Journal of Biomedical Research最新文献

Intermediate filaments (IFs) in human cells are the products of six distinct gene families, all sharing homology in a core rod domain. These IFs assemble into non-polar polymers, providing cytoplasmic and nuclear mechanical support. Recent research has revealed the active and dynamic properties of IFs and their binding partners. This regulation extends beyond cell mechanics to include migration, mechanotransduction, and tumor growth. This comprehensive review will catalog all human IF genes and IF-associated proteins (IFAPs), detailing their names, sizes, functions, associated human diseases, relevant literature, and links to resources like Uniprot and the Protein Atlas database. These links provide access to additional information such as protein structure, subcellular localization, disease-causing mutations, and pathology. Using this catalog, we will overview the current understanding of the biological functions of IFs and IFAPs. This overview is crucial for identifying gaps in their characterization and understanding IF-mediated mechanotransduction. Additionally, we will consider potential future research directions.

Cholestatic liver disease, caused by the accumulation of hazardous bile acids in the liver, may result in cirrhosis, fibrosis, or liver failure. Activation of SIRT6 prevents cholestasis-associated pathological events, such as oxidative stress and mitochondrial biogenesis disorders, and inhibits bile acid synthesis to alleviate cholestatic liver injury. However, it is still uncertain which pathway is responsible for the therapeutic effect of SIRT6 in reducing cholestasis. Therefore, we treated liver-specific Sirt6 knockout mice with N-Acetylcysteine, Keap1-Nrf2-IN-1, or acadesine to remove oxidative stress and/or trigger mitochondrial biogenesis after cholestatic liver disease modeling, but these measures did not significantly improve cholestatic symptoms. However, MDL801, a SIRT6 agonist that downregulating CYP7A1, the key enzyme in bile acid synthesis, exhibited favorable therapeutic effects. In addition, the hepatic knockdown of Cyp7A1 further confirmed that inhibition of hepatic bile acid synthesis might be the main pathway by which SIRT6 alleviates cholestatic liver disease. These findings provide a solid basis for the potential application of SIRT6 agonists in the treatment of cholestatic liver disease.

Rod-shaped gold nanomaterials, known as gold nanorods (GNRs), may undergo specific surface modification, because of their straightforward surface chemistry. This feature makes them appropriate for use as functional and biocompatible nano-formulations. By optimizing the absorption of longitudinally localized surface plasmon resonance in the near-infrared region, which corresponds to the near-infrared bio-tissue window, GNRs with appropriate modifications may improve the results of photothermal treatment (PTT). In dermatology, potential noninvasive uses of GNRs to enhance wound healing, manage infections, combat cutaneous malignancies, and remodel skin tissues via PTT have attracted research attention in recent years. The review discussed the basic properties of GNRs, such as their shape, size, optical performance, photothermal efficiency, and metabolism. Then, the disadvantages of using these particles in photodynamic therapy are highlighted. Next, biological applications of GNRs-based PTT are explored in detail. Finally, the limitations and future perspectives of this research are addressed, providing a comprehensive perspective on the potential GNRs with PTT.

In the present, we aimed to investigate the effect of anlotinib on the potential reversal of osimertinib resistance by inhibiting the formation of epithelial-to-mesenchymal transition (EMT) and angiogenesis. In a clinical case, anlotinib reversed osimertinib resistance in Non-small cell lung cancer (NSCLC). We performed an immunohistochemical experiment on tumor tissues from three non-small cell lung cancer patients exhibiting osimertinib resistance to analyze alterations in the expression levels of EMT markers and vascular endothelial growth factor A (VEGFA) before and after osimertinib resistance. The results revealed the downregulation of E-cadherin, coupled with the upregulation of vimentin and VEGFA in tumor tissues of patients exhibiting osimertinib resistance, compared with the expression in tissues of patients before taking osimertinib. Subsequently, we established osimertinib-resistant cell lines and found that the osimertinib-resistant cells acquired the EMT features. Then, we analyzed the synergistic effects of the combination therapy to verify whether anlotinib could reverse osimertinib resistance by inhibiting EMT. The expression levels of VEGFA and micro-vessels were analyzed in the combination group in vitro. Finally, we explored the reversal of osimertinib resistance in combination with anlotinib in vivo with 20 nude mice. The combined treatment of osimertinib and anlotinib effectively prevented the metastasis of resistant cells, which also inhibited tumor growth, exerted anti-tumor activity, and ultimately reversed osimertinib resistance in mice. The co-administration of osimertinib and anlotinib demonstrated their synergistic efficacy in inhibiting EMT and angiogenesis in three NSCLC patients, ultimately reversing osimertinib resistance.

Parasitic helminths, taxonomically comprising trematodes, cestodes, and nematodes, are multicellular invertebrates widely disseminated in nature and have afflicted people continuously for a long time. Helminths play potent roles in the host through generating a variety of novel molecules, including some excretory/secretory products and others that are involved in intracellular material exchange and information transfer as well as the initiation or stimulation of immune and metabolic activation. The helminth-derived molecules have developed powerful and diverse immunosuppressive effects to achieve immune evasion for parasite survival and establish chronic infections. However, they also improve autoimmune and allergic inflammatory responses and promote metabolic homeostasis by promoting metabolic reprogramming of various immune functions, and then inducing alternatively activated macrophages, T helper 2 cells, and regulatory T cells-mediated immune responses. Therefore, a deeper exploration of the immunopathogenic mechanism and immune regulatory mechanisms of helminth-derived molecules exerted in the host is crucial for understanding host-helminth interactions as well as the development of therapeutic drugs for infectious or non-infectious diseases. In this review, we focus on the properties of helminth-derived molecules to give an overview of the most recent scientific knowledge about their pathogenic and pharmacopeial roles in immune-metabolic homeostasis.