Proteomics: applications in basic and applied biology.

Clinical researchers, practicing physicians, patients, and the general public now live in a world in which the 2.9 billion nucleotide codes of the human genome are available as a resource for scientific discovery. Some of the findings from the sequencing of the human genome were expected, confirming knowledge presaged by many decades of research in both human and comparative genetics. Other findings are unexpected in their scientific and philosophical implications. In either case, the availability of the human genome is likely to have significant implications, first for clinical research and then for the practice of medicine. This article provides our reflections on what the new genomic knowledge might mean for the future of medicine and how the new knowledge relates to what we knew in the era before the availability of the genome sequence. In addition, practicing physicians in many communities are traditionally also ambassadors of science, called on to translate arcane data or the complex ramifications of biology into a language understood by the public at large. This article also may be useful for physicians who serve in this capacity in their communities. We address the following issues: the number of protein-coding genes in the human genome and certain classes of noncoding repeat elements in the genome; features of genome evolution, including large-scale duplications; an overview of the predicted protein set to highlight prominent differences between the human genome and other sequenced eukaryotic genomes; and DNA variation in the human genome. In addition, we show how this information lays the foundations for ongoing and future endeavors that will revolutionize biomedical research and our understanding of human health.

Implications of the human genome for understanding human biology and medicine.

Proteomics – post-genomic cartography to understand gene function

Toxicoproteomics -- a new preclinical tool.

Genomics and proteomics: The new millennium of drug discovery and development

It was recently reported that low blood lead levels impaired kidney function in men To develop a set of molecular markers of renal lead exposure and effect, we investigated changes in renal protein expression while approximating occupational lead exposure at subchronic, low blood levels Lead was administered to male Dutch Belted rabbits as a lead acetate solution adjusted weekly to achieve and maintain the target blood lead levels of 0, 20, 40, and 80 microg/dL for 15 weeks Lead exposure did not affect kidney or body weights The effect of increasing blood lead on protein expression was evaluated in rabbit kidney by large-scale two-dimensional electrophoresis (2-DE) Significant quantitative changes (p < 005) occurred in a dose-related manner in 12 proteins at 20 microg/dL exposure, 25 at 40 microg/dL, and 102 at 80 microg/dL At a higher level of significance (p < 0001), 40 microg/dL blood lead resulted in one protein alteration and 80 microg/dL affected 14 proteins A set of quantitatively altered charge variants was tentatively identified as glutathione-S-transferase (GST), based on similar observations in rodents subjected to short-term, very high lead exposure The significance of the protein alterations observed as markers of toxicity awaits their conclusive identification Investigation of the kidney 2-DE profile in lead-exposed rabbit may be useful in understanding the mechanism of lead nephrotoxicity in humans

Alterations in rabbit kidney protein expression following lead exposure as analyzed by two-dimensional gel electrophoresis.

A novel rat model of sarcopenic obesity based on aging and high-fat diet consumption

Background Few studies have focused on the incidence and correlation of social frailty (SF) with adverse health events in Southwest China. This study aims to explore the predictive value of SF for adverse health events. Methods A 6-year prospective cohort study was employed, a total of 460 community-dwelling older adults aged 65 years and above were analyzed to provide a baseline in 2014. Participants completed two longitudinal follow-ups at 3 (2017, 426 participants involved) and 6 (2020, 359 participants involved) years later. A modified social frailty screening index was used in this study, and adverse health events such as physical frailty (PF) deterioration, disability, hospitalization, falls, and mortality were evaluated. Results Among these participants in 2014, the median age was 71 years, 41.1% were male, and 71.1% were married or cohabiting, up to 112 (24.3%) of them were classified as SF. It was observed that aging (OR = 1.04, 95% CI = 1.00–1.07, P = 0.047) and having family members die in the past year (OR = 2.60, 95% CI = 0.93–7.25, P = 0.068) were risk factors of SF, whereas having a mate (OR = 0.40, 95% CI = 0.25–0.66, P = 0.000) and having family members to help with care (OR = 0.53, 95% CI = 0.26–1.11, P = 0.092) were protective factors of SF. The cross-sectional study demonstrated that SF was only significantly associated with disability (OR = 12.89, 95% CI = 2.67–62.13, P = 0.001) at wave 1. Baseline SF significantly explained the incidence of mortality at the 3-year (medium-term, OR = 4.89, 95% CI = 2.23–10.71, P = 0.000) and 6-year follow-ups (long-term, OR = 2.22, 95% CI = 1.15–4.28, P = 0.017). Conclusion SF prevalence was higher in the Chinese older population. Older adults with SF had a significantly increased incidence of mortality at the longitudinal follow-up. Consecutive comprehensive health management of SF (e.g., avoiding living alone and increasing social engagement) is urgently needed for the purposes of early prevention and multidimensional intervention in adverse health events, including disability and mortality.

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Incidence and predictive value of social frailty among community-dwelling older adults in Southwest China: A prospective cohort study

Obesity has been suggested as a risk factor for sarcopenia. Sarcopenic obesity (SO), as a new category of obesity, is a high-risk geriatric syndrome in elderly individuals. However, knowledge about the molecular pathomechanisms of SO is still sparse. In the present study, starting at 13 months, male Sprague-Dawley (SD) rats were fed a high-fat diet (HFD) and normal diet (ND) for 28 weeks to establish a rodent animal model of SO with an identical protocol, which was further assessed and verified as a successful SO model. Through RNA-seq analysis of gastrocnemius muscle in SO rats, we found that differentially expressed genes (DEGs) and alternative splicing events (ASEs) focused mainly on inflammatory, immune-response, skeletal muscle cell differentiation, fat cell differentiation and antigen processing and presentation. Furthermore, as the core regulation factor of skeletal muscle, the mef2c (myocyte enhancer Factor 2C) gene also has a significant alternative 3' splice site (A3SS) and down-regulated expression in HFD-induced SO. The alternative genes targeted by mef2c identified by GO analysis were enriched in transcript regulation of RNA polymerase II promoter. In conclusion, these explorative findings in aging high-fat-fed rats might serve as a firm starting point for understanding the pathway and mechanism of sarcopenic obesity.

Huan Zhu

Papers

Alterations in rabbit kidney protein expression following lead exposure as analyzed by two-dimensional gel electrophoresis.

A novel rat model of sarcopenic obesity based on aging and high-fat diet consumption

Incidence and predictive value of social frailty among community-dwelling older adults in Southwest China: A prospective cohort study

RNA analysis of diet-induced sarcopenic obesity in rats.