Associations of physical activity intensity, frequency, duration, and volume with the incidence of sarcopenia in middle-aged and older adults: a 4-year longitudinal study in China.

BACKGROUND: Physical activity (PA) plays an important role in the process of several chronic diseases. It may be also associated with the incidence of sarcopenia. This study aimed to determine the association of PA from different components including frequency, duration, intensity, and volume with the incidence of sarcopenia in middle-aged and older adults. METHODS: This study used data from the China Health and Retirement Longitudinal Study in 2011 and 2015. A total of 3,760 individuals aged ≥ 40 years were involved in this study. Sarcopenia was diagnosed using muscle mass, strength and physical performance according to the Asian Working Group for Sarcopenia. PA information including frequency, duration, intensity, and volume was obtained by a self-reported questionnaire. Logistic regression analysis was employed to examine the association between PA and the incidence of sarcopenia at 4-year follow-up. RESULTS: The incidence of sarcopenia was 5.9% during the 4-year follow-up. Compared to sedentary individuals, those taking 1-2 days or more per week, or a minimum of 10 min each time on vigorous-intensity PA (VPA) had a lower incidence of sarcopenia. Adults spending 3 days or more each week, a minimum of 30 min each time, or 150 min or more per week on moderate-intensity PA (MPA) had a lower presence of sarcopenia than sedentary adults. Adults taking 3 days or more per week, at least 30 min each time, or 150 min or more each week on light-intensity PA (LPA) tended to have a lower incidence of sarcopenia than sedentary individuals. Sensitivity analyses confirmed the robustness of the findings after removing persons with hypertension, dyslipidemia, or diabetes. CONCLUSIONS: These findings suggest that the frequency, duration, and volume of VPA or MPA are negatively associated with the presence of sarcopenia. Participation in LPA tends to have a lower incidence of sarcopenia in middle-aged and older adults.

Connecting the mechanisms of tumor sex differences with cancer therapy.

Sex differences in cancer incidence and survival are constant and pronounced globally, across all races and all age groups of cancer types. In 2016, after the National Institutes of Health proposed a policy of utilizing sex as a biological variable, researchers started paying more attention to the molecular mechanisms behind gender variations in cancer. Historically, most previous studies investigating sex differences have been centered on gonadal sex hormones. Nevertheless, sex differences also involve genetic and molecular pathways that run throughout the entire process of cancer cell proliferation, metastasis, and treatment response, in addition to sex hormones. In particular, there is significant gender dimorphism in the efficacy and toxicity of oncology treatments, including conventional radiotherapy and chemotherapy, as well as the emerging targeted therapies and immunotherapy. To be clear, not all mechanisms will exhibit gender bias, and not all gender bias will affect cancer risk. Our goal in this review is to discuss some of the significant sex-related changes in fundamental cancer pathways. To this purpose, we summarize the differential impact of gender on cancer development in three dimensions: sex hormones, genetics, and epigenetics, and focus on current hot subjects including tumor suppressor function, immunology, stem cell renewal, and non-coding RNAs. Clarifying the essential mechanisms of gender differences will help guide the clinical treatment of both sexes in tumor radiation and chemotherapy, medication therapy with various targets, immunotherapy, and even drug development. We anticipate that sex-differentiated research will help advance sex-based cancer personalized medicine models and encourage future basic scientific and clinical research to take sex into account.

Current trends of clinical trials involving CRISPR/Cas systems.

The CRISPR/Cas9 system is a powerful genome editing tool that has made enormous impacts on next-generation molecular diagnostics and therapeutics, especially for genetic disorders that traditional therapies cannot cure. Currently, CRISPR-based gene editing is widely applied in basic, preclinical, and clinical studies. In this review, we attempt to identify trends in clinical studies involving CRISPR techniques to gain insights into the improvement and contribution of CRISPR/Cas technologies compared to traditional modified modalities. The review of clinical trials is focused on the applications of the CRISPR/Cas systems in the treatment of cancer, hematological, endocrine, and immune system diseases, as well as in diagnostics. The scientific basis underlined is analyzed. In addition, the challenges of CRISPR application in disease therapies and recent advances that expand and improve CRISPR applications in precision medicine are discussed.

Single-cell analysis technologies for cancer research: from tumor-specific single cell discovery to cancer therapy.

Single-cell sequencing (SCS) technology is changing our understanding of cellular components, functions, and interactions across organisms, because of its inherent advantage of avoiding noise resulting from genotypic and phenotypic heterogeneity across numerous samples. By directly and individually measuring multiple molecular characteristics of thousands to millions of single cells, SCS technology can characterize multiple cell types and uncover the mechanisms of gene regulatory networks, the dynamics of transcription, and the functional state of proteomic profiling. In this context, we conducted systematic research on SCS techniques, including the fundamental concepts, procedural steps, and applications of scDNA, scRNA, scATAC, scCITE, and scSNARE methods, focusing on the unique clinical advantages of SCS, particularly in cancer therapy. We have explored challenging but critical areas such as circulating tumor cells (CTCs), lineage tracing, tumor heterogeneity, drug resistance, and tumor immunotherapy. Despite challenges in managing and analyzing the large amounts of data that result from SCS, this technique is expected to reveal new horizons in cancer research. This review aims to emphasize the key role of SCS in cancer research and promote the application of single-cell technologies to cancer therapy.

B7H6 Serves as a Negative Prognostic Marker and an Immune Modulator in Human Pancreatic Cancer.

Pancreatic cancer (PC), the third leading cause of cancer-related death in the U.S., is frequently found too late to be cured by traditional chemotherapy. Expression of B7 homolog 6 (B7H6), a member of the B7 family of immunoreceptors, has been found in PC and several other cancers. B7H6 is a ligand for cytotoxicity triggering receptor 3 (NKp30), which is expressed on NK cells. Here, we demonstrate that B7H6 can be detected in PC tissues but not normal organs. Its expression in patients associated significantly with tumor differentiation grade and lymphatic metastasis. The soluble form of B7H6 was detected in the PC patients' sera, and its concentration associated with tumor differentiation grade and tumor, node, metastasis (TNM) stages. Also, higher levels of B7H6 in PC patients' malignant tissues or serum correlated with shorter overall survival. In vitro, downregulation of B7H6 by CRISPR/Cas9 or siRNA technology had no significant impact on the viability or mobility of PC cells. Instead, knocking out B7H6 sensitized PC cells to NK-mediated cytotoxicity and cytokine production. These results indicate that B7H6 not only serves as a negative prognostic marker but also acts as an immune modulator in PC.