Inhibition of miR-29a-3p Alleviates Apoptosis of Lens Epithelial Cells via Upregulation of CAND1.

PURPOSE: Accumulated evidence has shown that microRNAs (miRNAs) are closely related to the pathogenesis and progression of senile cataracts. Here we investigate the effect of miR-29a-3p in cataractogenesis and determined the potential molecular mechanism involved. METHODS: In this study, we constructed a selenite cataract model in rats and obtained the miRNAs related to cataracts by whole transcriptome sequencing. To investigate the effect and mechanism of miR-29a-3p on cataracts, we performed several in vivo and in vitro experiments, including CCK8 assay, flow cytometry, luciferase reporter assay, Edu assay, and western blot analysis. RESULT: Sequencing data showed downregulation of miR-29a-3p in rats with selenite cataracts. Down-regulation of miR-29a-3p could promote lens epithelial cells (SRA01/04) proliferation and inhibit cell apoptosis, and miR-29a-3p silence could inhibit the development of cataracts. Additionally, CAND1 was a direct target gene for miR-29a-3p. CONCLUSION: These data demonstrate that miR-29a-3p inhibits apoptosis of lens epithelial cells by regulating CAND1, which may be a potential target for senile cataracts.

CCL2 Knockdown Attenuates Inflammatory Response After Spinal Cord Injury Through the PI3K/Akt Signaling Pathway: Bioinformatics Analysis and Experimental Validation.

Spinal cord injury (SCI) is a common clinical problem in orthopedics with a lack of effective treatments and drug targets. In the present study, we performed bioinformatic analysis of SCI datasets GSE464 and GSE45006 in the Gene Expression Omnibus (GEO) public database and experimentally validated CCL2 expression in an animal model of SCI. This was followed by stimulation of PC-12 cells using hydrogen peroxide to construct a cellular model of SCI. CCL2 expression was knocked down using small interfering RNA (si-CCL2), and PI3K signaling pathway inhibitors and activators were used to validate and observe the changes in downstream inflammation. Through data mining, we found that the inflammatory chemokine CCL2 and PI3K/Akt signaling pathways after SCI expression were significantly increased, and after peroxide stimulation of PC-12 cells with CCL2 knockdown, their downstream cellular inflammatory factor levels were decreased. The PI3K/Akt signaling pathway was blocked by PI3K inhibitors, and the downstream inflammatory response was suppressed. In contrast, when PI3K activators were used, the inflammatory response was enhanced, indicating that the CCL2-PI3K/Akt signaling pathway plays a key role in the regulation of the inflammatory response. This study revealed that the inflammatory chemokine CCL2 can regulate the inflammatory response of PC-12 cells through the PI3K/Akt signaling pathway, and blocking the expression of the inflammatory chemokine CCL2 may be a promising strategy for the treatment of secondary injury after SCI.

Transcriptome sequencing and microRNA-mRNA regulatory network construction in the lens from a Na2SeO3-induced Sprague Dawley rat cataract model.

BACKGROUND: A sight-threatening, cataract is a common degenerative disease of the ocular lens. This study aimed to explore the regulatory mechanism of age-related cataract (ARC) formation and progression. METHODS: Cataracts in Sprague Dawley rats were induced by adopting the method that injected selenite subcutaneously in the nape. We performed high-throughput RNA sequencing technology to identify the mRNA and microRNA(miRNA) expression profiles of the capsular membrane of the lens from Na2SeO3-induced and saline-injected Sprague Dawley rats. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were carried out to forecast the regulatory and functional role of mRNAs in cataracts by DAVID and Metascape. The protein-protein interaction(PPI) network of differentially expressed mRNA(DEmRNAs) was built via the STRING. Target miRNAs of hub genes were predicted by miRBD and TargetScan. Furthermore, differentially expressed miRNA(DEmiRNAs) were selected as hub genes' targets, validated by quantitative real-time polymerase chain reaction(qRT-PCR), and a DEmiRNA-DEmRNA regulatory network was constructed via Cytoscape. RESULT: In total, 329 DEmRNAs including 40 upregulated and 289 downregulated genes were identified. Forty seven DEmiRNAs including 29 upregulated and 18 downregulated miRNAs were detected. The DEmRNAs are involved in lens development, visual perception, and aging-related biological processes. A protein-protein interaction network including 274 node genes was constructed to explore the interactions of DEmRNAs. Furthermore, a DEmiRNA-DEmRNA regulatory network related to cataracts was constructed, including 8 hub DEmRNAs, and 8 key DEmiRNAs which were confirmed by qRT-PCR analysis. CONCLUSION: We identified several differentially expressed genes and established a miRNA-mRNA-regulated network in a Na2SeO3-induced Sprague Dawley rat cataract model. These results may provide novel insights into the clinical treatment of cataracts, and the hub DEmRNAs and key DEmiRNAs could be potential therapeutic targets for ARC.

CircRNA 06209 inhibits cataract development by sponging miR-6848-5p and regulating ALOX15 expression.

Cataract is the leading cause of blindness in the world, and there is a lack of effective treatment drugs. CircRNA plays an important part in a variety of diseases, however, the role of circRNA in cataracts remains largely unknown. In this study, we constructed a cataract model of rats and obtained the circRNAs related to cataracts by whole transcriptome sequencing and circRNA-mRNA co-expression network. To investigate the effect and mechanism of circRNA 06209 on cataracts, we performed several in vivo and in vitro experiments, including CCK8 assay, flow cytometry, dual luciferase reporter assay, RIP assay, actinomycin D assay, and Western blot analysis. We identify that a necroptosis-related circRNA, circRNA 06209, is down-regulated in cataracts. Vitro experiments showed that up-regulation of circRNA 06209 could promote cell proliferation and inhibit cell apoptosis. Vivo experiments revealed that circRNA 06209 overexpression could inhibit the development of cataracts. Mechanistically, circRNA 06209 acts as a miRNA sponge and competitively binds to miR-6848-5p to curb the inhibitory effect of miR-6848-5p on ALOX15, thereby affecting cell viability and apoptosis. This study found that circRNA 06209 plays a critical part in inhibiting cataracts through the miR-6848-5p/ALOX15 pathway, suggesting that circRNA 06209 may be a promising therapeutic target for cataracts.

Mechanisms involved in the HMGB1 modulation of tumor multidrug resistance (Review).

Tumor multidrug resistance (MDR) remains one of the most challenging barriers to successful cancer treatment. Several previous studies have suggested that high mobility group box 1 (HMGB1) may be a promising therapeutic target for overcoming cancer drug resistance. Emerging evidence has indicated that HMGB1 functions as a 'double­edged sword' that plays both pro­ and anti­tumor roles in the development and progression of multiple types of cancer. HMGB1 has also been found to be a key regulator of several cell death and signaling pathways, and is involved in MDR by mediating cell autophagy and apoptosis, ferroptosis, pyroptosis and multiple signaling pathways. Additionally, HMGB1 is regulated by a variety of non­coding RNAs (ncRNAs), such as microRNAs, long ncRNAs and circular RNAs that are involved in MDR. Thus far, studies have been conducted to identify strategies with which to overcome HMGB1­mediated MDR by the targeted silencing of HMGB1 and the targeted interference of HMGB1 expression using drugs and ncRNAs. Therefore, HMGB1 is closely associated with tumor MDR and is a promising therapeutic target.

[Network Meta-analysis of Qi-benefiting and blood-activating Chinese patent medicines against ischemic stroke].

This study aimed to compare the efficacy of Qi-benefiting and blood-activating Chinese patent medicines in the treatment of ischemic stroke with network Meta-analysis. CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, and Cochrane Library were searched from database inception to October 2022 for randomized controlled trial(RCT) on 11 Qi-benefiting and blood-activating Chinese patent medicines in the treatment of ischemic stroke. The risk of bias plot was made by RevMan 5.3, and network Meta-analysis and efficacy ranking were performed by Stata 17. Ninety-two RCTs were included, involving 10 608 patients. According to the network Meta-analysis, in terms of the clinical total effective rate, surface under the cumulative ranking curve(SUCRA) as followed: Qilong Capsules+conventional western medicine>Zhishe Tongluo Capsules+conventional western medicine>Longshengzhi Capsules+conventional western medicine>Naoxintong Capsules+conventional western medicine>Tongsaimai Tablets+conventional western medicine>Naoan Capsules+conventional western medicine>Naoluotong Capsules+conventional western medicine>Xiaoshuan Changrong Capsules+conventional western medicine>Dengzhan Shengmai Capsules+conventional western medicine=Tongxinluo Capsules+conventional western medicine>Naomaitai Capsules+conventional western medicine. In terms of the improvement in National Institute of Health stroke scale(NIHSS) score, SUCRA as followed: Longshengzhi Capsules+conventional western medicine>Naomaitai Capsules+conventional western medicine>Naoxintong Capsules+conventional western medicine>Dengzhan Shengmai Capsules+conventional western medicine>Xiaoshuan Changrong Capsules+conventional western medicine>Naoluotong Capsules+conventional western medi-cine>Tongxinluo Capsules+conventional western medicine>Naoan Capsules+conventional western medicine>Qilong Capsules+conventional western medicine. In terms of safety, the overall adverse reactions/events of Qi-benefiting and blood-activating Chinese patent medicines + conventional western medicine were less than those of the control group. Since Qilong Capsules+conventional western medicine and Zhishe Tongluo Capsules+conventional western medicine were preferred to improve the clinical total effective rate. In the aspect of improving NIHSS score, Longshengzhi Capsules+conventional western medicine and Naomaitai Capsules+conventional western medicine were first options. Due to the lack of direct comparisons between drugs, the overall quality of RCT was not high, so more studies are needed to verify the strength of the evidence.

[Mammalian DMRTs: Structure, function and relationship with cancer].

DMRT, a gene family related to sexual determination, encodes a large group of transcription factors (DMRTs) with the double-sex and mab-3 (DM) domain (except for DMRT8), which is able to bind to and regulate DNAs. Current studies have shown that the DMRT gene family plays a critical role in the development of sexual organs (such as gender differentiation, gonadal development, germ cell development, etc.) as well as extrasexual organs (such as musculocartilage development, nervous system development, etc.). Additionally, it has been suggested that DMRTs may be involved in the cancer development and progression (such as prostate cancer, breast cancer, lung cancer, etc.). This review summarizes the research progress about the mammalian DMRTs' structure, function and its critical role in cancer development, progression and therapy (mainly in human and mice), which suggests that DMRT gene could be a candidate gene in the study of tumor formation and therapeutic strategy.

Computational evaluation of the axis-blade angle for measurements of implant positions in trochanteric hip fractures: A finite element analysis.

BACKGROUND: Recently, a novel approach axis-blade angle (ABA) was developed to measure implant positions during trochanteric hip fracture surgery. It was defined as the sum of two angles α and ß measured between the femoral neck axis and helical blade axis in anteroposterior and lateral X-ray films, respectively. Although its clinical practicability has been confirmed, the mechanism is yet to be investigated by means of finite element (FE) analysis. METHODS: Computed tomography images of four femurs and dimensions of one implant at three angles were obtained to construct FE models. For each femur, 15 FE models in an arrangement (intramedullary nails at three angles multiplying five blade positions) were established. Under the simulation of normal walking loads, the ABA, von Mises stress (VMS), maximum/minimum principal strain and displacement were analyzed. RESULTS: When the ABA increased, all outcome indicators initially decreased till reaching inferior-middle site and then increased while the blade positions within the femoral head shifted from the superior-anterior quadrant toward the inferior-posterior quadrant, where the ABA were higher. Only the peak VMS of implant models in the inferior-posterior quadrant (particularly the inferior-middle site within) with blades in did not reach the yielding (risky) cut-off. CONCLUSIONS: From the perspective of angles, ABA, this study demonstrated the inferior-posterior quadrant as the relatively stable and safe regions, especially the inferior-middle site within. This was similar but more elaborate compared with previous studies and clinical practice. Therefore, ABA could be employed as a promising approach to anchor the implants into the optimal region.

Removal of Fermentation Inhibitors from Sugarcane Bagasse Hydrolysate via Post-cross-linked Hydrophilic-Hydrophobic Interpenetrating Polymer Networks.

The efficient and economical removal of fermentation inhibitors from the complex system of biomass hydrolysate was one of the basics and keys in bio-chemical transformation. In this work, post-cross-linked hydrophilic-hydrophobic interpenetrating polymer networks (PMA/PS_pc IPNs and PAM/PS_pc IPNs) were proposed to remove fermentation inhibitors from sugarcane bagasse hydrolysate for the first time. PMA/PS_pc and PAM/PS_pc IPNs can obviously enhance the adsorption performance towards fermentation inhibitors due to their higher surface area and hydrophilic-hydrophobic synergetic surface properties, especially PMA/PS_pc IPNs has higher selectivity coefficients of 4.57, 4.63, 4.85, 16.0, 49.43, and 22.69, and higher adsorption capacity of 24.7 mg/g, 39.2 mg/g, 52.4 mg/g, 9.1 mg/g, 13.2 mg/g, and 144.9 mg/g towards formic acid, acetic acid, levulinic acid (LA), 5-hydroxymethylfurfural (HMF), furfural, and acid-soluble lignin (ASL), respectively, in a lower total sugar loss of 2.03%. The adsorption kinetics and isotherm of PMA/PS_pc IPNs were studied to elucidate its adsorption behavior towards fermentation inhibitors. In addition, the cyclic utilization property of PMA/PS_pc IPNs was stable. Synthesizing PMA/PS_pc IPNs is a new strategy to provide an efficient adsorbent for the removal of fermentation inhibitors from lignocellulosic hydrolysate.

Regenerated cellulose as template for in-situ synthesis of monoclinic titanium dioxide nanocomposite carbon aerogel towards multiple application in water treatment.

Immobilizing catalyst system faces the challenge of balancing catalysts stability and exposure of active site in water treatment. In this study, a novel in-situ synthesis of monoclinic phase of titanium dioxide (TiO2(B)) in cellulose-derived carbon aerogel (TCA) is proposed for processing multi-task in water treatment. The homogeneous gelation reaction supported the high dispersion of TiO2(B) in carbon skeleton. Meanwhile, TiO2 acts as crosslinker to reinforce cellulose network, then the grain refinement of amorphous TiO2 is limited to obtain TiO2(B) during carbonization. Benefiting from the reinforced structure, TCA remains the porous structure after carbonization and exposes more adsorption site than carbon aerogel blended with anatase particles (ACA). The adsorption performance of TCA are 837.3 mg/g, 1156.2 mg/g and 512.6 mg/g on methylene blue, malachite green and crystal violet, respectively. Compared with ACA, the superior interaction between TiO2 and graphite-like carbon improves the degradation rate of tetracycline from 1.3 × 10-3 min-1 to 8.6 × 10-3 min-1, and maintains the degradation efficiency in 3 rounds cyclic test. Besides, TCA also exhibits nearly twice to ACA on absorption capacity of different oil. This facile in-situ synthesis method offers a new insight in fabricating carbon aerogel immobilized photocatalysts system for multi-task in water treatment.

Overexpression of MiR-633 Suppresses the Tumorigenicity of Gastric Cancer Cells and Induces Apoptosis by Targeting MAPK1.

OBJECTIVE: MicroRNA (miRNA/miR)-633 is dysregulated in several types of cancers and is involved in tumorigenesis. However, the function and role of this miRNA in gastric cancer (GC) are not fully understood. The aim of the present study was to evaluate miR-633 expression in GC cell lines and in GC tissue vs. adjacent normal tissue, and to determine its association with clinicopathological data. This work was extended to investigate the effects of miR-633 overexpression on tumor cells in vitro. METHODS: Reverse transcription-quantitative PCR (RT-qPCR) was used to detect and compare the expression level of miR-633 in GC cells, as well as in GC and normal adjacent tissue samples. The clinical significance of miR-633 was also analyzed. MiR-633 lentivirus (LV-miR-633) and negative control lentivirus (LV-NC) were generated and used to transduce SGC-7901 and HGC-27 GC cells in order to analyze the effect of miR-633 on their phenotype. The effects of miR-633 overexpression on GC cell proliferation, apoptosis, migration and invasion were investigated. The target gene of miR-633 was predicted, then confirmed using a dual luciferase reporter gene assay, RT-qPCR and Western blotting. RESULTS: MiR-633 was significantly downregulated in GC cell lines, as well as in GC tissue compared with adjacent normal tissue. Moreover, miR-633 expression was associated with the tumor/node/metastasis (TNM) stage, invasion depth, Borrmann classification and lymph node metastasis (P<0.05). Compared with the LV-NC group, transduction with LV-miR-633 reduced the proliferation, the number of clones, the wound healing rate, the number of invading cells and the number of cells in the G1 phase of the cell cycle (P<0.01). LV-miR-633 also increased the apoptosis rate (P<0.01). The expression level of mitogen-activated protein kinase (MAPK) 1, high-mobility group box 3 (HMGB3), claudin 1 (CLDN1) and MAPK13 were downregulated in LV-miR-633-transduced cells (P<0.01). The dual luciferase reporter assay confirmed that the 3'-untranslated region of MAPK1 was the target site of miR-633 (P<0.01). CONCLUSION: MiR-633 acts as a tumor suppressor in GC, and its expression level is associated with TNM stage, invasion depth, Borrmann type and lymph node metastasis. Overexpression of miR-633 inhibits the proliferation and migration of GC cells and induces apoptosis and cell cycle arrest at the in G1 phase. In addition, miR-633 negatively regulates the expression of MAPK1, HMGB3, CLDN1 and MAPK13 and directly targets MAPK1.

Drug-Related Problems of Children With Chronic Diseases in a Chinese Primary Health Care Institution: A Cross-Sectional Study.

Introduction: Drug-related problems (DRPs) refer to events or circumstances involving drug therapy that actually or potentially interfere with desired health outcomes. DRPs might be severe for children with chronic diseases managed at primary health care institutions, but the relevant research is scarce. Objective: In this cross-sectional study, we aimed to explore the prevalence, types, causes, and influencing factors of DRPs in children with chronic diseases in a Chinese primary health care institution. Methods: We recruited children with chronic diseases who visited the pediatric outpatient department in a primary health care institution from July 1 to 12 October 2021. Clinical pharmacists identified DRPs through medication therapy reviews, classified the types and causes of DRPs, and distinguished the manifested DRPs that affected the outcome and potential DRPs that were going to affect the outcome. Results: A total of 188 children with chronic diseases was included, and 584 DRPs were identified in 89.89% of participants. The most common type of DRPs was "treatment effectiveness" (a manifested problem or potential problem with the effect of the pharmacotherapy; 83.56%), of which 67.29% were potential DRPs. The second common type was "treatment safety" (patient suffers or could suffer from an adverse drug event; 14.21%), of which 89.16% were potential DRPs. The most common cause of DRPs was related to the process of use (42.24%), such as "patient uses/takes less drug than prescribed or does not take the drug at all," "patient stores drug inappropriately," and "patient administers/uses the drug in a wrong way." The second common cause was related to the process of dispensing (29.83%), such as "necessary information not provided or incorrect advice provided" and "prescribed drug is not available." The third common cause was related to the process of prescribing (26.21%), such as "drug dose is too low" and "no or incomplete drug treatment despite an existing indication." The number of combined medications was an influencing factor for the frequency of DRPs (p < 0.05). Conclusion: This cross-sectional study showed that the current situation regarding DRPs among children with chronic diseases managed in the primary health care institution was serious. The types of DRPs were mainly related to treatment effectiveness, and improper usage of medications was one of the main causes of DRPs. The number of combined drugs was the influencing factor for the frequency of DRPs. In the future, pharmacists should consider formulating pharmaceutical intervention strategies for this specific group according to the characteristics of DRPs.

Small biomarkers with massive impacts: PI3K/AKT/mTOR signalling and microRNA crosstalk regulate nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumours of the head and neck in Southeast Asia and southern China. The Phosphatidylinositol 3-kinase/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signalling pathway is involved in processes related to tumour initiation/progression, such as proliferation, apoptosis, metastasis, and drug resistance, and is closely related to the clinicopathological features of NPC. In addition, key genes involved in the PI3K/AKT/mTOR signalling pathway undergo many changes in NPC. More interestingly, a growing body of evidence suggests an interaction between this signalling pathway and microRNAs (miRNAs), a class of small noncoding RNAs. Therefore, in this review, we discuss the interactions between key components of the PI3K/AKT/mTOR signalling pathway and various miRNAs and their importance in NPC pathology and explore potential diagnostic biomarkers and therapeutic targets.

The Mechanism of Dendrobium officinale as a Treatment for Hyperlipidemia Based on Network Pharmacology and Experimental Validation.

Materials and Methods: The active compounds in DO, their targets, and targets associated with hyperlipidemia were screened across various databases, and the hidden targets of DO in treating hyperlipidemia were forecast. The compound-target (C-T), protein-protein interaction (PPI), and compound-target-pathway (C-T-P) networks of DO were set up with Cytoscape software. The hub genes and core clusters of DO predicted to be active against hyperlipidemia were calculated by Cytoscape. The DAVID database was adopted for Gene Ontology (GO) analysis and KEGG pathway enrichment analysis. Next, we used the high-sucrose-fat diet and alcohol (HFDA)-induced hyperlipidemia rats to evaluate the hypolipidemic effect of DO. Results: In this study, we obtained 264 compounds from DO, revealed 11 bioactive compounds, and predicted 89 potential targets of DO. The network analysis uncovered that naringenin, isorhamnetin, and taxifolin might be the compounds in DO that are mainly in charge of its roles in hyperlipidemia and might play a role by modulating the targets (including PPARG, ADIPOQ, AKT1, TNF, and APOB). The pathway analysis showed that DO might affect diverse signaling pathways related to the pathogenesis of hyperlipidemia, including PPAR signaling pathway, insulin resistance, AMPK signaling pathway, and non-alcoholic fatty liver disease simultaneously. Meanwhile, in the HFDA-induced hyperlipidemia rat model, DO could significantly decrease the level of TC, TG, LDL-c, and ALT in serum, and increase HDL-c as well. The liver pathological section indicated that DO could ease liver damage and lipid cumulation. Conclusion: In summary, the biological targets of the main bioactive compounds in DO were found to distribute across multiple metabolic pathways. These findings suggest that a mutual regulatory system consisting of multiple components, targets, and pathways is a likely mechanism through which DO may improve hyperlipidemia. Validation experiments indicated that DO may treat hyperlipidemia by affecting NAFLD-related signaling pathways.

[Effects of Zhongfeng capsule on autophagy related proteins expressions of brain tissue in rats with cerebral ischemia/reperfusion injury].

Objective: To investigate the effects of Zhongfeng capsule on the autophagy-related proteins expression in rats with cerebral ischemia/reperfusion injury (CI/ RI), and to explore its neural protection mechanisms of the decoction. Methods: Rat middle cerebral artery ischemia/reperfusion injury model (ischemia for 2 h, reperfusion for 24 h) was prepared by the improved line plug method. Sixty male SD rats were randomly divided into sham operation group, model group, butylphthalide group(0.054 g/kg), Zhongfeng capsule high-dose groups (1.08 g/kg), Zhongfeng capsule middle-dose groups (0.54 g/kg), Zhongfeng capsule low-dose groups (0.27 g/kg), with 10 rats in each group. Rats were treated with Zhongfeng capsule by gavage once a day for 10 days. The rats were sacrificed and the brain tissue was obtained after the experiment in each group. Score neurological deficit was evaluated after 24 h of the last intervention in rat of each group. The pathological changes of brain tissue were observed by HE staining. The serum levels of estradiol (E2) and follicle stimulating hormone (FSH) were determined by ELISA. The expressions of key genes and proteins of PI3K/Akt/Beclin1 signaling pathway in brain tissue were detected by qRT-PCR and Western blot respectively. Results: Compared with the sham operation group, the body weight and protein expressions of p-PI3k and p-Akt in brain tissue of rats were decreased significantly in the model group, while the brain index, neurological deficit score, gene and protein expressions of Beclin1 and LC3 were increased markedly in the model group(P＜0.05 or P＜0.01). In the model group, nerve cells of brain tissue were loosely packed, interstitial edema, triangular in shape, nuclear pyknosis and dark-blue staining were observed. Compared with the model group, the body weight of rats was increased obviously, the neurological deficit score was decreased significantly and the pathological injury of brain tissue was alleviated evidently in high-dose of Zhongfeng capsule group (P＜0.05). The brain index, the gene and protein expressions of Beclin1 and LC3 were decreased apparently in Zhongfeng capsule treatment groups(P＜0.05 or P＜0.01), while the expressions of p-PI3k and p-Akt in brain tissue were increased evidently in Zhongfeng capsule treatment groups(P＜0.05 or P＜0.01). Conclusion: Zhongfeng capsule can inhibit autophagy and improve brain neurons lesion of CIRI rats, the mechanism may be related to regulate the expression of Beclin1 and LC3 in PI3K/Akt/Beclin1 signaling pathway.

When to Reduce and Fix Displaced Lesser Trochanter in Treatment of Trochanteric Fracture: A Systematic Review.

Purpose: To systematically evaluate the benefits of reducing and fixing displaced lesser trochanter (LT) of trochanteric fractures and when this procedure is worth the effect. Methods: From database establishment through March 2021, four online databases (PubMed, Cochrane, Embase, and Web of Science) were searched for relevant literature that investigated reduction and fixation for displaced LT of trochanteric fractures. The papers were then screened by two reviewers independently and in duplicate according to prior inclusion and exclusion criteria. Demographic data as well as data on fracture types, surgical protocols, and surgical outcomes were recorded, analyzed, and interpreted. Results: Total 10 clinical studies with 928 patients were included, in which 48 cases had intact LT and 880 cases involved the displaced LT, of which 196 (22.27%) cases underwent reduction and fixation for LT while the rest of 684 (77.73%) cases not. In these studies, complications were evaluated as a more applicable predictive parameter for operation than postoperative hip function. Conclusion: It was beneficial to reduce and fix the displaced LT when one of the conditions below occurred: displacement distance of LT ≥2 cm, quantity of comminuted LT fragments ≥2, and range of LT fragments in medial wall ≥75%; the fracture line of LT fragments reaching or exceeding the midline of the posterior wall.

Optimal Formula of Angelica sinensis Ameliorates Memory Deficits in ß-amyloid Protein-induced Alzheimer's Disease Rat Model.

OBJECTIVE: Angelica (A.) sinensis is used as a traditional medical herb for the treatment of neurodegeneration, aging, and inflammation in Asia. A. sinensis optimal formula (AOF) is the best combination in A. sinensis that has been screened to rescue the cognitive ability in ß-amyloid peptide (Aß25-35)-treated Alzheimer's disease (AD) rats. The objective of this study was to investigate the effect of AOF on the learning and memory of AD rats as well as to explore the underlying mechanisms. METHODS: Male Wistar rats were infused with Aß25-35 for AD model induction or saline (negative control). Five groups of AD rats were fed on AOF at 20, 40, or 80 mL/kg every day, donepezil at 0.9 mg/kg every day (positive control), or an equal volume of water (AD model) intragastrically once a day for 4 weeks, while the negative control rats were fed on water. The Morris water maze test was used to evaluate the cognitive function of the rats. The Aß accumulation, cholinergic levels, and antioxidative ability were detected by ELISA. Additionally, the candidate mechanism was determined by gene sequencing and quantitative real-time polymerase chain reaction. RESULTS: The results showed that AOF administration significantly ameliorated Aß25-35-induced memory impairment. AOF decreased the levels of amyloid-ß precursor protein and Aß in the hippocampus, rescued the cholinergic levels, increased the activity of superoxide dismutase, and decreased the malondialdehyde level. In addition, AOF inhibited the expression of IL1b, Mpo, and Prkcg in the hippocampus. CONCLUSION: These experimental findings illustrate that AOF prevents the decrease in cognitive function and Aß deposits in Aß25-35-treated rats via modulating neuroinflammation and oxidative stress, thus highlighting a potential therapeutic avenue to promote the co-administration of formulas that act on different nodes to maximize beneficial effects and minimize negative side effects.

Diosmetin has therapeutic efficacy in colitis regulating gut microbiota, inflammation, and oxidative stress via the circ-Sirt1/Sirt1 axis.

Diosmetin (3',5,7 -trihydroxy-4'-methoxy flavone) is a natural flavonoid compound in the citrus species, it exhibits a variety of pharmacological activities, but little is known of its effects on colitis. In this study we evaluated the therapeutic effects of diosmetin on mouse models of chronic and acute colitis. Chronic colitis was induced in mice by drinking water containing 3% dextran sulfate sodium (DSS) from D0 to D8, followed by administration of diosmetin (25, 50 mg · kg-1 · d-1) for another 8 days. Acute colitis was induced by drinking water containing 5% DSS from D0 to D7, the mice concomitantly received diosmetin (25, 50 mg · kg-1 · d-1) from D1 to D7. During the experiments, body weight and disease activity index (DAI) were assessed daily. After the mice were sacrificed, colon tissue and feces samples were collected, and colon length was measured. We showed that in both models, diosmetin administration significantly decreased DAI score and ameliorated microscopic colon tissue damage; increased the expression of tight junction proteins (occludin, claudin-1, and zonula occludens-1), and reduced the secretion of proinflammatory cytokines IL-1ß, IL-6, TNF-α, and Cox-2 in colon tissue. We found that diosmetin administration remarkably inhibited colon oxidative damage by adjusting the levels of intracellular and mitochondrial reactive oxygen species, GSH-Px, SOD, MDA and GSH in colon tissue. The protection of diosmetin against intestinal epithelial barrier damage and oxidative stress were also observed in LPS-treated Caco-2 and IEC-6 cells in vitro. Furthermore, we demonstrated that diosmetin markedly increased the expression of Nrf2 and HO-1 and reduced the ratio of acetylated NF-κB and NF-κB by activating the circ-Sirt1/Sirt1 axis, which inhibited oxidative stress and inflammation in vivo and in vitro. Diosmetin reversed the effects of si-circSirt1 and si-Sirt1 in LPS-treated Caco-2 and IEC-6 cells. When the gut microbiota was analyzed in the mouse model of colitis, we found that diosmetin administration modulated the abundance of Bacteroidetes, Actinobacteria, Cyanobacteria and Firmicutes, which were crucial for inflammatory bowel disease. Our results have linked colitis to the circ-Sirt1/Sirt1 signaling pathway, which is activated by diosmetin. The results imply that diosmetin may be a novel candidate to alleviate DSS-induced colitis and can be a lead compound for future optimization and modification.

The protective effect of manganese superoxide dismutase from thermophilic bacterium HB27 on hydrochloric acid-induced chemical cystitis in rats.

PURPOSE: To evaluate the effects of manganese superoxide dismutase (Mn-SOD) from thermophilic bacterium HB27 (name as Tt-SOD) on chemical cystitis. METHODS: Control and experimental rats were infused by intravesical saline or hydrochloric acid (HCl) on the first day of the experiments. Saline, sodium hyaluronate (SH) or Tt-SOD were infused intravesically once a day for three consequent days. On the fifth day, the rats were weighted and sacrificed following a pain threshold test. The bladder was harvested for histological and biochemical analyses. RESULTS: Tt-SOD could reduce the bladder index, infiltration of inflammatory cells in tissues, serum inflammatory factors and SOD levels, mRNA expression of inflammatory factors in tissues, and increase perineal mechanical pain threshold and serum MDA and ROS levels in HCl-induced chemical cystitis. Furthermore, Tt-SOD alleviated inflammation and oxidative stress by the negative regulation of the NF-κB p65 and p38 MAPK signaling pathway. CONCLUSIONS: Intravesical instillation of Tt-SOD provides protective effects against HCl-induced cystitis.

Review of relationship between Toxoplasma gondii infection and neuropsychiatric diseases / 中国热带医学

@#Abstract: Toxoplasma gondii, an opportunistic pathogenic protozoan, is widely distributed worldwide and can cause zoonoses, which is a serious threat to human health. Nowadays, the relationship between T. gondii infection and neuropsychiatric diseases has attracted researchers' attention increasingly. T. gondii infection is related to the pathogenesis of many neuropsychiatric diseases by affecting the nervous system, such as schizophrenia, depression, Alzheimer's disease, and so on. This review will focus on the relationship between T. gondii infection and neuropsychiatric diseases and summarizes the possible mechanisms of disorders resulting from T. gondii infection． It is expected that the study on the related pathogenic mechanism of T. gondii will lead to new therapeutic directions and feasible solution for the clinical treatment of neuropsychiatric diseases caused by T. gondii infection.