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.

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.

Acute coronary syndrome (ACS) in patients with SARS-CoV-2 infection is primarily driven by inflammation-induced myocardial injury through both direct and indirect mechanisms. Effective clinical management requires a dual approach: addressing cardiovascular lesions while also mitigating virus-induced local and systemic inflammation. This comprehensive approach is essential for improving the diagnosis and treatment of SARS-CoV-2-associated ACS. Emerging evidence highlights the potential of myocardial protective agents, including angiotensin-converting enzyme 2-modulating drugs and traditional Chinese medicine, which not only stabilize plaques and improve endothelial function but also confer cardioprotective effects. Furthermore, advancements in nanotechnology offer promising strategies for targeted therapy—particularly through angiotensin-converting enzyme 2 receptor modulation—by enhancing the precision and efficacy of herbal medicine delivery. This review explores the complex interplay between SARS-CoV-2 infection and ACS pathogenesis, and evaluates the therapeutic potential of pharmacological, herbal, and nanotechnology-based interventions in managing this multifaceted condition.

Despite advancements in diagnostic and therapeutic strategies, hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality. Antioxidant-1 (ATOX1) has been implicated in oncogenic processes across various cancer types; however, its specific role in HCC remains unclear. This study aimed to investigate the function of ATOX1 and its underlying molecular mechanisms in HCC.

Immunohistochemical analysis was conducted to assess ATOX1 expression in HCC tissues. Cell Counting Kit-8, colony formation, Transwell migration, flow cytometry, and reactive oxygen species (ROS) assays were employed to evaluate the malignant behaviors of tumor cells. A xenograft mouse model was employed to assess the effects of ATOX1 knockdown on tumor growth in vivo. DCAC50 treatment was performed to inhibit the copper transport function of ATOX1. RNA sequencing was conducted to explore the potential molecular mechanisms of ATOX1 in HCC.

ATOX1 expression was significantly elevated in HCC tumor tissues. ATOX1 promoted cell proliferation, colony formation, and migration. Knockdown of ATOX1 suppressed tumor growth in vivo. Mechanistically, ATOX1 activated c-Myb, and thus enhanced the malignant phenotype of HCC cells via activation of the PI3K/AKT signaling pathway. Additionally, ATOX1 reduced intracellular copper accumulation and inhibited ROS production and apoptosis. Inhibition of ATOX1 by DCAC50 decreased cell proliferation while increasing ROS levels and apoptosis in HCC cells. Notably, acetylcysteine reversed the reduction in c-Myb expression induced by ATOX1 knockdown.

ATOX1 may promote HCC carcinogenesis through the activation of the c-Myb/PI3K/AKT pathway and the inhibition of copper accumulation and oxidative stress.

Type 1 diabetes (T1D) develops when the immune system targets and destroys pancreatic β-cells responsible for insulin production, ultimately resulting in reduced insulin levels. Islet transplantation has garnered significant attention as a potential treatment, but it presents numerous challenges that hinder its effectiveness for T1D patients. A primary issue is the immune system’s tendency to reject transplanted islets, leading to a gradual decline in their functionality. Furthermore, many individuals remain reliant on additional insulin therapy. These challenges are exacerbated by the global shortage of organ donors, which limits the availability of pancreata for transplantation. This review outlines several innovative strategies to regenerate insulin-producing β-cells for the treatment of T1D, with a primary focus on pancreatic progenitor and stem cells. The strategy of converting non-β cells, particularly pancreatic α-cells, into functional β-cells continues to show promise. Moreover, α-cells, which are less vulnerable to autoimmune attacks, present a distinct opportunity for β-cell regeneration in individuals with T1D. While the use of progenitor or stem cells for β-cell regeneration appears encouraging, various hurdles, such as immune rejection, suboptimal differentiation, and other challenges, still impede the implementation of this strategy. Nonetheless, this approach may ultimately pave the way for long-lasting treatment and potential cures for T1D.

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.

Gastrointestinal complications are common in patients after ischemic stroke. Gastric motility is regulated by gastric pace-making activity (also called gastric myoelectrical activity (GMA)) and autonomic function. The aim of this study was to evaluate GMA, assessed by noninvasive electrogastrography (EGG), and autonomic function, measured via spectral analysis of heart rate variability derived from the electrocardiogram in patients with ischemic stroke.

EGG and electrocardiogram were simultaneously recorded in both fasting and postprandial states in 14 patients with ischemic stroke and 11 healthy controls. Multi-channel surface EGG was used to measure GMA, and autonomic function was evaluated by heart rate variability spectral analysis.

Compared to healthy subjects, patients with ischemic stroke, especially those with a modified Rankin scale ≥ 4, had impaired GMA in both fasting and postprandial states. This included a lower percentage of normal gastric slow waves (the basic rhythmic waves of GMA) and a higher percentage of tachygastria, bradygastria, or arrhythmia. Patients with ischemic stroke also showed a decrease in the dominant frequency and power of the gastric slow waves. Autonomic functions were altered in ischemic stroke patients with a modified Rankin scale ≥ 4, as reflected by increased sympathetic activity and reduced parasympathetic activity.

Gastric pace-making activity is impaired in patients with severe ischemic stroke, as evidenced by a reduced percentage of normal gastric slow waves and a lower frequency of gastric slow waves, likely due to impaired autonomic functions.

Chronic hepatitis B virus (HBV)-infected patients may exhibit liver fibrosis and other pathological changes despite normal alanine aminotransferase (ALT). This study aimed to assess the efficacy and safety of tenofovir amibufenamide (TMF) in chronic HBV-infected patients with normal ALT levels.

The ongoing PROMOTE study (NCT05797714) is the first prospective, multicenter, randomized, open-label, blank-controlled clinical trial involving chronic HBV-infected patients with normal ALT levels. Participants were randomized in a 1:1 ratio to receive either TMF (TMF group) or no treatment (blank control group). The primary efficacy endpoint was the proportion of participants achieving HBV DNA levels <20 IU/mL at 48 weeks.

A total of 197 participants were enrolled, with 95 in the TMF group and 102 in the blank control group. At 48 weeks, a significantly greater proportion of participants in the TMF group achieved HBV DNA levels <20 IU/mL compared with the control group (74.2% vs. 9.0%, P < 0.001). The TMF group demonstrated more pronounced reductions in HBV DNA (−2.63 vs. −0.22 log10 IU/mL, P < 0.001), HBsAg (−0.07 vs. −0.04 log10 IU/mL, P = 0.02), and ALT levels (−14.09% vs. 0%, P = 0.003) compared with the blank control. In the TMF group, the proportion of participants with high-normal ALT levels (20–40 IU/L) was reduced. No significant differences were observed between the groups in creatinine, glomerular filtration rate, bone turnover biomarkers, lipid profiles, or phosphorus levels.

TMF treatment demonstrates significant efficacy in chronic HBV-infected patients with normal ALT levels and shows a favorable safety profile regarding bone, renal, and lipid parameters. The PROMOTE study is ongoing, and further results at 96 and 144 weeks are expected to provide additional insights.

Organoids are derived from self-organizing stem cells and form three-dimensional structures that are structurally and functionally similar to in vivo tissues. With the ability to replicate the in vivo microenvironment and maintain genetic stability, organoids have become a powerful tool for elucidating developmental mechanisms, accurately modeling disease processes, and efficiently screening drug candidates, and have also demonstrated significant value in the field of traditional Chinese medicine (TCM)-including applications in screening active components of TCM, studying TCM pharmacodynamic mechanisms, evaluating TCM safety, and verifying the effects of traditional non-pharmacological therapies such as acupuncture and yoga. Organoids can be cultured using air-liquid interface systems, bioreactors, and vascularization techniques. They are widely used in drug screening, disease modeling, precision medicine, and toxicity assessment. However, current limitations include high costs, difficulty in accurately replicating the microenvironment, and ethical concerns. In this review, we systematically retrieve, synthesize, and analyze relevant literature to elucidate the culture methods of organoid technology, its diverse applications across various fields, and the challenges it faces. In the future, integration with artificial intelligence may provide new insights and strategies for drug development and disease research and the modernization of TCM.

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.