Renal aging and mitochondrial quality control.

Mitochondria are dynamic organelles that participate in different cellular process that control metabolism, cell division, and survival, and the kidney is one of the most metabolically active organs that contains abundant mitochondria. Perturbations in mitochondrial homeostasis in the kidney can accelerate kidney aging, and maintaining mitochondrial homeostasis can effectively delay aging in the kidney. Kidney aging is a degenerative process linked to detrimental processes. The significance of aberrant mitochondrial homeostasis in renal aging has received increasing attention. However, the contribution of mitochondrial quality control (MQC) to renal aging has not been reviewed in detail. Here, we generalize the current factors contributing to renal aging, review the alterations in MQC during renal injury and aging, and analyze the relationship between mitochondria and intrinsic renal cells. We also introduce MQC in the context of renal aging, and discuss the study of mitochondria in the intrinsic cells of the kidney, which is the innovation of our paper. In addition, during kidney injury and repair, the specific functions and regulatory mechanisms of MQC systems in resident and circulating cell types remain unclear. Currently, most of the studies we reviewed are based on animal and cellular models, the relationship between renal tissue aging and mitochondria has not been adequately investigated in clinical studies, and there is still a long way to go.

ARID1A mutations in cancer development: mechanism and therapy.

AT-Rich Interaction Domain 1A (ARID1A) is an important SWItch/Sucrose Non-Fermentation (SWI/SNF) chromatin remodeling complex subunit, and its coding gene has a high mutation frequency in many cancers. Current studies have reported that ARID1A mutational status is correlated to cancer development, including cell proliferation, invasiveness, metastasis, and morphological alterations. ARID1A acts as a tumor suppressor, regulating gene transcription, participating in DNA damage response, and influencing tumor immune microenvironment and signaling pathways. The absence of ARID1A in cancer can lead to widespread dysregulation of gene expression in cancer initiation, promotion, and progression. For patients with ARID1A mutations, effective individualized treatment can improve the prognosis of patients. In this review, we aim to discuss the mechanism of ARID1A mutations in cancer development and explore the significance of discoveries for treatment.

Bibliometric and visualized analysis of the top-100 highly cited articles on immunotherapy for endometrial cancer.

BACKGROUND: Immunotherapy is a promising method for the treatment of endometrial cancer (EC). We aimed to conduct a comprehensive bibliometric study of the top 100 most-cited publications on immunotherapy for EC and provide a reference for future research. METHODS: Global publications on immunotherapy for EC published from 1985 to the present in the Web of Science core database were retrieved. We focused on the study of the top 100 most-cited articles by extracting information such as year, country, journal, author, institution, literature, and keywords. Microsoft Excel, VOSviewer, and R were used to perform descriptive statistics and visual analyses. RESULTS: The top 100 most-cited articles were published between 2002 and 2022, including 70 original papers and 30 reviews. The total frequency of citations per article ranges from 15 to 287. Developed countries dominated these publications, with the United States contributing the most (50 articles). According to Bradford Law, 6 journals, including Gynecologic Oncology and the Journal of Clinical Oncology, are highly recommended. Santin A. D. from Yale University and Makker.V. from Memorial Sloan Kettering Cancer Center have made positive contributions. Among the top ten most-cited articles, 7 focused on clinical trials exploring the efficacy of immunotherapy drugs, of which 4 were lenvatinib combined with pembrolizumab for the treatment of advanced EC. The immune-microenvironment, immune antitumor mechanisms, immunomodulatory drugs, especially anti-pd-1/pd-l1 checkpoint inhibitors, and their clinical trials are the focus of current research. CONCLUSION: The attention of researchers from different countries to EC immunotherapy, especially immunosuppressants, has brought a breakthrough in this field. A large number of clinical trials have evaluated the efficacy and safety of immune agents, and immune combination therapy (especially targeted therapy) shows positive therapeutic promise. Immunodrug sensitivity and adverse events remain urgent issues. The key to promoting the development of EC immunotherapy is to select the best patients according to the molecular classification and immunophenotype such as tumor mutation load, MMR status, pd-l1 expression, tumor infiltrating immune cells to truly achieve accurate and personalized treatment. More new and influential EC immunotherapies, such as adoptive cell immunotherapy, still need to be explored in future clinical practice.

Targeting oxidative phosphorylation as an approach for the treatment of ovarian cancer.

Ovarian cancer is an aggressive tumor that remains to be the most lethal gynecological malignancy in women. Metabolic adaptation is an emerging hallmark of tumors. It is important to exploit metabolic vulnerabilities of tumors as promising strategies to develop more effective anti-tumor regimens. Tumor cells reprogram the metabolic pathways to meet the bioenergetic, biosynthetic, and mitigate oxidative stress required for tumor cell proliferation and survival. Oxidative phosphorylation has been found to be altered in ovarian cancer, and oxidative phosphorylation is proposed as a therapeutic target for management of ovarian cancer. Herein, we initially introduced the overview of oxidative phosphorylation in cancer. Furthermore, we discussed the role of oxidative phosphorylation and chemotherapeutic resistance of ovarian cancer. The role of oxidative phosphorylation in other components of tumor microenvironment of ovarian cancer has also been discussed.

Development and identification of a new Vero cell-based live attenuated influenza B vaccine by a modified classical reassortment method.

BACKGROUND: It was to generate a new Vero and cold-adapted live attenuated influenza B vaccine with enough safety and immunogenicity. METHODS: According to modified classical reassortment method, the donor strain was B/Yunnan/2/2005Vca(B), and the parental virus strain was B/Brisbane/60/2008wt. After co-infection in Vero cells, the prepared antibody serum inhibited the donor strain growth, and screening conditions inhibited the parental virus growth, which induced the growth of the new reassortant virus B/Brisbane/60/2008Vca(B) grow. Through intraperitoneal injection (i.j.) and intranasal injection (n.j.) we evaluated the safety and immunogenicity of the vaccine. RESULTS: A high-yield of the reassortant virus was produced in Vero cells at 25°C, similar to the donor strains. After sequencing, it was found that B/Brisbane/60/2008Vca(B) Hemagglutinin (HA) and Neuraminidase (NA) gene fragments were from B/Brisbane/60/2008wt, while the other 6 gene fragments were from B/Yunnan/2/2005Vca(B). The n.j. immune pathway experiments showed no significant differences between the treatment and the PBS control group with respect to weight changes (P > 0.5). Furthermore, the new strain had a sufficient geometric mean titter (GMT) against B/Brisbane/60/2008wt. CONCLUSION: The new reassortant live attenuated influenza B vaccine was safe and having enough immune stimulating ability.

Do Biochemical Markers and Apa I Polymorphism in IGF-II Gene Play a Role in the Association of Birth Weight and Later BMI?

BACKGROUND: The aim of the study was to explore the mechanisms underlying the association of birth weight with later body mass index (BMI) from the biochemical markers related to metabolism and the Apa I polymorphism in IGF-II gene. METHODS: A total of 300 children were selected randomly from the Macrosomia Birth Cohort in Wuxi, China. The height and weight were measured and blood samples were collected. Plasma concentrations of 8 biochemical markers were detected. Apa I polymorphism was analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: Biochemical markers were detected for 296 subjects and 271 subjects were genotyped for the Apa I polymorphism. No association was found between birth weight and 8 biochemical markers. In boys, the BMIs of AA, AG and GG genotypes were 16.10 ± 2.24 kg/m(2), 17.40 ± 3.20 kg/m(2), 17.65 ± 2.66 kg/m(2). And there was statistical difference among the three genotypes. But in girls, there was no statistical difference. The birth weights of AA, AG and GG genotypes were 3751.13 ± 492.43 g, 3734.00 ± 456.88 g, 3782.00 ± 461.78 g. And there was no statistical difference among the three genotypes. CONCLUSION: Biochemical markers are not associated with birth weight. Apa I polymorphism may be related to childhood BMI, but it may be not associated with birth weight. Therefore, biochemical markers and Apa I polymorphism might not play a role in the association of birth weight and BMI.