Meta-analysis comparing different ultrasound detection methods to accurately assess wound healing and scar formation after caesarean section.

The accurate assessment of wound healing post-caesarean section, especially in twin pregnancies, remains a pivotal concern in obstetrics, given its implications for maternal health and recovery. Traditional methods, including conventional abdominal ultrasonography (CU), have been challenged by the advent of transvaginal ultrasonography (TU), offering potentially enhanced sensitivity and specificity. This meta-analysis directly compares the efficacy of TU and CU in evaluating wound healing and scar formation, crucial for optimizing postoperative care. Results indicate that TU is associated with significantly better outcomes in wound healing, demonstrated by lower REEDA scores (SMD = -20.56, 95% CI: [-27.34.20, -13.77], p < 0.01), and in scar formation reduction, evidenced by lower Manchester Scar Scale scores (SMD = -25.18, 95% CI: [-29.98, -20.39], p < 0.01). These findings underscore the potential of integrating TU into routine post-caesarean evaluation protocols to enhance care quality and patient recovery.

Velocity field and turbulence structure of the meandering flow produced by alternating deflectors.

Meandering flow can be formed during the advance of natural rivers by the scouring of river banks. However, this phenomenon is not common in artificial cement channels. This study used experimental scouring terrain data for a numerical simulation to study the meandering flow pattern formed between double alternating deflectors in a straight channel. The numerical results showed that the path of the accelerated flow generated by the upstream deflector was changed by installing a downstream deflector while the flow rate remained unchanged. Thus, a meandering flow formed, and a stable, narrow, high-speed zone formed in the downstream area. The accelerated flow between the two deflectors hit the channel bank soon after its direction changed. Then, a strong downward flow formed in this area, which may have produced an elliptical scour hole. A large-scale vortex structure was formed in the elliptical scour hole, which was influenced by the horseshoe vortex system before the downstream deflector.

[Anemoside B4 regulates fatty acid metabolism reprogramming in mice with colitis-associated cancer].

The study aimed to investigate the effect of anemoside B4(B4) on fatty acid metabolism in mice with colitis-associated cancer(CAC). The CAC model was established by azoxymethane(AOM)/dextran sodium sulfate(DSS) in mice. Mice were randomly divided into a normal group, a model group, and low-, medium-, and high-dose anemoside B4 groups. After the experiment, the length of the mouse colon and the size of the tumor were measured, and the pathological alterations in the mouse colon were observed using hematoxylin-eosin(HE) staining. The slices of the colon tumor were obtained for spatial metabolome analysis to analyze the distribution of fatty acid metabolism-related substances in the tumor. The mRNA levels of SREBP-1, FAS, ACCα, SCD-1, PPARα, ACOX, UCP-2, and CPT-1 were determined by real-time quantitative PCR(RT-qPCR). The results revealed that the model group showed decreased body weight(P<0.05) and colon length(P<0.001), increased number of tumors, and increased pathological score(P<0.01). Spatial metabolome analysis revealed that the content of fatty acids and their derivatives, carnitine, and phospholipid in the colon tumor was increased. RT-qPCR results indicated that fatty acid de novo synthesis and ß-oxidation-related genes, such as SREBP-1, FASN, ACCα, SCD-1, ACOX, UCP-2, and CPT-1 mRNA expression levels increased considerably(P<0.05, P<0.001). After anemoside B4 administration, the colon length increased(P<0.01), and the number of tumors decreased in the high-dose anemoside B4 group(P<0.05). Additionally, spatial metabolome analysis showed that anemoside B4 could decrease the content of fatty acids and their derivatives, carnitine, and phospholipids in colon tumors. Meanwhile, anemoside B4 could also down-regulate the expression of FASN, ACCα, SCD-1, PPARα, ACOX, UCP-2, and CPT-1 in the colon(P<0.05, P<0.01, P<0.001). The findings of this study show that anemoside B4 may inhibit CAC via regulating fatty acid metabolism reprogramming.

[UPLC-Q-TOF-MS metabolomic study on improvement of acute myocardial ischemia in rats by Dalbergia cochinchinensis heartwood].

This paper aimed to study the effect of Dalbergia cochinchinensis heartwood on plasma endogenous metabolites in rats with ligation of the left anterior descending coronary artery, and to analyze the mechanism of D. cochinchinensis heartwood in improving acute myocardial ischemic injury. The stability and consistency of the components in the D. cochinchinensis heartwood were verified by the establishment of fingerprint, and 30 male SD rats were randomly divided into a sham group, a model group, and a D. cochinchinensis heartwood(6 g·kg~(-1)) group, with 10 rats in each group. The sham group only opened the chest without ligation, while the other groups established the model of ligation. Ten days after administration, the hearts were taken for hematoxylin-eosin(HE) staining, and the content of heart injury indexes in the plasma creatine kinase isoenzyme(CK-MB) and lactate dehydrogenase(LDH), energy metabolism-related index glucose(Glu) content, and vascular endothelial function index nitric oxide(NO) was determined. The endogenous metabolites were detected by ultra-high-performance liquid chromatography-time-of-flight-mass spectrometry(UPLC-Q-TOF-MS). The results showed that the D. cochinchinensis heartwood reduced the content of CK-MB and LDH in the plasma of rats to relieve myocardial injury, reduced the content of Glu in the plasma, improved myocardial energy metabolism, increased the content of NO, cured the vascular endothelial injury, and promoted vasodilation. D. cochinchinensis heartwood improved the increase of intercellular space, myocardial inflammatory cell infiltration, and myofilament rupture caused by ligation of the left anterior descending coronary artery. The metabolomic study showed that the content of 26 metabolites in the plasma of rats in the model group increased significantly, while the content of 27 metabolites decreased significantly. Twenty metabolites were significantly adjusted after the administration of D. cochinchinensis heartwood. D. cochinchinensis heartwood can significantly adjust the metabolic abnormality in rats with ligation of the left anterior descending coronary artery, and its mechanism may be related to the regulation of cardiac energy metabolism, NO production, and inflammation. The results provide a corresponding basis for further explaining the effect of D. cochinchinensis on the acute myocardial injury.

[Molecular mechanism of Dalbergia cochinchinensis heartwood in regulation of energy metabolism to treat myocardial ischemia based on network pharmacology and experimental validation].

Dalbergia cochinchinensis(DC) is chemically similar to the valuable and scarce Chinese herb Dalbergiae Odoriferae Lignum, and both of them belong to the Dalbergia Leguminosae. DC is used for treating cardiovascular diseases and cancer. However, its potent active ingredient groups and molecular mechanisms in anti-myocardial ischemia are not fully clarified. In this study, the active ingredient groups, targets, and signaling pathways of DC heartwood for the treatment of myocardial ischemia were screened out based on network pharmacology and molecular docking technology, and the effects were verified by the rat model of acute myocardial ischemia induced by isoprenaline(ISO). The molecular mechanism of DC heartwood was elucidated based on the target of multi-ingredient and multi-target pathways. The crossing targets of DC heartwood for the treatment of myocardial ischemia were identified through the screening of active ingredients in DC heartwood and the prediction of targets. The Kyoto Encyclopedia of Genomes(KEGG) pathway enrichment and Gene Ontology(GO) functional annotation were performed. AutoDock was used to bind the active ingredient groups to the pathway targets. Finally, the molecular mechanism of myocardial ischemia treatment by DC heartwood extracts in the treatment of myocardial ischemia was revealed through the rat model of ISO-induced acute myocardial ischemia by performing electrocardiogram(ECG), hemodynamic, cardiac enzymes, hematoxylin-eosin(HE) staining, high-energy phosphate compounds, reverse transcription polymerase chain reaction(RT-PCR), and Western blot pharmacodynamic experiments, based on the multi-ingredient and multi-target action of active ingredient groups and pathway targets. The network pharmacology showed that the 18 ingredients of DC heartwood corresponded to 510 targets, 629 myocardial ischemia-related targets, and 101 cross-targets. GO and KEGG enrichment analyses showed that DC heartwood was involved in the hypoxic response, vasoconstriction, and nitric oxide biosynthesis, and had effects on the molecular functions of hemoglobin binding, protein binding, and adenosine triphosphate(ATP) binding. It regulated the signaling pathways such as hypoxia-inducible factor 1(HIF-1), vascular endothelial growth factor(VEGF), and phosphatidylinositol-3-kinase/protein kinase B(PI3 K/AKT) to act on myocardial ischemia. Experimental studies showed that DC heartwood slowed down the heart rate and ST segment change(ΔST), and increased systolic blood pressure(SBP), diastolic blood pressure(DBP), and mean arterial pressure(MBP) in rats with ISO-induced acute myocardial ischemia. It also reduced plasma lactate dehydrogenase(LDH), creatine kinase isoenzyme MB(CK-MB), and glutamate transaminase(AST) levels, relieved myocardial fiber disorders and inflammatory cell infiltration, and increased ATP and cellular energy(EC) levels. DC heartwood increased the mRNA expressions of calmodulin-dependent protein kinase kinase(CAMKK) in the myocardial tissue, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3(PFKFB3), mammalian target of rapamycin(mTOR), PI3 K, VEGF, endothelial nitric oxide synthase(eNOS), HIF-1α in the myocardial tissue. It decreased the mRNA expression of pyruvate dehydrogenase(PDH), and increased the protein expressions of PFKFB3, VEGFA, and eNOS. Molecular docking showed that liquiritigenin, stigmasterol, isodalbergin, latifolin, 4-methoxydalbergione, dibutyl terephthalate, 2,4-dihydroxy-5-methoxybenzophenone in DC heartwood produced bio-binding activities with epidermal growth factor receptor(EGFR), HIF-1α, CAMKK, PI3 K, mTOR, and PDH, respectively. Therefore, the active ingredient groups of DC heartwood act on the HIF-1 signaling pathway, regulate cardiomyocyte energy metabolism, and increase ATP energy charge in a multi-ingredient and multi-target manner, improving cardiac function and histopathological changes to protect rats with acute myocardial ischemia induced by ISO.

Highland barley Monascus purpureus Went extract ameliorates high-fat, high-fructose, high-cholesterol diet induced nonalcoholic fatty liver disease by regulating lipid metabolism in golden hamsters.

ETHNOPHARMACOLOGICAL RELEVANCE: Hepatocyte lipid accumulation is the main feature in the early stage of nonalcoholic fatty liver disease (NAFLD). Highland barley Monascus purpureus Went (HBMPW), a fermentation product of Hordeum vulgare Linn. var. nudum Hook. f. has traditionally been used as fermented foods in Tibet with the effect of reducing blood lipid in folk medicine. AIM OF THE STUDY: This study investigated the protective effects and molecular mechanism of highland barley Monascus purpureus Went extract (HBMPWE) on NAFLD in syrian golden hamster fed with high-fat, high-fructose, high-cholesterol diet (HFFCD). MATERIALS AND METHODS: HFFCD-induced NAFLD golden hamster model was established and treated with HBMPWE. Liver index, biochemical index, and hematoxylin and eosin (HE) staining were observed. Liver metabolomics and western blot analysis were employed. RESULTS: Our study found that HBMPWE ameliorated HFFCD induced dyslipidemia, weight gain and elevated the liver index. In addition, HBMPWE treatment significantly attenuated lipid accumulation in the liver and modulated lipid metabolism (sphingolipid, glycerophospholipid). Our data demonstrated that HBMPWE not only regulated the expression of proteins related to fatty acid synthesis and decomposition (SREBP-1/ACC/FAS/AceS1, PPARα/ACSL/CPT1/ACOX1), but also regulated the expression of proteins related to cholesterol synthesis and clearance (HMGCR, LDLR, CYP7A1). CONCLUSIONS: HBMPWE improved NAFLD through multiple pathways and multiple targets in body metabolism and could be used as a functional food to treat NAFLD and other lipid metabolic disorders.

[Study on effect of anemoside B4 in improving COPD rats by regulating IL-12/STAT4 and IL-4/STAT6 signaling pathways].

To study the effect of anemoside B4 on rats with chronic obstructive pulmonary disease (COPD).Seventy-two SD male rats were randomly divided into blank group and model group.The method of exposure to cigarette smoke and combined with lipopolysaccharide (LPS) was used to replicate the rat model of COPD.After the model was maintained for 5 weeks,the rats were randomly divided into model group,dexamethasone group (0.81 mg·kg~(-1)) and anemoside B4 low,medium and high (2,4,8 mg·kg~(-1)) dose groups,a group of 12 animals were administered,and then the administration was started.The administration was maintained until the28th day,and the pulmonary function parameters of rats were measured by an animal pulmonary function instrument.After testing the rat lung function parameters,immediately draw rat alveolar lavage fluid (BALF),and use high-throughput protein chip technology to determined the expression levels of inflammatory cytokines in rat BALF.HE staining was used to observe the general pathological changes of rat lung and tracheal tissue.Masson staining was used to observe the collagen deposition in rat lung tissue.Real-time q PCR method was used to determine the mRNA expression level of related genes in rat lung tissue.Western blot method was used to determine the expression levels of related proteins in rat lung tissues.According to the findings,compared with the model group,the dexamethasone group and the anemoside B4 drug groups had different degrees of increase in the lung function parameters of rats (P<0.01,P<0.05),improved the expression level of inflammatory cytokines in the BALF of rats to varying degrees (P<0.01,P<0.05),and improved the pathological structure of rat lung tissue to varying degrees.Relative mRNA expressions of matrix metalloproteinase 2 (MMP-2),matrix metalloproteinase 12 (MMP-12),matrix metalloproteinase inhibitor 1 (TIMP-1),interleukin-6 (IL-6),and transforming growth factor-ß1 (TGF-ß1) were significantly reduced (P<0.01);whereas relative mRNA expressions of matrix metalloproteinase 9(MMP-9) and matrix metalloproteinase inhibitor 2 (TIMP-2) were increased significantly (P<0.01).The mRNA and protein expression levels of T-box transcription factor (T-bet),interleukin-12 (IL-12) and signal transducer and activator of transcription 4(STAT4) reduced to varying degrees (P<0.01,P<0.05).The mRNA of transcription factor GATA3 (binding protein-3),interleukin-4 (IL-4) and signal transducer and activator of transcription 6 (STAT6) in rat lung tissues and the protein expression levels of IL-4 and STAT6 were increased to varying degrees (P<0.01,P<0.05).In conclusion,anemoside B4 has a certain protective effect on COPD rats caused by cigarette smoke exposure and combined with LPS.The mechanism of action may be related to the regulation of IL-12/STAT4 and IL-4/STAT6 signaling pathways.

Effects of Eucommia ulmoides extract against renal injury caused by long-term high purine diets in rats.

Diets of overloaded purine-rich foods for a long time are one of the important reasons to cause renal lesions. Eucommia ulmoides is one of the traditional Chinese medicine herbs, which has been used to recover functions of the kidney. However, its mechanism remains unclear. The aim of this study was to explore the effects and protective mechanism of Eucommia ulmoides extract on renal injury caused by long-term high purine diets in rats. SD rats underwent an intragastric adenine (200 mg kg-1 d-1) administration for 9 weeks and were treated for 15 weeks. The results demonstrated that Eucommia ulmoides extract significantly reduced serum Cre and BUN levels in rats. H&E and Masson's trichrome stains showed notable lowering of the infiltration of inflammatory cells, the formation of fibrous tissues and collagen fibers, and improvement in the pathological morphology of kidneys. It also suppressed the protein and mRNA expressions of TGF-ß1 and α-SMA and enhanced E-cadherin expression. Meanwhile, Eucommia ulmoides extract prominently inhibited the mRNA expression of Col I, Col III, Col IV, TIMP-1, and TIMP-2 and promoted expressions of MMP-1, MMP-2 and MMP-9. Through our study, it is the first time to prove that Eucommia ulmoides extract could ameliorate renal interstitial fibrosis and may involve in the regulation of the extracellular matrix (ECM) degradation enzyme (MMPs/TIMPs) system, promotion of the expression of E-cadherin, and suppression of expressions of TGF-ß1 and α-SMA. The results provide a significant implication for the utilization of Eunomia Ulmoides extract as functional foods to enhance renal functions and improve renal injury caused by high purine diets.

Remote clinical training practice in the neurology internship during the COVID-19 pandemic.

Background: During the current COVID-19 pandemic, offline clinical education was mandated to suspend at the neurology department of many teaching hospitals globally, yet there is insufficient evidence regarding the preferred practice and methods for online neurology intern training course.Objective: The investigation aimed to examine whether the online neurology training course based on Small Private Online Course (SPOC) and blending learning mode can achieve a good effect and cater for interns from different medical programs and whether the learning group size affects the teaching effect.Design: The subjects were 92 students enrolled in the neurology internship at the Second Xiangya Hospital of China from 9 March to 9 August 2020. After completing the online course, the final scores and evaluation results were compared among different groups of interns, and their preference to distinct contents of the course was analyzed. Statistical analysis was performed using the SPSS program (version 22.0).Results: Our online course received consistent positive recognition from the interns. Ninety-nine percent of the interns recommended incorporating the online course into the conventional offline training program after the pandemic. There was no significant difference between interns from different programs concerning the final scores and course evaluation. A smaller learning group size (<15 students) could achieve a better teaching effect than a larger group size (p < 0.05). The interns preferred interactive discussions, and course contents that they can get practice and feedback from, rather than video watching and didactic lectures.Conclusions: The online neurology intern training course based on SPOC and blending learning mode is worthy of popularization in a large student base. The teaching effect of an online intern training program may be improved by limiting the group size to less than 15 students and encouraging more interactive discussion, more practice and feedback.

Latifolin protects against myocardial infarction by alleviating myocardial inflammatory via the HIF-1α/NF-κB/IL-6 pathway.

CONTEXT: The Traditional Chinese herb medicine Dalbergia odorifera T. Chen (Fabaceae), exerted a protective effect on myocardial ischaemia. Latifolin is a neoflavonoid extracted from Dalbergia odorifera. It has been reported to have the effects of anti-inflammation and cardiomyocyte protection. OBJECTIVE: To investigate whether latifolin can improve myocardial infarction (MI) through attenuating myocardial inflammatory and to explore its possible mechanisms. MATERIALS AND METHODS: Left coronary artery was ligated to induce a rat model of MI, and the rats were treated with sodium carboxymethyl cellulose (CMC-Na) or different doses of latifolin (25, 50, 100 mg/kg/d) by oral gavage for 28 days. Serum contents of myocardial enzyme were measured at seven and fourteen days after treatment. Cardiac function, infarct size, histopathological changes and inflammatory cells infiltration was assessed at 28 days after treatment. Western blotting was used to investigate the underlying mechanisms. RESULTS: Latifolin treatment markedly decreased the contents of myocardial enzymes, and increased left ventricular ejection fraction (85.27% vs. 59.11%) and left ventricular fractional shortening (62.71% vs. 45.53%). Latifolin was found to significantly reduced infarction size (27.78% vs. 39.07%), myocardial fibrosis and the numbers of macrophage infiltration (436 cells/mm2 vs. 690 cells/mm2). In addition, latifolin down-regulated the expression levels of hypoxia-inducible factor-1α (0.95-fold), phospho-nuclear factor-κB (0.2-fold) and interleukin-6 (1.11-fold). DISCUSSION AND CONCLUSIONS: Latifolin can protect against myocardial infarction by improving myocardial inflammation through the HIF-1α/NF-κB/IL-6 signalling pathway. Accordingly, latifolin may be a promising drug for pharmacological treatment of ischaemic cardiovascular disease.

A study on the hydrodynamic performance of manta ray biomimetic glider under unconstrained six-DOF motion.

A manta ray biomimetic glider is designed and studied with both laboratory experiments and numerical simulations with a new dynamic update method called the motion-based zonal mesh update method (MBZMU method) to reveal its hydrodynamic performance. Regarding the experimental study, an ejection gliding experiment is conducted for qualitative verification, and a hydrostatic free-fall experiment is conducted to quantitatively verify the reliability of the corresponding numerical simulation. Regarding the numerical simulation, to reduce the trend of nose-up movement and to obtain a long lasting and stable gliding motion, a series of cases with the center of mass offset forward by different distances and different initial angles of attack have been calculated. The results show that the glider will show the optimal gliding performance when the center of mass is 20mm in front of the center of geometry and the initial attack angle range lies between A0 = -5° to A0 = -2.5° at the same time. The optimal gliding distance can reach six times its body length under these circumstances. Furthermore, the stability of the glider is explained from the perspective of Blended-Wing-Body (BWB) configuration.

[Expression characteristics of inflammatory and apoptosis factors and regulatory effect of anemoside B4 in mice with acute kidney injury].

This paper was aimed to observe the effect of anemoside B4(hereinafter referred to as B4) on cisplatin-induced acute kidney injury in mice, and to investigate its possible mechanism in renal protection from inflammation and apoptosis aspects. Mice were divided into normal group, model group, dexamethasone positive group and B4 high, middle and low dose groups(5, 2.5, and 1.25 mg·kg~(-1 )doses). All the other mice groups except normal group were given with tail vein injection of cisplatin(15 mg·kg~(-1)) to induce acute kidney injury models. The drug administration was started on the day of modeling, and lasted for 4 days. After 1 hour of the last injection, orbital blood was collected. After the serum was separated, serum urea nitrogen(BUN), creatinine(Cre), total protein(TP), and albumin(ALB) were tested by using an automatic biochemical analyzer; the changes of kidney pathological morphology were observed by PAS staining; the protein expression levels of inflammatory factors including nucleotide binding oligomerization domain-like receptor(NLRP3), cysteinyl aspartate specific proteinase 1(caspase-1), interleukin-18(IL-18), interleukin-1ß(IL-1ß), tumor necrosis factor(TNF-α), and interleukin-6(IL-6) and apoptosis factors including p53, caspase-3, cleaved-caspase-3, Bcl-2 associated X protein(Bax), and B-cell lymphoma-2(Bcl-2) were analyzed by Western blot. The results showed that B4 significantly reduced the serum BUN and Cre contents, and alleviated pathological changes in renal tissues, such as the shedding and degeneration of renal tubular epithelial cells, tubulin tubule type. B4 significantly down-regulated the protein expressions of p53, Bax, cleaved-caspase-3 in the kidney and up-regulated the expression of Bcl-2/Bax. In model group, however, no significant up-regulation was observed in the protein expression levels of inflammatory cytokines(NLRP3, pro-caspase-1, IL-18, IL-1ß, TNF-α, IL-6). The results suggested that B4 had a certain protective effect on cisplatin-induced acute kidney injury, and could activate p53 signaling pathway related apoptotic factors. B4 renal protective effect was mainly related to the regulation of p53 signaling pathway, while NLRP3 inflammasome and related inflammatory factors had no obvious response in this model.

[Study on therapeutic effect and its related mechanism of anemoside B4 on ischemia reperfusion injury induced by renal artery and vein ligation in rats].

The aim of this paper was to investigate the effect and mechanism of anemoside B4 on renal ischemia reperfusion injury in rats. A total of 50 rats were randomly divided into the model group(NS) and anemoside B4 low-dose(1.25 mg·kg~(-1)), medium-dose(2.5 mg·kg~(-1)) and high-dose(5 mg·kg~(-1)) groups after the right kidney was removed and the left kidney was ligated to make the ischemia reperfusion model. Another 10 rats were selected as sham operation group only for normal control group(NS, received normal saline). Automatic biochemical analyzer was used to measure serum blood urea nitrogen(BUN), creatinine(Cre), cerebrospinal fluid(CSF) and urinemicroalbumin(mALB) levels after 5 days of tail vein injection treament. Total urine protein and total urinary albu-min were calculated and kidney samples were collected. Histopathological changes of renal tissues were observed by PAS staining. Western blot analysis was performed to detect the protein expressions of TLR4 and NF-κB in renal inflammatory factors related to NLRP3 pathway and TLR4/NF-κB pathway. The results showed that the levels of BUN, Cre, urinary total protein and urinary total albumin in the model group were significantly increased(P<0.01), with severe renal tubule injury was serious, manifested by obvious expansion of renal tubules, more serious tubular proteins, and some tubular epithelial cells were exfoliated. At the same time, the expression of inflammatory factors related to NLRP3 pathway and TLR4/NF-κB pathway increased significantly(P<0.01 or P<0.05). The levels of BUN, Cre were reduced in different doses of anemoside B4(P<0.05). The levels of total urinary protein and total urinary albumin were decreased in the low and high dose groups of anemoside B4.The level of total urinary albumin in the high-dose group of anemoside B4 was significantly reduced(P<0.05).Renal tubular injury was alleviated, tubular epithelial cell exfoliation was reduced, and the expression of related inflammatory factors was reduced in different degrees(P<0.01 or P<0.05). This study showed that anemoside B4 could alleviate renal ischemia-reperfusion injury in rats. And its mechanism may be related to the inhibition of inflammatory factors related to response mediated by NLRP3 pathway and TLR4/NF-κB pathway by anemoside B4.

Inhibitory Effect of Corilagin on miR-21-Regulated Hepatic Fibrosis Signaling Pathway.

Corilagin is a polyphenol that can be extracted from many medicinal plants and shows multiple pharmacological effects. We aimed to investigate the role of corilagin on miR-21-regulated hepatic fibrosis, especially miR-21-regulated TGF-ß1/Smad signaling pathway, in hepatic stellate LX2 cell line and Sprague-Dawley rats. The mRNA or protein levels of miR-21, Smad7, connective tissue growth factor (CTGF), α-smooth muscle actin (α-SMA), tissue inhibitor of metalloproteinase-1 (TIMP-1), matrix metalloproteinase-9 (MMP-9), collagen type I alpha 1 (COL1A1), Smad2, Smad3, Smad2/3, p-Smad2, p-Smad3, p-Smad2/3, and transforming growth factor-ß1 (TGF-ß1) in LX2 cells and liver tissues were determined. Furthermore, gain-of and loss-of function of miR-21 in miR-21-regulated TGF-ß1/Smad signaling pathway were analyzed in LX2 cells. Liver tissues and serum were collected for pathological analysis, immunohistochemical staining, and enzyme-linked immunosorbent assay (ELISA). Corilagin treatment reduced mRNA or protein levels of miR-21, CTGF, α-SMA, TIMP-1, TGF-ß1, COL1A1, p-Smad2, p-Smad3, and p-Smad2/3 both in vitro and in vivo. While corilagin increased mRNA and protein levels of Smad7 and MMP-9. After gain-of and loss-of function of miR-21, the downstream effectors of miR-21-regulated TGF-ß1/Smad signaling pathway in LX2 cells changed accordingly, and the changes were inhibited by corilagin. Simultaneously, administration of corilagin not only ameliorated pathological manifestation of liver fibrosis but also reduced levels of α-SMA and COL1A1 in liver tissues and TGF-ß1, ALT levels in serum. Corilagin is able to potentially prevent liver fibrosis by blocking the miR-21-regulated TGF-ß1/Smad signaling pathway in LX2 cells and CCl4-induced liver fibrosis rats, which may provide a novel therapeutic strategy for liver fibrosis.

Procyanidin A1 Alleviates Inflammatory Response induced by LPS through NF-κB, MAPK, and Nrf2/HO-1 Pathways in RAW264.7 cells.

Inflammation is a complex physiological process that poses a serious threat to people's health. However, the potential molecular mechanisms of inflammation are still not clear. Moreover, there is lack of effective anti-inflammatory drugs that meet the clinical requirement. Procyanidin A1 (PCA1) is a monomer component isolated from Procyanidin and shows various pharmacological activities. This study further demonstrated the regulatory role of PCA1 on lipopolysaccharide (LPS)-stimulated inflammatory response and oxidative stress in RAW264.7 cells. Our data showed that PCA1 dramatically attenuated the production of pro-inflammatory cytokines such as NO, iNOS, IL-6, and TNF-α in RAW264.7 cells administrated with LPS. PCA1 blocked IκB-α degradation, inhibited IKKα/ß and IκBα phosphorylation, and suppressed nuclear translocation of p65 in RAW264.7 cells induced by LPS. PCA1 also suppressed the phosphorylation of JNK1/2, p38, and ERK1/2 in LPS-stimulated RAW264.7 cells. In addition, PCA1 increased the expression of HO-1, reduced the expression of Keap1, and promoted Nrf2 into the nuclear in LPS-stimulated RAW264.7 cells. Cellular thermal shift assay indicated that PCA1 bond to TLR4. Meanwhile, PCA1 inhibited the production of intracellular ROS and alleviated the depletion of mitochondrial membrane potential in vitro. Collectively, our data indicated that PCA1 exhibited a significant anti-inflammatory effect, suggesting that it is a potential agent for the treatment of inflammatory diseases.

Anemoside B4 Protects Rat Kidney from Adenine-Induced Injury by Attenuating Inflammation and Fibrosis and Enhancing Podocin and Nephrin Expression.

Anemoside B4 (B4) isolated from Radix Pulsatilla has anti-inflammatory activities in the colon and antitumor effects. However, its role in the prevention and treatment of kidney injury has not been reported. Here, we reported the effects of B4 on chronic kidney injury (CKI) and studied its related mechanism based on an adenine-induced kidney injury model in rats. The results showed that serum BUN (blood urea nitrogen), Crea (creatinine), and urinary proteins increased significantly after oral administration of adenine. Meanwhile, the adenine contents in both renal tissue and urine increased markedly compared with those of normal rats. Moreover, IL-1ß, IL-6, TNFα, and NFκB expression was upregulated in the kidney. Simultaneously, the expression of NLRP3 (the nucleotide-binding and oligomerization domain-like receptor, leucine-rich repeat and pyrin domain-containing 3) in the inflammasome, which consists of Caspase 1, ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain), and IL-18, was significantly upregulated. B4 could significantly decrease BUN and Crea; reduce urinary proteins in rats; suppress the expression of IL-6, IL-1ß, NFκB, NLRP3, Caspase 1, ASC, and IL-18; and increase urinary adenine contents and promote its excretion. In addition, B4 also upregulated the expression of podocin and nephrin, two major podocyte proteins, and reduced the fiber collagen in the renal interstitial, suggesting that B4 could protect the glomerular matrix from adenine injury in addition to its anti-inflammatory effects. The results of this study show new perspective of B4 as a potential drug against adenine-induced renal injury.

Association between KIF1B rs17401966 genetic polymorphism and hepatocellular carcinoma susceptibility: an updated meta-analysis.

BACKGROUND: Several studies have focused on the association between KIF1B rs17401966 polymorphism and susceptibility to hepatitis B virus-related (HBV-related) hepatocellular carcinoma (HCC), but the conclusions have been inconsistent. We have conducted this updated meta-analysis to explore the association between KIF1B rs17401966 polymorphism and HCC susceptibility. METHODS: Eligible studies were identified through systematic searches in PubMed, OVID, ISI Web of Science, Chinese National Knowledge Infrastructure, and Wanfang databases. The quality of evidence was systematically assessed by use of the Newcastle-Ottawa Scale for case control studies in meta-analyses. RESULTS: Ten studies containing 18 independent case-control studies were included. The results revealed a significant association between KIF1B rs17401966 polymorphism and susceptibility to HCC under a random-effect allelic model (OR = 0.85, 95% CI 0.76-0.94, P = 0.003); HBV-positive subgroup (OR = 0.82, 95% CI 0.72-0.95, P = 0.007); and Chinese-subgroup (OR = 0.82, 95% CI 0.72-0.93, P = 0.002). CONCLUSIONS: G-allele appears to be a protective allele of KIF1B for HCC, especially in HBV-positive and Chinese populations. More well-designed studies with larger sample size and various ethnic groups and risk factors are needed to establish that KIF1B rs17401966 polymorphism is significantly associated with risk of HCC.

Dihydrotanshinone exhibits an anti-inflammatory effect in vitro and in vivo through blocking TLR4 dimerization.

Dihydrotanshinone (DHT), one of the major ingredients of Salvia miltiorrhiza Bunge (Danshen), displays many bioactivities. However, the activity and underlying mechanism of DHT in anti-inflammation have not yet been elucidated. In this study, we investigated the anti-inflammatory activity and molecular mechanism of action of DHT both in vitro and in vivo. Our data showed that DHT significantly decreased the release of inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1ß in lipopolysaccharide (LPS)-stimulated RAW264.7 cells, THP-1 cells, and bone marrow-derived macrophages (BMDMs), and altered the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). In addition, flow cytometry results indicated that DHT reduced the calcium influx, and generation of reactive oxygen species (ROS), and nitric oxide (NO) generation in LPS-stimulated RAW264.7 cells. Moreover, DHT suppressed the transcription of nuclear factor-κB (NF-κB), the expressions of NF-κB proteins, and nuclear translocation of NF-κB/p65, thereby suggesting that the NF-κB pathway played a role in the anti-inflammatory action of DHT. In addition, DHT attenuated LPS-challenged activator protein-1 (AP-1) activity, resulting from interference of the mitogen-activated protein kinase (MAPK) pathway. The molecular docking simulation of DHT to toll-like receptor 4 (TLR4) suggested that DHT binds to the active sites of TLR4 to block TLR4 dimerization, which was further corroborated by cellular thermal shift assay and co-immunoprecipitation (Co-IP) experiments. Furthermore, the recruitment of myeloid differentiation primary response gene 88 (MyD88) and the expression of transforming growth factor-b (TGF-b)-activated kinase 1 (p-TAK1) were disturbed by the inhibition of TLR4 dimerization. Thus, investigating the molecular mechanism of DHT indicated that TLR4-MyD88-NF-κB/MAPK signaling cascades were involved in the anti-inflammatory activity of DHT in vitro. In in vivo mouse models, DHT significantly ameliorated LPS-challenged acute kidney injury, inhibited dimethylbenzene-induced mouse ear oedema, and rescued LPS-induced sepsis in mice. Taken together, our results indicated that DHT exhibited significant anti-inflammatory activity both in vitro and in vivo, suggesting that DHT may be a potential therapeutic agent for inflammatory diseases.

Proteomic profiling of the neurons in mice with depressive-like behavior induced by corticosterone and the regulation of berberine: pivotal sites of oxidative phosphorylation.

Chronic corticosterone (CORT) stress is an anxiety and depression inducing factor that involves the dysfunction of glucocorticoid receptor (GR), brain-derived neurotrophic factor (BDNF), and neuronal plasticity. However, the regulation of proteomic profiles in neurons suffering CORT stress is remaining elusive. Thus, the proteomic profiles of mouse neuronal C17.2 stem cells were comprehensively investigated by TMT (tandem mass tag)-labeling quantitative proteomics. The quantitative proteomics conjugated gene ontology analysis revealed the inhibitory effect of CORT on the expression of mitochondrial oxidative phosphorylation-related proteins, which can be antagonized by berberine (BBR) treatment. In addition, animal studies showed that changes in mitochondria by CORT can affect neuropsychiatric activities and disturb the physiological functions of neurons via disordering mitochondrial oxidative phosphorylation. Thus, the mitochondrial energy metabolism can be considered as one of the major mechanism underlying CORT-mediated depression. Since CORT is important for depression after traumatic stress disorder, our study will shed light on the prevention and treatment of depression as well as posttraumatic stress disorder (PTSD).

Identification of Compounds Targeting Hepatitis B Virus Core Protein Dimerization through a Split Luciferase Complementation Assay.

The capsid of the hepatitis B virus is an attractive antiviral target for developing therapies against chronic hepatitis B infection. Currently available core protein allosteric modulators (CpAMs) mainly affect one of the two major types of protein-protein interactions involved in the process of capsid assembly, namely, the interaction between the core dimers. Compounds targeting the interaction between two core monomers have not been rigorously screened due to the lack of screening models. We report here a cell-based assay in which the formation of core dimers is indicated by split luciferase complementation (SLC). Making use of this model, 2 compounds, Arbidol (umifenovir) and 20-deoxyingenol, were identified from a library containing 672 compounds as core dimerization regulators. Arbidol and 20-deoxyingenol inhibit the hepatitis B virus (HBV) DNA replication in vitro by decreasing and increasing the formation of core dimer and capsid, respectively. Our results provided a proof of concept for the cell model to be used to screen new agents targeting the step of core dimer and capsid formation.