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OBJECTIVE@#Xiaotan Sanjie recipe (XTSJ), a Chinese herbal compound medicine, exerts a significant inhibitory effect on gastric cancer (GC) metastasis. This work investigated the mechanism underlying the XTSJ-mediated inhibition of GC metastasis.@*METHODS@#The effect of XTSJ on GC metastasis and the associated mechanism were investigated in vitro, using GC cell lines, and in vivo, using a GC mouse model, by focusing on the expression of Glc-N-Ac-transferase V (GnT-V; encoded by MGAT5).@*RESULTS@#The migration and invasion ability of GC cells decreased significantly after XTSJ administration, which confirmed the efficacy of XTSJ in treating GC in vitro. XTSJ increased the accumulation of E-cadherin at junctions between GC cells, which was reversed by MGAT5 overexpression. XTSJ administration and MGAT5 knockdown alleviated the structural abnormality of the cell-cell junctions, while MGAT5 overexpression had the opposite effect. MGAT5 knockdown and XTSJ treatment also significantly increased the accumulation of proteins associated with the E-cadherin-mediated adherens junction complex. Furthermore, the expression of MGAT5 was significantly lower in the lungs of BGC-823-MGAT5 + XTSJ mice than in those of BGC-823-MGAT5 + solvent mice, indicating that the ability of gastric tumors to metastasize to the lung was decreased in vivo following XTSJ treatment.@*CONCLUSION@#XTSJ prevented GC metastasis by inhibiting the GnT-V-mediated E-cadherin glycosylation and promoting the E-cadherin accumulation at cell-cell junctions. Please cite this article as: Huang N, He HW, He YY, Gu W, Xu MJ, Liu L. Xiaotan Sanjie recipe, a compound Chinese herbal medicine, inhibits gastric cancer metastasis by regulating GnT-V-mediated E-cadherin glycosylation. J Integr Med. 2023; 21(6): 561-574.
Subject(s)
Male , Mice , Animals , Stomach Neoplasms/genetics , Drugs, Chinese Herbal/pharmacology , Glycosylation , Cell Line, Tumor , Cadherins/metabolismABSTRACT
BACKGROUND@#Core muscle functional strength training (CMFST) has been reported to reduce injuries to the lower extremity. However, no study has confirmed whether CMFST can reduce the risk of low back pain (LBP).@*OBJECTIVE@#This study identified the effects of CMFST on the incidence of LBP in military recruits.@*DESIGN, SETTING, PARTICIPANTS AND INTERVENTION@#We performed a prospective, open-label, randomized, controlled study in a population of young healthy male naval recruits from a Chinese basic combat training program. Participants were randomly assigned to either the core group or the control group. In additional to normal basic combat training, recruits in the core group underwent a CMFST program for 12 weeks, while recruits in the control group received no extra training.@*MAIN OUTCOME MEASURES@#At the beginning of the study and at the 12th week, the number of participants with LBP was counted, and lumbar muscle endurance was measured. In addition, when participants complained of LBP, they were assessed using the visual analog scale (VAS) and Roland Morris Disability Questionnaire (RMDQ).@*RESULTS@#A total of 588 participants were included in the final analysis (295 in the core group and 293 in the control group). The incidence of LBP in the control group was about twice that of the core group over the 12-week study (20.8% vs 10.8%, odds ratio: 2.161-2.159, P < 0.001). The core group had better lumbar muscle endurance at 12 weeks than the control group ([200.80 ± 92.98] s vs [147.00 ± 84.51] s, P < 0.01). There was no significant difference in VAS score between groups, but the core group had a significantly lower RMDQ score at week 12 than the control group (3.33 ± 0.58 vs 5.47 ± 4.41, P < 0.05).@*CONCLUSION@#This study demonstrated that the CMFST effectively reduced the incidence of LBP, improved lumbar muscle endurance, and relieved the dysfunction of LBP during basic military training.
Subject(s)
Humans , Male , Low Back Pain/prevention & control , Military Personnel , Muscles , Prospective Studies , Resistance Training , Treatment OutcomeABSTRACT
OBJECTIVE@#This test was designed to evaluate the effect of lower-limb dominance and non-dominance shuttle runs under load carriage during different exercise load at the same exercise intensity on the balance responses.@*METHODS@#Ten healthy young males were joined in this experiment, they were (20.80±2.04) years old and (173.99±2.87) cm tall. In a randomized cross-over design, they performed four times shuttle runs under unilateral load carriage:20 m×5 at dominant side, 20 m×5 at non-dominant side, 20 m×10 at dominant side, 20 m×10 at non-dominant side respectively. Balance abilities were evaluated immediately and 20 minute post-exercise respectively, and R-R interval was recorded.@*RESULTS@#The HR, EPOC and TRIMP for all exercise load were increased significantly after shuttle runs compared to rest (0.05), which showed symmetrical change. In addition, during 20 minute recovery, the balance ability for all exercise load was returned to the rest value (>0.05).@*CONCLUSIONS@#The shuttle runs could impair the trunk control ability immediately post-exercise, the magnitude of mediolateral movement was increased as the exercise load increased. The changes of balance responses were similar between the dominant and the non-dominant side, the dominant and the non-dominant side might show cross-effects.
Subject(s)
Adolescent , Humans , Male , Young Adult , Exercise , Exercise Test , Lower Extremity , Movement , RunningABSTRACT
BACKGROUND: Eccentric exercise displays many advantages over concentric and isometric contractions, and it has been applied in exercise training and rehabilitation. The existing researches focus on the underlying mechanisms at molecular and neural levels, and the specific adaptation after eccentric exercise may be related to the adaptive signaling pathway. OBJECTIVE: To review the unique physiological characteristics and mechanisms of eccentric exercise, thereby providing reference for in-depth understanding of eccentric exercise. METHODS: The relevant articles were searched in PubMed (1990-2017) and CNKI (2010-2017) with the keywords of "eccentric exercise, negative muscle work, eccentric exercise training, downhill run, concentric exercise, positive muscle work, concentric exercise training, and uphill running" in English and Chinese, respectively. Ultimately, the articles eligible for physiological characteristics, acute response and adaptive mechanism were enrolled. RESULTS AND CONCLUSION: Totally 98 articles were retrieved, and 54 pertinent papers were enrolled for analysis based on the inclusion and exclusion criteria. The mechanical, molecular and neural mechanisms of eccentric contractions differ from those of concentric and isometric contractions. Special metabolic and cardiorespiratory responses after eccentric exercise reflect the advantages in making programs of exercise training and rehabilitation. Particularly, compared with concentric exercise, fewer motor units are recruited during eccentric exercise and exert muscle a greater stimulation, which involves the process of exercise-induced muscle damage and the activation of satellite cells. The content of satellite cells after eccentric exercise is higher than that of concentric exercise, suggesting that satellite cells may play an important role in the muscle damage reconstruction caused by eccentric exercise. In conclusion, eccentric exercise is of great significance for exercise training and rehabilitation, while further study on the adaptive mechanism of eccentric exercise is necessary.
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<p><b>OBJECTIVE</b>To evaluate the relationship between peroxisome proliferator-activated receptor-γ2 (PPARγ2) Pro12Ala polymorphism and type 2 diabetes mellitus (T2DM) in Chinese Han population.</p><p><b>METHODS</b>PubMed, Chinese Biomedicine Database (CBM), China National Knowledge Infrastructure (CNKI) and Wanfang database were searched for all relevant articles investigating the association between PPARγ2 Pro12Ala polymorphism and T2DM that were available from January, 1990 to June, 2011. A total of 29 relevant articles were selected. A Meta-analysis was performed to estimate heterogeneity and the pooled odds ratio (OR) to evaluate the relationship between PPARγ2 Pro12Ala polymorphism and T2DM. The sensitivity analysis was also assessed.</p><p><b>RESULTS</b>A total of 21 qualified articles including 3870 patients with T2DM and 3333 healthy controls were analyzed in the study. The frequencies of the allele Ala12 in T2DM and control groups were 4.13% (320/7740) and 4.56% (304/6666), respectively. There were not heterogeneity (χ(2) = 25.96, P = 0.17) among the 21 qualified articles. The pooled OR (95%CI) value of the frequencies of the PPARγ2 genotype (PA + AA)/PP calculated by fixed effects model was 0.96 (0.81 - 1.14) (P = 0.64). There was not heterogeneity among the remaining articles after excluding the article with the largest weight and the article with larger frequencies of the allele Ala12 respectively (χ(2) values were 24.23, 16.87 respectively, both P values > 0.05). The pooled OR (95%CI) value of the frequencies of the PPARγ2 genotype (PA + AA)/PP of the remaining articles were 1.01 (0.84 - 1.21) and 1.07 (0.89 - 1.28) after excluding the article with the largest weight and the article with larger frequencies of the allele Ala12 (both P values > 0.05).</p><p><b>CONCLUSION</b>PPARγ2 Pro12Ala polymorphism was not associated with type 2 diabetes mellitus in Chinese Han population.</p>
Subject(s)
Humans , Alleles , Asian People , Genetics , China , Diabetes Mellitus, Type 2 , Genetics , Gene Frequency , Genotype , PPAR gamma , Genetics , Polymorphism, Single NucleotideABSTRACT
The IgG binding domain of Streptococcal Protein G which can selectively immobilizes the Fc regions of immunoglobulin G(IgG) is a kind of good material for oriented immobilization of antibodies in antibody microarrays.Here,genetically engineered three glutathione S-transferase(GST) fused proteins,bearing one,two and three B-Domains respectively(GST-GBx).The IgG-bindding ability of GST-GBx was investigated by ELISA.The data revealed that when the B-domain's quantity of GST-GBx is identical,the GST-GB3 is the most efficient protein among three GST-GBx protein both the capacity and sensibility of binding IgG.The GST-GB2 is the next one and GST-GB1 is the least one.Thus,the GST-GB3 has significantly predominance in comparison to GST-GB2 and GST-GB1.
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<p><b>OBJECTIVE</b>To investigate cell apoptosis induced by survivin ASODN and clarify the precise mechanism of anti-apoptotic action of survivin.</p><p><b>METHODS</b>Cells of lung cancer cell line NCI-H446 were treated with survivin ASODN at different concentrations. The changes of survivin mRNA and protein expression were assessed by RT-PCR and Western blot assay. The apoptosis index (AI) and proliferation index (PI) were determined by flow cytometry (FCM). After 500 mmol/L survivin ASODN treatment, cells were stained with Rh123 to detect changes of mitochondrial membrane potential (deltapsim) by FCM. The concentration of cytoplasmic cytochrome c (cyt-c) was continuously determined by ELISA. Relative activities of caspase-9 and caspase-3 were assessed by colorimetric assay. The expression of caspase-8 protein was measured by Western blot assay. The apoptotic rates of lung cancer cells induced by survivin ASODN with or without mitochondrial permeability transition pole (MPTP) inhibitor CsA treatment were assessed by FCM.</p><p><b>RESULTS</b>Down-regulated survivin mRNA was shown to be in dose-dependent and time-dependent manners. Its maximal effect was achieved at a concentration of 500 nmol/L for 72 h, at which mRNA was down-regulated by 62.7%, the expression of survivin protein in NCI-H446 cells was also obviously decreased. After treatment with survivin ASODN at concentration of 500 mmol/L for 72 h, AI was 48.35%, higher than that of control, lipofectin, NSODN, survivin ASODN 100 mmol/L and 300 mmol/L groups (3.75%, 3.41%, 4.69%, 19.85% and 34.39%, respectively). PI was 24.38%, lower than that of control, lipofectin, NSODN, survivin ASODN100 and 300 mmol/L groups (75.74%, 73.12%, 71.76%, 51.03% and 38.94%, respectively). Deltapsim was decreased in 9.54% of NCI-H446 cells treated with survivin ASODN for 3 h and 97.06% for 24 h. Following it, release of cyt-c from mitochondria to cytosol and activation of caspase-9 and caspase-3 increased significantly. The above mentioned indicators changed with a time-dependent and time diversity relationship. In the presence of CsA, the apoptotic rate of lung cancer cells induced by survivin ASODN was decreased significantly. No up-regrulation and activation in caspase-8 protein was observed.</p><p><b>CONCLUSION</b>Survivin inhibits apoptosis via regulation of mitochondrial-dependent pathway. survivin ASODN can not only induce apoptosis but also inhibit cell proliferation through blocking the expression of survivin mRNA and protein.</p>