Metabolic dysfunction-associated fatty liver disease (MAFLD) poses a significant challenge in modern medicine due to its high prevalence. The pathogenesis of MAFLD involves a complex dysmetabolic process consistent with the “multiple-hit” hypothesis. This process includes excessive triglyceride (TC) accumulation within hepatocytes, lipotoxicity, insulin resistance (IR), chronic low-grade inflammation, and increased oxidative stress. The role of leptin in the liver has been extensively studied, demonstrating both direct effects on hepatic cells and indirect actions mediated through the central nervous system (CNS). In MAFLD, leptin modulates several physiological processes: it improves glucose metabolism by enhancing insulin sensitivity and lowering glucose levels; regulates lipid metabolism by promoting β-oxidation and TC export while inhibiting lipogenesis; and contributes to fibrogenesis by upregulating transforming growth factor-β (TGF-β) expression and activating hepatic stellate cells (HSCs) and the immune response. This review explores the structure of leptin, its primary physiological functions, its potential role in MAFLD pathogenesis, and its promise as a novel therapeutic target.

The COVID-19 pandemic profoundly impacted university students, presenting multifaceted challenges including the abrupt transition to virtual learning and significant disruptions to emotional well-being and dietary habits. This study aimed to investigate the dietary and nutritional characteristics associated with academic stress among Mexican university students during the COVID-19 lockdown.

This cross-sectional study was conducted with a sample of 114 university students in Mexico. Participants completed a self-reported questionnaire assessing dietary patterns, nutritional intake, and academic stress levels. Informed consent was obtained from all participants prior to data collection.

Among study participants (n = 114), 57.8% experienced moderate academic stress, while 25.7% reported high academic stress during the COVID-19 lockdown. Notably, 13.5% of students demonstrated food cravings that were significantly associated with increased consumption of red and fatty meats (P = 0.030) and sausages (P = 0.017). A negative virtual education experience was associated with food cravings towards high-calorie and saturated-fat foods (P = 0.014), as well as elevated academic stress levels (P = 0.009). Furthermore, high academic stress levels were positively associated with food cravings (P = 0.020), particularly towards carbohydrate-rich foods (P = 0.037).

The COVID-19 lockdown substantially disrupted the dietary habits and nutritional status of university students, with academic stress serving as a significant mediating factor.

Cardiovascular diseases account for approximately 80% of all deaths caused by known medical conditions, making them the leading cause of mortality worldwide. The present study investigates the use of electrocardiogram (ECG) non-linear features and different topological medical features (heart rate, anthropometry, blood, glucose, and lipid profile, and heart rate variability) to discriminate between different Framingham Cardiovascular Risk Scale status groups in adult obesity using machine learning.

We conducted a cross-sectional study between November 2023 and May 2024 in Fortaleza, Ceará, Brazil. Based on the Framingham Cardiovascular Risk Scale, patients were categorized into three cardiovascular risk groups: Low (22 participants), Moderate (14 participants), and High (17 participants). From ECG signals at two different positions (ECG_Down and ECG_UP), 27 non-linear features were extracted using multi-band analysis. Additionally, 42 medical features provided by physicians were included. From a pool of 19 machine learning classifiers, models were trained and tested within a nested leave-one-out cross-validation procedure using information solely from ECG, solely from medical features, and combining both (multimodal), respectively, to distinguish between Low vs. Moderate, Low vs. High, Moderate vs. High, and All vs. All.

The multimodal model presented the best results for every comparison group, reaching (1) 88.89% Accuracy and 0.8831 area under the curve (AUC) for Low vs. Moderate; (2) 97.44% Accuracy and 0.9706 AUC for Low vs. High; (3) 93.55% Accuracy and an AUC of 0.9412 for Moderate vs. High; (4) 86.79% Accuracy and 0.9346 AUC for All vs. All.

The multimodal model outperformed single-source models in cardiovascular risk classification. ECG-derived non-linear features, especially from ECG_Down, were key drivers, with medical features adding complementary value. The results support its potential use in clinical triage and diagnosis.

Ferroptosis plays an essential role in chronic liver diseases, and cyclooxygenase-2 (COX-2) affects liver fibrosis through multiple mechanisms. However, research on COX-2 regulation of ferroptosis in chronic liver injury remains limited. This study aimed to investigate whether and how COX-2 regulates ferroptosis in chronic liver injury.

In vivo, a thioacetamide (TAA)-induced chronic liver injury model, characterized by significant liver lipid peroxidation and oxidative stress, was used. COX-2+/+ and COX-2–/– mice were treated with TAA or normal saline. In vitro, primary mouse hepatocytes were isolated and treated with dimethyl sulfoxide (DMSO), erastin+DMSO, etoricoxib+erastin+DMSO, and tBHQ+erastin+DMSO. Mitochondrial morphology, iron metabolism, lipid peroxidation, and oxidative stress were assessed to verify ferroptosis. The nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway was measured to investigate the relationship between COX-2 and ferroptosis.

TAA-treated COX-2–/– mice presented milder liver fibrosis, whereas TAA-treated COX-2–/– mice livers and etoricoxib+erastin+DMSO-treated primary hepatocytes exhibited alleviated mitochondrial damage compared with TAA-treated COX-2+/+ littermates and erastin+DMSO-treated primary hepatocytes, respectively. The knockout of COX-2 decreased ferrous ion concentration (p < 0.01) and mitigated lipid peroxidation in TAA-treated livers (p < 0.05). Furthermore, both COX-2 knockout and etoricoxib restored reduced glutathione (p < 0.05) and glutathione peroxidase 4 (p < 0.05), while decreasing malondialdehyde levels (p < 0.05). Additionally, COX-2 inhibition upregulated Nrf2, which helped alleviate erastin+DMSO-induced ferroptosis (p < 0.01).

Ferroptosis contributes to the progression of chronic liver injury. Inhibition of COX-2 upregulates Nrf2, mitigating hepatocyte ferroptosis in chronic liver injury.

Atypical teratoid/rhabdoid tumor (AT/RT) is a rare and highly aggressive embryonal tumor that predominantly affects infants and young children. This malignancy arises from primitive neuroectodermal cells and exhibits heterogeneous differentiation into various embryonic tissues. Due to its rarity and complexity, diagnosing and managing AT/RT present significant challenges. Recent studies have summarized the key features of cerebellar and supratentorial AT/RT cases; however, critical gaps remain in understanding their diffuse leptomeningeal variants and long-term functional outcomes. Here, we report a case of a two-year-old child diagnosed with cerebellar AT/RT, who presented with vomiting and gait instability. The patient underwent a gross total resection followed by adjuvant radiotherapy and chemotherapy. Despite achieving radiological remission, the patient survived for only eight months and experienced severe neurological deficits, including persistent ataxia and recurrent infections. This case highlights the disconnect between surgical success and long-term quality of life. It underscores the importance of integrating molecular diagnostics and palliative care to address the multifaceted burden of AT/RT.

Gut dysbiosis has been reported in severe liver diseases. However, information on the impact of hepatitis E virus infection on the gut microbiota, and the association between enteric microbiota disturbances and acute hepatitis E (AHE), is limited, particularly in elderly patients with AHE (AHE-elderly). Our objective was to characterize the AHE-specific microbiome in elderly patients and evaluate its association with clinical outcomes.

Fecal samples and clinical data were collected from 58 AHE-elderly patients (46 self-healing cases, 12 non-self-healing cases) and 30 elderly patients with healthy controls (hereinafter referred to as HCs-elderly). Gut microbiota composition was analyzed using 16S rRNA gene sequencing. Bioinformatic analyses, including alpha diversity and STAMP, were performed. The predictive potential of Bacteroides fragilis was assessed using statistical analysis and receiver operating characteristic curves.

Alpha diversity indices showed no significant differences in microbial diversity between the AHE-elderly and HCs-elderly groups, nor between self-healing and non-self-healing groups among AHE-elderly patients. Nevertheless, a trend toward altered species richness was observed. In the AHE-elderly group, the relative abundance of Firmicutes, Lactobacillales, and Bacilli increased significantly. Meanwhile, compared with the self-healing group, Bacteroidetes were more abundant in the non-self-healing group. At the species level, Bacteroides fragilis was the most abundant in the non-self-healing group, significantly contributing to the divergence in gut microbiota between the two groups.

The relative abundance of Bacteroidetes significantly distinguished AHE-elderly patients from healthy controls and could more accurately predict recovery outcomes in elderly AHE patients. These findings suggest new strategies for preventing and managing AHE recurrence in the elderly patients.

Since the adoption of novel prognostic scores, such as the iterative model for end-stage liver disease (MELD 3.0) and the gender-equity model for liver allocation (GEMA), their utility has markedly expanded to diverse clinical scenarios. However, data concerning their prognostic value in more generalized cirrhotic populations are scarce. In this study, we aimed to elucidate the MELD 3.0/GEMA-Na for long-term mortality risk stratification and refine their usage scope.

This study retrospectively reviewed 310 hospitalized patients with decompensated cirrhosis. Discrimination and stratification were compared between MELD 3.0/GEMA-Na and other scores. Validation was performed in another 120 subjects.

In the investigated cohort, the median MELD-Na, MELD 3.0, and GEMA-Na were 9 (7, 12), 12 (10, 17), and 12 (9, 17), respectively. Compared to their predecessors, both MELD 3.0 and GEMA-Na models exhibited consistently better discriminative ability, especially in relation to long-term mortality. This effect was more pronounced for GEMA-Na, which was the only score to present an area under the receiver operating characteristic curve greater than 0.8 up to two years (0.807). Statistical analysis indicated that a MELD 3.0 score of 18 and a GEMA-Na score of 20 were the most optimal cutoffs to rank the risk of death, both of which were independently associated with two-year all-cause transplant-free mortality (MELD 3.0: hazard ratio: 1.13, 95% confidence interval: 1.10, 1.17; GEMA-Na: hazard ratio: 1.12, 95% confidence interval: 1.10, 1.17, both P < 0.001). Similar findings were affirmed in the validation cohort.

MELD 3.0 is superior to other MELD-based scores for long-term prognostication in hospitalized patients with cirrhosis, while GEMA-Na demonstrated even better accuracy and performance.

The incidence of metabolic dysfunction-associated steatotic liver disease (MASLD) has been escalating annually, positioning it as the leading cause of chronic liver disease worldwide. Ursolic acid has demonstrated promising therapeutic efficacy in managing MASLD, thereby justifying the need for an in-depth exploration of its pharmacological mechanisms. This study aimed to investigate elucidate the therapeutic mechanisms by which ursolic acid modulates estrogen conversion in the treatment of MASLD.

Building upon prior studies that have highlighted the potent anti-inflammatory effects of ursolic acid and its specific targeting of 17β-hydroxysteroid dehydrogenase 14 (HSD17B14), this investigation employed a western diet to induce MASLD in murine models with varying severities over different time intervals.

The protein expression of HSD17B14 initially increased, followed by a subsequent decrease. This trend was accompanied by corresponding changes in 17β-estradiol (E2) and estrone (E1) levels. Intervention with ursolic acid resulted in a reduction in HSD17B14 and E1 levels during the phase of high HSD17B14 expression, while simultaneously elevating E2 levels. In steatotic hepatocytes, E1 promoted cellular inflammation, whereas E2 exhibited anti-inflammatory effects. However, the alleviated effects of E2 were antagonized by HSD17B14. As expected, ursolic acid modulated HSD17B14, thereby mitigating the inflammatory response in steatotic hepatocytes.

HSD17B14, a crucial enzyme regulating the balance between E1 and E2, catalyzes the conversion of estrogen E2 into E1, thereby exacerbating tissue inflammation induced by metabolic stress. Ursolic acid, by modulating HSD17B14-mediated estrogen conversion, appears to ameliorate immune-related inflammation in MASLD.