ToxinPred analysis was performed, which revealed that most of the peptides are non-toxic. According to the allergenicity analysis, most of the top-ranked peptides are likely non-allergenic.

Thus, our study reveals a less labor-intensive method for discovering new therapeutic targets derived from C. vulgaris, which hold both pharmacological and medical significance.

Glutathione peroxidase 4 (GPX4) is a key factor in ferroptosis, which is involved in ischemia-reperfusion injury. However, little is known about its role in hepatic ischemia-reperfusion injury (HIRI). This study aimed to investigate the role of GPX4 methylation in ferroptosis during HIRI.

For the in vitro experiments, an oxygen and glucose deprivation cell model was established. For the in vivo experiments, an ischemia-reperfusion model was created by subjecting mice to simulated HIRI. Ferroptosis occurrence, GPX4 promoter methylation, and global methylation levels were then assessed.

Ferroptosis was observed in oxygen and glucose deprivation, characterized by a significant decrease in cellular viability (P < 0.05), an increase in lipid peroxidation (P < 0.01), iron overload (P < 0.05), and down-regulation of GPX4 (P < 0.05). This ferroptosis was exacerbated by GPX4 knockdown (P < 0.01) and mitigated by exogenous glutathione (P < 0.01). Similarly, ferroptosis was evident in mice subjected to HIRI, with a down-regulation of GPX4 mRNA and protein expression (all P < 0.01), and an upregulation of acyl-CoA synthetase long-chain family member 4 mRNA and protein (all P < 0.01), as well as prostaglandin-endoperoxide synthase 2 mRNA and protein expression (all P < 0.05). Methylation levels increased, evidenced by upregulation of DNA methylation transferase expression (P < 0.05) and down-regulation of Ten-eleven translocation family demethylases (P < 0.01), along with an upregulation of GPX4 promoter methylation.

Ferroptosis may be the primary mode of cell death in hepatocytes following ischemia-reperfusion injury. The methylation of the GPX4 promoter and elevated levels of global hepatic methylation are involved in the regulation of ferroptosis.

The World Health Organization System for Reporting Pancreaticobiliary Cytopathology introduces a seven-tier category system to standardize terminology and nomenclature. This system includes the following categories: Insufficient/non-diagnostic, benign/negative for malignancy, atypia, pancreaticobiliary neoplasm low-risk/grade, pancreaticobiliary neoplasm high-risk/grade, suspicious for malignancy, and malignant categories. Adopting a standardized reporting scheme facilitates consistent diagnostic criteria among pathologists, thereby reducing report variability and enhancing communication with the clinical team for optimal patient management. The report also highlights the role of critical ancillary tests in improving diagnostic accuracy for pancreatic lesions and discusses practical approaches to managing solid and cystic pancreatic lesions.

Achalasia is a rare esophageal motility disorder characterized by the inability of the lower esophageal sphincter to relax and the absence of normal esophageal peristalsis. This condition leads to difficulties in swallowing (dysphagia), regurgitation of food, and chest pain. Clinical observations suggest an association between achalasia and esophageal tumors, as achalasia can increase the risk of developing esophageal cancer. We explore the pathophysiology of achalasia, its clinical manifestations, and the associated risk of esophageal malignancies, supported by recent research and clinical evidence, including specific case studies.

Portal vein thrombosis (PVT) is a challenging complication in liver cirrhosis, with no currently available sensitive diagnostic markers. This study aimed to investigate the potential of neutrophil extracellular traps (NETs) and Deoxyribonuclease (DNase) as diagnostic indicators for PVT in chronic hepatitis B (CHB)-related decompensated cirrhosis.

We analyzed 145 CHB-related decompensated cirrhosis patients from the Ditan study and 33 from the Changgung validation study, categorizing them based on PVT occurrence. Plasma samples were assessed for NET markers, including cell-free DNA (cfDNA) and histone-DNA complexes, along with DNase activity.

PVT patients exhibited elevated levels of cfDNA and histone-DNA complexes, and reduced DNase activity. This pattern persisted regardless of hepatocellular carcinoma (HCC) status. Histone-DNA levels, DNase activity, and hemoglobin were identified as independent risk factors for PVT. Receiver operating characteristic curve analysis revealed that high histone-DNA levels may serve as a potential diagnostic marker for PVT, with an area under the curve of 0.8628 in the Ditan study and 0.7521 in the Changgung study. When combined with cfDNA and DNase activity, the area under the curve improved to 0.8774 in the Ditan study and 0.7975 in the Changgung study.

Imbalances in NET homeostasis are associated with PVT in CHB-related decompensated cirrhosis, including cases involving HCC. Histone-DNA complexes, a significant risk factor for PVT, show potential as a diagnostic marker for PVT in decompensated cirrhosis, particularly in HBV-related HCC.

Patients with obstructive sleep apnea (OSA) and metabolic syndrome (MetS) have a higher prevalence and mortality rate of cardiovascular diseases, posing a significant burden on both individuals and society. Although the precise pathophysiological relationship between OSA and MetS remains unclear, their bidirectional interaction may create a harmful cycle of mutual reinforcement. This review explored the current treatment progress for OSA and MetS, including continuous positive airway pressure therapy, weight management, and metabolic surgeries. Studies indicate that while continuous positive airway pressure therapy effectively alleviates OSA symptoms, its impact on metabolic markers is limited, emphasizing the importance of long-term weight control. Metabolic surgeries, such as gastric bypass and sleeve gastrectomy, significantly reduce weight and directly improve metabolic abnormalities associated with MetS, such as insulin resistance and dyslipidemia, thereby lowering the risk of cardiovascular diseases. In contrast, mandibular advancement devices primarily improve symptoms of OSA and indirectly enhance metabolic function by improving sleep quality and reducing intermittent hypoxemia. Although mandibular advancement devices have a limited direct impact on metabolic parameters, they may offer potential benefits in lowering blood pressure and managing MetS. Understanding and breaking the cycle between OSA and MetS can significantly reduce the associated cardiovascular risks.

Fuzi, the processed product of daughter roots of Aconitum carmichaelii Debx., is a well-known Chinese medicine for the treatment of heart failure (HF) and related cardiac diseases. This study aimed to investigate the molecular mechanism of the cardioprotective effects of Fuzi water decoction (FWD) and Fuzi water-soluble alkaloids (FWA) on the model of HF.

The HF model of rats was prepared through intravenous injection of propafenone hydrochloride. The normal group, model group, FWD-treated groups (1.25 g/kg, 2.5 g/kg, 5 g/kg) and positive group (Shenfu Injection, 3.3 mL/kg) were set up. Heart rate, LV+dp/dtmax, and LV-dp/dtmax were recorded at 5 m, 10 m, 20 m, 30 m, and 60 m after drug administration, respectively. The contents of atrial natriuretic peptide, brain natriuretic peptide (BNP), angiotensin II, and aldosterone in serum were determined 20 m post-administration. An in vitro cardiomyocyte hypertrophy model with HDAC2 overexpression was constructed and verified by lentivirus transfection. The experiment included a blank group, FWD-treated groups (3 mg/mL, 1.5 mg/mL), and FWA-treated groups (4 mg/mL, 2 mg/mL). For transcriptome analysis, the model group, blank group, and FWD-treated group (2.5 g/kg) at 20 m and 60 m in vivo, and different dose groups in vitro, were selected to analyze the therapeutic mechanisms of FWD and FWA.

All FWD treatment groups showed an increased heart rate, among which the groups with 2.5 g/kg and 5 g/kg FWD showed better effects, significantly increasing LV+dp/dtmax and LV-dp/dtmax after 20 m of administration and significantly reducing BNP and aldosterone serum levels. In the constructed cardiomyocyte hypertrophy model, HDAC2 expression, atrial natriuretic peptide and BNP protein levels, and cell surface area increased. Transcriptome data from both in vivo and in vitro showed that FWD and FWA could exert cardioprotective effects through pathways such as the PI3K-Akt signaling pathway, NF-κB signaling pathway, and ATP-binding cassette (ABC) transporters, involving key genes such as ITGB1, TLR2, and CDKN1A. Fuzi inhibited the hypertrophic gene HDAC2. Additionally, based on weighted gene co-expression network analysis, ABC transporters may be an important molecular pathway for FWA in treating HF.

Both FWD and FWA can ameliorate HF by regulating apoptosis, proliferation, and anti-fibrosis, with ABC transporters potentially being the main pathway for the action of FWA.

Aquaporin-4 (AQP4) plays a crucial role in the glymphatic system and is vital for maintaining homeostasis in the central nervous system. This study aimed to investigate the effects of N-(1,3,4-thiadiazol-2-yl)-3-pyridinecarboxamide (TGN-020), a selective AQP4 inhibitor, on glymphatic function and to assess its impact on short-term behavior in mice.

In this laboratory study, mice were randomly assigned to TGN-020-treated and control groups. We evaluated glymphatic function by measuring the distribution of Evans blue dye in the brain following injection into the cisterna magna. Behavioral assessment of cognitive function was performed using open field and Morris water maze tests. AQP4 protein expression levels were analyzed via immunohistochemistry. Statistical comparisons were conducted using the one-way analysis of variance to evaluate the results among groups.

Our findings revealed that the areas of Evans blue dye in the dorsal (p < 0.001) and ventral (p < 0.001) surfaces of the brain were significantly reduced in the TGN-020 group compared to the control group, indicating impaired glymphatic function. However, behavioral tests demonstrated no significant short-term changes; the mean distance traveled in the open field was 4,345 cm in the control group and 4,049 cm in the TGN-020 group (p = 0.5625), while the mean speed was 2.649 cm/s for controls and 2.868 cm/s for the TGN-020 group (p = 0.6762). In the Morris water maze, latency was comparable (36.33 s for TGN-020 vs. 34.89 s for controls, p = 0.758). Additionally, no significant differences in AQP4 expression intensity were observed between the two groups.

Our study demonstrates that acute inhibition of AQP4 through a single dose of TGN-020 significantly impairs glymphatic function without inducing short-term behavioral abnormalities in mice. These findings contribute to understanding AQP4’s role in the glymphatic system and its potential implications for neurological function.

Reprogramming of lipid metabolism has emerged as a significant characteristic of malignancy during tumor development. Research indicates a critical link between lipid metabolism and the tumor immune microenvironment. This relationship not only facilitates cancer progression by remodeling the tumor microenvironment but also influences the functionality of immune cells. Alterations in lipid metabolism regulate the function and status of immune cells within the microenvironment, impacting immune evasion and the therapeutic efficacy of tumors. Consequently, targeting lipid metabolism is a viable strategy for intervening in tumorigenesis and tumor development. This review examines the roles of key lipid molecules, such as fatty acids and cholesterol, within the tumor microenvironment, highlighting how aberrant lipid metabolism can alter immune cell function. By investigating the interactions between lipid metabolism and immune cells in this setting, the review offers novel insights into early diagnosis, screening, and immunotherapy of malignant tumors. Furthermore, lipid metabolic reprogramming may act as a biomarker for monitoring early immune escape from tumors and predicting therapeutic outcomes, thereby enhancing early diagnosis and personalized cancer treatment.