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PURPOSE: This study aimed to analyze the interindividual differences of the maximal oxygen uptake (VÌO 2max ) response to 12 wk of high-intensity interval training (HIIT), and the genotype-phenotype models were constructed to predict the effect of HIIT on VÌO 2max . METHODS: A total of 228 physically inactive adults who completed a 12-wk HIIT were analyzed. A genome-wide association study (GWAS) was conducted to identify genetic variants associated with the VÌO 2max response. Nonresponders, responders, and the highest training responders were defined as the effect sizes (ES) <0.2, ≥0.2, and ≥0.8, respectively. We generated polygenic predictor score (PPS) using lead variants and constructed a predictive model for VÌO 2max response based on a linear stepwise regression analysis. RESULTS: The VÌO 2max increased significantly after HIIT (~14%, P < 0.001), but with interindividual differences (-7.8 to 17.9 mL·kg -1 ·min -1 ). In 27% of participants, the VÌO 2max showed no improvement. We identified one genetic locus near the γ-aminobutyric acid type A receptor subunit beta 3 gene ( GABRB3 , rs17116985) associated with VÌO 2max response at the genome-wide significance level ( P < 5 × 10 -8 ), and an additional nine single nucleotide polymorphisms (SNPs) at the suggestive significance level ( P < 1 × 10 -5 ). The SNPs rs474377, rs9365605, and rs17116985, respectively, explained 11%, 9%, and 6.2% of variance in VÌO 2max response. The 13 SNPs ( P < 1 × 10 -5 ) were found on chromosome 6 (position: 148209316-148223568). Individuals with a PPS greater than 1.757 had the highest response, and those with a PPS lower than -3.712 were nonresponders. The PPS, baseline VÌO 2max , sex, and body mass explained 56.4% of the variance in the VÌO 2max response; the major predictor was the PPS, which explained 39.4% of the variance. CONCLUSIONS: The PPS, baseline VÌO 2max , sex, and body mass could explain the variance in VÌO 2max response. Individuals who had a PPS greater than 1.757 had the highest training response after 12 wk of HIIT. Genetic variants in a region on chromosome 6, especially the sterile alpha motif domain containing 5 gene ( SAMD5 ), which had been explored influencing angiogenesis, might have a potential role in the VÌO 2max response.
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Treinamento Intervalado de Alta Intensidade , Adulto , Humanos , Estudo de Associação Genômica Ampla , População do Leste Asiático , Consumo de Oxigênio/fisiologia , Fenótipo , GenótipoRESUMO
The brain-gut-microbiota axis is a complex multi-organ bidirectional signaling system between the brain and microbiota that participates in the host immune system. The spleen, as the largest immune organ in the body, has a key role in the brain-gut-microbiota axis. Here, we investigated whether splenectomy could affect depression-like phenotypes and the composition of the gut microbiota in adult mice. In behavioral tests, splenectomy did not cause depression-like behaviors in mice. Conversely, splenectomy led to significant alterations in the diversity of gut microbes compared with the findings in control (no surgery) and sham-operated mice. In an unweighted UniFrac distance analysis, the boxplots representing the splenectomy group were distant from those representing the other two groups. We found differences in abundance for several bacteria in the splenectomy group at the taxonomic level compared with the other two groups. Finally, splenectomy induced significant changes in lactic acid and n-butyric acid levels compared with those in the other groups. Interestingly, there were significant correlations between the counts of certain bacteria and lactic acid (or n-butyric acid) levels in all groups. These data suggest that splenectomy leads to an abnormal composition of the gut microbiota. It is likely that the spleen-gut-microbiota axis plays a crucial role in the composition of the gut microbiota by regulating immune homeostasis.
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AIM: Although opioids have been used as treatment of neuropathic pain, opioids have abuse potential in humans. Since soluble epoxide hydrolase (sEH) in the metabolism of polyunsaturated fatty acids plays a key role in the pain, sEH inhibitors would be promising new therapeutic drugs for neuropathic pain. In this study, we examined the effect of the sEH inhibitor TPPU on rewarding effects in mice using the conditioned place preference (CPP) paradigm. METHODS: The rewarding effects of morphine (10 mg/kg) and TPPU (3, 10, or 30 mg/kg) in mice were examined using CPP paradigm. Furthermore, the effect of TPPU (30 mg/kg) on morphine-induced rewarding effects was examined. RESULTS: TPPU (3, 10, or 30 mg/kg) did not increase CPP scores in the mice whereas morphine significantly increased CPP scores in the mice. Furthermore, pretreatment with TPPU did not block the rewarding effects of morphine in the mice, suggesting that sEH does not play a role in the rewarding effect of morphine. CONCLUSION: This study suggests that TPPU did not have rewarding effects in rodents. This would make sEH inhibitors potential therapeutic drugs without abuse potential for neuropathic pain.
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Analgésicos Opioides/farmacologia , Inibidores Enzimáticos/farmacologia , Epóxido Hidrolases/antagonistas & inibidores , Morfina/farmacologia , Compostos de Fenilureia/farmacologia , Piperidinas/farmacologia , Recompensa , Animais , Condicionamento Clássico/efeitos dos fármacos , Condicionamento Clássico/fisiologia , Epóxido Hidrolases/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , SolubilidadeRESUMO
The DMT1 gene encodes divalent metal transporter 1, a membrane iron transport protein. Divalent metal transporter 1 influences cellular iron availability, which might further affect aerobic exercise capacity. Short tandem repeat (STR) polymorphisms have been used as genetic markers in the literature, yet the STR polymorphisms of the DMT1 gene have not been well studied. In this current study, we explored the polymorphisms of the DMT1 gene in a group of elite long-distance runners and controls, by using the PCR-RFLP (Restriction Fragment Length Polymorphism) and Gene scan technology. We found that the genotype frequency of the homozygous 258 bp STR polymorphism of the DMT1 gene (258 bp/258 bp) was significantly higher in the athlete group than in the controls (χ 2 = 14.01, p = 0.006) so does the allele frequency of the 258 bp STR polymorphism (χ 2 = 12.867, p = 0.008). These data suggested that the STR polymorphism of the DMT1 gene might be correlated with aerobic exercise capacity and the 258 bp homozygous (25 bp/258 bp) could be used as a molecular marker for the talent identification of elite long-distance runners.
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The inducible nitric oxide synthase/nitric oxide (iNOS/NO) signaling pathway and inflammatory cytokines play important roles in the pathogenesis of exercise-induced fatigue. Studies have found that Mongolian warm acupuncture (WA) could alleviate exercise-induced fatigue. However, the exact mechanisms underlying its effects remain unclear. In the present study, we investigated the effects of Mongolian WA on iNOS/NO signaling pathway and proinflammatory cytokines in a chronic exhaustive swimming-induced fatigue rat model. Animals were randomly divided into Control group, Ctrl + WA group, Model group, and Model + WA group. The body weight, exhaustive swimming time test, and Morris water maze test were performed before and after the chronic exhaustive swimming. The serum levels of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), and iNOS were detected by enzyme linked immunosorbent assay (ELISA). The mRNA expressions of IL-1ß, IL-6, TNF-α, IFN-γ, and iNOS in the hippocampus were measured by real-time polymerase chain reaction (RT-PCR). Moreover, the protein expression of iNOS in the hippocampus was measured by western blot, and the NO productions in the serum and hippocampus were detected by Griess reaction system. Chronic exhaustive exercise significantly reduced the body weight and exhaustive swimming time, and induced impairment in learning and memory, and which were reversed by WA treatment. Chronic exhaustive exercise also increased the expressions of iNOS and proinflammatory cytokines, while WA treatment significantly decreased the level of iNOS and proinflammatory cytokines. However, chronic exhaustive exercise did not affect the NO production. These findings demonstrated that WA could alleviate the chronic exhaustive swimming-induced fatigue and improve the learning and memory ability, and the actions might be related to the reduction of inflammatory response and iNOS expression.
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Incidence and progression of non-small-cell lung cancer (NSCLC) is a multi-factor, multi-step process. The present study investigated the association between the expression level of microRNA (miR)-4458 in NSCLC and paracarcinoma liver tissues and survival rates, and studied the biological functions of miR-4458 at the cellular and protein level. NSCLC and paracarcinoma tissues were sequenced using a miR expression chip. The association between miR-4458 expression and tumor-node-metastasis staging, total survival rate and relapse-free survival rate was analyzed. miR-4458 was subjected to target gene prediction. The target protein of cyclin D1 (CCND1) was verified with western blot analysis, immunohistochemistry and a luciferase reporter assay. The relative level of miR-4458 in paracarcinoma tissues of 9 NSCLC patients decreased from 2.38 to 0.65 (P<0.001). Total five-year survival rates of the high-expression miR-4458 group (29.21%) significantly exceeded that of the low-expression group (14.37%) (P=0.025). The viability of human lung carcinoma A549 and H460 cells transfected with miR-4458 decreased significantly compared with cells transfected with a normal control (blank control plasmid) within 72 h (P<0.001). The percentage of A549 and H460 cells transfected with a miR-4458 mimic at the cell cycle stage G0/G1 was 69.94±8.05 and 68.15±7.75%, respectively. The percentages increased significantly compared with the control group (46.06±6.93 for A549 cells; 45.22±7.24 for H640 cells; P<0.001). CCND1 mRNA was downregulated significantly in H460 cells 72 h subsequent to the addition of miR-4458 mimics (P<0.001). The activity of mutant-CCND1 altered slightly, while the fluorescence intensity of the wild-type-CCND1 group decreased significantly following the addition of miR-4458 mimics. In conclusion, miR-4458 was expressed at low levels in lung cancer tissues, and it arrested cells in vitro at stage G0/G1 and inhibited cell proliferation. Therefore, miR-4458 may participate in the onset of lung cancer as a suppressor gene by inhibiting CCND1.
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Rapid eye movement (REM) sleep is closely associated with nervous functions. The present study aimed to evaluate the effects of gabazine and tiagabine on the cognitive functions (CF) of REM sleep-deprived and sleep recovered rats. Rats were divided into REM sleep deprivation, blank control (CC) and environmental groups. The REM sleep deprivation group was further divided into non-operation (nonOP), sham-operated (Sham), gabazine (SR) and tiagabine groups. Each group was evaluated over five time points: Sleep deprived for 1 day (SD 1 day), SD 3 day, SD 5 day, sleep recovery 6 h (RS 6 h) and RS 12 h. A rat model of REM sleep deprivation was established by a modified multi-platform water method, with CF assessed by Morris water maze. Hypothalamic γ-aminobutyric acid (GABA) and glutamic acid contents were measured via high performance liquid chromatography. The number and morphology of hypocretin (Hcrt) neurons and Fos in the hypothalamus, and GABAARα1-induced integral optical density were detected by immunofluorescence. Compared to the CC group, the nonOP and Sham group rats CF were significantly diminished, Fos-positive and Fos-Hcrt double positive cells were significantly increased, and GABA content and GABAARα1 expression levels were significantly elevated (P<0.05). The tiagabine and CC groups exhibited similar results at three time points. The CF of rats in the SR group were diminished and the number of Fos-positive and Fos-Hcrt double positive cells were significantly increased (P<0.05) at RS 6 h and RS l2 h. GABA content and GABAARα1 expression levels were significantly increased in the SR group at all time points (P<0.05), whereas only GABAARα1 expression levels were significantly increased in the tiagabine group at SD 5 day (P<0.05). The results of the present study indicated that REM sleep deprivation diminished CF, increased the number of Hcrt neurons, GABA content and GABAARα1 expression. Furthermore, all alterations were positively correlated with deprivation time and corrected by sleep recovery, as demonstrated by single-factor multi-level variance analysis at the various time points in each group. Therefore, the Hcrt nervous system may be an eligible therapeutic target for the treatment of insomnia.
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Objective. Insomnia is one of the most common sleep disorders. Hypnotics have poor long-term efficacy. Mongolian medical warm acupuncture has significant efficacy in treating insomnia. The paper evaluates the role of Mongolian medical warm acupuncture in treating insomnia by investigating the Mongolian medicine syndromes and conditions, Pittsburgh sleep quality index, and polysomnography indexes. Method. The patients were diagnosed in accordance with International Classification of Sleep Disorders (ICSD-2). The insomnia patients were divided into the acupuncture group (40 cases) and the estazolam group (40 cases). The patients underwent intervention of Mongolian medical warm acupuncture and estazolam. The indicators of the Mongolian medicine syndromes and conditions, Pittsburgh sleep quality index (PSQI), and polysomnography indexes (PSG) have been detected. Result. Based on the comparison of the Mongolian medicine syndrome scores between the warm acupuncture group and the drug treatment group, the result indicated P < 0.01. The clinical efficacy result showed that the effective rate (85%) in the warm acupuncture group was higher than that (70%) in the drug group. The total scores of PSQI of both groups were approximated. The sleep quality indexes of both groups decreased significantly (P < 0.05). The sleep quality index in the Mongolian medical warm acupuncture group decreased significantly (P < 0.01) and was better than that in the estazolam group. The sleep efficiency and daytime functions of the patients in the Mongolian medical warm acupuncture group improved significantly (P < 0.01). The sleep time was significantly extended (P < 0.01) in the Mongolian medical warm acupuncture group following PSG intervention. The sleep time during NREM in the Mongolian warm acupuncture group increased significantly (P < 0.01). The sleep time exhibited a decreasing trend during REM and it decreased significantly in the Mongolian warm acupuncture group (P < 0.01). The percentage of sleep time in the total sleep time during NREM3+4 in the Mongolian medical warm acupuncture group increased significantly. Conclusion. Mongolian medical warm acupuncture is efficient and safe in treating insomnia. It is able to better improve the patients' sleep time and daytime functions. It is better than that in the estazolam group following drug withdrawal in terms of improving the sleep time. It is more effective in helping the insomnia patients than hypnotics.
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Hepatic resection had an impressive growth over time. It has been widely performed for the treatment of various liver diseases, such as malignant tumors, benign tumors, calculi in the intrahepatic ducts, hydatid disease, and abscesses. Management of hepatic resection is challenging. Despite technical advances and high experience of liver resection of specialized centers, it is still burdened by relatively high rates of postoperative morbidity and mortality. Especially, complex resections are being increasingly performed in high risk and older patient population. Operation on the liver is especially challenging because of its unique anatomic architecture and because of its vital functions. Common post-hepatectomy complications include venous catheter-related infection, pleural effusion, incisional infection, pulmonary atelectasis or infection, ascites, subphrenic infection, urinary tract infection, intraperitoneal hemorrhage, gastrointestinal tract bleeding, biliary tract hemorrhage, coagulation disorders, bile leakage, and liver failure. These problems are closely related to surgical manipulations, anesthesia, preoperative evaluation and preparation, and postoperative observation and management. The safety profile of hepatectomy probably can be improved if the surgeons and medical staff involved have comprehensive knowledge of the expected complications and expertise in their management. This review article focuses on the major postoperative issues after hepatic resection and presents the current management.