Elliottpoole9175

Our study suggests that living in adverse neighborhood environments can speed up epigenetic aging, while positive neighborhood attributes may buffer effects.Metabolome profiles are largely unknown for pancreatic head cancers, in which the predominant anatomical feature is the exosure of bile, pancreatic juice, and duodenal juice. In this research, 30 head and 30 body/tail cytological samples acquired by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) of pancreatic adenocarcinoma were delivered for liquid chromatography coupled with mass spectrometry (LC-MS). Transcriptome analysis was performed using the sequencing data from The Cancer Genome Atlas (TCGA) cohort. LC-MS obtained 4,857 features in EUS-FNA cytological samples, and 586 metabolites were certified. Among them, 30 differential metabolites were identified. In the TCGA cohort, 247 differential metabolism genes were selected from 1,583 differential genes. The integrated analysis identified the top three enriched metabolic pathways as follows branched chain amino acid (BCAA) biosynthesis; glycerophospholipid metabolism; and phenylalanine metabolism. In cell line, BCAA promoted pancreatic cancer proliferation and inhibited Oxaliplatin-induced apoptosis. In conclusion, metabolomic analysis with the EUS-FNA sample is feasible for pancreatic cancer. The integrated analysis can identify key metabolites and enzyme-coded genes between pancreatic head and body/tail adenocarcinoma. Anti-BCAA metabolism therapy may exert promising effect, especially for the body/tail cancer.Postoperative gastrointestinal function influences postoperative recovery and length of hospital stay for patients undergoing colorectal surgery. https://www.selleckchem.com/products/z-yvad-fmk.html Goal-directed fluid therapy (GDFT) restricts fluid administration to an amount required to prevent dehydration. Although the fluid management of GDFT could decrease the incidence of postoperative complications in patients who undergo high-risk surgery, certain patients may not respond to GDFT. Thus, to achieve optimal treatment, identification of patients suitable for GDFT is necessary. Metabolomic profiling of 48 patients undergoing surgery for colorectal cancer was performed. Patients were divided into delayed- and enhanced-recovered groups based on gastrointestinal function within 72 hours, and the results of omics analysis showed differential serum metabolites between the two groups of patients in the post anesthesia care unit 24 hours after surgery. A support vector machine model was applied to evaluate the curative effects of GDFT in different patients. Four metabolites, oleamide, ubiquinone-1, acetylcholine, and oleic acid, were found to be highly associated with postoperative gastrointestinal function and could be used as potential biomarkers. Moreover, four pathways were found to be highly related to postoperative gastrointestinal recovery. Among them, the vitamin B6 metabolism pathway may be a common pathway for improving postoperative recovery in various diseases. Our findings proposed a novel method to predict postoperative recovery of gastrointestinal function based on metabolomic profiling and suggested the potential mechanisms contributing to gastrointestinal function after surgical resection of colorectal cancer under the fluid management of GDFT.If age boundaries are arbitrarily or roughly defined, age-related analyses can result in questionable findings. Here, we aimed to delineate the uniquely age-dependent immune features of coronavirus disease 2019 (COVID-19) in a retrospective study of 447 patients, stratified according to age distributions of COVID-19 morbidity statistics into well-defined age-cohorts (2-25y, 26-38y, 39-57y, 58-68y, and 69-79y). Age-dependent susceptibilities and severities of the disease were observed in COVID-19 patients. A comparison of the lymphocyte counts among the five age-groups indicated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection led to age-dependent lymphopenia. Among the lymphocyte subsets, the CD8+ T cell count alone was significantly and age-dependently decreased (520, 385, 320, 172, and 139 n/μl in the five age-groups, respectively). In contrast, the CD4+ T cell, B cell, and natural killer cell counts did not differ among age-cohorts. Age and CD8+ T cell counts (r=‒0.435, p less then 0.0001) were negatively correlated in COVID-19 patients. Moreover, SARS-CoV-2 infection age-dependently increased the plasma C-reactive protein concentrations (2.0, 5.0, 9.0, 11.6, and 36.1 mg/L in the five age-groups, respectively). These findings can be used to elucidate the role of CD8+ T cells in age-related pathogenesis and to help develop therapeutic strategies for COVID-19.Caloric restriction has been shown to robustly ameliorate age-related diseases and to prolong lifespan in several model organisms, and these beneficial effects are dependent on the stimulation of autophagy. Autophagy dysfunction contributes to the accumulation of altered macromolecules, and is a key mechanism of promoting aging and age-related disorders, as neurodegenerative ones. We have previously shown that caloric restriction (CR), and CR mimetics Neuropeptide Y (NPY) and ghrelin, stimulate autophagy in rat cortical neurons, however by unknown molecular mechanisms. Overall, we show that CR, NPY, and ghrelin stimulate autophagy through PI3K/AKT/MTOR inhibition and ERK1/2-MAPK activation. The knowledge of these kinases in autophagy regulation and the contribution to the understanding of molecular mechanism facilitates the discovery of more targeted therapeutic strategies to stimulate autophagy, which is relevant in the context of age-related disorders.Licochalcone A (LA), a flavonoid found in licorice, has anticancer, antioxidant, anti-inflammatory, and neuroprotective properties. Here, we explored the effect of injecting LA into the tail vein of middle-aged C57BL/6 mice on their cognitive ability as measured by the Morris water maze (MWM) test and cerebral blood flow (CBF). The related mechanisms were assessed via RNA-seq, and T (CD3e+) and B (CD45R/B220+) cells in the spleen and whole blood were quantified via flow cytometry. LA improved the cognitive ability, according to the MWM test results, and upregulated the CBF level of treated mice. The RNA-seq results indicate that LA affected the interleukin (IL)-17 signaling pathway, which is related to T- and B-cell proliferation, and the flow cytometry data suggest that LA promoted T- and B-cell proliferation in the spleen and whole blood. We also performed immune reconstruction via a tail vein injection of lymphocytes into B-NDG (NOD-PrkdcscidIl2rgtm1/Bcge) mice before treating them with LA. We tested cognitive ability by subjecting these animals to new object recognition tests and quantified the splenic and whole blood T and B cells. Cognitive ability improved after immune reconstruction and LA treatment, and LA promoted T- and B-cell proliferation in the spleen and whole blood. This study demonstrates that LA, by activating the IL-17 signaling pathway, promotes T- and B-cell proliferation in the spleen and whole blood of mice and improves cognitive ability. Thus, LA may have immune-modulating therapeutic potential for improving cognition.Panax ginseng is a perennial plant in the Araliaceae family. In this study, we investigated the protective effects of ginseng stem-leaf saponins (GSLS) isolated from P. ginseng against D-galactose-induced reproductive function decline, oxidative stress, and inflammatory response. Reproductive injuries were induced in mice via the subcutaneous injection of D-galactose (300 mg/kg) for six weeks. The mice were then treated with GSLS by intragastric administration. GSLS inhibited markers of oxidative stress and inflammatory cytokines induced by D-galactose in serum, liver and kidney, whereas GSLS increased the activities of antioxidant enzymes. Compared to the mice treated only with D-galactose, GSLS treatment significantly increased the average path velocity, straight line velocity, curvilinear velocity, and amplitude of the lateral head displacement of mouse sperm. Meanwhile, GSLS significantly increased the testosterone level and reduced the cortisol, FSH, and LH levels. Histopathological examination revealed alterations in the number and the arrangement of spermatogenic cells in the seminiferous tubules of the mice in the GSLS group. GSLS treatment suppressed MAPKs pathway activation in testes. These results suggest that GSLS can attenuate D-galactose-induced oxidative stress and inflammatory response in serum, liver and kidney, and ameliorate reproductive damage by inhibiting MAPKs signaling pathway.At present, immunotherapy is widely used for different mismatch repair (dMMR) or highly microsatellite instability (MSI-H) colorectal cancer patients, and tumor mutation burden (TMB) is a valuable independent predictor of response to immunotherapy. However, specific gene mutations and their relationship with TMB and tumor-infiltrating immune cells in colon cancer remains unclear. In the present study, we analyzed somatic mutation data of colon cancer from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) datasets, and found that 17 frequently mutated genes were occurred in both cohorts, including APC, TP53, TNN, KRAS, MUC16, MUC4 (mucin 4), SYNE1, FLG, FAT4, OBSCN, FAT3, RYR2, PIK3CA, FBXW7, DNAH11, MUC5B and ZFHX4. Interestingly, only MUC4 mutation was associated with higher TMB and patient clinical prognosis among the 17 mutated genes. Moreover, according to gene set enrichment analysis (GSEA) and the CIBERSORT algorithm, we revealed that MUC4 mutation activated signaling pathways involved in the immune system and enhanced the antitumor immune response. In conclusion, MUC4 may have important clinical implications for immune therapy of colon cancer.Összefoglaló. A Cronkhite-Canada-szindróma egy extrém ritka, nem öröklődő, gyomor-bél rendszeri polyposissal, fehérjevesztő enteropathiával és ectodermalis elváltozásokkal járó megbetegedés. A világon eddig összesen körülbelül 500 esetet jegyeztek fel. Az etiológia pontosan nem tisztázott, hátterében elsősorban autoimmun folyamatot feltételeznek. A diagnózis a páciens kórtörténetén, a fizikális vizsgálaton, az endoszkópos képen és a szövettani leleten alapul. A jelen közleményben egy 71 éves férfi beteg esetét mutatjuk be. A klinikai kép és az elvégzett vizsgálatok alapján a tünetek hátterében Cronkhite-Canada-szindrómát igazoltunk, majd a szakirodalomban leggyakrabban alkalmazott kombinált protonpumpagátló, kortikoszteroid és meszalazin adását vezettük be, illetve táplálásterápiát alkalmaztunk. Tudomásunk szerint Cronkhite-Canada-szindrómás beteg esete Magyarországon elsőként kerül ismertetésre. Orv Hetil. 2021; 162(11) 432-438. Summary. Cronkhite-Canada syndrome is an extremely rare, noninherited disease, characterized by gastrointestinal polyposis, protein-losing enteropathy and ectodermal abnormalities. Approximately 500 cases have been reported worldwide. The aetiology is unknown, most probably autoimmune mechanisms may be involved. The diagnosis is based on patient history, physical examination, endoscopic findings and histology. Here we report the case of a 71-year-old male, diagnosed with Cronkhite-Canada syndrome. The treatment consisted of proton-pump inhibitor, corticosteroids, mesalazin and nutritional therapy. To the best of our knowledge, this is the first report of Cronkhite-Canada syndrome in Hungary. Orv Hetil. 2021; 162(11) 432-438.