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Glioblastoma is the most aggressive primary brain tumor in adults. The prognosis of patients with primary glioblastoma treated with the current standard of care, tumor resection followed by radiation therapy and auxiliary temozolomide, remains poor. Integrative genomic analyses have identified essential core signaling pathways and frequent genetic aberrations, which provide potential drug targets for glioblastoma treatment. Drugs against these therapeutic targets have been developed rapidly in recent years. Although some have shown promising effects on models in preclinical studies, many have shown only modest efficacy in clinical trials. New therapeutic strategies and potent drugs are urgently needed to improve the prognosis of patients with glioblastoma. The goal of this review is to summarize the current advances in drug development for targeted glioblastoma therapies and to reveal the major challenges encountered in clinical trials or treatment. This study will provide new perspectives for future studies of targeted therapeutic drug development and provide insights into the clinical treatment of glioblastoma. [ABSTRACT FROM AUTHOR]

Ongoing studies have determined that the gut microbiota is a major factor influencing both health and disease. Host genetic factors and environmental factors contribute to differences in gut microbiota composition and function. Intestinal dysbiosis is a cause or a contributory cause for diseases in multiple body systems, ranging from the digestive system to the immune, cardiovascular, respiratory, and even nervous system. Investigation of pathogenesis has identified specific species or strains, bacterial genes, and metabolites that play roles in certain diseases and represent potential drug targets. As research progresses, gut microbiome–based diagnosis and therapy are proposed and applied, which might lead to considerable progress in precision medicine. We further discuss the limitations of current studies and potential solutions. [ABSTRACT FROM AUTHOR]

Gemin5 acts as a U1 small nuclear RNA (snRNA)‐binding protein in U1 small nuclear ribonucleic protein (snRNP) biogenesis. Here, we report a role for Gemin5 in unassembled U1 snRNP disposal under survival of motor neuron (SMN) protein‐deficient conditions. We demonstrate that non‐Sm protein‐associated U1 snRNA and U1A are enriched in cytoplasmic granules and colocalize to P bodies in SMN‐deficient cells. Immunoprecipitation assays show increased associations of the U1 snRNP component U1A with P body components and Gemin5 in SMN‐deficient cells. More importantly, Gemin5 knockdown eliminates the unassembled U1 snRNP granules and rescues U1 snRNA levels in SMN‐deficient cells. Taken together, our study provides direct evidence that Gemin5 is involved in unassembled‐U1 snRNA disposal under conditions of SMN deficiency. [ABSTRACT FROM AUTHOR]

Antibiotic production is often governed by large gene clusters composed of genes related to antibiotic scaffold synthesis, tailoring, regulation, and resistance. With the expansion of genome sequencing, a considerable number of antibiotic gene clusters has been isolated and characterized. The emerging genome engineering techniques make it possible towards more efficient engineering of antibiotics. In addition to genomic editing, multiple synthetic biology approaches have been developed for the exploration and improvement of antibiotic natural products. Here, we review the progress in the development of these genome editing techniques used to engineer new antibiotics, focusing on three aspects of genome engineering: direct cloning of large genomic fragments, genome engineering of gene clusters, and regulation of gene cluster expression. This review will not only summarize the current uses of genomic engineering techniques for cloning and assembly of antibiotic gene clusters or for altering antibiotic synthetic pathways but will also provide perspectives on the future directions of rebuilding biological systems for the design of novel antibiotics. [ABSTRACT FROM AUTHOR]

Aims: We performed cell and animal experiments to explore the therapeutic effect of artemisinin on Parkinson's disease (PD) and the TLR4/Myd88 signaling pathway., Methods: C57 mice were randomly divided into the blank, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced and artemisinin-treated groups. Clinical symptoms, the number of dopaminergic (DAergic) neurons in the substantia nigra, and microglial cell activation were compared among the three groups. Subsequently, BV-2 cell activation and TLR4/Myd88 pathway component expression were compared among the blank, MPP + -treated, artemisinin-treated, and TLR4 activator-treated groups., Results: Behavioral symptoms were improved, the number of DAergic neurons in the substantia nigra of the midbrain was increased, and microglial cell activation was decreased in artemisinin-treated MPTP-induced PD model mice compared with control-treated MPTP-induced PD model mice (p < 0.05). The cell experiments revealed that artemisinin treatment reduced MPP + -induced BV-2 cell activation and inhibited the TLR4/Myd88 signaling pathway. Moreover, the effect of artemisinin on the BV-2 cell model was inhibited by the TLR4 activator LPS (p < 0.05)., Conclusion: Artemisinin may reduce damage to DAergic neurons in a PD mouse model by decreasing microglial activation through the TLR4-mediated MyD88-dependent signaling pathway. However, this finding cannot explain the relationship between microglia and DAergic neurons., (© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)