ABSTRACT
With the gradual aggravation of aging in China， the prevalence of osteoporosis is increasing year by year. Osteoporosis has become a major public health problem threatening the health of middle-aged and elderly people， especially middle-aged and elderly women. There are many predisposing factors and complex pathogenesis of osteoporosis. The interpretation of osteoporosis has been the focus of clinical research in recent years. How to prevent and treat osteoporosis more effectively has also become a major problem faced by researchers. In recent years， the balance and homeostasis of calcium and phosphorus regulated by intestinal absorption， renal excretion and bone have become one of the hot topics， and the balance and homeostasis of calcium and phosphorus in vivo are the key to normal bone homeostasis. At the same time， as a complex microbial community living in the gastrointestinal tract， intestinal flora can produce a variety of regulators affecting metabolism. It has been widely confirmed that it acts on the body indirectly or directly， in multiple ways and targets to prevent and treat osteoporosis. Therefore， further exploring the role and mechanism of intestine kidney bone axis in osteoporosis plays a far-reaching significance for the prevention and treatment of osteoporosis. In recent years， scholars have made a lot of exploration on the prevention and treatment of osteoporosis with traditional Chinese medicine （TCM）， and found that TCM can intervene the expression of intestinal flora and play the effect of prevention and treatment of osteoporosis. Based on the "intestine kidney bone axis"， this paper briefly discusses the integrated traditional Chinese and western medicine of kidney and osteoporosis， intestine and osteoporosis， intestine kidney axis， the treatment of kidney from intestine， intestine and osteoporosis， and the application of TCM in regulating intestinal flora in osteoporosis， in order to provide new ideas for the prevention and treatment of osteoporosis.
ABSTRACT
With the gradual aggravation of aging in China， the prevalence of osteoporosis is increasing year by year. Osteoporosis has become a major public health problem threatening the health of middle-aged and elderly people， especially middle-aged and elderly women. There are many predisposing factors and complex pathogenesis of osteoporosis. The interpretation of osteoporosis has been the focus of clinical research in recent years. How to prevent and treat osteoporosis more effectively has also become a major problem faced by researchers. In recent years， the balance and homeostasis of calcium and phosphorus regulated by intestinal absorption， renal excretion and bone have become one of the hot topics， and the balance and homeostasis of calcium and phosphorus in vivo are the key to normal bone homeostasis. At the same time， as a complex microbial community living in the gastrointestinal tract， intestinal flora can produce a variety of regulators affecting metabolism. It has been widely confirmed that it acts on the body indirectly or directly， in multiple ways and targets to prevent and treat osteoporosis. Therefore， further exploring the role and mechanism of intestine kidney bone axis in osteoporosis plays a far-reaching significance for the prevention and treatment of osteoporosis. In recent years， scholars have made a lot of exploration on the prevention and treatment of osteoporosis with traditional Chinese medicine （TCM）， and found that TCM can intervene the expression of intestinal flora and play the effect of prevention and treatment of osteoporosis. Based on the "intestine kidney bone axis"， this paper briefly discusses the integrated traditional Chinese and western medicine of kidney and osteoporosis， intestine and osteoporosis， intestine kidney axis， the treatment of kidney from intestine， intestine and osteoporosis， and the application of TCM in regulating intestinal flora in osteoporosis， in order to provide new ideas for the prevention and treatment of osteoporosis.
ABSTRACT
Objective To investigate the regulatory effects of miR-145 on the proliferation,cell cycle and apoptosis of a human keratinocyte cell line HaCaT.Methods miR-145 mimics and negative control (NC) mimics were chemically synthesized and then transiently transfected into HaCaT cells respectively.After additional culture for different durations,real-time PCR was performed to determine the expression level of miR-145,MTS assay to estimate cell proliferation,and flow cytometry to detect cell apoptosis and cycle.Luciferase assay,real-time PCR and Western blot were conducted to determine whether NRAS was the target gene of miR-145.Results The miR-145 expression level in miR-145 mimic-transfected cells increased by 85.00 ± 1.21 folds compared with NC mimic-transfected cells (t =115.90,P ＜ 0.0001).The transfection with miR-145 mimics significantly inhibited the proliferation of HaCaT cells (F =8.76,P =0.008),and the inhibitory effect significantly varied with the duration (24-96 hours) of culture after transfection,with no interaction effect between the transfection with miR-145 mimics and culture duation (F =1.21,P =0.18).Compared with NC mimic-transfected cells,those transfected with miR-145 mimics showed a significant increase in the proportion of early apoptotic cells (18.9％ ± 4.1％ vs.4.3％ ± 1.2％,t =7.126,P ＜ 0.01),late apoptotic cells (9.3％ ± 2.3％ vs.3.6％ ± 1.6％,t =12.38,P ＜ 0.01),G1-phase cells (85.83％ ± 5.2％ vs.62.08％ ± 6.23％,t =11.78,P =0.007),but a significant decrease in the percentage of G2-phase cells (6.26％ ± 1.2％ vs.19.36％ ± 3.45％,t =7.610,P =0.017) and S-phase cells (7.91％ ± 1.3％ vs.18.56％ ± 5.23％,t =7.230,P=0.019).As luciferase assay showed,luciferase activity was significantly lower in HaCaT cells cotransfected with miR-145 mimics and a recombinant luciferase reporter vector psi-CHECK2-NRAS-wild carrying the wild-type 3'UTR of NRAS than in those cotransfected with NC mimics and the vector psi-CHECK2-NRAS-wild (t =11.09,P =0.008),but similar between cells cotransfected with miR-145 mimics and a recombinant luciferase reporter vector psi-CHECK2-NRAS-mut carrying the mutant-type 3'UTR of NRAS and those cotransfected with NC mimics and the vector psi-CHECK2-NRAS-mut (P ＞ 0.05).Real-time PCR and Western blot revealed that the overexpression of miR-145 mimics had no significant effect on NRAS mRNA expression (P ＞ 0.05),but significantly inhibited NRAS protein expression (1.52 ± 0.07 vs.0.20 ± 0.02,t =28.43,P＜ 0.01).Conclusion miR-145 might inhibit proliferation and promote apoptosis of HaCaT cells by influencing cell cycle via NRAS.
ABSTRACT
A considerable amount of evidence established that gap junctional intercellular communication (GJIC) suppresses tumor development by halting the stage of tumor promotion.Consistently,GJIC is downregulated in tumors.The downregulation of GJIC is caused by not only the reduced expression level of connexin proteins but also their aberrant cytoplasmic localization.Although it has been thought long that cytoplasmic localization of conncxin proteins is merely one of the mechanisms of the downregu]ation of GJIC,careful studies with human tumor samples indicated that the expression level of intracytoplasmic connexin proteins had different biological functions.