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Liver disease is a serious threat to human health. However, there is still no effective medical treatment for end-stage liver diseases such as cirrhosis and liver failure. Mesenchymal stem cells (MSCs) are expected to be used clinically for liver cirrhosis caused by various etiologies, acute-on-chronic liver failure, chronic liver failure, and complications post-liver transplantation by their multi-directional differentiation and immunomodulatory abilities. MSCs can directly differentiate into hepatocyte-like cells and indirectly secrete soluble factors to achieve goals such as antioxidant, anti-regulated cell death, anti-fibrosis, inhibiting inflammation, inhibiting immune response, etc., so to reduce liver damage and improve survival rate. A sound quality standard evaluation system and a more in-depth mechanism exploration are the prerequisites for MSCs to be used in the clinical treatment of liver diseases in the future.

Organoids are miniature, highly accurate representations of organs that capture the structure and unique functions of specific organs. Although the field of organoids has experienced exponential growth, driven by advances in artificial intelligence, gene editing, and bioinstrumentation, a comprehensive and accurate overview of organoid applications remains necessary. This review offers a detailed exploration of the historical origins and characteristics of various organoid types, their applications—including disease modeling, drug toxicity and efficacy assessments, precision medicine, and regenerative medicine—as well as the current challenges and future directions of organoid research. Organoids have proven instrumental in elucidating genetic cell fate in hereditary diseases, infectious diseases, metabolic disorders, and malignancies, as well as in the study of processes such as embryonic development, molecular mechanisms, and host–microbe interactions. Furthermore, the integration of organoid technology with artificial intelligence and microfluidics has significantly advanced large‐scale, rapid, and cost‐effective drug toxicity and efficacy assessments, thereby propelling progress in precision medicine. Finally, with the advent of high‐performance materials, three‐dimensional printing technology, and gene editing, organoids are also gaining prominence in the field of regenerative medicine. Our insights and predictions aim to provide valuable guidance to current researchers and to support the continued advancement of this rapidly developing field. [ABSTRACT FROM AUTHOR]

Many drug and therapeutic modalities have emerged over the past few years. However, successful commercialization is dependent on their safety and efficacy evaluations. Several preclinical models are available for drug-screening and safety evaluations, including cellular- and molecular-level models, tissue and organoid models, and animal models. Organoids are three-dimensional cell cultures derived from primary tissues or stem cells that are structurally and functionally similar to the original organs and can self-renew, and they are used to establish various disease models. Human hepatobiliary organoids have been used to study the pathogenesis of diseases, such as hepatitis, liver fibrosis, hepatocellular carcinoma, primary sclerosing cholangitis and biliary tract cancer, as they retain the physiological and histological characteristics of the liver and bile ducts. Here, we review recent research progress in validating drug toxicity, drug screening and personalized therapy for hepatobiliary-related diseases using human hepatobiliary organoid models, discuss the challenges encountered in current research and evaluate the possible solutions. [ABSTRACT FROM AUTHOR]

A study published in the Journal of Internal Medicine examined why severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) affects older adults more severely than children. The study found that age, comorbidity, and early antiviral treatment were major risk factors for poor prognosis in COVID-19 patients. The authors conducted an in vitro study using nasal epithelial cells (NECs) and found age-specific responses to SARS-CoV-2 infection. Older adult NECs showed a higher abundance of basaloid-like cells, which are associated with tissue injury and fibrosis. In contrast, pediatric NECs exhibited a stronger antiviral response. The study concluded that the higher abundance of goblet 2 inflammatory epithelial cells in children contributes to their better resistance to SARS-CoV-2. However, the authors noted that immunosenescence and chronic inflammation in older adults are also critical factors in the progression of SARS-CoV-2 infections. Further research is needed to understand the overall immune landscape of SARS-CoV-2 infection. [Extracted from the article]

A novel influenza A (H7N9) virus of avian origin emerged in eastern China in the spring of 2013. This virus causes severe disease in humans, including acute and often lethal respiratory failure. As of January 2014, 275 cases of H7N9-infected patients had been reported, highlighting the urgency of identifying biomarkers for predicting disease severity and fatal outcomes. Here, we show that plasma levels of angiotensin II, a major regulatory peptide of the renin-angiotensin system, are markedly elevated in H7N9 patients and are associated with disease progression. Moreover, the sustained high levels of angiotensin II in these patients are strongly correlated with mortality. The predictive value of angiotensin II is higher than that of C-reactive protein and some clinical parameters such as the PaO2/FiO2 ratio (partial pressure of arterial oxygen to the fraction of inspired oxygen). Our findings indicate that angiotensin II is a biomarker for lethality in flu infections.

Preclinical studies have proven that nanosecond pulsed electric field (nsPEF) ablation can be a safe and effective treatment for humans with unresectable liver cancer that are ineligible for thermal ablation. The concomitant activation of antitumor immunity by nsPEF can also potentially prevent tumor recurrence. However, whether nsPEF exhibits similar efficacy in a clinical setting remains to be investigated. A prospective clinical trial (clinicaltrials.gov identifier: NCT04039747) was conducted to evaluate the safety and efficacy of ultrasound (US)‐guided nsPEF ablation in 15 patients with unresectable liver cancer that were ineligible for thermal ablation. We found that nsPEF ablation was safe and produced a 12‐month recurrence‐free survival (RFS) and local RFS of 60% (9/15) and 86.7% (13/15), respectively, in the enrolled patients. Integrative proteomic and metabolomic analysis showed that sphingolipid metabolism was the most significantly enriched pathway in patient sera after nsPEF without recurrence within 8 months. A similar upregulation of sphingolipid metabolism was observed in the intratumoral mononuclear phagocytes (MNPs), rather than other immune and nonimmune cells, of an nsPEF‐treated mouse model. We then demonstrated that lymphocyte antigen 6 complex, locus C2‐positive (Ly6c2+) monocytes first differentiated into Ly6c2+ monocyte‐derived macrophages with an increase in sphingolipid metabolic activity, and subsequently into Ly6c2+ dendritic cells (DCs). Ly6c2+ DCs communicated with CD8+ T cells and increased the proportions of IFN‐γ+ CD8+ memory T cells after nsPEF, and this finding was subsequently confirmed by depletion of liver Ly6c2+ MNPs. In conclusion, nsPEF was a safe and effective treatment for liver cancer. The alteration of sphingolipid metabolism induced by nsPEF was associated with the differentiation of Ly6c2+ MNPs, and subsequently induced the formation of memory CD8+ T cells with potent antitumor effect. [ABSTRACT FROM AUTHOR]