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OBJECTIVE@#To determine the effects of Chinese medicine (CM) involving triple rehabilitation therapy on the progression of knee osteoarthritis (KOA).@*METHODS@#A total of 722 patients recruited from 38 community health service centers located in China from March 2013 to March 2017 were randomly divided into treatment and control groups equally, using a cluster randomization design. Health education combined with CM involving triple rehabilitation therapy for KOA (electro-acupuncture, Chinese medicinal herb fumigating-washing, and traditional exercises) was administered in the treatment group while conventional rehabilitation therapy (physical factor therapy, joint movement training, and muscle strength training) was administered in the control group. Patients with a visual analog scale (VAS) scores ≽4 were treated with dispersible meloxicam tablets (7.5 mg, once daily). The Lequesne index scores, VAS scores, range of motion (ROM), lower limb muscle strength, knee joint circumference, quantitative scores of KOA symptoms, and the short-form 36 item health survey questionnaire (SF-36) scores were measured for each patient at 5 checkpoints (before treatment, at the 2nd week and the 4th week during the 4-week treatment period, at 1 month and 3 months after end of treatment), and adverse reactions were observed also.@*RESULTS@#A total of 696 patients completed the entire process, with 351 in the treatment group and 345 in the control group. At all treatment checkpoints, the treatment group demonstrated better outcomes than the control group with regard to the total Lequesne index scores, effective rate and improvement rate of the total Lequesne index scores, VAS scores, lower limb muscle strength, knee circumference, quantitative scores of KOA symptoms, and SF-36 scores as well (P<0.05 or P<0.01). No adverse reactions were encountered in this study.@*CONCLUSIONS@#CM involving triple rehabilitation therapy can alleviate KOA-related pain and swelling, improve lower limb muscle strength, promote flexion and activity of the knee and improve the quality of life in patients undergoing KOA. It is suitable for patients with early or mid-stage KOA. (Registration No. ChiCTR-TRC-12002538).
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Humans , Medicine, Chinese Traditional , Osteoarthritis, Knee/therapy , Outpatients , Quality of Life , Treatment OutcomeABSTRACT
Objective To analyze the advantages, disadvantages, opportunities and challenges for schistosomiasis elimination in Laos, so as to propose the corresponding healthy policies and suggestions. Methods A SWOT analysis was performed to analyze the strength, weakness, opportunity and threat for the schistosomiasis elimination program in Laos, and the corresponding policy suggestions were proposed. Results The national schistosomiasis elimination program of Laos receives governmental emphases and great supports. A strategy based on mass drug administration was proposed and a sentinel site-bases surveillance system has been built for schistosomiasis elimination in Laos; however, there are several challenges for the national schistosomiasis elimination program in Laos, including insufficient financial supports, inadequate professional capability, weak schistosomiasis control awareness in community populations and difficulty in vector control. Conclusions Persistent governmental leadership, increasing financial supports, strengthening professional team building and improving schistosomiasis control awareness in community populations are required to facilitate the progress towards schistosomiasis elimination in Laos.
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This study aimed to explore the anti-tumor activity and mechanisms of action of isorhamnetin, a compound isolated from Astragalus membranaceus, in combination with sorafenib for treatment of renal cell carcinoma (RCC). The anti-tumor activity of isorhamnetin in combination with sorafenib was detected by MTT assay with cells in culture or Renca xenograft model in mice. Western blot was used to study the mechanisms of isorhamnetin in combination with sorafenib. Lymphocyte proliferation assay was also used to investigate the effects of the two drugs in combination. The results indicated that isorhamnetin inhibited the proliferation of RCC cells, with IC50 for A498, 786-O and Renca cell lines with being 31.7, 28.8 and 106.0 μmol·L-1, respectively. Isorhamnetin in combination with sorafenib improved the anti-lymphocyte proliferation activity of sorafenib with the IC50 down to 12.0 μmol·L-1. Isorhamnetin inhibited the growth of RCC in mice slightly with the inhibition efficiency at 26.9%. With 50.0 mg·kg-1 isorhamnetin in combination with 20.0 mg·kg-1 sorafenib, the anti-tumor activity of sorafenib was enhanced, with inhibition of growth rate increased to 60.7%. Meanwhile, isorhamnetin in combination with sorafenib could promote the lymphocytes proliferation in Renca xenograft model. Western blot results showed that combination of isorhamnetin and sorafenib could inhibit c-Raf/MEK/ERK and AKT/mTOR signaling pathways. In conclusion, the combination of isorhamnetin with sorafenib could increase the anti-tumor activity of sorafenib in RCC in vitro and in vivo. The mechanisms may be related to the inhibition of c-Raf/MEK/ERK and AKT/mTOR signaling pathways. Procedures for animal study were performed with approval of the Animal Care and Use Committee of the Chinese Academy of Medical Sciences and Peking Union Medical College.
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OBJECTIVE The aim of the present study was to investigate the anti-tumor effect and mechanism of a novel compound, C3C12PPD, a bioactive unnatural ginsenoside by metabolically engi-neered yeasts based on a new UDP-glycosyl- transferase from Bacillus subtilis. METHODS MTT assay was used to analyze the anti-proliferation activity of C3C12PPD in vitro. The effect of anti-tumor activity was observed by mouse Lewis xenograft model in vivo.The effects of C3C12PPD on suppressing the angio-genesis and invasion of A549 cells were investigated in vitro using Transwell and tube formation assays. RNAseq was used to find tagets of C3C12PPD. Western blotting was performed to investigate the expres-sion level of proteins in tumor tissues treated with C3C12PPD. RESULTS C3C12PPD could inhibit the growth of lung cancer in vitro and in viv o. At the dosage of 10.0 mg·kg-1, C3C12PPD inhibited tumor growth by 40.0% (P<0.05) in tumor weight in mouse Lewis xenograft. The inhibition of tube formation was 77.5%(P<0.01)and 80.3%(P<0.01)following treatment with 1×10-4and 2×10-4mol·L-1C3C12PPD for 5 h, whereas the proliferation of EA.hy926 cells was not influenced under the above concentrations. Under the concentrations of 1×10-4mol·L-1,C3C12PPD inhibited invasive ability of A549 cells(P<0.05).The results of RNAseq susgested that antitumor activity of C3C12PPD were associated with epithelial-mesenchymal transition (EMT) and angiogenesis. Moreover, the proteins related to EMT, Raf/MEK/ERK and AKT/mTOR signal pathways were effected by C3C12PPD analysed by western blotting. CONCLUSION These data suggested that C3C12PPD was able to supress lung cancer through inhibit EMT, invision and angiogenesis.
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OBJECTIVE Evidience appears that parthenolide (PN) induces anti-tumor effects by NF-κB signal pathway. MCL3 the derivative of PN,is sesquiterpene lactone synthesized by the group of Professor Pan Xiandao.The study was to explore the anti-tumor activity and mechanism of MCL3 in glioma. METHODS The effect of MCL3 on the proliferation of glioma cell lines was examined by MTT assay. Apoptotic activity was investigated by flow cytometry. The Transwell cell invasion assay was used to determine the effect of MCL3 on the G422 cell invasive ability.The effect of MCL3 on the angio-genesis was analyzed by a capillary-like tube formation assay. The subcutaneously transplanted and orthotopic G422 cell xenograft models were used to detect the effect of MCL3 on tumor growth in vivo. The pathological changes were analyzed by H&E staining. Protein level related to the NF-κB signal pathway was dertimined by Western blotting. The effect of MCL3 on the NF-κB transcriptional activity was examined by a dual-luciferase reporter assay.RESULTS The anti-proliferative activity was observed following treatment with MCL3 for 96 h in G422, U-87 MG, U251 and Hs683 cell lines, and the IC50 was 8.94 μmol·L-1,6.44 μmol·L-1,14.8 μmol·L-1,18.9 μmol·L-1,respectively.The percentage of apop-totic cells increased in MCL3-treated G422 cells,and the apoptosis rate was 26.4%(the apoptosis rate was 5.68% in control group).MCL3 could inhibit the invasion in G422 cells,and the invasive inhibition rate was 43.63%(P<0.01)at 10.0 μmol·L-1.MCL3 inhibited tube formation of EA.hy926 cells,and the inhibitory rate was 81.67%(P<0.01)at 10.0 μmol·kg-1.At 40.00 mg·kg-1,MCL3 supressed tumor growth by 79.03% (P<0.01) in tumor weight in subcutaneously transplanted G422 xenograft models, and by 69.97% (P<0.01) in volume in orthopotic G422 xenograft models. H&E staining demonstrated that MCL3 could decrease tumor angiogenesis and invasion, increased necrosis of tumor cells. The dual-luciferase reporter assay showed that MCL3 inhibited NF-κB transcriptional actvity, and the inhibition rate was 50.07%(P<0.05)at 10.0 μmol·L-1compared with control.Moreover,MCL3 inhibited the phos-phorylation of NF-κB in nuclear mediated by supression of phosphorylated IKKα/β and IκB,and decreased the expression of IL-6 regulated by NF-κB.Eventually,the phosphorylation of State3 decreased following the administration of MCL3, resulting in the downregulation of State3 taget genes, including HIF, VEGF,FAK,MMP-2,MMP-9,Bcl-2 and Bcl-xL.CONCLUSION The anti-tumor effect of MCL3 was partly due to the inhibition of NF-κB/IL-6/State3 pathway in glioma.
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Objective To investigate the effect of short-term global health training on tropical diseases in China,so as to provide the reference in professional trainings.Methods The study took the short-term global health training project on tropical diseases in China as an example.The structured questionnaires were distributed to each trainee pre-and post-training course. Results A total of 89 trainees were included in the survey,and 68.5%(61 cases)of the trainees were older than 35 years and 85.4%(76 cases)of the trainees came from provincial institutes.The passing rate for the test of global health knowledge was sig-nificantly improved from the pre-training test(18.0%,16/89)to the post one(68.2%,58/85)(χ2=44.930,P<0.05).The knowledge of global health was closely related to the professionals'capacity,i.e.,the education level,age,professional title, and experience of international cooperation,but was not statistically related to their genders. Conclusion This kind of short-term trainings not only greatly improves the professionals'knowledge of tropical diseases control,but also is expected to play a leading role in the international cooperation of global health and tropical diseases control in the future.
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The abnormal activation of hedgehog (HH) signaling pathway plays an important role in the development and progression of glioblastoma (GBM). As a transcription factor at the end of the HH pathway, the final effector of glioma-associated oncogene homoglog-1 (GLI1) is an important target in the treatment of GBM. The study was designed to evaluate the anti-tumor activities and mechanisms of a novel GLI1 inhibitor FL18 in GBM. MTT and colony formation assay were performed to determine anti-proliferation activity of FL18 in vitro. The effect of FL18 on cell apoptosis was measured by flow cytometry (FCM) analysis. Transwell experiment was used to explore the inhibitory activity of FL18 in cell invasion. In vivo experiments, the subcutaneously transplanted and orthotopic U-87 MG GBM xenograft model were used to study the activity of FL18 on tumor growth. The optimized dual report gene screening model was used to detect the effect of FL18 on the transcriptional activity of GLI1. Western blot assay was used to study the mechanisms of action of FL18. The results showed that the IC50 of FL18 in glioblastoma was in the nanomole level in vitro. It was observed that 22.5 and 45 mg·kg-1 FL18 reduced the tumor volume with the rate of 55.4% and 89.8% in xenograft model in mice in situ. The IC50 of FL18 on the inhibition of GLI1 transcriptional activity was 3.32×10-11 mol·L-1 analyzed by the optimized dual report gene screening model. By the Western blot experiments, it was proved that FL18 inhibited expression of GLI1 without influencing the upstream canonical HH/SMO signaling and cross-talk oncogenic pathway, such as ERK and AKT signaling. The results also demonstrated that FL18 significantly downregulated GLI1 target genes such as Bcl-2, MMP2 and MMP9 and increased the expression of c-caspase3, c-PARP and Bax. These data suggest that FL18 may generate the anti-glioma activity by inhibition of GLI1.