ABSTRACT
Glucosyltransferases (Gtfs) play critical roles in the etiology and pathogenesis of Streptococcus mutans (S. mutans)- mediated dental caries including early childhood caries. Gtfs enhance the biofilm formation and promotes colonization of cariogenic bacteria by generating biofilm extracellular polysaccharides (EPSs), the key virulence property in the cariogenic process. Therefore, Gtfs have become an appealing target for effective therapeutic interventions that inhibit cariogenic biofilms. Importantly, targeting Gtfs selectively impairs the S. mutans virulence without affecting S. mutans existence or the existence of other species in the oral cavity. Over the past decade, numerous Gtfs inhibitory molecules have been identified, mainly including natural and synthetic compounds and their derivatives, antibodies, and metal ions. These therapeutic agents exert their inhibitory role in inhibiting the expression gtf genes and the activities and secretion of Gtfs enzymes with a wide range of sensitivity and effectiveness. Understanding molecular mechanisms of inhibiting Gtfs will contribute to instructing drug combination strategies, which is more effective for inhibiting Gtfs than one drug or class of drugs. This review highlights our current understanding of Gtfs activities and their potential utility, and discusses challenges and opportunities for future exploration of Gtfs as a therapeutic target.
Subject(s)
Humans , Biofilms , Dental Caries/prevention & control , Glucosyltransferases/antagonists & inhibitors , Streptococcus mutans/enzymologyABSTRACT
<p><b>OBJECTIVE</b>To assess the association of programmed cell death 1 (PDCD1) gene polymorphisms with the susceptibility and/or progression of colorectal cancer.</p><p><b>METHODS</b>A hospital-based case-control study was carried out, which recruited 426 colorectal cancer patients and 500 healthy individuals. Five single nucleotide polymorphisms, namely rs36084323, rs11568821, rs2227981, rs2227982 and rs10204525, were selected for the study and genotyped with a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay.</p><p><b>RESULTS</b>The G allele of rs36084323 under a dominant model was associated with increased risk of advanced TNM staging of colorectal cancer progression (OR=1.59, 95%CI=1.02-2.48). Haplotypes G-G-C-T-A and A-G-C-C-G of the rs36084323, rs11568821, rs2227981, rs2227982, and rs10204525 were negatively associated with the occurrence of colorectal cancer.</p><p><b>CONCLUSION</b>The G allele of rs36084323 is associated with increased risk of advanced TNM staging of colorectal cancer. Conversely, the incidence of colorectal cancer is negatively associated with the haplotypes G-G-C-T-A and A-G-C-C-G of rs36084323, rs11568821, rs2227981, rs2227982, and rs10204525.</p>
Subject(s)
Humans , Asian People , Genetics , Case-Control Studies , China , Ethnology , Colorectal Neoplasms , Genetics , Pathology , Genetic Predisposition to Disease , Haplotypes , Neoplasm Staging , Polymorphism, Single Nucleotide , Programmed Cell Death 1 Receptor , GeneticsABSTRACT
Objective To explore the effect of Ginkgo biloba extract (EGb761) on apoptosis of K-ras mutational human colon cancer cells DLD1(DLD1/G13D)and its mechanism. Methods Human colon cancer cell lines DLD1/G13D and DLD1 with K-ras wild type(DLD1/WT)were cultured in vitro,the cell proliferation and apoptosis after 24 h of EGb761 were measured. Proteins involved in related signal pathway were detected by Western blot or ELISA. Results EGb761 reduced cell proliferation and induced cell apoptosis in a concentration-dependent manner in DLD1/WT and DLD1/G13D cells. EGb761 downregulated the expression of RIP1, impaired the phosphorylation of IκB and decreased the level of NF-κB in DLD1/WT and DLD1/G13D cells[DLD1/G13D: (24±4)%, DLD1/WT: (29±9)%(P<0.05). Conclusion EGb761 restrains the proliferation and induces the apoptosis of DLD1/WT and DLD1/G13D cells. The mechanism may be related to the degradation of RIP-1 and inhibition of activation of NF-κB signaling pathway.
ABSTRACT
Objective To explore the effect of Ginkgo biloba extract (EGb761) on apoptosis of K-ras mutational human colon cancer cells DLD1(DLD1/G13D)and its mechanism. Methods Human colon cancer cell lines DLD1/G13D and DLD1 with K-ras wild type(DLD1/WT)were cultured in vitro,the cell proliferation and apoptosis after 24 h of EGb761 were measured. Proteins involved in related signal pathway were detected by Western blot or ELISA. Results EGb761 reduced cell proliferation and induced cell apoptosis in a concentration-dependent manner in DLD1/WT and DLD1/G13D cells. EGb761 downregulated the expression of RIP1, impaired the phosphorylation of IκB and decreased the level of NF-κB in DLD1/WT and DLD1/G13D cells[DLD1/G13D: (24±4)%, DLD1/WT: (29±9)%(P<0.05). Conclusion EGb761 restrains the proliferation and induces the apoptosis of DLD1/WT and DLD1/G13D cells. The mechanism may be related to the degradation of RIP-1 and inhibition of activation of NF-κB signaling pathway.