Inhibitory gamma-aminobutyric acidergic neurons in the anterior cingulate cortex participate in the comorbidity of pain and emotion

Pain is often comorbid with emotional disorders such as anxiety and depression.Hyperexcitability of the anterior cingulate cortex has been implicated in pain and pain-related negative emotions that arise from impairments in inhibitory gamma-aminobutyric acid neurotransmission.This review primarily aims to outline the main circuitry(including the input and output connectivity)of the anterior cingulate cortex and classification and functions of different gamma-aminobutyric acidergic neurons;it also describes the neurotransmitters/neuromodulators affecting these neurons,their intercommunication with other neurons,and their importance in mental comorbidities associated with chronic pain disorders.Improving understanding on their role in pain-related mental comorbidities may facilitate the development of more effective treatments for these conditions.However,the mechanisms that regulate gamma-aminobutyric acidergic systems remain elusive.It is also unclear as to whether the mechanisms are presynaptic or postsynaptic.Further exploration of the complexities of this system may reveal new pathways for research and drug development.

Map activation of various brain regions using different frequencies of electroacupuncture ST36,utilizing the FosCreER strategy

Objective:Electroacupuncture(EA)is an alternative treatment option for pain.Different frequencies of EA have different painrelieving effects;however,the central mechanism is still not well understood.Methods:The Fos2A-iCreER(TRAP):Ai9 mice were divided into three groups(sham,2 Hz,and 100 Hz).The mice were intraperitoneally injected with 4-hydroxytamoxifen(4-OHT)immediately after EA at Zusanli(ST36)for 30 min to record the activated neurons.One week later,the mice were sacrificed,and the number of TRAP-treated neurons activated by EA in the thalamus,amygdala,cortex,and hypothalamus was determined.Results:In the cortex,2 Hz EA activated more TRAP-treated neurons than 100 Hz EA did in the cingulate cortex area 1(Cg1)and primary somatosensory cortex(S1),and 2 and 100 Hz EAs did not differ from sham EA.TRAP-treated neurons activated by 2 Hz EA were upregulated in the insular cortex(IC)and secondary somatosensory cortex(S2)compared with those activated by 100 Hz and sham EA.In the thalamus,the number of TRAP-treated neurons activated by 2 Hz EA was elevated in the paraventricular thalamic nucleus(PV)compared with those activated by sham EA.In the ventrolateral thalamic nucleus(VL),the number of TRAPtreated neurons activated by 2 Hz EA was significantly upregulated compared with those activated by 100 Hz EA,and sham EA showed no difference compared with 2 or 100 Hz EA.TRAP-treated neurons were more frequently activated in the ventral posterolateral thalamic nucleus(VPL)by 2 Hz EA than by 100 Hz or sham EA.Conclusions:Low-frequency EA ST36 effectively activates neurons in the Cg1,S1,S2,IC,VPL,PV,and VL.The enhanced excitability of the aforementioned nuclei induced by low-frequency EA may be related to its superior efficacy in the treatment of neuropathological pain.

Hupo powder promotes autophagy of menstrual blood-derived stem cells from patients with endometriosis

Objective:To explore the effect of Hupo powder(HP)on autophagy in menstrual blood-derived stem cells(MenSCs)with endometriosis(EMT).Methods:EMT MenSCs(E-MenSCs)and healthy MenSCs(H-MenSCs)were isolated from the menstrual blood of patients with EMT and healthy female participants,respectively.We identified their stem cells’characteristics via adipogenic and osteogenic differentiation.Twelve male SpragueeDawley rats received 0.9% NaCl and HP-dispensing granules by gastric irrigation to prepare blank serum and medicated serum,respectively.We used serum concentrations of 5%,10%,and 20%,each at administered times of 12,24,and 48 h to select the best condition.These cells were divided into three groups:blank serum of the control group,blank serum of the model group,and medicated serum of the HP group.H-MenSCs were used in the control group,while E-MenSCs were used in the model and HP groups.We analyzed cell viability using a cell counting kit-8 assay,observed cell morphology,evaluated the amounts of auto-phagosomes and autolysosomes by transmission electron microscopy,and detected the protein expression of autophagy markers(LC3-II and Beclin1)by Western blot.Results:E-MenSCs and H-MenSCs became long fusiform with a diffuse radial pattern,forming lipid droplets and calcium nodules after adipogenic and osteogenic differentiation.We then used the best conditiond 20% serum and 48 hdfor the subsequent experiments.In contrast to the model group,the HP group exhibited lower cell viability(=0.007),larger amounts of autophagosomes and autolysosomes(P<0.001 and P=0.001,respectively),and higher expression of LC3-II and Beclin1(P=0.021 and P=0.019,respectively).Conclusion:Hupo powder can promote autophagy in E-MenSCs,which might be one of the mechanisms underlying its therapeutic effects.

Exploration on the mechanism of therapeutic and toxic bidirectional effects of Haizao Yuhu decoction based on machine learning and data mining

Objective:To explore the bidirectional mechanism of Haizao Yuhu decoction(HYD)on goiter and drug-induced liver injury(DILI)based on machine learning and data mining.Methods:Firstly,compounds of HYD were selected from the TCMSP,TCMIP,and BATMAN databases,then the TCMSP was used to acquire the targets of compounds.Targets of goiter and DILI were obtained from the GeneCards database.Secondly,common targets of“HYD-goiter”and“HYD-DILI”as well as related compounds were used to construct the networks and perform Random Walk with Restart(RWR)algorithm and network stability test.Finally,core targets in the“HYD-goiter”and“HYD-DILI”networks were used for molecular docking with core compounds and searched for validation on PubChem,and the relevant experimental data of our group were quoted to verify the analysis results.Results:There were 22 intersection targets of HYD and DILI,326 of HYD and goiter.RWR analysis showed that MAPK1,MAPK3,AKT1,etc.may be the core targets of HYD treating goiter,RELA,TNF,IL4,etc.may be the core targets of the bidirectional effect,and eckol may be the core compound in bidirectional effect.Network stability test indicated that the HYD had a high stability on treating goiter and playing a bidirectional effect.The core targets and core compounds docked well,and 37.3%of targets had been confirmed by experiments and 29.8%core targets had been confirmed.Our previous experimental result confirmed that the HYD could treat goiter usefully by reducing the expression levels of PI3K and AKT mRNA,and down-regulating the expression of Cyclin D1 and Bcl-2 mRNA.Conclusion:HYD containing“sargassum-liquorice”combination may have a bidirectional effect on treating goiter and causing DILI.We offered a new way for more explorations on the therapeutic and toxic bidirectional mechanisms based on machine learning and data mining.

Novel method for extracting exosomes of hepatocellular carcinoma cells

AIM: To develop a novel method for the rapid and efficient extraction of exosomes secreted by tumor cells.

Effect of salvianolate on intestinal epithelium tight junction protein zonula occludens protein 1 in cirrhotic rats

AIM:To study the effect of salvianolate on tight junctions(TJs) and zonula occludens protein 1(ZO-1) in small intestinal mucosa of cirrhotic rats.METHODS:Cirrhosis was induced using carbon tetrachloride.Rats were randomly divided into the untreated group,low-dose salvianolate(12 mg/kg) treatment group,medium-dose salvianolate(24 mg/kg) treatment group,and high-dose salvianolate(48 mg/kg) treatment group,and were treated for 2 wk.Another 10 healthy rats served as the normal control group.Histological changes in liver tissue samples were observed under a light microscope.We evaluated morphologic indices of ileal mucosa including intestinal villi width and thickness of mucosa and intestinal wall using a pathological image analysis system.Ultrastructural changes in small intestinal mucosa were investigated in the five groups using transmission electron microscopy.The changes in ZO-1 expression,a tight junction protein,were analyzed by immunocytochemistry.The staining index was calculated as the product of the staining intensity score and the proportion of positive cells.RESULTS:In the untreated group,hepatocytes showed a disordered arrangement,fatty degeneration was extensive,swelling was obvious,and disorganized lobules were divided by collagen fibers in hepatic tissue,which were partly improved in the salvianolate treated groups.In the untreated group,abundant lymphocytes infiltrated the fibrous tissue with proliferation of bile ducts,and collagen fibers gradually decreased and damaged hepatic lobules were partly repaired following salvianolate treatment.Compared with the untreated group,no differences in intestinal villi width between the five groups were observed.The villi height as well as mucosa and intestinal wall thickness gradually thickened with salvianolate treatment and were significantly shorter in the untreated group compared with those in the salvianolate treatment groups and normal group(P < 0.01).The number of microvilli decreased and showed irregular lengths and arrangements in the untreated group.The intercellular space between epithelial cells was wider.The TJs were discontinuous,which indicated disruption in TJ morphology in the untreated group.In the treated groups,the microvilli in the intestinal epithelium were regular and the TJs were gradually integrated and distinct.The expression of ZO-1 decreased in the small intestine of the untreated cirrhotic rats.The high expression rate of ZO-1 in ileal mucosa in the untreated group was significantly lower than that in the medium-dose salvianolate group(21.43% vs 64.29%,χ 2 = 5.25,P < 0.05),high-dose salvianolate group(21.43% vs 76.92%,χ 2 = 8.315,P < 0.01) and normal group(21.43% vs 90%,χ 2 = 10.98,P < 0.01).CONCLUSION:Salvianolate improves liver histopathological changes,repairs intestinal mucosa and TJ structure,and enhances ZO-1 expression in the small intestinal mucosa in cirrhotic rats.

Conventional versus drug-eluting bead transarterial chemoembolization:A better option for treatment of unresectable hepatocellular carcinoma

Transarterial chemoembolization(TACE) is a minimally invasive procedure involving intra-arterial catheter-based chemotherapy to selectively administer high doses of cytotoxic drugs to the tumor bed along with ischemic necrosis induced by arterial embolization.Chemoembolization forms the essential core of management in patients with hepatocellular carcinoma(HCC) who are not suitable for curative therapies such as transplantation,resection,or percutaneous ablation.TACE of hepatic cancer(s) has proven to be helpful in achieving local tumor control,and has supported the ability to prevent tumor progression,prolong patient life,and manage patient symptoms.Recent data have demonstrated that,in patients with single-nodule HCC ≤3 cm without vascular invasion,the 5-year overall survival with TACE was found to be comparable with hepatic resection and radiofrequency ablation.Used for several years,Lipiodol continues to play a vital role as a tumor-seeking and radiopaque drug delivery vector in interventional oncology.Efforts have been made to enhance the administration of chemotherapeutic agents to tumors.Compared with conventional TACE,drug-eluting bead TACE is a fairly new drug delivery embolization technique that permits fixed dosing and has the ability to provide sustained release of anticancer agents over a period of time.The present review discusses the basic procedure of TACE and its properties,and the effectiveness of conventional and drug-eluting bead chemoembolization systems currently available or presently undergoing clinical evaluation.

Comparison of tumor response following conventional versus drug-eluting bead transarterial chemoembolization in early-and very early-stage hepatocellular carcinoma

Objective:To compare the safety of conventional transarterial chemoembolization(cTACE)vs drug-eluting bead TACE(DEB-TACE)in very early-and early-stage hepatocellular carcinoma(HCC).Methods:Data of patients with early-and very early-stage HCC treated with cTACE or DEB-TACE were evaluated retrospectively in this study.A total of 40 patients were included,20 treated with cTACE and 20 with DEB-TACE.The cTACE and DEB-TACE groups were comprised of 80%and 75%males,while there were 20%females in cTACE group and 25%in Deb-TACE group respectively.The mean age of patients in cTACE group was 57.43+5.6 years,while it was 56.4+5.5 years in DEB-TACE group.All patients had liver status of Child–Pugh Class A and a score≤7 in Child-Pugh class type B in very early-(stage 0)or early-phase(stage A)stages according to the Barcelona Clinic Liver Cancer(BCLC)system.Results:The Child-Pugh class degradation in the cTACE group was slightly higher than that in the DEB-TACE group.Serious complications like peritumoral parenchymal ischemia were observed in 4 patients in the cTACE group and 5 in the DEB-TACE group.Localized bile duct dilation was seen in 2 patients in the cTACE group and 6 in the DEB-TACE group.No significant variation in serious complications between the two groups was established in localized bile duct dilatation.Other minor complications noted were liver failure,liver abscess,liver infarction,acute cholecystitis,biliary tree necrosis,and mortality.Further,no substantial variation in tumor response between the groups was reported immediately and 1-year post-procedural assessment.Conversion rate to other treatment modalities such as surgical resection,radiofrequency ablation(RFA),or swap between cTACE and DEB-TACE was substantially higher in the DEB-TACE group(40%)than in the cTACE group(10%)at the 1-year completion period of the study.Conclusion:In terms of tumor response,the DEB-TACE group showed a better response,to some extent,as an initial therapy for HCC in the early stages as compared to the cTACE group,and DEB-TACE also exhibited better clinical efficacy in patients with HCC.

Venous thromboembolism in patients with COVID-19.A prevalent and a preventable complication of the pandemic

Coronavirus disease 2019 or most commonly known as COVID-19 is a trending global infectious disease which a few months ago was affirmed as a global health emergency or a pandemic by the WHO Emergency Committee.The common symptoms manifested in this pandemic disease are high grade fever,cough,fatigue,shortness of breath and flu like symptom which can evolve into severe respiratory disorders such as pneumonia,acute respiratory distress syndrome(ARDS)and/or end-organ failure.Factors that contribute to the severity or high mortality rate in COVID-19 include old age,comorbidities like hypertension,diabetes,hyperlipidaemia,neutrophilia,and organ and coagulation dysfunction.Disseminated intravascular coagulation and other various coagulopathies including Venous thromboembolism have known to become a major contributing factor to high mortality rate.Venous thromboembolism is a disease which is a combination of deep vein thrombosis and pulmonary embolism.Prophylactic anticoagulation in patients prone to or with a pre-existing history of venous thromboembolism is associated with decreased mortality in severe COVID-19 pneumonia.This review article focuses upon COVID-19 and increased incidence of venous thromboembolism in patients infected by COVID-19 along with the role it has in high mortality rate in COVID-19 patients.

Global trends of fMRI studies on acupuncture for CNS diseases over the past two decades:A bibliometric analysis

Background:Extensive global research has been conducted to explore the neural mechanisms involved in acupuncture treatment for central nervous system(CNS)disorders.However,there is a lack of bibliometric analysis specifically focusing on functional magnetic resonance imaging(fMRI)studies examining the effects of acupuncture on CNS diseases.Objective:This study aims to fill this gap by offering a theoretical framework for the current clinical application and future research directions.It presents a comprehensive overview of the current state,hotspots,and global trends in fMRI studies on therapeutic applications and potential mechanisms of acupuncture for CNS diseases over the past two decades.Methods:The publications were analyzed using VOSviewer 1.6.18 and CiteSpace 6.1.R6 software running on the Java platform.All publications were acquired from the Science Citation Index-Expanded of the Web of Science Core Collection.The document types were limited to original articles and review articles,with publication dates spanning from October 24,2003 to October 24,2023.Only publications written in the English language were considered for analysis.Results:fMRI has the advantages of non-invasiveness,high spatial resolution,and signals directly from neural activity in the brain.Compared to the other three brain imaging techniques,fMRI has the most significant articles on acupuncture treatment for CNS diseases in the past two decades,with a substantial increase.As of October 24,2023,227 records of fMRI studies on acupuncture for CNS diseases were identified.Notably,a discernible upward trend exists in this domain’s overall number of annual publications.It is worth highlighting that China has emerged as the primary contributor to this field.The five most prominent topics explored in fMRI studies on acupuncture for CNS diseases encompassed the concepts of"acupuncture""fMRI""electroacupuncture""functional connectivity"and"stimulation".Furthermore,the frontier areas of investigation encompassed the topics of"migraine without aura""ischemic stroke""prophylaxis"and"randomized controlled trial".Conclusion:fMRI studies on acupuncture treatment in CNS diseases have potential applications,and the number of publications on this topic is expected to increase rapidly in future research,which may focus on migraine without aura,ischemic stroke,and randomized controlled trials.fMRI studies of acupuncture for CNS diseases have connected various brain areas,focusing on the default mode network.In addition,strengthening collaboration among different academic groups across countries is imperative.

Controlled-release hydrogel loaded with magnesium-based nanoflowers synergize immunomodulation and cartilage regeneration in tendon-bone healing

Tendon-bone interface injuries pose a significant challenge in tissue regeneration,necessitating innovative approaches.Hydrogels with integrated supportive features and controlled release of therapeutic agents have emerged as promising candidates for the treatment of such injuries.In this study,we aimed to develop a temperature-sensitive composite hydrogel capable of providing sustained release of magnesium ions(Mg^(2+)).We synthesized magnesium-Procyanidin coordinated metal polyphenol nanoparticles(Mg-PC)through a self-assembly process and integrated them into a two-component hydrogel.The hydrogel was composed of dopamine-modified hyaluronic acid(Dop-HA)and F127.To ensure controlled release and mitigate the“burst release”effect of Mg^(2+),we covalently crosslinked the Mg-PC nanoparticles through coordination bonds with the catechol moiety within the hydrogel.This crosslinking strategy extended the release window of Mg^(2+)concentrations for up to 56 days.The resulting hydrogel(Mg-PC@Dop-HA/F127)exhibited favorable properties,including injectability,thermosensitivity and shape adaptability,making it suitable for injection and adaptation to irregularly shaped supraspinatus implantation sites.Furthermore,the hydrogel sustained the release of Mg^(2+)and Procyanidins,which attracted mesenchymal stem and progenitor cells,alleviated inflammation,and promoted macrophage polarization towards the M2 phenotype.Additionally,it enhanced collagen synthesis and mineralization,facilitating the repair of the tendon-bone interface.By incorporating multilevel metal phenolic networks(MPN)to control ion release,these hybridized hydrogels can be customized for various biomedical applications.

Multi-omics profiling:the way toward precision medicine in metabolic diseases

Metabolic diseases including type 2 diabetes mellitus(T2DM),non-alcoholic fatty liver disease(NAFLD),and metabolic syndrome(MetS)are alarming health burdens around the world,while therapies for these diseases are far from satisfying as their etiologies are not completely dear yet.T2DM,NAFLD,and MetS are all complex and multifactorial metabolic disorders based on the interactions between genetics and environment.Omics studies such as genetics,transcriptomics,epigenetics,proteomics,and metabolomics are all promising approaches in accurately characterizing these diseases.And the most effective treatments for individuals can be achieved via omics pathways,which is the theme of precision medicine.In this review,we summarized the multi-omics studies of T2DM,NAFLD,and MetS in recent years,provided a theoretical basis for their pathogenesis and the effective prevention and treatment,and highlighted the biomarkers and future strategies for precision medicine.

FABP4 secreted by M1-polarized macrophages promotes synovitis and angiogenesis to exacerbate rheumatoid arthritis

Increasing evidence shows that adipokines play a vital role in the development of rheumatoid arthritis(RA).Fatty acid-binding protein 4(FABP4),a novel adipokine that regulates inflammation and angiogenesis,has been extensively studied in a variety of organs and diseases.However,the effect of FABP4 on RA remains unclear.Here,we found that FABP4 expression was upregulated in synovial M1-polarized macrophages in RA.The increase in FABP4 promoted synovitis,angiogenesis,and cartilage degradation to exacerbate RA progression in vivo and in vitro,whereas BMS309403(a FABP4 inhibitor)and anagliptin(dipeptidyl peptidase 4 inhibitor)inhibited FABP4 expression in serum and synovial M1-polarized macrophages in mice to alleviate RA progression.Further studies showed that constitutive activation of mammalian target of rapamycin complex 1(mTORC1)by TSC1 deletion specifically in the myeloid lineage regulated FABP4 expression in macrophages to exacerbate RA progression in mice.In contrast,inhibition of mTORC1 by ras homolog enriched in brain(Rheb1)disruption specifically in the myeloid lineage reduced FABP4 expression in macrophages to attenuate RA development in mice.Our findings established an essential role of FABP4 that is secreted by M1-polarized macrophages in synovitis,angiogenesis,and cartilage degradation in RA.BMS309403 and anagliptin inhibited FABP4 expression in synovial M1-polarized macrophages to alleviate RA development.Hence,FABP4 may represent a potential target for RA therapy.

Exosomes derived from BMSCs ameliorate cyclophosphamide-induced testosterone deficiency by enhancing the autophagy of Leydig cells via the AMPK-mTOR signaling pathway

Cyclophosphamide-induced testosterone deficiency (CPTD) during the treatment of cancers and autoimmune disorders severelyinfluences the quality of life of patients. Currently, several guidelines recommend patients suffering from CPTD receive testosteronereplacement therapy (TRT). However, TRT has many disadvantages underscoring the requirement for alternative, nontoxictreatment strategies. We previously reported bone marrow mesenchymal stem cells-derived exosomes (BMSCs-exos) could alleviatecyclophosphamide (CP)-induced spermatogenesis dysfunction, highlighting their role in the treatment of male reproductive disorders.Therefore, we further investigated whether BMSCs-exos affect autophagy and testosterone synthesis in Leydig cells (LCs). Here,we examined the effects and probed the molecular mechanisms of BMSCs-exos on CPTD in vivo and in vitro by detecting theexpression levels of genes and proteins related to autophagy and testosterone synthesis. Furthermore, the testosterone concentrationin serum and cell-conditioned medium, and the photophosphorylation protein levels of adenosine monophosphate-activatedprotein kinase (AMPK) and mammalian target of rapamycin (mTOR) were measured. Our results suggest that BMSCs-exos couldbe absorbed by LCs through the blood–testis barrier in mice, promoting autophagy in LCs and improving the CP-induced low serumtestosterone levels. BMSCs-exos inhibited cell death in CP-exposed LCs, regulated the AMPK-mTOR signaling pathway to promoteautophagy in LCs, and then improved the low testosterone synthesis ability of CP-induced LCs. Moreover, the autophagy inhibitor,3-methyladenine (3-MA), significantly reversed the therapeutic effects of BMSCs-exos. These findings suggest that BMSCs-exospromote LC autophagy by regulating the AMPK-mTOR signaling pathway, thereby ameliorating CPTD. This study provides novelevidence for the clinical improvement of CPTD using BMSCs-exos.

Efficiency and safety of acupuncture for women with premature ovarian insufficiency:study protocol for a randomized controlled trial

Acupuncture has been widely used as an alternative and complementary therapy for premature ovarian insufficiency(POI)in China.However,research to date has not shown that acupuncture is effective for POI compared with hormone replacement therapy(HRT).We will conduct a randomized,controlled,and outcome assessor-blind trial to evaluate the efficacy and safety of acupuncture on POI.Seventy-six patients with POI will be randomly assigned to two groups.The treatment group will receive twenty-eight one-hour sessions of acupuncture treatments,and the control group will receive 12-week HRT.The whole study will consist of a 12-week treatment plan and a 12-week follow-up session.The primary outcome is measured by changes in serum anti-Müllerian hormone and follicle-stimulating hormone(FSH)levels at weeks 12 and 24.Secondary outcome measures include estradiol,luteinizing hormone(LH),LH/FSH ratio,Kupperman index,and menstrual condition.This trial is expected to clarify whether or not acupuncture is effective and safe for POI compared with HRT.

Low-dose Simvastatin Increases Skeletal Muscle Sensitivity to Caffeine and Halothane

Objective To determine whether the myotoxic side effects of statin simvastatin affect skeletal muscle's sensitivity to caffeine and halothane. Methods Primary cultured neonate rat skeletal myotubes were treated with 0.01-5.0 μmol/L simvastatin for 48 hours. MTT was used to evaluate cellular viability. The gross morphology and microstructure of the myotubes were observed with a light and electron microscope, respectively. The intracellular calcium concentrations([Ca^(2+)]i) at rest and in response to caffeine and halothane were investigated by fluorescence calcium imaging. Data were analyzed by analysis of variance(ANOVA) test. Results Simvastatin(0.01-5.0 μmol/L) decreased myotube viability, changed their morphological features and microstructure, and increased the resting [Ca^(2+)]i in a dose-dependent manner. Simvastatin did not change myotube's sensitivity to low doses of caffeine(0.625-2.5 mmol/L) or halothane(1.0-5.0 mmol/L). In response to high-dose caffeine(10.0 mmol/L, 20.0 mmol/L) and halothane(20.0 mmol/L, 40.0 mmol/L), myotubes treated with 0.01 μmol/L simvastatin showed a significant increase in sensitivity, but those treated with 1.0 μmol/L and 5.0 μmol/L simvastatin showed a significant decrease. The sarcoplasmic reticulum Ca^(2+) storage peaked in the myotubes treated with 0.01 μmol/L simvastatin, but it decreased when cells were treated with higher doses of simvastatin(0.1-5.0 μmol/L).Conclusions The myotoxic side effect of simvastatin was found to change the sensitivity of myotubes in response to high-dose caffeine and halothane. When dose was low, sensitivity increased mainly because of increased Ca^(2+) content in the sarcoplasmic reticulum, which might explain why some individuals with statin-induced myotoxic symptoms may show positive caffeine-halothane contracture test results. However, when the dose was high and the damage to the myotubes was severer, sensitivity was lower. It is here supposed that the damage itself might put individuals with statin-induced myotoxic symptoms at greater risks of presenting with rhabdomyolysis during surgery or while under anesthesia.

Efficacy of electroacupunture at Zusanli(ST36)on jumping-injured muscle based on transcriptome sequencing and genes analysis

METHODS:In the present study,female SpragueDawley rats were randomly divided into four groups with 6 of each,including normal control group(NC),jumpinginduced muscle injury model group(JI),JI with electroacupuncture stimulation treatment group(EA),and JI with non-electroacupuncture stimulation group(NEA).Transmission electron microscopy,transcriptome sequencing and analysis,prediction of protein interaction networks,real-time polymerase chain reaction verification,and Western blotting were performed on the gastrocnemius muscle of ipsilateral lower limbs.RESULTS:The structural repair of injured gastrocnemius myofibers following jumping training in EA rats was better than that of NEA rats.A total of 136 genes were differentially expressed in EA rats relative to JI rats,with 55 genes upregulated and 81 genes downregulated.According to results of transcriptome analysis,and prediction of protein mutual interaction by the online STRING database,Heat shock protein beta-7(Hspb7)and myozenin2(Myoz2)genes were targeted.Expressions of Hspb7 and Myoz2 mRNAs were increased in EA rats relative to JI rats(P<0.05).The expression of Hspb7 protein was upregulated in EA rats relative to that in NC,JI,and NEA rats(P<0.01,<0.05,and<0.05,respectively).The expression of Myoz2 protein was upregulated in EA rats relative to that in NC and JI rats(both P<0.01,respectively).CONCLUSIONS:The present results suggest that electroacupuncture stimulation at Zusanli(ST36)could improve muscle healing following jumping-induced muscle injury,owing to the upregulation of Hspb7 and Myoz2 proteins.

Electroacupuncture Alleviates HIF1-α-mediated Early Mitophagy in Spinal Cord Injury

Background:The inhibitory microenvironment around spinal cord injury(SCI)severely restricted functional repair after injury.Mitophagy was one of the important measures to maintain cellular homeostasis and ensure the harmonious nerve cell microenvironment.Hypoxia-inducible factor1α(HIF1-α)can mediate mitochondrial autophagy in neurodegenerative diseases,but the mechanisms are complex and diverse,which need to be further elucidated.Electroacupuncture plays a significant role in improving the neural microenvironment after spinal cord injury,promote long-term neurological function recovery in SCI patients,but whether electroacupuncture can participate in HIF1-α mediated mitophagy remains unknown.Objective:Investigated the effects of HIF1-α on mitochondrial autophagy in rats with spinal cord contusion and the potential mechanism of electroacupuncture.Methods:Following the successful construction of an SCI model of Sprague-Dawley rat utilizing a modified Allen method,electroacupuncture intervention was performed at T9 and T11 Jiaji acupoint(EX-B2),with further molecular biology and morphology examined by perfusion.To observe the effect of HIF1-α on local damage repair,the stereotypic injection of Hif1a knockdown virus was performed,and the changes of mitophagy in damaged local area was detected employing Western blotting,real-time fluorescence quantitative PCR,immunofluorescence,transmission electron microscopy and Nissl staining.Results:HIF1-α as well as its mitophagy receptor BNIP3 and NIX are upregulated after spinal cord injury.Elec-troacupuncture treatment or local inhibition of HIF1-α expression can reverse the early autophagy state after spinal cord injury,reduce cell apoptosis and injury area,promote neuronal survival.Conclusion:Electroacupuncture may serve as a promising strategy for spinal cord injury treatment,by alleviating HIF1-α mediated early mitochondrial autophagy.

Two-dimensional correlation spectroscopic studies on coordination between carbonyl group of butanone and metal ions

Two dimensional asynchronous spectra were used to characterize coordination between carbonyl group of butanone and metal ions by using an approach proposed in our recent paper.Spectral variation of n-π^＊transition band of carbonyl group is used to probe the coordination even if metal ions does not possess any characteristic peak in spectra.Experimental results indicate that Ca^2＋ and Al^3＋ show considerable ability to coordinate with the carbonyl group of butanone and bring about spectral variation of the n-π-＊transition band,which is manifested by cross peaks in 2D asynchronous spectra.

PDZK1 protects against mechanical overload-induced chondrocyte senescence and osteoarthritis by targeting mitochondrial function

Mechanical overloading and aging are two essential factors for osteoarthritis(OA)development.Mitochondria have been identified as a mechano-transducer situated between extracellular mechanical signals and chondrocyte biology,but their roles and the associated mechanisms in mechanical stress-associated chondrocyte senescence and OA have not been elucidated.