Physical exercise reverses immuno-cold tumor microenvironment via inhibiting SQLE in non-small cell lung cancer

Dear Editor,Physical exercise has been shown to be associated with reduced cancer incidence and cancer-associated mortality[1,2],but the underlying mechanisms are obscure.Immunometabolic regulation has emerged as one of the most prominent mechanisms explaining the effects of exercise on cancer[1,2].Physical exercise primarily lowers blood cholesterol and triglycerides,and protects against cardiovascular diseases[3].However,whether physical exercise can modulate cholesterol metabolism in tumor cells is currently unknown.

Mechanism underlying the effects of exercise against type 2 diabetes:A review on research progress

Exercise has emerged as one of the important and effective non-drug therapies used for management of type 2 diabetes(T2D)in certain nations.The present report summarizes the latest findings from the research on the beneficial effect of exercise on T2D.The objectives were to provide references for the theoretical study and the clinical practice of exercise-based management of T2D,in addition to identify the limitations of the existing literature,thereby provide direction for future research in this field.

Research progress on the mechanism of exercise against depression

The substantial global health burden of depression encourages the development of innovative and broadly effective interventions.This paper aimed to examine recent advancements by which exercise works as an antidepressant and recommends optimal types and quantity of exercise as supplemental therapies in treating depression.Sedentary behavior and low physical activity significantly influence the onset of depression.Being an effective treatment option,exercise can significantly reduce depression risk.Exercise exerts antidepressant effects as it modulates neurotransmitters,neuroplasticity,the immune system,and hormone levels.Effective exercise forms include yoga,strength training,and walking/jogging.Tailored exercise regimens that consider individual preferences and tolerability can improve outcomes.Regular exercise enhances general well-being and reduces depressive symptoms.Additional research is needed to understand the complex basis of exercise's effects on depression.Exercise is a cost-effective and accessible intervention for depression management that needs additional exploration.Thus,customized exercise programs,as per each patient’s needs,are essential for their successful implementation clinically.

Long head of biceps tendon transposition for massive and irreparable rotator cuff tears:A systematic review and meta-analysis

BACKGROUND Superior capsular reconstruction(SCR)with long head of biceps tendon(LHBT)transposition was developed to massive and irreparable rotator cuff tears(MIRCTs);however,the outcomes of this technique remain unclear.AIM To perform a systematic review of biomechanical outcomes and a meta-analysis of clinical outcomes after LHBT transposition for MIRCTs.METHODS We performed a systematic electronic database search on PubMed,EMBASE,and Cochrane Library.Studies of SCR with LHBT transposition were included according to the inclusion and exclusion criteria.Biomechanical studies were assessed for main results and conclusions.Included clinical studies were evaluated for quality of methodology.Data including study characteristics,cohort demographics,and outcomes were extracted.A meta-analysis was conducted of the clinical outcomes.RESULTS According to our inclusion and exclusion criteria,a total of six biomechanical studies were identified and reported an overall improvement in subacromial contact pressures and prevention of superior humeral migration without limiting range of motion(ROM)after LHBT transposition for MIRCTs.A total of five clinical studies were included in the meta-analysis of LHBT transposition outcomes,consisting of 253 patients.The results indicated that compared to other surgical methods for MIRCTs,LHBT transposition had advantages of more significant improvement in ROM(forward flexion mean difference[MD]=6.54,95%confidence interval[CI]:3.07-10.01;external rotation[MD=5.15,95%CI:1.59-8.17];the acromiohumeral distance[AHD][MD=0.90,95%CI:0.21-1.59])and reducing retear rate(odds ratio=0.27,95%CI:0.15-0.48).No significant difference in American Shoulder and Elbow Surgeons score,visual analogue scale score,and University of California at Los Angles score was demonstrated between these two groups for MIRCTs.CONCLUSION In general,SCR with LHBT transposition was a reliable and economical technique for treating MIRCTs,both in terms of biomechanical and clinical outcomes,with comparable clinical outcomes,improved ROM,AHD,and reduced the retear rates compared to conventional SCR and other established techniques.More high-quality randomized controlled studies on the long-term outcomes of SCR with LHBT transposition are required to further assess.

Bone marrow mesenchymal stem cell-derived exosomal microRNAs target PI3K/Akt signaling pathway to promote the activation of fibroblasts

BACKGROUND Fibroblast plays a major role in tendon-bone healing.Exosomes derived from bone marrow mesenchymal stem cells(BMSCs)can activate fibroblasts and promote tendon-bone healing via the contained microRNAs(miRNAs).However,the underlying mechanism is not comprehensively understood.Herein,this study aimed to identify overlapped BMSC-derived exosomal miRNAs in three GSE datasets,and to verify their effects as well as mechanisms on fibroblasts.AIM To identify overlapped BMSC-derived exosomal miRNAs in three GSE datasets and verify their effects as well as mechanisms on fibroblasts.METHODS BMSC-derived exosomal miRNAs data(GSE71241,GSE153752,and GSE85341)were downloaded from the Gene Expression Omnibus(GEO)database.The candidate miRNAs were obtained by the intersection of three data sets.TargetScan was used to predict potential target genes for the candidate miRNAs.Functional and pathway analyses were conducted using the Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)databases,respectively,by processing data with the Metascape.Highly interconnected genes in the protein-protein interaction(PPI)network were analyzed using Cytoscape software.Bromodeoxyuridine,wound healing assay,collagen contraction assay and the expression of COL I andα-smooth muscle actin positive were applied to investigate the cell proliferation,migration and collagen synthesis.Quantitative real-time reverse transcription polymerase chain reaction was applied to determine the cell fibroblastic,tenogenic,and chondrogenic potential.RESULTS Bioinformatics analyses found two BMSC-derived exosomal miRNAs,has-miR-144-3p and hasmiR-23b-3p,were overlapped in three GSE datasets.PPI network analysis and functional enrichment analyses in the GO and KEGG databases indicated that both miRNAs regulated the PI3K/Akt signaling pathway by targeting phosphatase and tensin homolog(PTEN).In vitro experiments confirmed that miR-144-3p and miR-23b-3p stimulated proliferation,migration and collagen synthesis of NIH3T3 fibroblasts.Interfering with PTEN affected the phosphorylation of Akt and thus activated fibroblasts.Inhibition of PTEN also promoted the fibroblastic,tenogenic,and chondrogenic potential of NIH3T3 fibroblasts.CONCLUSION BMSC-derived exosomes promote fibroblast activation possibly through the PTEN and PI3K/Akt signaling pathways,which may serve as potential targets to further promote tendon-bone healing.

Establishment of an adult zebrafish model of retinal neurodegeneration induced by NMDA

AIM: To establish a model of retinal neurodegeneration induced by N-Methyl-D-aspartic acid(NMDA) in adult zebrafish.METHODS: We compared the effects of three different NMDA delivery methods on retinal neurodegeneration in adult zebrafish: immersion(I.M.), intravitreal injection(I.V.), and intraperitoneal injection(I.P.), and examined retinal pathology and degeneration by hematoxylin and eosin and TUNEL staining in the treated zebrafish. Effects of the NMDA receptor antagonist MK-801 and the natural product resveratrol on NMDA-induced retinal neurodegeneration were also assessed.RESULTS: The thickened inner retina was seen in histology with 100 μmol/L NMDA by I.M. administration. Significant apoptosis in the retinal ganglion cell layer and retinal thickness reduction occurred in 0.5 mol/L NMDA I.P. administration group.Seizure-like behavioral changes, but no retinal histological alteration occurred in 16 mg/kg NMDA I.P. administration group. Resveratrol and MK-801 prevented NMDA-induced retinal neurodegeneration in the zebrafish. CONCLUSION: Among the three drug administration methods, I.V. injection of NMDA is the most suitable for establishment of an acute retinal damage model inzebrafish. I.M. with NMDA is likely the best for use as a chronic retinal damage model. I.P. treatment with NMDA causes brain damage. Resveratrol and MK801 may be a clinically valuable treatment for retinal neurodegeneration.

Comparison of three administration modes for establishing a zebrafish seizure model induced by N-Methyl-D-aspartic acid

BACKGROUND Epilepsy is a complex neurological disorder characterized by recurrent,unprovoked seizures resulting from the sudden abnormal discharge of brain neurons.It leads to transient brain dysfunction,manifested by abnormal physical movements and consciousness.It can occur at any age,affecting approximately 65 million worldwide,one third of which are still estimated to suffer from refractory seizures.There is an urgent need for further establishment of seizure models in animals,which provides an approach to model epilepsy and could be used to identify novel anti-epileptic therapeutics in the future.AIM To compare three administration modes for establishing a seizure model caused by N-Methyl-D-aspartic acid(NMDA)in zebrafish.METHODS Three administration routes of NMDA,including immersion,intravitreal injection and intraperitoneal injection,were compared with regard to their effects on inducing seizure-like behaviors in adult zebrafish.We evaluated neurotoxicity by observing behavioral changes in zebrafish and graded those behaviors with a seizure score.In addition,the protective effects of MK-801(Dizocilpine)and natural active constituent resveratrol against NMDA-induced alterations were studied.RESULTS The three NMDA-administration methods triggered different patterns of the epileptic process in adult zebrafish.Seizure scores were increased after increasing NMDA concentration regardless of the mode of administration.However,the curve of immersion continuously rose to a high plateau(after 50 min),while the curves of intravitreal injection and intraperitoneal injection showed a spike in the early stage(10-20 min)followed by a steady decrease in seizure scores.Furthermore,pretreatment with resveratrol and MK-801 significantly delayed seizure onset time and lowered seizure scores.CONCLUSION By comparing the three methods of administration,intravitreal injection of NMDA was the most suitable for establishing an acute epileptic model in zebrafish.Thus,intraperitoneal injection in zebrafish can be applied to simulate diseases such as epilepsy.In addition,NMDA immersion may be an appropriate method to induce persistent seizures.Moreover,MK-801 and resveratrol showed strong anti-epileptic effects;thus,both of them may be clinically valuable treatments for epilepsy.

Exosomes derived from inflammatory myoblasts promote M1 polarization and break the balance of myoblast proliferation/differentiation

BACKGROUND Acute muscle injuries are one of the most common injuries in sports.Severely injured muscles are prone to re-injury due to fibrotic scar formation caused by prolonged inflammation.How to regulate inflammation and suppress fibrosis is the focus of promoting muscle healing.Recent studies have found that myoblasts and macrophages play important roles in the inflammatory phase following muscle injury;however,the crosstalk between these two types of cells in the inflammatory environment,particularly the exosome-related mechanisms,had not been well studied.AIM To evaluate the effects of exosomes from inflammatory C2C12 myoblasts(IFC2C12-Exos)on macrophage polarization and myoblast proliferation/differentiation.METHODS A model of inflammation was established in vitro by lipopolysaccharide stimulation of myoblasts.C2C12-Exos were isolated and purified from the supernatant of myoblasts by gradient centrifugation.Multiple methods were used to identify the exosomes.Gradient concentrations of IF-C2C12-Exos were added to normal macrophages and myoblasts.PKH67 fluorescence tracing was used to identify the interaction between exosomes and cells.Microscopic morphology,Giemsa stain,and immunofluorescence were carried out for histological analysis.Additionally,ELISA assays,flow cytometry,and western blot were conducted to analyze molecular changes.Moreover,myogenic proliferation was assessed by the BrdU test,scratch assay,and CCK-8 assay.RESULTS We found that the PKH-67-marked C2C12-Exos can be endocytosed by both macrophages and myoblasts.IF-C2C12-Exos induced M1 macrophage polarization and suppressed the M2 phenotype in vitro.In addition,these exosomes also stimulated the inflammatory reactions of macrophages.Further-more,we demonstrated that IF-C2C12-Exos disrupted the balance of myoblast proliferation/differentiation,leading to enhanced proliferation and suppressed fibrogenic/myogenic differentiation.CONCLUSION IF-C2C12-Exos can induce M1 polarization,resulting in a sustained and aggravated inflammatory environment that impairs myoblast differentiation,and leads to enhanced myogenic proliferation.These results demonstrate why prolonged inflammation occurs after acute muscle injury and provide a new target for the regulation of muscle regeneration.

Physical energy-based ultrasound shifts M1 macrophage differentiation towards M2 state

Recently,we read with interest the article entitled“Unveiling the Morphogenetic Code:A New Path at the Intersection of Physical Energies and Chemical Signaling”.In this paper,the investigation into the systematic and comprehensive bio-effects of physical energies prompted us to reflect on our research.We believe that ultrasound,which possesses a special physical energy,also has a certain positive regulatory effect on macrophages,and we have already obtained some preliminary research results that support our hypothesis.

Comment on “Outcomes of different minimally invasive surgical treatments for vertebral compression fractures: An observational study”

Recently we read the article entitled“Outcomes of different minimally invasive surgical treatments for vertebral compression fractures:An observational study”.This was an observational study that reviewed the safety and efficacy of different cement augmentation modalities for vertebral compression fractures under osteoporotic condition.Overall,this is a valuable study that can provide a reference for clinical practice.On the other hand,we also noticed some points in the article and are willing to share our views.Further studies with a higher level of evidence can add more knowledge regarding relevant concerns.

Management of hip fracture in COVID-19 infected patients

Given that the global population of elderly individuals is expanding and the difficulty of recovery,hip fractures will be a huge challenge and a critical health issue for all of humanity.Although people have spent more time at home during the coronavirus disease 2019(COVID-19)pandemic,hip fractures show no sign of abating.Extensive studies have shown that patients with hip fracture and COVID-19 have a multifold increase in mortality compared to those uninfected and a more complex clinical condition.At present,no detailed research has systematically analyzed the relationship between these two conditions and proposed a comprehensive solution.This article aims to systematically review the impact of COVID-19 on hip fracture and provide practical suggestions.We found that hip fracture patients with COVID-19 have higher mortality rates and more complicated clinical outcomes.Indirectly,COVID-19 prevents hip fracture patients from receiving regular medical treatment.With regard to the problems we encounter,we provide clinical recommendations based on existing research evidence and a clinical flowchart for the management of hip fracture patients who are COVID-19 positive.Our study will help clinicians adequately prepare in advance when dealing with such patients and optimize treatment decisions.

New-onset depression after hip fracture surgery among older patients:Effects on associated clinical outcomes and what can we do?

BACKGROUND Hip fracture in the elderly is a worldwide medical problem.New-onset depression after hip fracture has also received attention because of its increasing incidence and negative impact on recovery.AIM To provide a synthesis of the literature addressing two very important questions arising from postoperative hip fracture depression(PHFD)research:the risk factors and associated clinical outcomes of PHFD,and the optimal options for intervention in PHFD.METHODS We searched the PubMed,Web of Science,EMBASE,and PsycINFO databases for English papers published from 2000 to 2021.RESULTS Our results showed that PHFD may result in poor clinical outcomes,such as poor physical function and more medical support.In addition,the risk factors for PHFD were summarized,which made it possible to assess patients preoperatively.Moreover,our work preliminarily suggested that comprehensive care may be the optimal treatment option for PHFDs,while interdisciplinary intervention can also be clinically useful.CONCLUSION We suggest that clinicians should assess risk factors for PHFDs preoperatively,and future research should further validate current treatment methods in more countries and regions and explore more advanced solutions.

Geographic variation in photoperiodic diapause induction and diapause intensity in Sericinus montelus （Lepidoptera Papilionidae）

Due to the risk of extinction and ornamental value of the swallowtail butterfly, Sericinus montelus Gray （Lepidoptera： Papilionidae） in China, knowledge about local adaptations is important for the conservation and economical utilization of the species. In the present study, photoperiodie diapause induction and diapause intensity of S. montelus populations from Jiamusi （46°37＇N）, Beijing （40° 15＇N）, Zibo （36°48＇N）, Fangxian （32°36＇N）, Wuhan （30°33＇N） and Huaihua （27°33＇N） were characterized at 25℃. Logistic regression analysis revealed a significant population x hours of light interaction, confirming that photoperiodic responses varied among populations. The critical photoperiod was positively correlated with latitude and increased toward the north at a rate of about 1 h for each 6.67 degrees of latitude. Survival analyses indicated that survival time of diapausing pupae before adult eclosion differed significantly among populations at 25℃ and 16 ： 8 L ＂D h. The mean duration of pupal diapause was also positively correlated with latitude. Our study reveals geographic variation in the critical photoperiod for diapause induction and in diapause intensity of S. montelus. These results provide useful information for our general understanding about seasonal adaptation in insects and may also be used to predict how geographic populations respond to climate warming.