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ObjectiveTo explore the mechanism and pathway of Gandou Fumu decoction （GDFMD） in the development of liver fibrosis in Wilson's disease （WD）. MethodFirst， 30 TX-j mice were randomly divided into the model group， high-dose， medium-dose， and low-dose GDFMD groups， and penicillamine group， with six mice in each group， and another six wild-type mice were used as the normal group. The high-dose， medium-dose， and low-dose GDFMD groups were intragastrically administered drugs of 13.92， 6.96， 3.48 g·kg-1. In the penicillamine group， 0.1 g·kg-1 of penicillamine was given by intragastric administration. The model group and the normal group were given equal volume of normal saline， once a day， for four consecutive weeks. Samples were collected four weeks after gavage， and enzyme-linked immunosorbent assay （ELISA） was used to detect type Ⅲ procollagen peptide （PCⅢ）， collagen type Ⅳ （Col Ⅳ）， hyaluronic acid （HA）， and laminin （LN）. Hematoxylin-eosin （HE）， Masson， and picric acid-Sirus red collagen （Sirus Red） staining were used to observe the histopathological changes of liver fibrosis. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， immunohistochemistry， and Western blot were used to observe the expressions of α-smooth muscle actin （α-SMA） and collagen type Ⅰ （Col Ⅰ）， which were related to the activation of hepatic stellate cells （HSCs）. The expression of miR-29b-3p was observed by Real-time PCR. The expression of Unc-51-like kinase 1 （ULK1） and its downstream-related factors were observed by Western blot. The downstream genes of miR-29b-3p were verified by the dual luciferase reporter gene detection method. ResultCompared with the normal group， the four items of liver fibrosis （PCⅢ， Col Ⅳ， HA， and LN） in the model group were significantly abnormal （P<0.01）， and the pathology was significantly abnormal. The expression of HSC activation-related indicators including α-SMA and Col Ⅰ， as well as α-SMA mRNA and Col Ⅰ mRNA was up-regulated （P<0.05， P<0.01）， and miR-29b-3p expression was down-regulated （P<0.01）. ULK1， p-ULK1， autophagy-related gene 13 （Atg13）， p-Atg13， Beclin-1， FAK family kinase-interacting protein of 200 kDa （FIP200）， activating molecule in BECN1-regulated autophagy protein 1 （AMBKA1）， and microtubule-associated protein 1 light chain 3Ⅱ/Ⅰ（LC3Ⅱ/Ⅰ） were up-regulated （P<0.05， P<0.01）. p62 protein expression was down-regulated （P<0.01）. Compared with the model group， the four items of liver fibrosis in the high-dose， medium-dose， and low-dose GDFMD groups and the penicillamine group were significantly improve （P<0.01）， and the pathological conditions were improved. The expression of HSC activation-related indicators including α-SMA and Col Ⅰ， as well as α-SMA mRNA and Col Ⅰ mRNA was down-regulated （P<0.05， P<0.01）， and the expression of miR-29b-3p was up-regulated （P<0.01）. ULK1， p-ULK1， Atg13， p-Atg13， Beclin-1， FIP200， AMBKA1， and LC3Ⅱ/Ⅰ were down-regulated （P<0.05， P<0.01）， and p62 protein expression was up-regulated （P<0.01）. The prediction software predicted that there was a binding site between miR-29b-3p and ULK1. The dual-luciferase reporter gene detection method indicated that the luciferase activity of the ULK1-WT plasmid-transfected cell group was reduced when miR-29b-3p mimics were co-cultured （P<0.01）. ConclusionGDFMD can regulate ULK1-mediated autophagy by up-regulating miR-29b-3p and further exert its anti-hepatic fibrosis effect in Wilson's disease.
ABSTRACT
Liver fibrosis is the initial stage of the development of various chronic liver diseases into liver cirrhosis and is a reversible process. As a subset of extracellular vesicles that can carry active substances such as proteins, lipids, and RNA, exosomes are involved in intercellular signal communication and have attracted more and more attention in recent years. Studies have shown that non-coding RNAs in exosomes play an important role in the development and progression of liver fibrosis. This article discusses the mechanism of action of exosome long non- coding RNAs (including MALAT1, H19, GAS5, MEG3, PVT1, and P21), exosome short non-coding RNAs (including micro-RNA, small nucleolus RNA, PIWI-interacting RNA, and small interference RNA), and exosome circular RNA in the development and progression of liver fibrosis, and it is concluded that exosomes from different sources (such as hepatocytes and cholangiocytes) carrying non-coding RNAs mainly affect the activation, proliferation, migration, and transformation of hepatic stellate cells. In-depth studies of exosome non-coding RNAs in the future are expected to find potential new targets for the treatment of liver fibrosis.
ABSTRACT
Liver fibrosis is the initial stage of the development of various chronic liver diseases into liver cirrhosis and is a reversible process. As a subset of extracellular vesicles that can carry active substances such as proteins, lipids, and RNA, exosomes are involved in intercellular signal communication and have attracted more and more attention in recent years. Studies have shown that non-coding RNAs in exosomes play an important role in the development and progression of liver fibrosis. This article discusses the mechanism of action of exosome long non- coding RNAs (including MALAT1, H19, GAS5, MEG3, PVT1, and P21), exosome short non-coding RNAs (including micro-RNA, small nucleolus RNA, PIWI-interacting RNA, and small interference RNA), and exosome circular RNA in the development and progression of liver fibrosis, and it is concluded that exosomes from different sources (such as hepatocytes and cholangiocytes) carrying non-coding RNAs mainly affect the activation, proliferation, migration, and transformation of hepatic stellate cells. In-depth studies of exosome non-coding RNAs in the future are expected to find potential new targets for the treatment of liver fibrosis.
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Objective@#To explore the curative effect and safety of botulintum toxin A (BTX-A) on depressive disorder in patients with Parkinson′s disease (PD).@*Methods@#Forty-two cases of PD with depression prospectively recruited in the Second Hospital Affiliated to Soochow University from August 2016 to November 2018 were divided into two groups: 28 patients in BTX-A group (administered with 100 U BTX-A injection on patients′ eyebrow, forehead, bilateral lateral canthus and temporal region at 20 loci), 14 patients in sertraline (control) group (administered with 50-100 (55.36±14.47) mg/d sertraline). The scores of Hamilton Depression Rating Scale (HAMD), Self-rating Depression Scale (SDS), Hamilton Rating Scale for Anxiety (HAMA), Self-rating Anxiety Scale (SAS) after treatment for 2 weeks, 4 weeks, 8 weeks and 12 weeks were compared with the scores of each emotional rating scale for baseline respectively. Meanwhile, the differences in the scores of each emotional scale between the two treatment groups were compared. In addition, the remission rates of depression and anxiety (defined as HAMD, HAMA scores<7) at each follow-up time point between the two groups were compared to evaluate the efficacy and safety of BTX-A in the treatment of PD patients with depression.@*Results@#The scores of HAMD, HAMA, SDS, SAS in the BTX-A group and the sertraline group reduced compared to baseline after treatment (at the 2nd, 4th, 8th, 12th weeks). The scores of HAMD and SDS in the BTX-A group (HAMD scores: F=12.930, P<0.01; SDS scores: F=5.022, P=0.001) and those in the sertraline group (HAMD scores: F=2.883, P=0.030; SDS scores: F=3.427, P=0.013) were significantly lower compared to baseline, but there was no statistically significant difference in the scores of HAMD and SDS between the two groups (P>0.05). HAMD score showed that the remission rate of depression in the BTX-A group (17.9% (5/28), 35.7% (10/28)) was higher than that of the sertraline group (2/14, 4/14) at the 2nd and 4th weeks. At the 8th and 12th weeks, the remission rate of depression in the sertraline group (7/14, 9/14) was higher than that of the BTX-A group (46.4% (13/28), 53.6% (15/28)). There was no statistically significant difference in remission rate of depression between the two groups at each follow-up time point (P>0.05). There was no statistically significant difference in HAMD scores between males and females in the BTX-A group (P>0.05). Two of the 28 patients in the BTX-A group had frown muscle stiffness, which lasted for two weeks and improved in one month. Two patients in the sertraline group had headache and dizziness, and two patients had dry mouth and nausea, which improved after two weeks. There was no statistically significant difference in the incidence of adverse reactions between the two groups (P=0.197).@*Conclusion@#BTX-A intraocular facial muscle injection can significantly improve the depressive symptoms of PD patients, and the effect lasts for a long time, with low incidence of side effects and high safety, which can be considered as a safe and effective new method for PD patients with depressive symptoms.
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Objective To explore the curative effect and safety of botulintum toxin A (BTX?A) on depressive disorder in patients with Parkinson′s disease (PD). Methods Forty?two cases of PD with depression prospectively recruited in the Second Hospital Affiliated to Soochow University from August 2016 to November 2018 were divided into two groups: 28 patients in BTX?A group (administered with 100 U BTX?A injection on patients′eyebrow, forehead, bilateral lateral canthus and temporal region at 20 loci), 14 patients in sertraline (control) group (administered with 50-100 (55.36±14.47) mg/d sertraline). The scores of Hamilton Depression Rating Scale (HAMD), Self?rating Depression Scale (SDS), Hamilton Rating Scale for Anxiety (HAMA), Self?rating Anxiety Scale (SAS) after treatment for 2 weeks, 4 weeks, 8 weeks and 12 weeks were compared with the scores of each emotional rating scale for baseline respectively. Meanwhile, the differences in the scores of each emotional scale between the two treatment groups were compared. In addition, the remission rates of depression and anxiety (defined as HAMD, HAMA scores<7) at each follow?up time point between the two groups were compared to evaluate the efficacy and safety of BTX?A in the treatment of PD patients with depression. Results The scores of HAMD, HAMA, SDS, SAS in the BTX?A group and the sertraline group reduced compared to baseline after treatment (at the 2nd, 4th, 8th, 12th weeks). The scores of HAMD and SDS in the BTX?A group (HAMD scores: F=12.930, P<0.01; SDS scores: F=5.022, P=0.001) and those in the sertraline group (HAMD scores: F=2.883, P=0.030; SDS scores:F=3.427, P=0.013) were significantly lower compared to baseline, but there was no statistically significant difference in the scores of HAMD and SDS between the two groups (P>0.05). HAMD score showed that the remission rate of depression in the BTX?A group (17.9% (5/28), 35.7% (10/28)) was higher than that of the sertraline group (2/14, 4/14) at the 2nd and 4th weeks. At the 8th and 12th weeks, the remission rate of depression in the sertraline group (7/14, 9/14) was higher than that of the BTX?A group (46.4% (13/28), 53.6% (15/28)). There was no statistically significant difference in remission rate of depression between the two groups at each follow?up time point (P>0.05). There was no statistically significant difference in HAMD scores between males and females in the BTX?A group (P>0.05). Two of the 28 patients in the BTX?A group had frown muscle stiffness, which lasted for two weeks and improved in one month. Two patients in the sertraline group had headache and dizziness, and two patients had dry mouth and nausea, which improved after two weeks. There was no statistically significant difference in the incidence of adverse reactions between the two groups (P=0.197). Conclusion BTX?A intraocular facial muscle injection can significantly improve the depressive symptoms of PD patients, and the effect lasts for a long time, with low incidence of side effects and high safety, which can be considered as a safe and effective new method for PD patients with depressive symptoms.
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Objective To assess the effects of Jinghou Zengzhi Recipe(JHZZR),a Chinese prescription with the action of tonifying Qi and blood ,on the ovary apoptosis and expression of Bim in ovarian granulosa cells (GCs) of controlled ovarian hyperstimulation(COH) rats , and analyze the possible therapeutic mechanism. Methods A model of COH rats were prepaered and 30 female SD rats were randomly divided into 5 groups , including control group,positive control group,low,medium and high concentration group in six rats in each group. The apoptosis index(AI)in ovarian GCs were detected by TUNEL ,and the expression of Bim by qPCR. Results The AI of ovarian GCs in high and medium concentration group were obviously lower(P 0.05)comparing with control group. The mRNA levels of Bim were lower(P0.05)during the three concentration groups in Bim mRNA. Conclusion JHZZR can inhibit the ovarian GCs apoptosis of COH rats through decreasing the expression of Bim mRNA ,which improve the quality of ovarian follicle.
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Objective To study whether the effects of bone mineral density by a kidney-tonifying herbal fufang treatment in senile osteoporosis mice (P6) is by the mechanism of improving the expression level of GH mRNA and IGF-1 mRNA. Methods The experimental points four groups as following:SAMR1 mice which feed saline lavage,SAMP6 divid as saline lavage group,subcutaneous injection of rhGH group and a kidney-tonifying herbal fufang treatment group. All intervention is one time everyday. After 3 months and 6 months intervention,we measure the BMD and the expression level of the GH mRNA and of IGF-1 mRNA. Results After 3 months intervention,the BMD of R1 group and the Kidney group were higher than the P6 blank group;but there is no difference in BMD between RhGH group and the P6 blank group. The effect of GH mRNA and IGF-1 mRNA expression levels:the R1 group,rhGH and kidney group were higher than the P6 blank group. After six months intervention,the BMD of the rhGH group and kidney group are higher than the P6 blank group. GH mRNA and IGF-1 mRNA expression levels:GH group and kidney group are higher than the P6 blank group. The expression level of GH mRNA and IGF-1 mRNA in four groups has positive correlation. After six months intervention ,we found the positive correlation between the expression level of GH mRNA and IGF-1 mRNA and each part of the whole body BMD. Conclusion A kidney-tonifying herbal fufang can improve the bone mineral density of P6,and its mechanism may be related to improve expression level of GH mRNA and IGF-1 mRNA.