BACKGROUND:In recent years,numerous studies have shown that autophagy and mitophagy play an important role in the regulation of bone metabolism.Under non-physiological conditions,mitophagy breaks the balance of bone metabolism and triggers metabolism disorders,which affect osteoblasts,osteoclasts,osteocytes,chondrocytes,bone marrow mesenchymal stem cells,etc. OBJECTIVE:To summarize the mechanism of mitophagy in regulating bone metabolic diseases and its application in clinical treatment. METHODS:PubMed,Web of Science,CNKI,WanFang and VIP databases were searched by computer using the keywords of"mitophagy,bone metabolism,osteoblasts,osteoclasts,osteocytes,chondrocytes,bone marrow mesenchymal stem cells"in English and Chinese.The search time was from 2008 to 2023.According to the inclusion criteria,90 articles were finally included for review and analysis. RESULTS AND CONCLUSION:Mitophagy promotes the generation of osteoblasts through SIRT1,PINK1/Parkin,FOXO3 and PI3K signaling pathways,while inhibiting osteoclast function through PINK1/Parkin and SIRT1 signaling pathways.Mitophagy leads to bone loss by increasing calcium phosphate particles and tissue protein kinase K in bone tissue.Mitophagy improves the function of chondrocytes through PINK1/Parkin,PI3K/AKT/mTOR and AMPK signaling pathways.Modulation of mitophagy shows great potential in the treatment of bone diseases,but there are still some issues to be further explored,such as different stages of drug-activated mitophagy,and the regulatory mechanisms of different signaling pathways.

Background Imidacloprid is a neonicotinoid insecticide that is widely used in agricultural production, with a high detection rate in human biological samples. Previous studies have shown a high correlation between imidacloprid exposure and liver injury, but the specific mechanism is still unknown. Objective To observe potential toxic effects of HepG2 cells and its perturbation of non-targeted metabolic profile after imidacloprid exposure, and to explore possible molecular mechanisms of hepatotoxicity of imidacloprid by analyzing invovlved biological processes and signaling pathways. Methods HepG2 cell suspension was prepared and seeded in a 96-well plate, which was divided into blank control group, dimethyl sulfoxide (DMSO) solvent control group and imidacloprid exposure groups with multiple concentrations. Each group was set with 5 parallel samples. The viability of HepG2 cells viability were determined after 8 h of exposure to different concentrationsof imidacloprid (1, 2.5, 5, 7.5, 10 mmol·L⁻¹), and the dose-effect relationship was analyzed. A proper concentration (3 mmol·L⁻¹ with 80% viability) was chosen for imidacloprid exposure, non-targeted metabolomic analysis was applied to the cultivated HepG2 cells using UHPLC-Q-TOF/MS technology, the differential metabolites between groups were screened, and the bioprocess and related signaling pathways of their enrichment were annotated using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Results Compared to the other two groups, the survival rates of HepG2 cells in the imidacloprid exposure groups decreased. A survival rate of about 86% of HepG2 cells was found in HepG2 cells exposed to 2.5 mmol·L⁻¹ imidacloprid exposure. The non-targeted metabolomics studies showed that 61 metabolites were significantly affected in HepG2 cells after 3 mmol·L⁻¹ imidacloprid exposure, including creatine (variable importance in projection VIP=1.11, P<0.001), arginine (VIP=1.47, P=0.048), taurine (VIP=4.28, P=0.001), and α-D-glucose (VIP=1.90, P=0.006). The differential metabolites enriched in bioprocess and related signaling pathways were mainly directed to mTOR signaling pathways (P<0.001), arginine and proline metabolism (P=0.002), and galactose metabolism (P=0.015). Conclusion Imidacloprid exposure can significantly inhibit the survival rate of HepG2 cells, and interfere with the mTOR signaling pathway, arginine and proline metabolism, galactose metabolism, and so on.

Depression is a mental disorder with high morbidity, disability and relapse rates. Ginkgo biloba extract (GBE), a traditional Chinese medicine, has a long history of clinical application in the treatment of cerebral and mental disorders, but the key mechanism remains incompletely understood. Here we showed that GEB exerted anti-depressant effect in mice through regulating gut microbial metabolism. GBE protected against unpredictable mild stress (UMS)-induced despair, anxiety-like and social avoidance behavior in mice without sufficient brain distribution. Fecal microbiome transplantation transmitted, while antibiotic cocktail abrogated the protective effect of GBE. Spatiotemporal bacterial profiling and metabolomics assay revealed a potential involvement of Parasutterella excrementihominis and the bile acid metabolite ursodeoxycholic acid (UDCA) in the effect of GBE. UDCA administration induced depression-like behavior in mice. Together, these findings suggest that GBE acts on gut microbiome-modulated bile acid metabolism to alleviate stress-induced depression.
Humans ; Mice ; Animals ; Depression/drug therapy* ; Gastrointestinal Microbiome ; Plant Extracts ; Ginkgo biloba

Objective To analyze the clinical efficacy of thalidomide combined with anti tuberculosis drugs in the treatment of pulmonary tuberculosis,in order to evaluate its application value and safety. Methods Seventy-two pulmonary tuberculosis patients in the Qianshan Hospital of Anshan from Jan. 2012 to Aug. 2014 were selected as the subject. Patients were randomly divided into control group and observation group with 36 cases in each group. Patients in the control group were only received anti-tuberculosis drug treatment,while in the treatment group were given thalidomide combined with anti tuberculosis drug treatment. Efficacy rate of thalidomide treatment after two weeks was evaluated by X-ray examination. Incidence of sputum smear negative conversion rate and adverse reaction were recorded. Results There were 10 cases with obvious tuberculosis absorption,19 cases with lesions absorption,7 cases with no absorption in observation group. In control group, there were 5 cases with obvious tuberculosis absorption,12 cases with lesions absorption,17 cases with no absorption and the lesion increased in 2 cases. The focus absorption in observation group was superior to the control group( Z =11. 854,P ﹤0. 001 ). There were 6 cases with void closure,4 cases with decreased void closure,1 cases with unchanged and 1 cases with new cavity in observation group. There were 1 cases with void closure,3 cases with decreased void closure,6 cases with unchanged and 3 cases with new cavity in control group,and there was significant difference(Z=15. 536,P﹤0. 001). Sputum smear negative rate in observation group after treatment was 85. 0%(17/20),significantly higher than that in control group(50. 0%(11/22),χ2=5. 775,P=0. 016). Cases of adverse reactions in observation group was 8(22. 2%),lower than that in control group(17 cases,(47. 2%);χ2 =4. 963,P=0. 026). There were 2 cases with abnormal liver function without changing the original treatment symptomatic liver after treatment,in observation group. Of 8 cases with abnormal liver function in control group,5 cases change treatment schedule including 3 cases of modified pyrazinamide for streptomycin,2 cases converted to rifampicin for Levofloxacin. The syndromes including eukopenia,skin rash, anorexia and lethargy were disappeared after treatment. Conclusion The effect of Thalidomide combined with anti tuberculosis drugs in the treatment of pulmonary tuberculosis is significant and safety,which can be used as a routine drug treatment of tuberculosis in clinical trials.

Objective To evaluate the osteogenesis of alveolar bone graft (ABG) in patients with alveolar cleft by cone beam CT (CBCT).Methods ABG surgery was performed in 20 patients with unilateral complete alveolar cleft.The patients were followed up for 3 and 6 months after surgery and the osteogenesis of the bone graft was evaluated by CBCT.The bone density and the height of labial and palatal bone graft area were analyzed.Results There was no significant difference in the bone density between 3 months [(403.79 ± 64.70) HU] and 6 months[(411.45 ±42.62) HU] (P =0.329).However,there was significant difference in bone height in the labial and palatal side between 3 months and 6 months (labial P =0.020,palatal P =0.008).Conclusions The osteogenesis was the best 3 months after bone graft.The following treatment can start in this stage.

Extracellular matrix (ECM)is not only one of current hot-points in medical cell biology,but also one tricky part for undergraduates to learn. This article compared chapters of ECM in medical cell biology courses and spotlighted that ECM chapter was often neglected in some domes-tic universities. Then it analyzed the possible causes,such as variable arrangement of ECM section in current textbooks. Lastly,the article recommended several suggestions,including giving a timely re-vision of the old ECM knowledge,designing an appropriate strategy for teaching,enumerating certain representative diseases to improve the ECM education. It appealed our teachers to pay more attention to how to make the module of ECM master well in near future.

Objective To investigate the compliance status of secondary prevention in patients with coronary artery disease (CAD) following revascularization.MethodsA total of 512 patients with CAD who received procedures for coronary revascularization were enrolled in the study from January 2009 to October 2010,including 472 cases of percutaneous coronary intervention stenting,25 cases of coronary artery bypass grafting and 15 cases of stenting plus bypass.The demographic information,prophylactic drug therapies, lifestylechangesandmodifiableriskfactorsweresurveyedwithquestionnaires,anthroposomatologicalmeasurementsandlaboratorytestsinpatients3monthsaftercoronary revascularization.ResultsThe proportion of patients on statins,aspirin,β-blockers,angiotensin-converting enzymeinhibitors/angiotensinreceptorblockers(ACEIs/ARBs)andinfluenzavaccinationwere 81.4％ (417/512),93.9％ ( 481/512 ),82.0％ ( 420/512 ),76.2％ ( 390/512 ) and 3.7％ ( 19/512 ) respectively.Based on the criteria recommended by the American Heart Association/American College of Cardiology (AHA/ACC)Guidelines for Secondary Prevention for Patients with Coronary and Other Atherosclerotic Vascular Disease: 2006 Update, the percentages of achieving therapeutic targets of modifiable risk factor management were as follows:glycosylated hemoglobin (90.2％,462/512 ),total cholesterol ( 68.6％,351/512 ),triglycerides ( 58.8％,301/512 ),high-density lipoprotein cholesterol ( 91.6％,469/512 ),low-density lipoprotein cholesterol ( 44.5 ％,228/512 ),systolic pressure ( 75.2 ％,385/512 ) and diastolic pressure (90.4％,463/512 ) respectively.And the proportions of improved lifestyle were as follows:smoking cessation/non-smoking 81.4％ (417/512),diet control 78.5％ ( 402/512 ),achieving weight targets 61.7％ (316/512)and regular exercise 58.2％ (298/512).ConclusionsThere is a relatively high percentage of standardized antiplatelet therapy and continuous statins medication in patients with coronary artery disease following revascularization. However,many significant modifiable risk factors have not been controlled optimally and lifestyle of patients needs further improvement. There is still a considerable scope for further improvement of secondary prevention in this group of patients.

RNA silencing is a conserved eukaryotic pathway involved in the suppression of gene expression via sequence-specific interactions that are mediated by 21-23 nt RNA molecules. During infection, RNAi can act as an innate immune system to defend against viruses. As a counter-defensive strategy, silencing suppressors are encoded by viruses to inhibit various stages of the silencing process. These suppressors are diverse in sequence and structure and act via different mechanisms. In this review, we discuss whether RNAi is a defensive strategy in mammalian host cells and whether silencing suppressors can be encoded by mammalian viruses. We also review the modes of action proposed for some silencing suppressors.
Animals ; Gene Expression Regulation, Viral ; Gene Silencing ; Host-Pathogen Interactions ; Humans ; Mammals ; virology ; MicroRNAs ; genetics ; metabolism ; Plant Viruses ; physiology ; Plants ; virology ; RNA, Small Interfering ; genetics ; metabolism ; Repressor Proteins ; genetics ; metabolism ; Viral Proteins ; genetics ; metabolism ; Viruses ; growth & development

Objective To evaluate the clinical effects of large dosage capoten(captopril)combined with irbesartan in the treatment of congestive heart failure(CHF).Methods One hundreds thirty nine patients of CHF were occasionally divided into two groups:large dosage capoten group(n=61)and large dosage capoten+irbesartan group (n=78).240 days later,the changes of cardiothoracic ratio(CTR),left ventricular end diastolic diameter(LEVD),left ventricular end contract surface(LVES),left ventricular eiection fraction(LVEF),6-minute walking test (6MWT),admission frequency,and mortality rate were observed before and after therapy.Results Large dosage capoten+irbesartan group can significantly reduce the admission frequency of CHF patients(P＜0.01),while large dosage capoten group was better than large dosage capoten+irbesartan group in 6MWT,LEVD,LVES,and LVEF (P＜0.05).There was no significant difference in CTR and mortality rate between two groups(P＞0.05)Conclusion Capoten combined with irbesartan have better clinical effects than single capoten in the treatment of CHF and it was worthy of extending in clinic.

Aim To investigate the effects of tyrosine kinase inhibitor A77-1726 on IL-13 induced STAT6 phosphorylation and c-fos expression in Dami cell and to provide novel experimental basis to the clinical application of A77-1726 and the study of IL-13 pathway.Methods Total RNA was extracted from Dami cells incubated with or without IL-13 and A77-1726 respectively for various time points.RT-PCR and agar gel electrophoresis were used to examine the expression of c-fos mRNA.The expression of STAT6 and c-fos proteins was detected by Western blot.A densitometric rel-ative quantitation of PCR and Western blot products was quantitated using Image Quant software.Results STAT6 was phosphorylated by treatment of 100 ?g?L-1 IL-13 in Dami cells.Phosphorylation of STAT6 induced by IL-13 was inhibited by treatment of 50?mol?L-1 A77-1726.The expression of c-fos mRNA was significantly induced by IL-13 treatment in Dami cells(P