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The rapidly developing resistance of cancers to chemotherapy agents and the severe cytotoxicity of such agents to normal cells are major stumbling blocks in current cancer treatments. Most current chemotherapy agents have significant cytotoxicity, which leads to devastating adverse effects and results in a substandard quality of life, including increased daily morbidity and premature mortality. The death receptor of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can sidestep p53-dependent pathways to induce tumor cell apoptosis without damaging most normal cells. However, various cancer cells can develop resistance to TRAIL-induced apoptosis via different pathways. Therefore, it is critical to find an efficient TRAIL sensitizer to reverse the resistance of tumor cells to TRAIL, and to reinforce TRAIL's ability to induce tumor cell apoptosis. In recent years, traditional Chinese medicines and their active ingredients have shown great potential to trigger apoptotic cell death in TRAIL-resistant cancer cell lines. This review aims to collate information about Chinese medicines that can effectively reverse the resistance of tumor cells to TRAIL and enhance TRAIL's ability to induce apoptosis. We explore the therapeutic potential of TRAIL and provide new ideas for the development of TRAIL therapy and the generation of new anti-cancer drugs for human cancer treatment. This study involved an extensive review of studies obtained from literature searches of electronic databases such as Google Scholar and PubMed. "TRAIL sensitize" and "Chinese medicine" were the search keywords. We then isolated newly published studies on the mechanisms of TRAIL-induced apoptosis. The name of each plant was validated using certified databases such as The Plant List. This study indicates that TRAIL can be combined with different Chinese medicine components through intrinsic or extrinsic pathways to promote cancer cell apoptosis. It also demonstrates that the active ingredients of traditional Chinese medicines enhance the sensitivity of cancer cells to TRAIL-mediated apoptosis. This provides useful information regarding traditional Chinese medicine treatment, the development of TRAIL-based therapies, and the treatment of cancer.
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Objective To investigate the relationship of angiotensin converting enzyme (ACE I/D) gene I/D polymorphism with vitiligo.Methods PubMed,the Cochrane Library,China academic journal full-text database and VIP database and Wan fang database were searched according to the inclusion and exclusion criteria,and the quality of included studies was assessed.The data were quantitatively analyzed by Stata 12.0 software.Results Nine articles were included.Meta analysis results showed that the susceptibility of vitiligo difference was statistically significant in the total population of ACE I/D genotype (DD + II)vs.DI (OR=0.759,95％ CI:0.643 ～0.896,P=0.001),the (DD+DI) vs.II (OR=1.523,95％ CI:1.153 ～2.011,P =0.003).The genotype subgroup analysis showed the D vs.I (OR =1.381,95％ CI:1.054 ～1.810,P=0.019),DDvs.II (OR=1.830,95％ CI:1.110～3.017,P=0.018),(DD+ II) vs.DI (OR=0.814,95％ CI:0.667 ～0.994,P=0.043),and the (DD+ID) vs.II (OR=1.690,95％ CI:1.147 ～2.489,P =0.008) in Asian.The difference was statistically significantly related to vitiligo.Arab genotype (DD + II) vs.DI (OR =0.545,95％ CI:0.354 ～ 0.840,P =0.006) was associated with vitiligo occurrence.Begg's inspection publication bias analysis showed all genetic types did not exist any publication bias.Conclusions The ACE gene I/D polymorphism may be associated with vitiligo susceptibility.
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Objective To study the regulatory effect of ethanol extract of glossy privet fruit and its monomer tyrosol on the adhesion and migration of human epidermal melanocytes.Methods Epidermal melanocytes were isolated from human foreskin,and subjected to a primary culture.Mter 3-5 passages,the melanocytes were treated with various concentrations of ethanol extract of glossy privet fruit (0.0375-0.6 mg/ml)and tyrosol (0.125-2 mmol/L) for 24-72 hours.The XTT colorimetric assay was carried out to evaluate the proliferation of melanocytes,fibronectin (FN)-coated culture plates were used to evaluate the adhesion activity of melanocytes,and Transwell assay was conducted to assess the migration activity of melanocytes.Confocal laser microscopy was utilized to observe the structure and distribution of actin cytoskeleton in melanocytes,and cellular fluorescence intensity was determined by a semi-quantitative analysis.Statistical analysis was carried out by using unpaired t test.Results The adhesion activity of melanocytes to FN was significantly enhanced by the ethanol extract of 0.0375-0.6 mg/ml from glossy privet fruit (P ＜ 0.05 or 0.01),and by tyrosol of 0.5-2 mmol/L (P ＜ 0.05 or 0.01).As XTT assay showed,neither the ethanol extract of 0.15 mg/ml nor tyrosol of 2 mmol/L had cytotoxicity or promotive effect on cell proliferation.Hence,0.15 mg/ml and 2 mmol/L were determined as the working concentrations of ethanol extract and tyrosol respectively.The number of cells migrating through micropore membranes per high-power field (× 200) was 43.7 and 51.0 in melanocytes treated with the ethanol extract of 0.15 mg/ml and tyrosol of 2 mmol/L,respectively,significantly higher than that in untreated melanocytes (20.3,both P ＜ 0.01).Compared with untreated melanocytes,those treated with the ethanol extract of 0.15 mg/ml and those with tyrosol of 2 mmol/L showed higher intracellular fluorescence intensity (P ＜ 0.01) and more stress fiber bundles which congregated inside the cell membrane and around the nuclei.Conclusions The ethanol extract of glossy privet fruit and its monomer tyrosol can promote the adhesion and migration of human melanocytes in vitro,likely by promoting the congregation of actin cytoskeleton in melanocytes.
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Objective To evaluate the effect of tacalcitol on the proliferation,adhesion,migration and c-kit mRNA expression of cultured human epidermal melanocytes.Methods Cultured epidermal melanocytes from the prepuce of adolescent males were treated with various concentrations of tacalcitol.Then,cell proliferation was evaluated by tetrazolium salt (XTT) assay after 24,48 and 72 hours of treatment,adhesive activity by using fibronectin-coated culture plates after 72 hours,migratory activity by Transwell assay using a microporous membrane after 24 hours,and the c-kit mRNA expression was semiquantitatively analyzed by reverse transcription PCR after 72 hours of treatment.Statistical analysis was done by repeated-measure analysis of variance and completely random design analysis of variance.Results As repeated-measure analysis of variance showed,tacalcitol of 10-10,10-9,10-8,10-7 and 10-6 mol/L significantly promoted the proliferation of melanocytes (F =9.47,P ＜ 0.01),with significant differences in the promoting effect among various durations of treatment with different concentrations of tacalcitol (F =14.44,P ＜ 0.01),and with significant interaction effect between drug concentration and treatment duration (F =2.47,P ＜ 0.01).The highest proliferation level was observed in melanocytes treated with tacalcitol of 10-s mol/Lfor 72 hours.There was a significant increase in the adhesion rate of human epidermal melanocytes to fibronectin after treatment with tacalcitol of 10-8-10-7 mol/L for 72 hours (both P ＜ 0.01),number of melanocytes migrating through micropore membranes per high-power field (× 200) after treatment with tacalcitol of 10-9-10-8 mol/L for 24 hours (both P ＜ 0.01),and in the c-kit mRNA expression in melanocytes treated with tacalcitol of 10-9-10-7mol/L for 72 hours (all P ＜ 0.01).Conclusion Tacalcitol can promote melanocytes to proliferate,migrate,express c-kit mRNA,and adhere to fibronectin.
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Objective To investigate the relationship between the single nucleotide polymorphisms (SNPs) of TLR9 gene and the occurrence of condyloma acuminatum (CA). Methods Peripheral venous blood was obtained from 63 patients with CA and 23 normal human controls with informed consent. DNA was extracted from the blood samples and subjected to the amplification of TLR9 gene by PCR followed by sequence analysis. Results There were 4 SNPs, i.e., SNP1, SNP2, SNP3 and SNP4 at positions 1174, 1635, 1269 and 1724 of the TLR9 gene, respectively. Of these SNPs, SNP1 was located in intron 1, SNP2, SNP3 and SNP4 in exon 2. The registration number is rs352139 for SNP1, rs352140 for SNP2 in NCBI database. SNP3 and SNP4 were newly discovered positions. The frequency at SNP1 position was 0.690 and 0.609 for allele A in the patients and controls, respectively, 0.309 and 0.391 for allele G, respectively (both P > 0.05). No significant difference was observed between the patients and controls in the frequency of allele A or allele G at position SNP2 (0.302 vs. 0.698, 0.369 vs. 0.630, both P > 0.05). There were 4 haplotypes at the SNP1 and SNP2 positions, including AA, AG, GA and GG, with no significant difference in the frequency between the patients and controls (all P> 0.05). Conclusions There are 4 SNPs including SNP1, SNP2, SNP3 and SNP4 in the TLR9 gene in Guangdong Han population. SNP1 and SNP2 appear unrelated to the liability to CA.