Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of hepatic fibrosis, yet its prevalence in asymptomatic populations remains unclear. This study aimed to assess the prevalence of steatosis and significant fibrosis in asymptomatic individuals without known liver disease in the Greater Vancouver Area.

Interested individuals voluntarily registered online via the Canadian Liver Foundation website or by telephone. Inclusion criteria included age ≥ 19 years, no known liver disease, and low alcohol intake (<30 g/day for men, <20 g/day for women). Demographic and clinical data were collected, and all participants underwent transient elastography after a 3-h fast. The study aimed to collect 4,500 analyzable scans while reflecting the region’s ethnic diversity.

A total of 4,193 participants were analyzed. The median age was 62 years, the median body mass index was 25.4, and 45% were male. Asian individuals comprised 42% of the cohort. Steatosis was present in 59.6% of participants, and 45.7% met diagnostic criteria for MASLD. Significant fibrosis (F2–F4) was found in 8.6%. Age, male sex, ethnicity, cardiac disease, diabetes, hypertension, and obesity were significantly associated with fibrosis. Logistic regression analysis confirmed age, weight, diabetes, dyslipidemia, hypertension, and obesity as independent predictors.

A substantial proportion of asymptomatic individuals in Greater Vancouver have undetected MASLD and significant fibrosis. Early identification of high-risk groups may support broader implementation of transient elastography screening. This study provides one of the first North American population-based estimates of MASLD and fibrosis stratified by ethnicity, offering new insights into liver disease distribution among Caucasian, Chinese, and South Asian populations.

Shenqi Fuzheng (SQ) is a widely used Chinese medicine formula known for its immune-enhancing and Qi-supplementing properties. However, the blood-absorbed components of SQ and their pharmacokinetics remain underexplored. This study aimed to comprehensively analyze the chemical constituents of SQ and investigate their absorption and pharmacokinetic behavior in rat plasma.

Ultra-performance liquid chromatography-triple quadrupole time-of-flight mass spectrometry (hereinafter referred to as UPLC-Triple-TOF/MS) is employed to identify the chemical components in SQ extract and quantify the components absorbed into the blood after oral administration in rats. This method provides fragmentation patterns of compounds and key pharmacokinetic profiles of blood-absorbed compounds.

A total of 105 compounds are identified from the SQ extract, and 40 are detected in the blood following oral administration. Organic acids and amino acids are found at higher concentrations in the bloodstream. Compounds such as Astragalosides promptly enter the bloodstream within 5 m after administration, with levels declining after 15 m. Flavonoids are absorbed within 15–30 m, and the peak of alkaloids occurs approximately 1 h after administration.

This study provides new insights into the chemical composition and pharmacokinetics of SQ, highlighting the dynamic changes in the content of absorbed compounds in the blood. It further promotes the comprehensive characterization of traditional Chinese medicine formulations through UPLC-Triple-TOF/MS. Future research should focus on elucidating the pharmacological activities of the identified compounds and investigating their potential synergistic effects within the formulation.

Prognostic scores are valuable tools for predicting survival in patients with chronic liver disease. Recently, the albumin-bilirubin (ALBI) score has emerged as a potential prognostic indicator in liver-related conditions. This study aimed to compare the prognostic efficacy of the ALBI score with the Model for End-stage Liver Disease (MELD), MELD-Na+, and Child-Turcotte-Pugh (CTP) scores in predicting survival among patients with alcohol-associated liver disease (ALD).

This study included consecutive ALD patients admitted to the Medicine and Gastroenterology wards of MKCG Medical College and Hospital, Berhampur, Odisha, India, between November 2019 and November 2022. Upon hospitalization, baseline characteristics, clinical and laboratory parameters, ALBI, MELD, MELD-Na+, and CTP scores were recorded. The accuracy of these scores in predicting survival up to three years was compared.

A total of 490 ALD patients were included. Higher ALBI scores were observed in patients who died during hospitalization (p < 0.001), at 28 days (p < 0.001), 90 days (p < 0.001), six months (p < 0.001), one year (p < 0.001), two years (p < 0.001), and three years (p < 0.001), compared to those who survived. However, the area under the receiver operating characteristic (AUROC) curves showed that the ALBI score was inferior to MELD, MELD-Na+, and CTP scores in predicting survival at admission [AUROC: ALBI (0.719), MELD-Na+ (0.823), MELD (0.817), CTP (0.770)] and at three years [AUROC: ALBI (0.755), MELD-Na+ (0.787), MELD (0.758), CTP (0.784)]. Furthermore, Cox regression analysis revealed that components used in the MELD, MELD-Na+, and CTP scores—such as serum creatinine, serum sodium, and hepatic encephalopathy—were independent predictors of mortality, whereas the components of the ALBI score (serum albumin and serum bilirubin) were not.

All hospitalized ALD patients had a grade 3 ALBI score, with significantly higher scores observed among non-survivors compared to survivors. However, MELD, MELD-Na+, and CTP scores were superior to the ALBI score in predicting survival both during hospitalization and over a three-year follow-up period.

Despite significant advances in Parkinson’s disease (PD) treatment, it remains incurable, with limited therapeutic options. Currently, repurposing already tested, safe drugs has emerged as an effective therapeutic strategy against various neurodegenerative diseases, including PD. Using a drug-repurposing approach, the current study investigated the neuroregenerative potential of polysialic acid mimicking compounds, 5-nonyloxytryptamine oxalate (5-NOT) and Epirubicin (Epi), an anti-cancer drug, in 1-methyl-4-phenylpyridinium (MPP+)-treated human neuroblastoma SH-SY5Y cells as a PD model.

The excitotoxic model was established by exposing SH-SY5Y cells to 500 µM of MPP+ and subsequently treating them with the test compounds. The effect of MPP+-induced toxicity on cellular and nuclear morphology, as well as on the expression of neuroplasticity and cell survival proteins, were studied by immunostaining, gelatin zymogram, and Western blot assays.

Treatment with 5-NOT and Epi significantly promoted the survival of MPP+-challenged SH-SY5Y cells and prevented changes in their cellular and nuclear morphology by regulating the expression of microtubule-associated protein (MAP-2) and polysialylated-neural cell adhesion molecule (PSA-NCAM) and NCAM synaptic plasticity proteins. Further, 5-NOT and Epi treatment also protected SH-SY5Y cells by restoring levels of nitric oxide, matrix metalloproteinase, and stress response proteins. Interstingly, 5-NOT attenuated MPP+-induced toxicity in SH-SY5Y cells by regulating the intrinsic protein kinase AKT/BAD apoptotic pathway and the P-38 MAP kinase synaptic plasticity pathway.

These preliminary findings suggest that 5-NOT, as a potential polysialic acid glycomimetic, may serve as a promising drug candidate for targeting neurodegeneration of dopaminergic neurons, a hallmark feature of PD.

Spinal cord injury (SCI) significantly impacts the central nervous system, with limited effective treatments available. Brain-derived neurotrophic factor (BDNF) plays a crucial role in neuronal growth, survival, and regeneration after SCI. MicroRNAs, particularly miR-124-3p, have been implicated in SCI pathophysiology. However, the relationship between miR-124-3p and BDNF in the context of SCI remains unclear. This study aimed to investigate the correlation between miR-124-3p expression and BDNF levels in a rat model of spinal cord injury and to assess how the timing of injury affects this relationship.

This study included 72 male Wistar rats divided into three groups: intact (n = 8), sham (n = 32), and SCI (n = 32). SCI diagnosis was confirmed through behavioral-motor function analysis using the Basso, Beattie & Brenham score and histological examination with crystal violet staining. The expression levels of miR-124-3p and BDNF were assessed using real-time polymerase chain reaction in all groups at four time points (one hour, one day, three days, and seven days post-injury).

In the SCI group, a marked reduction in miR-124-3p expression was observed relative to both the sham and intact groups. Conversely, there was a substantial elevation in BDNF expression within the SCI group in comparison to the sham and intact groups. The findings underscore a negative association between miR-124-3p expression and BDNF messenger RNA levels.

The downregulation of miR-124-3p and concurrent upregulation of BDNF suggest a potential regulatory role of miR-124-3p in modulating BDNF expression during SCI. These findings provide new insights into the molecular mechanisms underlying SCI and suggest that miR-124-3p and BDNF could serve as potential therapeutic targets. Further research is needed to explore the translational potential of these findings for developing novel diagnostic and therapeutic strategies for SCI.

Given the high burden of hepatocellular carcinoma (HCC), risk stratification in patients with cirrhosis is critical but remains inadequate. In this study, we aimed to develop and validate an HCC prediction model by integrating radiomics and deep learning features from liver and spleen computed tomography (CT) images into the established age-male-ALBI-platelet (aMAP) clinical model.

Patients were enrolled between 2018 and 2023 from a Chinese multicenter, prospective, observational cirrhosis cohort, all of whom underwent 3-phase contrast-enhanced abdominal CT scans at enrollment. The aMAP clinical score was calculated, and radiomic (PyRadiomics) and deep learning (ResNet-18) features were extracted from liver and spleen regions of interest. Feature selection was performed using the least absolute shrinkage and selection operator.

Among 2,411 patients (median follow-up: 42.7 months [IQR: 32.9–54.1]), 118 developed HCC (three-year cumulative incidence: 3.59%). Chronic hepatitis B virus infection was the main etiology, accounting for 91.5% of cases. The aMAP-CT model, which incorporates CT signatures, significantly outperformed existing models (area under the receiver-operating characteristic curve: 0.809–0.869 in three cohorts). It stratified patients into high-risk (three-year HCC incidence: 26.3%) and low-risk (1.7%) groups. Stepwise application (aMAP → aMAP-CT) further refined stratification (three-year incidences: 1.8% [93.0% of the cohort] vs. 27.2% [7.0%]).

The aMAP-CT model improves HCC risk prediction by integrating CT-based liver and spleen signatures, enabling precise identification of high-risk cirrhosis patients. This approach personalizes surveillance strategies, potentially facilitating earlier detection and improved outcomes.

Persistent liver injury halts the regenerative capacity of hepatocytes and activates mechanisms that result in the replacement of normal hepatic parenchyma with extracellular matrix deposits. As liver fibrosis develops, the liver undergoes architectural changes and alterations in microcirculation that lead to increased intrahepatic vascular resistance and portal hypertension. Thrombocytopenia is a prevalent condition in patients with chronic liver disease and portal hypertension. Multiple mechanisms related to increased platelet destruction or decreased platelet production contribute to thrombocytopenia. Increased platelet destruction occurs due to splenic sequestration caused by hypersplenism or immune-mediated conditions. Decreased platelet production results from a decline in thrombopoietin production, bone marrow suppression by medications, or toxic insults. Therapies aimed at improving thrombocytopenia are controversial, and individual factors must be considered. Although hepatic venous pressure gradient measurement is the gold standard for diagnosing portal hypertension, non-invasive tests show adequate correlation with hepatic venous pressure gradients. Various clinical risk scores consider platelet counts as independent predictors of adverse liver outcomes, such as the development of esophageal varices and the presence of advanced fibrosis. Nonselective beta-blockers are the cornerstone of long-term management for clinically significant portal hypertension. Indications for transjugular intrahepatic portosystemic shunt placement include failure to control portal hypertension-related bleeding, early rebleeding, and refractory or recurrent ascites. Ultimately, liver transplantation is the only definitive cure for portal hypertension and its major complications, including thrombocytopenia. Understanding the mechanisms underlying thrombocytopenia in patients with portal hypertension and chronic liver disease is essential for accurate diagnosis and effective patient management. This review aimed to evidence on the pathophysiological mechanisms linking chronic liver disease, portal hypertension, and thrombocytopenia, and to discuss their diagnostic and therapeutic implications.

Emergency department (ED) presentations are associated with higher cancer mortality. This study aimed to investigate the prevalence, frequency, and risk factors in Australian patients diagnosed with malignant skin cancers.

This data-linkage cohort study examined adult patients presenting to the ED at the Royal Melbourne and Western Health hospitals within 12 months of a malignant skin cancer diagnosis. Multivariable logistic and Poisson regressions were used to analyze factors influencing the prevalence and frequency of ED presentations.

A total of 3,873 patients were diagnosed with skin malignancies between 2010 and 2018, of which 631 were diagnosed with melanoma. The prevalence of ED presentation was 29%, representing 2,119 episodes of care (median: 0; range: 0–14). Risk factors for a higher prevalence and frequency included: age ≥75 years (odds ratio (OR) = 1.78 [95% confidence interval 1.47–2.15]; incidence risk ratio (IRR) = 1.52 [1.35–1.70]); male (OR = 1.17 [1.01–1.36]; IRR = 1.23 [1.12–1.35]); socioeconomic status levels of 0–30% (OR = 1.59 [1.24–2.03]; IRR = 1.69 [1.45–1.96]) and 71–100% (OR = 1.30 [1.07–1.58]; IRR = 1.27 [1.12–1.45]); preferred language other than English (OR = 1.47 [1.17–1.84]; IRR = 1.49 [1.32–1.69]); and experience with any systemic therapy or radiotherapy (OR = 3.77 [2.12–6.71]; IRR = 2.36 [1.82–3.05]). Age < 65 years was protective (OR = 0.72 [0.59–0.89]; IRR = 0.78 [0.68–0.90]). Other preferred languages and cancer treatment experience were also risk factors in the sub-cohort with melanoma.

This study reports the prevalence and frequency of ED presentations following a skin cancer diagnosis and their association with socioeconomic and linguistic factors in Australia. Increased awareness of these factors could help address health inequities and potentially reduce the need for ED presentations.

Leishmaniasis is a dangerous yet neglected tropical disease affecting a vast population of the world. Several medicinal plants and their constituents (natural products/phytochemicals) have been considered of prime importance for the management of leishmaniasis over the years. The present review sheds light on the molecular mechanisms of the constituents obtained from medicinal plants that are pre-clinically effective against leishmaniasis. Various mechanisms by which medicinal plant-derived natural products elicit their action against leishmaniasis are illustrated in the literature. The mechanisms identified include: disruption of cytoplasmic and mitochondrial membranes, induction of apoptosis and autophagy, modulation of gene expression and immunological pathways, pro-oxidant effects (disrupting redox balance) with mitochondrial dysfunction, cell cycle arrest, impaired cellular bioenergetics, i.e., adenosine triphosphate production and coagulation of cellular contents within Leishmania parasites. Future phytochemical and pharmacological (especially clinical) studies are necessary to further understand the mechanistic details of medicinal plant-derived natural compounds and to develop new phytotherapeutic entities from nature against leishmaniasis.