Phacoemulsification combined with capsular tension ring and intraocular lens implantation in the treatment of high myopia with cataract / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To observe the efficacy of phacoemulsification combined with capsular tension ring and intraocular lens implantation in the treatment of high myopia with cataract.METHODS: Retrospective study. A total of 82 cases(82 eyes)of high myopia complicated with cataract who admitted to the cataract department of our hospital from December 2021 to April 2023 were selected as study objects, and they were divided into control group(n=39)and combination group(n=43)according to whether or not the capsular tension ring was used intraoperatively. Patients in the control group were treated with intraocular lens implantation alone, and those in the combination group were treated with phacoemulsification combined with capsular tension ring and intraocular lens implantation. The preoperative and postoperative best corrected visual acuity, central anterior chamber depth, trabecular ciliary process, visual quality and complications were compared.RESULTS: At 1 mo after surgery, the best corrected visual acuity(LogMAR)of both groups increased significantly(combination group: 0.64±0.28 vs 0.12±0.14; control group: 0.62±0.26 vs 0.23±0.25, both P<0.001). Central anterior chamber depth in both groups were higher than those before surgery(combination group: 2.57±0.56 vs 1.97±0.40 mm; control group: 2.22±0.45 vs 1.89±0.37 mm; both P<0.001), and the best corrected visual acuity and central anterior chamber depth of the combination group were significantly better than those of the control group(both P<0.05). The distance of trabecular ciliary process showed no statistical significance(combination group: 0.68±0.22 vs 0.74±0.20 mm; control group: 0.74±0.19 vs 0.78±0.17 mm, both P>0.05). The visual quality scores of the combination group were all higher than the control group at 1 mo after surgery [watching TV: 3.00±0.38 vs 2.22±0.46 points; reading books: 2.85±0.42 vs 2.21±0.44 points; night vision: 2.71±0.34 vs 2.37±0.41 points; fine operation: 2.82±0.38 vs 2.33±0.40 points, all P<0.001]. The incidence of complication in the combination group was significantly lower than that of the control group(33% vs 14%, P<0.05).CONCLUSION: Phacoemulsification combined with capsular tension ring and intraocular lens implantation can effectively promote the recovery of visual function, improve the structure of chamber angle, and reduce the incidence of complications in the treatment of patients with high myopia and cataract.

Exploration of Role of Yin and Yang Syndrome Differentiation in Parkinson's Disease / 中国实验方剂学杂志

The syndrome differentiation of Yin and Yang has the function of controlling the other six principles in the eight principles syndrome differentiation，which is a higher level or general induction of the disease. In the clinical process of traditional Chinese medicine，syndrome differentiation of Yin and Yang runs through the whole process of disease diagnosis and treatment. For Parkinson's disease，syndrome differentiation of Yin and Yang is particularly important. Different symptoms，the transformation of pathogenesis during the development of the disease and the treatment of traditional Chinese and western medicine all reflect the characteristics of Yin and Yang opposition restriction，mutual root and mutual use，and the transformation of ebb and flow. This article discusses the background，application and value of Yin-Yang syndrome differentiation from three aspects：the origin and application of yin-yang syndrome differentiation，the basis of Parkinson's disease syndrome differentiation，and the status and role of Yin-Yang syndrome differentiation in Parkinson's disease. It is of great significance to guide the diagnosis and treatment of Parkinson's disease with "Yin-Yang as the key point".

The Physiological Functions and Polymorphisms of Type II Deiodinase

Type II deiodinase (DIO2) is thought to provide triiodothyronine (T3) to the nucleus to meet intracellular needs by deiodinating the prohormone thyroxine. DIO2 is expressed widely in many tissues and plays an important role in a variety of physiological processes, such as controlling T3 content in developing tissues (e.g., bone, muscles, and skin) and the adult brain, and regulating adaptive thermogenesis in brown adipose tissue (BAT). However, the identification and cloning of DIO2 have been challenging. In recent years, several clinical investigations have focused on the Thr92Ala polymorphism, which is closely correlated with clinical syndromes such as type 2 diabetes, obesity, hypertension, and osteoarthritis. Thr92Ala-DIO2 was also found to be related to bone and neurodegenerative diseases and tumors. However, relatively few reviews have synthesized research on individual deiodinases, especially DIO2, in the past 5 years. This review summarizes current knowledge regarding the physiological functions of DIO2 in thyroid hormone signaling and adaptive thermogenesis in BAT and the brain, as well as the associations between Thr92Ala-DIO2 and bone and neurodegenerative diseases and tumors. This discussion is expected to provide insights into the physiological functions of DIO2 and the clinical syndromes associated with Thr92Ala-DIO2.

Activation of TGR5 Attenuates Renal Fibrosis after Renal Ischemia Reperfusion Injury / 中山大学学报(医学科学版)

ObjectiveTo investigate the role of bile acid receptor TGR5 activation in renal fibrosis induced by unilateral ischemia reperfusion injury and contralateral nephrectomy （uIRIx） model. MethodsIn vivo： C57BL/6J mice were randomly divided into Sham group， uIRIx group and uIRIx+ lithcholic acid （LCA） group with 6 mice in each group. Kidney fibrosis was induced by uIRIx model， kidney function was evaluated by blood and urine biochemical indexes， and the degree of kidney injury was evaluated by HE staining. Masson staining and immunohistochemistry were used to evaluate the degree of renal fibrosis， and Western Blotting was used to detect the expression of related index proteins of renal cortical fibrosis. Sham group and uIRIx group were set in TGR5+/+ mice and TGR5-/- mice respectively， with 6 mice in each group. The degree of renal fibrosis in each group was detected by Western Blotting. In vitro： TGF-β1 was administered to induce pro-fibrosis response in human renal tubular epithelial cell line （HK2 cells）， LCA was used for drug intervention， cytoskeleton was labeled with phalloidin-FITC staining and the expression of fibrosis related indicator protein in HK2 cells was detected by Western Blotting. ResultsIn vivo： Compared with the Sham group， plasma creatinine level （P=0.007） and urinary albumin/creatinine ratio （P=0.041） in uIRIx group were significantly increased， renal cortical protein TGR5 expression （P=0.002） was decreased， Fibronectin expression （P=0.020） and COL1A1 expression （P<0.001） were increased. At the same time， the kidney structure was damaged and collagen deposition was aggravated. LCA intervention effectively improved the kidney function and alleviated the degree of kidney injury and fibrosis. TGR5 gene knockout increased uIRIx-induced Fibronectin expression （P<0.001） and COL1A1 expression （P=0.001） compared with TGR5+/+ mice. In vitro： TGF-β1 induced morphological changes of HK2 cells， cytoskeletal depolymerization and recombination， and promoted the up-regulation of fibrosis index protein. LCA effectively inhibited the morphological changes and skeletal depolymerization induced by TGF-β1， and down-regulated the expression of fibrosis related indicator proteins. ConclusionsLCA alleviated renal fibrosis induced by uIRIx model， and knockout of TGR5 gene aggravated uIRIx induced renal fibrosis； In HK2 cells， LCA alleviated fibrogenic reaction induced by TGF-β1. This indicates that activation of TGR5 alleviates renal fibrosis induced by uIRIx.

Emodin Ameliorates High Glucose-Induced Podocyte Apoptosis via Regulating AMPK/mTOR-Mediated Autophagy Signaling Pathway / 中国结合医学杂志

OBJECTIVE@#To investigate the effect of emodin on high glucose (HG)-induced podocyte apoptosis and whether the potential anti-apoptotic mechanism of emodin is related to induction of adenosine-monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR)-mediated autophagy in podocytes (MPC5 cells) in vitro.@*METHODS@#MPC5 cells were treated with different concentrations of HG (2.5, 5, 10, 20, 40, 80 and 160 mmol/L), emodin (2, 4, 8 µ mol/L), or HG (40 mmol/L) and emodin (4 µ mol/L) with or without rapamycin (Rap, 100 nmol/L) and compound C (10 µ mol/L). The viability and apoptosis of MPC5 cells were detected using cell counting kit-8 (CCK-8) assay and flow cytometry analysis, respectively. The expression levels of cleaved caspase-3, autophagy marker light chain 3 (LC3) I/II, and AMPK/mTOR signaling pathway-related proteins were determined by Western blot. The changes of morphology and RFP-LC3 fluorescence were observed under microscopy.@*RESULTS@#HG at 20, 40, 80 and 160 mmol/L dose-dependently induced cell apoptosis in MPC5 cells, whereas emodin (4 µ mol/L) significantly ameliorated HG-induced cell apoptosis and caspase-3 cleavage (P<0.01). Emodin (4 µ mol/L) significantly increased LC3-II protein expression levels and induced RFP-LC3-containing punctate structures in MPC5 cells (P<0.01). Furthermore, the protective effects of emodin were mimicked by rapamycin (100 nmol/L). Moreover, emodin increased the phosphorylation of AMPK and suppressed the phosphorylation of mTOR. The AMPK inhibitor compound C (10 µ mol/L) reversed emodin-induced autophagy activation.@*CONCLUSION@#Emodin ameliorated HG-induced apoptosis of MPC5 cells in vitro that involved induction of autophagy through the AMPK/mTOR signaling pathway, which might provide a potential therapeutic option for diabetic nephropathy.

Gut microbiota as a target for traditional Chinese medicine in the treatment of cardiovascular disease: potential mechanisms and therapy strategies / 药学学报

Cardiovascular disease (CVD) is a major contributor to patient deaths worldwide, and its pathogenesis is complex and mortality rates are increasing every year. Numerous researches have shown that the gut microbiota and its metabolites were closely associated with the development of CVD, and gut microbiota was expected to be a potential new target for the treatment of CVD. Traditional Chinese medicine (TCM), characterized by its multi-component, multi-target and integrity, can play a therapeutic role in CVD by regulating the gut microbiota, which has obvious advantages in stabilizing the disease, improving heart function and enhancing quality of life, and is an ideal intestinal microecological regulator. Therefore, this review will mainly discuss the intimate association of gut microbiota and its metabolites with CVD, and the therapeutic strategies of TCM targeting gut microbiota to improve CVD, including regulating the composition of gut microbiota, protecting the intestinal mucosal barrier, influencing the intestinal immune function and modulating the metabolites of gut microbiota, in order to provide a reference for the research of TCM targeting gut microbiota for CVD.

Cloning and expression analysis of ANR genes from different species of Lonicera japonica Thunb / 药学学报

Anthocyanidin reductase (ANR) is one of the key enzyme in the flavonoid biosynthetic pathway, and its catalytic activity is important for the synthesis of plant anthocyanin. In this study, specific primers were designed according to the transcriptome data of Lonicera japonica Thunb., and the CDS, gDNA and promoter sequences of ANR genes from Lonicera japonica Thunb. and Lonicera japonica Thunb. var. chinensis (Wats.) Bak. were cloned. The results showed that the CDS sequences of LjANR and rLjANR were 1 002 bp, the gDNA sequences were 2 017 and 2 026 bp respectively, and the promoter sequences were 1 170 and 1 164 bp respectively. LjANR and rLjANR both contain 6 exons and 5 introns, which have the same length of exons and large differences in introns. The promoter sequences both contain a large number of light response, hormone response and abiotic stress response elements. Bioinformatics analysis showed that both LjANR and rLjANR encoded 333 amino acids and were predicted to be stable hydrophobic proteins without transmembrane segments and signal peptides. The secondary structures of LjANR and rLjANR were predicted to be mainly consisted of α-helix and random coil. Sequence alignment and phylogenetic analysis showed that LjANR and rLjANR had high homology with Actinidia chinensis var. chinensis, Camellia sinensis and Camellia oleifera, and were closely related to them. The expression levels of LjANR and rLjANR were the highest in flower buds and the lowest in roots. The expression patterns at different flowering stages were similar, with higher expression levels in S1 and S2 stages and then gradually decreased until reaching the lowest level in S4 stage, after a slow increase in S5 stage, the expression levels decreased again. The expression levels of ANR genes in the two varieties showed significant differences in roots, S2 and S5 stages, while the differences in stems, flower buds, S1, S3 and S6 stages were extremely significant. The prokaryotic expression vector pET-32a-LjANR was constructed for protein expression. The target protein was successfully expressed of about 59 kD. This study lays a foundation for further study on the function of ANR gene and provides theoretical guidance for breeding new varieties of Lonicera japonica Thunb.

Phosphodiesterase 5 Inhibitors Attenuate Unilateral Ureteral Obstruction-Induced Renal Fibrosis / 中山大学学报(医学科学版)

ObjectiveTo investigate whether phosphodiesterase （PDE） 5 inhibitors sildenafil （SIL） or LW1646 prevented renal interstitial fibrosis induced by unilateral ureteral obstruction （UUO）. MethodsMale C57BL/6 mice were randomly divided into four groups （n =6）， namely the Sham group， 7UUO group， 7UUO+SIL group and 7UUO+LW1646 group. Sildenafil （SIL） or LW1646， or vehicle was administered 1 hour before surgery， and the mice were continuously treated once daily （i. g.， 50 mg/kg） for 7 days. The obstructed kidneys were harvested on day 7. Hematoxylin-eosin （HE） and Masson’s staining was used to examine renal histology. Immunoblotting and RT-qPCR were used to detect the expression levels of protein and mRNA for fibrosis， apoptosis， endoplasmic reticulum （ER） stress， autophagy， and pro-fibrotic factors. Human proximal tubule epithelial cells （HK-2） were treated with TGF-β1 for 48 hours or tunicamycin for 24 hours， respectively， to evaluate whether cyclic guanosine monophosphate （cGMP） or PDE5 inhibitors prevents ER stress and pro-fibrotic responses. ResultsAt the 7th days after UUO， the body weight of the mice showed a significant decrease （P< 0.000 1） compared with that in the sham group. The obstructed kidneys showed a significant tubular dilation and interstitial inflammation. The levels of protein and mRNA expression in apoptosis， ER stress， autophagy-related protein and pro-fibrotic factors were also markedly increased in UUO mice （P <0.05）. In contrast， SIL or LW1646 treatment was associated with attenuated tubular dilation， infiltration of inflammatory cells and collagen content in the obstructed kidney of the mice. The protein and mRNA expression levels of renal TGF-β1 were markedly decreased， and the protein expression levels of apoptosis， endoplasmic reticulum stress， and autophagy markers were also significantly downregulated by PDE5 inhibitors. In HK-2 cells， TGF-β1 induced increased expression levels of fibronectin and BiP， which was at least partially reversed by cGMP， a product of PDE inhibition. Additionally， PDE5 inhibitors were found to modulate aberrant levels of autophagy and apoptosis. ConclusionIn conclusion， PDE5 inhibitors， in particular， LW1646， can alleviate the progression of fibrosis by improving ER stress， apoptosis and autophagy as well as downregulating protein and mRNA expression of TGF-β1.

The effect of LeCompte maneuver on mid-to-long term reintervention after arterial switch operation in children with side-by-side Taussig-Bing anomaly / 中国胸心血管外科临床杂志

@#Objective    To explore the effect of LeCompte maneuver on in-hospital mortality and mid-to-long term reintervention after single-stage arterial switch operation in children with side-by-side Taussig-Bing anomaly. Methods     Clinical data of patients diagnosed with side-by-side Taussig-Bing anomaly and undergoing single-stage arterial switch operation in Shanghai Children’s Medical Center from 2006 to 2017 were retrospectively analyzed. Patients were divided into two groups based on whether LeCompte maneuver was performed: a LeCompte maneuver group and a non LeCompte maneuver group. The clinical data of two groups were compared. Results    Finally 92 patients were collected. LeCompte maneuver was performed in 32 out of 92 patients with a median age of 65.0 days and an average weight of 4.3 kg, among whom 24 (75.0%) were male. Fifteen (46.9%) patients received concomitant aortic arch repair while 12 (37.5%) patients were associated with coronary artery malformation. LeCompte maneuver was not performed in 60 patients with a median age of 81.0 days and an average weight of 4.8 kg, among whom 45 (75.0%) were male. Twenty-two (36.7%) patients received concomitant aortic arch repair while 35 (58.3%) patients were associated with coronary artery malformation. The average cardiopulmonary bypass duration of the LeCompte maneuver group showed no statistical difference from the non LeCompte maneuver group (179.0±60.0 min vs. 203.0±74.0 min, P=0.093). The in-hospital mortality of the two groups were 6 (18.8%) and 7 (11.7%), respectively, which also showed no statistical difference (P=0.364). The median follow-up period was 4.1 (1.6, 7.5) years for 79 patients with 8 lost to follow-up, and no death was observed. Kaplan-Meier curve and log-rank test showed no statistical difference in overall mid-to-long term reintervention rate (P=0.850) as well as right ventricular outflow tract and pulmonary artery reintervention rate (P=0.240) with or without LeCompte maneuver. Conclusion    Whether or not to perform LeCompte maneuver shows no statistical impact on in-hospital mortality and mid-to-long term reintervention rate of single-stage arterial switch operation for side-by-side Taussig-Bing anomaly.

Non-targeted LC-MS profiling reveals association between human early embryo grades and levels of amino acids and carnitines in embryo culture medium / 中华检验医学杂志

Objective:In order to determine the development potential of human embryos in vitro, amino acid and carnitine levels were measured in the culture medium of different grades of early human embryos. Methods:From the infertile couples who received in vitro fertilization-embryo transfer treatment in the Department of Reproductive Medicine of Linyi People′s Hospital from June 2022 to December 2022, the age of the women was defined as 25-35 years old [31.5(26.5, 33.25)] with 8-20 eggs, 126 cultured cells and embryos of the third day were randomly collected from infertile couples. They were divided into three groups according to the morphological level of the corresponding embryos: excellent, neutral and poor. Amino acids and L-carnitines levels in culture medium were detected by liquid chromatography-mass spectrometry (LC-MS). Using analysis of variance to compare differences among groups, correlation analysis, factor analysis was performed to analyze the association between the levels of amino acids and L-carnitines and development potential of early human embryos.Results:The value of Methionine/Phenylalanine was found statistically different among superior embryo (3.09±1.67), moderate embryo (4.00±1.19) and inferior embryo (4.99±2.04). The difference between the three groups was statistically different ( F=7.09, P<0.05): superior embryo vs moderate embryo ( t=-0.91, P<0.05), superior embryo vs inferior embryo ( t=-1.91, P<0.05), moderate embryo vs inferior embryo ( t=-0.99, P<0.05). Among different amino acids, Phe had the strongest positive correlation with Tyr ( r=0.99, P<0.01). Among different carnitines, C 8/C 10 has the strongest positive correlation with C 5DC+C 6OH/C 16( r=0.44, P<0.01). The weight value of leucine (isoleucine), arginine, valine/phenylalanine, glycine, tyrosine and carnitine(C 5DC+C 6OH)/C 8 calculated by the least square fitting model is 2.22, 1.99, 1.65, 1.54, 1.21 and 1.15 respectively. Conclusion:Leucine, arginine, valine/phenylalanine, glycine, tyrosine and carnitine (C 5DC+C 6OH)/C 8 in embryo culture medium were significantly correlated with the levels of early human embryos in vitro.

Comparison of frailty assessment and related tools in elderly hospitalized patients with atrial fibrillation / 中华老年医学杂志

Objective:We evaluated frailty in elderly hospitalized patients with atrial fibrillation and analyzed the relevance, consistency, and diagnostic power of different frailty tools.Methods:From September 2018 to April 2019, a total of 197 elderly patients with atrial fibrillation aged ≥ 65 years in Beijing Hospital, Chinese PLA General Hospital, and Beijing Tsinghua Changgung Hospital were prospectively enrolled.Five frailty tools, including the clinical frailty scale(CFS), FRAIL scale(FRAIL), Fried frailty phenotype(Fried), Edmonton frail scale(EFS), and comprehensive geriatric assessment-frailty index(CGA-FI), were used for frailty assessment.Results:A total of 197 hospitalized elderly patients with atrial fibrillation were enrolled, with an average age of(77.5±7.1)years old(57.4% male). The prevalence of frailty, according to the five frailty tools, were 25.4%(FRAIL), 27.9%(EFS), 34.5%(Fried), 40.6%(CFS), and 42.6%(CGA-FI), respectively.CFS had a good correlation(correlation coefficient 0.80)and and consistency(Kappa value 0.71, 95% CI 0.61~0.81)with CGA-FI.The combined frailty index was used as the gold standard for frailty diagnosis.The results showed that CFS and CGA-FI had high diagnostic sensitivity(95.9 % and 98.0 %, respectively)and specificity(77.7 % and 75.7 %, respectively). Conclusions:Frailty is common in elderly hospitalized patients with atrial fibrillation, showing multidimensional features, and physical weakness is not prominet.CFS and CGA-FI are recommended for the assessment of frailty in patients with atrial fibrillation, which had good correlation and consistency.

Mechanism of grape seed proanthocyanidin oligomers inhibiting polarization of type Al astrocytes / 中国药理学通报

Aim To explore the mechanism of grape seed proanthocyanidins (GSPs) targeting astrocytes (AS), so as to regulate the phenotype and function of AS and maximize their neuroprotective effect. Methods The effects of GSPs on the phenotype, secretion of pro-inflammatory factors and neurotrophic factors of Al AS induced by TNF-α, IL-1α and Clq were investigated by RT-PCR, Elisa and Western blot in vitro. And JNK phosphorylation was determined using Western blot. Results GSPs significantly reduced the expression of C3d and Clq of Al AS markers and inhibited the phosphorylation of JNK. Moreover, compared with the model group, GSPs could significantly inhibit the release of pro-inflammatory cytokines IL-6, IL-1 α, IL-17 and H

Mechanism of Modified Danggui Shaoyao San in treatment of chronic atrophic gastritis based on network pharmacology and experimental verification / 中国药理学通报

Aim To predict the targets of Modified Danggui Shaoyao San ( MDSS) in the treatment of chronic atrophic gastritis ( CAG) based on network pharmacology and vertify the results based on experim-ention. Methods TCMSP, SWISS TARGETS, GENE CARDS and OMIM databases were used to screen the therapeutic targets of MDSS for CAG. STRING database and Cytoscape software were used to construct the protein interaction network and screen the core targets. Metascape database was used for GO analysis and KEGG enrichment pathways. And molecular docking was used for target validation. CAG rat model was pre¬pared by N-methyl-N'-nitroso-N-nitroguanidine free drink combined with sodium salicylate gastric lavage. The pathology of rat gastric mucosa was observed by hematoxylin-eosin staining,and the ultrastructure of ep¬ithelial cells was observed by transmission electron mi-croscopy. The serum IL-6 and IL-10 content was detected by enzyme-linked immunosorbent assay, and the expression of JAK2, STAT3 , p-STAT3 , c-MYC mRNA and protein in rats was detected by qPCR and Western blot. Results MDSS acted on 189 targets, mainly involved in response to oxidative stress and apoptotic signaling pathway. KEGG analysis related to pathways in cancer and JAK-STAT signaling pathway. The experimental results showed that the MDSS could improve the degree of atrophy of gastric mucosa in CAG rats and improve the status of epithelial cells, down-regulate the serum IL-6 content of CAG rats, up-regulate the IL-10 content, and reduce the expression of JAK2, STAT3 , p-STAT3 , c-MYC mRNA and protein in gastric mucosa with statistical significance. Conclusions MDSS treats CAG through multiple active ingredients, targets, and pathways, the mechanism of which may be related to the inhibition of the JAK2/STAT3 signaling pathway.

Procyanidin B2 protects H / 中国药理学通报

Aim To explore the protective effect of proanthocyanidin B2 (PC-B2) on oxidative damage of PC 12 cells induced by hydrogen peroxide (H

Study on the efficacy of the resolving depression and tranquilizing TCM sachets in alleviating sleep disorders of soldiers in naval vessels / 药学实践杂志

Objective To explore the efficacy of the resolving depression and tranquilizing herbal sachets in alleviating sleep disorders of soldiers in naval vessels. Methods Fifty-nine soldiers with sleep disorders (PSQI scale score ≥8 and SAS scale score ≥50) were selected before training at sea, and were randomly divided into sachet treatment group, mindfulness meditation group and control group. During the training period, the sachet treatment group was given traditional Chinese medicine sachet treatment, the mindfulness meditation group was trained in mindfulness meditation, and the control group was not given any intervention. Results Compared with the control group, the PSQI and SAS scores of soldiers in both the experimental sachet treatment group and the positive meditation group were significantly improved; compared with the pre-intervention data, the PSQI and SAS scores of both the positive meditation group and the sachet treatment group were significantly decreased, and the degree of decrease was comparable. Conclusion The homemade improving depression and tranquilizing TCM sachets have the effect of alleviating the sleep disorders of naval troops served on vessels, which is equivalent to mindfulness meditation. It is easy to use and operate, which is suitable for promotion in the military.

The deubiquitinating enzyme 13 retards non-alcoholic steatohepatitis via blocking inactive rhomboid protein 2-dependent pathway

Nowadays potential preclinical drugs for the treatment of nonalcoholic steatohepatitis (NASH) have failed to achieve expected therapeutic efficacy because the pathogenic mechanisms are underestimated. Inactive rhomboid protein 2 (IRHOM2), a promising target for treatment of inflammation-related diseases, contributes to deregulated hepatocyte metabolism-associated nonalcoholic steatohepatitis (NASH) progression. However, the molecular mechanism underlying Irhom2 regulation is still not completely understood. In this work, we identify the ubiquitin-specific protease 13 (USP13) as a critical and novel endogenous blocker of IRHOM2, and we also indicate that USP13 is an IRHOM2-interacting protein that catalyzes deubiquitination of Irhom2 in hepatocytes. Hepatocyte-specific loss of the Usp13 disrupts liver metabolic homeostasis, followed by glycometabolic disorder, lipid deposition, increased inflammation, and markedly promotes NASH development. Conversely, transgenic mice with Usp13 overexpression, lentivirus (LV)- or adeno-associated virus (AAV)-driven Usp13 gene therapeutics mitigates NASH in 3 models of rodent. Mechanistically, in response to metabolic stresses, USP13 directly interacts with IRHOM2 and removes its K63-linked ubiquitination induced by ubiquitin-conjugating enzyme E2N (UBC13), a ubiquitin E2 conjugating enzyme, and thus prevents its activation of downstream cascade pathway. USP13 is a potential treatment target for NASH therapy by targeting the Irhom2 signaling pathway.

Overexpression of CLEC5A inhibits cell proliferation and metastasis and reverses epithelial-mesenchymal transition in hepatocellular carcinoma / 南方医科大学学报

OBJECTIVE@#To evaluate the effects of CLEC5A expression level on cell proliferation, migration and invasion and epithelial-mesenchymal transition (EMT) in hepatocellular carcinoma (HCC) and explore the role of CLEC5A in the tumorigenesis and progression of HCC.@*METHODS@#The expression level of CLEC5A was detected in 50 pairs of HCC and adjacent tissues using immunohistochemical staining, and its association with clinicopathological parameters of HCC patients was analyzed. Cultured HCC cell line SK-HEP-1 was transfected with a lentiviral vector overexpressing CLEC5A, and the transfection efficiency was verified using real-time fluorescence quantitative PCR and Western blotting. The changes in proliferation, migration and invasion abilities of the transfected cells were analyzed using CCK-8, 5-ethynyl-29-deoxyuridine (EdU) and Transwell assays, and EMT of the cells was determined using Western blotting.@*RESULTS@#The protein expression level of CLEC5A was significantly lower in HCC tissues than in the adjacent tissues (P < 0.001). The expression level of CLEC5A was significantly correlated with tumor size (P=0.008), tumor number (P=0.010), histological differentiation (P=0.016), microvascular invasion (P=0.024) and BCLC stage (P=0.040). In SK-HEP-1 cells, overexpression of CLEC5A obviously inhibited the cell proliferation, migration and invasion and reversed EMT phenotype of the cells.@*CONCLUSION@#CLEC5A is a potential HCC suppressor gene and may serve as a promising therapeutic target for HCC.

Teriparatide regulates osteoblast differentiation in high-glucose microenvironment through the cAMP/PKA/CREB signaling pathway / 南方医科大学学报

OBJECTIVE@#To investigate the effect of teriparatide on the differentiation of MC3T3-E1 cells in high-glucose microenvironment and explore the possible mechanism.@*METHODS@#MC3T3-E1 cells cultured in normal glucose or high-glucose (25 mmol/L) medium were treated with 10 nmol/L teriparatide with or without co-treatment with H-89 (a PKA inhibitor). CCK-8 assay was used to detect the changes in cell proliferation, and cAMP content in the cells was determined with ELISA. Alkaline phosphatase (ALP) activity and mineralized nodules in the cells were detected using ALP kit and Alizarin red staining, respectively. The changes in cell morphology were detected by cytoskeleton staining. Real-time PCR was used to detect the mRNA expressions of PKA, CREB, RUNX2 and Osx in the treated cells.@*RESULTS@#The treatments did not result in significant changes in proliferation of MC3T3-E1 cells (P > 0.05). Compared with the cells in routine culture, the cells treated with teriparatide showed significantly increased cAMP levels (P < 0.05) with enhanced ALP activity and increased area of mineralized nodules (P < 0.05). Teriparatide treatment also resulted in more distinct visualization of the cytoskeleton in the cells and obviously up-regulated the mRNA expressions of PKA, CREB, RUNX2 and Osx (P < 0.05). The opposite changes were observed in cells cultured in high glucose. In cells exposed to high glucose, treatment with teriparatide significantly increased cAMP levels (P < 0.05), ALP activity and the area of mineralized nodules (P < 0.05) and enhanced the clarity of the cytoskeleton and mRNA expressions of PKA, CREB, RUNX2 and Osx; the effects of teriparatide was strongly antagonized by co-treatment with H-89 (P < 0.05).@*CONCLUSION@#Teriparatide can promote osteoblast differentiation of MC3T3-E1 cells in high-glucose microenvironment possibly by activating the cAMP/PKA/CREB signaling pathway.

Effect of MiR-424-5p on the Drug Resistance of Diffuse Large B-Cell Lymphoma Cells by Regulating PD-1/PD-L1 Signaling Pathway / 中国实验血液学杂志

OBJECTIVE@#To explore the effect of microRNA-424-5p (miR-424-5p) on the drug resistance of diffuse large B-cell lymphoma (DLBCL) cells by regulating the programmed death receptor-1 (PD-1)/programmed death ligand-1 (PD-L1) signaling pathway.@*METHODS@#Human DLBCL cell line CRL2631 cells were induced to construct CRL2631-CHOP resistant cell line. RT-qPCR and Western blot were used to detect the expression levels of MiR-424-5p, PD-L1 mRNA and protein, and multidrug resistance gene-1 (MDR-1) protein in CRL2631 cells and CRL2631-CHOP cells, respectively. The target genes of MiR-424-5p was verified by dual luciferase reporter assay. The miRNA simulation/interference technology and thiazole blue (MTT) method were used to detect the resistance of CRL2631 cells and CRL2631-CHOP cells to CHOP.@*RESULTS@#Compared with CRL2631 cells, the drug resistance of CRL2631-CHOP cells to CHOP and the levels of MDR-1 protein (P<0.05), PD-L1 mRNA and protein in the cells were significantly increased (both P<0.001), while the relative level of MiR-424-5p was significantly reduced (P<0.001). The result of the dual luciferase reporter assay showed that PD-L1 was the direct downstream target gene of MiR-424-5p (P<0.001). After transfection of MiR-424-5p inhibitor, the resistance of CRL2631 cells to CHOP drugs increased, and the expression level of MDR-1 protein (P<0.01), PD-L1 mRNA and protein also increased significantly (both P<0.01). After transfection of MiR-424-5p mimics, the resistance of CRL2631-CHOP cells to CHOP drugs decreased, and the expression level of MDR-1 protein (P<0.001), PD-L1 mRNA and protein also decreased significantly (both P<0.001). Overexpression of PD-L1 could reverse the inhibitory effect of upregulating MiR-424-5p on PD-L1 (P<0.001).@*CONCLUSION@#Down-regulation of MiR-424-5p enhances the drug resistance of DLBCL cells by regulating the PD-1/PD-L1 signaling pathway.

Age-related changes for the predictors of benign prostatic hyperplasia in Chinese men aged 40 years or older / 亚洲男科学杂志(英文版)

A cross-sectional study was conducted to estimate the age-stratified normal levels and age-related changes in the risk predictors of benign prostatic hyperplasia (BPH) progression. A total of 4706 male participants aged 40 years or older in Zhengzhou (China) were enrolled. The values of the International Prostate Symptom Score (IPSS), prostate-specific antigen (PSA), prostate volume (PV), and postvoid residual urine volume (PVR) significantly increased with age. Nonlinear relationships between age and IPSS scores ≥8 (P for nonlinearity = 0.046), PSA level ≥1.6 ng ml-1, PV ≥31 ml, or PVR ≥39 ml (all P for nonlinearity <0.001) were observed. After the age of 61 years, the risk indicators related to BPH progression were positively correlated with age (odds ratio [OR] >1), regardless of the predictors of the IPSS score, PSA level, PV, or PVR; and the OR values increased gradually. Therefore, after the age of 61 years, the risk predictors related to BPH progression were positively correlated with age.