Effectiveness of resistance training in modulating inflammatory biomarkers among Asian patients with sarcopenia: a systematic review and meta-analysis of randomized controlled trials.

Objective: Given the high incidence of sarcopenia among Asians, it is imperative to identify appropriate intervention methods. The International Clinical Practice Guidelines for Sarcopenia, developed by the International Conference on Sarcopenia and Frailty Research (ICFSR) task force, recommends resistance training (RT) as a primary treatment for managing sarcopenia. Inflammatory biomarkers serve as indicators of sarcopenia. However, there is currently insufficient conclusive evidence regarding the effectiveness of RT in modulating inflammatory biomarker levels among Asian participants with sarcopenia. Data sources: Four databases were utilized for this study until October 9, 2023. This study focused on randomized controlled trials (RCTs) that examined the effects of RT on interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and interleukin-10 (IL-10) about sarcopenia. This study has been registered in the PROSPERO database (CRD42024501855). Results: The meta-analysis included six studies from Asians involving 278 participants. The results showed a significant decrease in RT for IL-6 (weighted mean difference (WMD) = -0.73, 95% confidence interval (CI) = -1.02 to -0.44; n=5). However, no significant differences were found for TNF-α (WMD = -1.00, 95% CI = -2.47 to 0.46; n=5), CRP (WMD = -0.45, 95% CI = -1.14 to 0.23; n=3), and IL-10 (WMD = 0.13, 95% CI = -3.99 to 4.25; n=2). Subgroup analysis revealed that factors including gender selection, intervention methods, frequency, period, and duration could have a particular effect on the part of inflammatory biomarkers. Conclusion: RT has been shown to reduce part of the level of inflammatory markers, specifically IL-6, in Asian sarcopenia participants. However, other inflammatory factors, such as TNF-α, CRP, and IL-10, did not show significant changes. Further research should confirm the impact of RT on these indicators and explore the potential effects of various factors on different inflammatory markers, such as diet, body composition, and medications. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=501855, identifier CRD42024501855.

Intramuscular Pressure and Patient-Reported Outcomes in Patients Surgically Treated for Anterior Chronic Exertional Compartment Syndrome.

Background: Chronic exertional compartment syndrome (CECS) causes exercise-induced leg pain. The diagnosis is confirmed by intramuscular pressure (IMP) measurements. Fasciotomy has been demonstrated to be a successful treatment for CECS; however, few studies have examined postoperative IMP and long-term outcomes. Purpose: To evaluate long-term outcomes and postoperative IMP in patients surgically treated for anterior CECS, and to identify possible preoperative or postoperative factors associated with overall satisfaction with treatment at follow-up. Study Design: Case-control study; Level of evidence, 3. Methods: A consecutive series of 209 patients who underwent fasciotomy of the anterior compartment for CECS between 2009 and 2019 and had at least 1 year of follow-up were approached for inclusion. A total of 144 patients (69%), with a follow-up time of 1 to 11.5 years, were ultimately included. All patients underwent preoperative and postoperative 1-minute postexercise IMP measurements of the anterior compartment and completed a questionnaire covering pain and activity parameters at both time points. The follow-up questionnaire included an additional question on overall satisfaction with treatment, and surgical details were collected from the patient's medical records. Results: The median IMP was significantly lower at follow-up than at baseline (17 mm Hg [range, 5-91 mm Hg] vs 49 mm Hg [range, 25-130 mm Hg]; P < .001). The overall satisfaction rate was 77%, and 83% reported a decreased pain level. The group of patients who were satisfied with the treatment included more men and had a higher ΔIMP and a lower revision rate (P < .05). Among the 16 patients (11%) who had undergone revision fasciotomies before follow-up, the satisfaction rate was 56%, and 64% reported a decrease in pain level. Conclusion: Fasciotomy significantly reduced 1-minute postexercise IMP in patients with CECS and resulted in satisfaction and decreased pain in more than three-quarters of the patients at long-term follow-up. The male sex and a significant decrease in IMP were both positively associated with treatment satisfaction. Patients who underwent revision surgery before the follow-up had lower satisfaction rates and less pain reduction than the overall group.

Self-reported prevalence and potential factors influencing cardio-cerebral vascular disease among the Chinese elderly: A national cross-sectional study.

Background: Aging is an essential national condition throughout China in the 21st century. Cardio-cerebral vascular disease (CCVD) is a common chronic vascular disease in the elderly. Despite aging becoming an increasingly pressing issue, there has been no comprehensive national investigation into the risk factors, prevalence, and management of CCVD among the elderly population in China. Materials and methods: Through the 4th Survey of the Aged Population in Urban and Rural China (SSAPUR), a nationally representative sample of 224,142 adults aged more than 60 years was surveyed using a multistage, stratified sampling method. The 4th SSAPUR was used to investigate CCVD in the elderly. Univariate and multivariate logistic proportional regression analyses explored the risk factors. These risk factors were then entered into a multivariate linear regression model to identify independent predictive factors for CCVD. Disease management was assessed from the self-reported history of physician diagnosis, treatments, and hospital visits among individuals with CCVD. Results: After excluding samples with missing information, 215,041 individuals were included in the analysis. The overall prevalence of CCVD was 26%. Living in a rural area, being older, being female, having low literacy, smoking, getting little sleep, losing a spouse, being single, not getting enough exercise, having a bad financial situation, and not taking part in public welfare programs were the main risk factors for CCVD among the elderly in China (P < 0.05). In the multivariate linear regression model, holding all other variables at any fixed value, CCVD remained associated with "urban and rural" (ß = 0.012, P < 0.001), "age" (ß = -0.003, P < 0.001), "sex" (ß = -0.022, P < 0.001), "education level" (ß = -0.017, P < 0.001), "marriage" (ß = 0.004, P = 0.047), "smoking" (ß = 0.012, P = 0.003), "drinking" (ß = -0.015, P = 0.001), and "sleep" (ß = 0.008, P = 0.005). There were no collinearity problems among these factors. Conclusion: Major risk factors for prevalent CCVD among the elderly in China include the following: rural residence, female, low literacy level, poor sleep quality, bereavement, non-marriage, living alone, lack of exercise, poor financial situation, and non-participation in public welfare activities. Chinese national policies for preventing, controlling, and managing risk factors for CCVD in the elderly must be urgently developed.

Serum irisin levels in patients with myasthenia gravis.

OBJECTIVE: Myasthenia gravis (MG) is an autoimmune disorder whose main symptoms are muscle weakness and fatigue. Irisin is a novel skeletal muscle-derived myokine participating in several physiological and pathological processes. The initial objective of the project was to explore serum levels of irisin in patients with MG, as well as its correlation with disease severity. METHODS: We retrospectively evaluated serum levels of irisin in 77 MG patients and 57 healthy controls (HCs) by enzyme-linked immunosorbent assay. Further, clinical parameters were measured properly. RESULTS: Serum irisin levels were significantly elevated in MG patients compared with HCs (p < 0.001). Furthermore, serum irisin levels were associated with the myasthenia gravis activities of daily living score in ocular myasthenia gravis (OMG) patients (r = 0.476, p = 0.004), but there was no relationship to be considered of any relevant value in generalized myasthenia gravis (GMG) patients. Acetylcholine receptor antibody-positive MG patients had higher serum irisin levels compared with HCs. Thymoma, endotracheal intubation, or intensive care unit treatments subsequently were not found to have effect on serum levels of irisin, but tendencies of increase were observed in negative ones. CONCLUSIONS: Serum irisin levels were elevated in patients with MG, suggesting its possible involvement in MG. And irisin is expected to be a signal to evaluate the activities of daily living of OMG patients, while its effect needs further study.

Right coronary artery-left ventricular fistula with giant right coronary artery of diffuse ectasia: a case report.

BACKGROUND: Coronary artery fistula complicated with giant coronary artery ectasia (CAE) is a rare cardiac malformation, and its surgical indications and treatment strategies still need further discussion. CASE SUMMARY: In this case, a 41-year-old man had complained of occasional dizziness for 2 years, but he did not seek medical attention until he started to feel palpitations. A right coronary artery (RCA)-left ventricular (LV) fistula with giant RCA of diffuse ectasia was firstly revealed by transthoracic echocardiography. A widened left ventricle and significantly constricted right atrium and right ventricle were also detected by three-dimensional coronary artery computed tomography. Surgical treatment, including the repair of the RCA-LV fistula, the resection and reconstruction of the dilated RCA and coronary artery bypass grafting (CABG) under hypothermic cardiopulmonary bypass, were performed to correct the malformation. The patient presented a favourable health condition without any discomfort at the 1-year follow-up. DISCUSSION: CAE can be caused by various congenital or acquired factors. Surgical treatment, such as transcatheter embolization excision, surgical ligation or resection for symptomatic patients with CAE three times or larger than the reference diameter, has been reported to have satisfactory results. Additionally, CABG can be selected if myocardial perfusion is compromised and the distal branch is of reasonable size. In this case, the giant ectasia of the RCA may have been a consequence of the congenital RCA-LV fistula. Atherosclerosis, with calcified plaques in the RCA, and the patient's long-term history of smoking may have contributed to the development of giant ectasia of the RCA.

Significantly lower intramuscular pressure in the posterior and lateral compartments compared with the anterior compartment suggests alterations of the diagnostic criteria for chronic exertional compartment syndrome in the lower leg.

PURPOSE: To investigate distributions and identify possible differences in intramuscular pressure (IMP) values at 1 min post-exercise between the four muscle compartments of the lower leg, in patients with exertional leg pain with or without chronic exertional compartment syndrome (CECS). METHODS: A consecutive series of patients seeking orthopaedic consultation for exertional leg pain underwent IMP measurements between 2009 and 2018. The diagnosis of CECS was confirmed (n = 442) or ruled out (n = 422), based on the patient's history, clinical examination, and IMP measurements. RESULTS: The median (range) 1 min post-exercise IMP values in affected compartments in the patients diagnosed with CECS were 33 (25-53) mmHg (deep posterior), 35 (27-54) mmHg (superficial posterior), 40 (26-106) mmHg (lateral), and 47 (24-120) mmHg (anterior). In patients with no CECS, the median (range) 1 min post-exercise IMP values in the compartments were 12 (2-28) mmHg (deep posterior), 12 (2-27) mmHg (superficial posterior), 14 (2-26) mmHg (lateral), and 18 (4-34) mmHg (anterior). The IMP was significantly lower in the lateral and both posterior compartments than in the anterior compartment in both patients diagnosed with CECS and patients without CECS. CONCLUSION: The study demonstrates significantly lower IMP values in the posterior and lateral compartments compared to the anterior compartments. These findings suggest a lowering of the IMP 1 min post-exercise cut-off value for diagnosing CECS in the lateral and both posterior compartments, which may lead to improved treatment of patients with suspected CECS in the lower leg. LEVEL OF EVIDENCE: Level II.

Identification of Transcriptional Variation in Aortic Remodeling Using a Murine Transverse Aortic Constriction (TAC) Model.

Arterial remodeling is a major pathological consequence of hypertension, which is recognized as the most common chronic non-communicable disease. However, the detailed mechanism of how arterial remodeling is induced by hypertension has not yet been fully elucidated. Evaluating the transcriptional changes in arterial tissue in response to elevated blood pressure at an early stage may provide new insights and identify novel therapeutic candidates in preventing arterial remodeling. Here, we used the ascending aorta of the transverse aortic constriction (TAC) model to induce arterial remodeling in C57BL/6 male mice. Age-matched mice were subjected to sham surgery as controls. The TAC model was only considered successful if the mice conformed to the criteria (RC/LC blood flow velocity with 5-10-fold change) 1 week after the surgery. Two weeks after surgery, the ascending aorta developed severe remodeling in TAC mice as compared to the sham group. High throughput sequencing was then applied to identify differentially expressed (DE) transcripts. In silicon analysis were then performed to systematically network transcriptional changes. A total of 1,019 mRNAs were significantly changed between TAC and the sham group at the transcriptional level. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis revealed that stress/stimulus/immune-related biological processes played a crucial role during arterial remodeling. Our data provide a comprehensive understanding of global gene expression changes in the TAC model, which suggests that targeting inflammation and vascular smooth cell transformation are potential therapeutic strategies to interfere with the aortic remodeling at an early stage in the development of hypertension.

LncRNA KCNQ1OT1 Regulates Endoplasmic Reticulum Stress to Affect Cerebral Ischemia-Reperfusion Injury Through Targeting miR-30b/GRP78.

Endoplasmic reticulum stress (ERS) plays an important role in cerebral ischemia-reperfusion injury (CIRI) by regulating apoptosis. Although the role of long non-coding RNA (LncRNA) KCNQ1OT1 in CIRI has been reported, the specific mechanism is still unclear. In this paper, the regulation of ERS by LncRNA KCNQ1OT1 in CIRI and its mechanism were studied. Transient middle cerebral artery occlusion (tMCAO) model was established in SD rats with KCNQ1OT1 intervention. PC12 cells were used to construct the OGD/R cell model. The expressions of LncRNA KCNQ1OT1 and miR-30b were detected by RT-qPCR. TCC staining was used to detect the extent of cerebral ischemia. TUNEL staining was used to detect apoptosis level, and Western blot was used to detect the expressions of ERS and apoptosis-related proteins. The targeted binding of LncRNA KCNQ1OT1, miR-30b, and GRP78 was detected by double luciferase assay. The expressions of LncRNA KCNQ1OT1 and miR-30b were interfered by cell transfection. Cell proliferation was detected by CCK-8. The level of LncRNA KCNQ1OT1 was increased and that of miR-30b was decreased in the blood samples of patients with CIRI. In tMCAO rats with KCNQ1OT1 intervention, the expression of miR-30b was increased, and the ischemic range of brain tissues was decreased. What's more, the level of ERS was decreased, and the apoptosis of brain tissues was decreased. LncRNA KCNQ1OT1 could regulate miR-30b/GRP78 in OGD/R cells in a targeted way. Intervention of KCNQ1OT1 could promote the proliferation of OGD/R cells, inhibiting the level of ERS and cell apoptosis. Further inhibition of miR-30b could reverse the effect of intervention of KCNQ1OT1. LncRNA KCNQ1OT1 regulates ERS to affect CIRI through targeting miR-30b/GRP78.

Increased serum IL-36γ levels are associated with disease severity in myasthenia gravis patients.

BACKGROUND: Interleukin 36 (IL-36), as a gradually recognized cytokine, is involved in the occurrence and evolution of autoimmune diseases. Nevertheless, the relationship between myasthenia gravis (MG) and IL-36 is rarely reported. METHODS: We evaluated the serum levels of IL-36 (IL-36α, IL-36ß and IL-36γ) by enzyme-linked immunosorbent assay (ELISA). Further, clinical parameters in 97 MG patients and 49 healthy controls (HCs) were carefully measured. RESULTS: Serum IL-36γ levels were significantly elevated in the MG patients compared with the HCs (p < 0.0001). Compared to those in remission, patients in the acute phase exhibited higher levels of IL-36α and IL-36γ (p = 0.038 and p = 0.011, respectively). Furthermore, patients with generalized MG (GMG) exhibited markedly higher serum IL-36γ levels than those with ocular MG (OMG) (p = 0.003). CONCLUSIONS: The serum levels of IL-36γ in patients with MG were increased and positively correlated with disease severity and may thus have potential as a serological MG marker.

KCNQ1OT1 Exacerbates Ischemia-Reperfusion Injury Through Targeted Inhibition of miR-140-3P.

Potassium voltage-gated channel subfamily Q member 1 opposite strand 1 (KCNQ1OT1), a long non-coding RNA found in the KCNQ1 locus, has been evidenced to play important roles in the aggravation of inflammatory and oxidative stresses under hypoxia, but whether and how KCNQ1OT1 contributes to neuronal damages in the cerebral ischemic stroke remains unknown. In the present study, we found a dominant upregulation of KCNQ1OT1 both in the plasma of cerebral ischemia patients and in an oxygen-glucose deprivation and reperfusion (OGD/R) model in PC12 cells. KCNQ1OT1 knocking-down significantly ameliorated the inflammation, oxidative stress, and cell apoptosis induced by OGD/R. We further demonstrated that KCNQ1OT1 directly bound to and suppressed the expression of miR-140-3p. Overexpressing miR-140-3p significantly alleviated both the inflammation, oxidative stress, and cell apoptosis in OGD/R, while all those cytoprotective effects of miR-140-3p-overexpression were hindered by the co-overexpression of KCNQ1OT1. Furthermore, we found a direct interaction between miR-140-3p and the hypoxia-inducible factor-1α (HIF-1α), which was suppressed by the upregulation of KCNQ1OT1 in OGD/R. Our results indicate that KCNQ1OT1 exacerbates cerebral ischemia-reperfusion injury by targeted binding to miR-140-3p, thus interfering its direct interaction with HIF-1α. These data provide novel therapeutic targets in the cerebral ischemic stroke.

Different clinical characteristics of longitudinally extensive transverse myelitis with and without connective tissue disorders: a single-center retrospective study.

BACKGROUND AND OBJECTIVE: Autoimmune longitudinal extensive transverse myelitis (LETM) is often combined with connective tissue disorders (CTD). The purpose of this study was to compare the clinical characteristics of autoimmune LETM with and without CTD. METHODS: Ninety-two patients diagnosed with autoimmune LETM were enrolled from our clinical database and divided into two groups depending on whether they had a concomitant diagnosis of CTD. Differences in clinical, serological, and imaging characteristics between the two groups were evaluated and compared. RESULTS: Fifty-nine LETM patients without CTD and 33 LETM patients with CTD were included. LETM patients with CTD had higher Kurtzke Expanded Disability Status Scale at nadir and more severe sensory dysfunction (p < 0.05) than those without CTD. It was also found that LETM patients with CTD, compared with those without CTD, had elevated levels of immune inflammation markers such as IgG, IgA, and globulins (p < 0.05). These abovementioned characteristics were more prominent in patients with aquaporin-4 antibodies (AQP4-ab) than in those without them. In addition, the most common type of CTD in LETM was Sjögren syndrome (SS), which was usually diagnosed at the time of LETM or later. CONCLUSION: LETM patients with CTD, especially those with AQP4-ab, had greater sensory dysfunction and higher levels of inflammatory markers than did LETM patients without CTD. Multicenter cooperation and long-term follow-up are necessary to further study the inherent implications and prognosis of the disease.

Nifurtimox Hampered the Progression of Astroglioma In vivo Via Manipulating the AKT-GSK3ß axis.

BACKGROUND: Astroglioma, one major form of brain tumors, has remained principally tough to handle for decades, due to the complexity of tumor pathology and the poor response to chemo- and radio-therapies. METHODS: Our previous study demonstrated that nifurtimox could regulate the signaling axis of AKT-GSK3ß in various tumor types including the astroglioma U251 cells. Intriguingly, earlier case studies suggested that nifurtimox could possibly permeate the blood brain barrier and arrest neuroblastoma in the brain. These observations jointly encouraged us to explore whether nifurtimox would hinder the growth of astroglioma in vivo. RESULTS: Our results exhibited that nifurtimox could competently hinder the development of astroglioma in the mouse brain as compared to temozolomide, the first line of drug for brain tumors. Meanwhile the surviving rate, as well as the body-weight was dramatically upregulated upon nifurtimox treatment, as compared to that of temozolomide. These findings offered nifurtimox as a better alternative drug in treating astroglioma in vivo. CONCLUSION: Persistently, the manipulation of the signaling axis of AKT-GSK3ß in astroglioma was found in line with earlier findings in neuroblastoma when treated with nifurtimox.

A model for evaluation of the electric activity and oxygenation in the erector spinae muscle during isometric loading adapted for spine patients.

BACKGROUND: Simultaneous measurement of electromyography (EMG) and local muscle oxygenation is proposed in an isometric loading model adjusted for patients that have undergone spinal surgery. METHODS: Twelve patients with degenerative lumbar spinal stenosis (DLSS) were included. They were subjected to a test protocol before and after surgery. The protocol consisted of two parts, a dynamic and an isometric Ito loading with a time frame of 60 s and accompanying rest of 120 s. The Ito test was repeated three times. EMG was measured bilaterally at the L4 level and L2 and was recorded using surface electrodes and collected (Biopac Systems Inc.). EMG signal was expressed as RMS and median frequency (MF). Muscle tissue oxygen saturation (MrSO2) was monitored using a near-infrared spectroscopy (NIRS) device (INVOS® 5100C Oxymeter). Two NIRS sensors were positioned bilaterally at the L4 level. The intensity of the leg and back pain and perceived exertion before, during, and after the test was evaluated with a visual analogue scale (VAS) and Borg RPE-scale, respectively. RESULTS: All patients were able to perform and complete the test protocol pre- and postoperatively. A consistency of lower median and range values was noted in the sensors of EMG1 (15.3 µV, range 4.5-30.7 µV) and EMG2 (13.6 µV, range 4.0-46.5 µV) that were positioned lateral to NIRS sensors at L4 compared with EMG3 (18.9 µV, range 6.5-50.0 µV) and EMG4 (20.4 µV, range 7.5-49.0 µV) at L2. Right and left side of the erector spinae exhibited a similar electrical activity behaviour over time during Ito test (60 s). Regional MrSO2 decreased over time during loading and returned to the baseline level during recovery on both left and right side. Both low back and leg pain was significantly reduced postoperatively. CONCLUSION: Simultaneous measurement of surface EMG and NIRS seems to be a promising tool for objective assessment of paraspinal muscle function in terms of muscular activity and local muscle oxygenation changes in response to isometric trunk extension in patients that have undergone laminectomy for spinal stenosis.

Houshiheisan promotes angiogenesis via HIF-1α/VEGF and SDF-1/CXCR4 pathways: in vivo and in vitro.

RATIONALE: Houshiheisan (HSHS), a classic prescription in traditional Chinese medicine (TCM), has remarkable efficacy in the treatment of ischemic stroke. OBJECTIVE: To investigate the pro-angiogenic effect and molecular mechanism of HSHS for stroke recovery. METHODS AND RESULTS: The rat permanent middle cerebral artery occlusion (pMCAO) model was constructed by suture method, HSHS (5.25 or 10.5 g/kg) and Ginaton (28 mg/kg) treatment was intragastrically administrated at 6 h after modeling which remained for 7 consecutive days. Pathological evaluation conducted by Hematoxylin-Eosin (HE) staining and the results showed that HSHS alleviated blood vessel edema, reduced the damage to blood vessels and neurons in the ischemic areas. Immunostaining, quantitative real-time fluorescence PCR results showed that HSHS up-regulated pro-angiogenic factors including platelet endothelial cell adhesion molecule-1 (cluster of differentiation 31 (CD31)), vascular endothelial growth factor (VEGF), vascular endothelial growth factor A (VEGFA), VEGF receptor 2 (VEGFR2), angiopoietin-1 (Ang-1), while down-regulated angiopoietin-2 (Ang-2), stromal cell derived factor-1 (SDF-1), and cxc chemokine receptor 4 (CXCR4) expression in infarct rat cortex, and similar results were obtained in subsequent Western blot experiment. Furthermore, CCK8 assay and transwell migration assay were performed to assess cell proliferation, migration, and tube formation. The medicated serum (MS) of HSHS appeared to have beneficial effects for immortalized human umbilical vein cells (Im-HUVECs) on proliferation and migration after persistence hypoxia. Western blot analysis revealed that the expression of hypoxia inducible factor-1α (HIF-1α), VEGFA, Ang-1, Ang-2, and CXCR4 were significantly up-regulated while Ang-2 was down-regulated by HSHS MS treatment compared with vehicle group in vitro. CONCLUSION: The present study suggests a novel application of HSHS as an effective angiogenic formula for stroke recovery.

An MRI Study of Neurovascular Restorative After Combination Treatment With Xiaoshuan Enteric-Coated Capsule and Enriched Environment in Rats After Stroke.

Xiaoshuan enteric-coated capsule (XSEC) is a Chinese medicinal compound widely used for treatment of ischemic cerebrovascular diseases. Enriched environment (EE) is an effective rehabilitative protocol designed to enhance sensorimotor, cognitive and social stimulation. This study aimed to apply magnetic resonance imaging (MRI) to non-invasively assess whether EE could augment the therapeutic benefits of XSEC on post-ischemic neurovascular remodeling. Male Sprague-Dawley rats were subjected to permanent middle cerebral artery occlusion (MCAO) and treated with XSEC and EE alone or combination for 30 consecutive days. Beam walking test and Morris water maze (MWM) test were performed to evaluate motor and cognitive function, respectively. Multimodal MRI was applied to examine alterations to brain structures, intracranial vessels, and cerebral perfusion on the 31st day after MCAO. Double-immunofluorescent staining was used to evaluate neurogenesis and angiogenesis. Western blot and RT-PCR were used to detect the expressions of vascular endothelial growth factor (VEGF), angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), and the axon guidance molecules. Combination therapy with XSEC and EE significantly reduced cystic volume compared with XSEC and EE monotherapies. In line with this, combination treated rats performed better in the beam walking test and exhibited improved spatial memory in the probe trial of the MWM. Moreover, XSEC and EE combination treatment improved cerebral blood flow (CBF), amplified angiogenesis and upregulated VEGF protein levels. This proangiogenic effect was consistent with the increased progenitor cell proliferation and neuronal differentiation in the peri-infarct cortex and striatum. Specifically, the combined therapy of XSEC and EE markedly increased the Netrin-1 and Robo-1 protein expression levels compared with vehicle group, while no difference was observed between XSEC or EE monotherapy and vehicle group. Together, these findings indicate that the combination of XSEC and EE benefits neurovascular reorganization. This correlates with restoration of CBF, promotion of neurogenesis and angiogenesis, and activation of the intrinsic axonal guidance molecules, thereby facilitating greater physical rehabilitation after ischemic stroke.

Ti3C2 MXenes nanosheets catalyzed highly efficient electrogenerated chemiluminescence biosensor for the detection of exosomes.

Exosomes have been reported to play an important role in the anti-tumor immune response, tumor diagnosis and other processes, and are promising biomarkers for early cancer diagnosis. In this work, a sensitive electrogenerated chemiluminescence (ECL) biosensor was developed for detection of exosomes using aptamer modified two-dimensional material Ti3C2 MXenes nanosheets as the ECL nanoprobe because of its large surface area, the excellent conductivity and catalytic properties. The exosomes can be high efficiently captured onto the electrode surface by an EpCAM protein recognized aptamer modified on the electrode surface. In addition, the ECL nanoprobe can also recognize the exosomes, and significantly enhanced the ECL signals of luminol. Based on this strategy, a highly sensitive ECL biosensor for MCF-7 exosomes detection was obtained. The detection limit is 125 particles µL-1, which was over 100 times lower than that of conventional ELISA method. The as prepared ECL biosensor was performed successfully for MCF-7 exosomes detection in the serum. This strategy provided a feasible, sensitive and reliable tool for the exosomes detection in exosomes-related clinical diagnostics.

Universal Ti3C2 MXenes Based Self-Standard Ratiometric Fluorescence Resonance Energy Transfer Platform for Highly Sensitive Detection of Exosomes.

Exosomes, as novel noninvasive biomarkers for disease prediction and diagnosis, have shown fascinating prospects in monitoring cancer-linked public health issues. Herein, a unique Cy3 labeled CD63 aptamer (Cy3-CD63 aptamer)/Ti3C2 MXenes nanocomplex was constructed as a self-standard ratiometric fluorescence resonance energy transfer (FRET) nanoprobe for quantitative detection of exosomes. The Cy3-CD63 aptamer can be selectively adsorbed onto the Ti3C2 MXene nanosheets by hydrogen bond and metal chelate interaction between the aptamer and MXenes, and the fluorescence signal from Cy3-CD63 aptamer was quenched quickly owing to the FRET between the Cy3 and MXenes. The fluorescence of Cy3 greatly recovered after the addition of the exosomes which can specifically combine with the aptamer and release from the surface of Ti3C2 MXenes due to the high affinity between the aptamer and CD63 protein on exosome surface. Meanwhile, the self-fluorescence signal of MXenes in the whole process showed little change, which can be used as a standard reference. Based on the self-standard turn-on FRET biosensing platform the detection limit of exosome was determined as 1.4 × 103 particles mL-1, which was over 1000× lower than that of conventional ELISA method. This fluorescence sensor can also be used for the identification of multiple biomarkers on the exosome surface and different kinds of exosomes, combining with the fluorescent confocal scanning microscope image. The proposed strategy not only provides a universal nanoplatform for exosomes, but also can be extensively expanded to multiple biomarkers detection, which may promise the prospect of MXenes as robust candidates in biological fields.

Bu Shen Yi Sui capsule promotes remyelination correlating with Sema3A/NRP-1, LIF/LIFR and Nkx6.2 in mice with experimental autoimmune encephalomyelitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Bu Shen Yi Sui capsule (BSYSC), based on traditional Chinese formula Liu Wei Di Huang pill, is effective for the treatment of multiple sclerosis (MS) in clinical experience and trials. Our previous studies confirmed that BSYSC had the neuroprotective effect in MS and its animal model, experimental autoimmune encephalomyelitis (EAE); however, its mechanism of action was not clear. Thus, the effect of BSYSC on remyelination and the underlying mechanisms were investigated in the EAE mice. MATERIALS AND METHODS: The EAE model was established by injecting subcutaneously myelin oligodendrocyte protein (MOG) 35-55 in mice. Mice were treated with BSYSC (3.02 g/kg) or vehicle daily by oral gavage for 40 days. The body weight and clinical score of mice were evaluated. Brain was observed by magnetic resonance imaging. The inflammation infiltrate of brain and spinal cord was determined by hematoxylin-eosin staining, while the structure of myelin sheath was visualized by transmission electron microscopy on days 23 and 40 post immunization (dpi), respectively. The protein and mRNA levels of platelets-derived growth factor receptor (PDGFR) α and 2', 3'-cyclic nucleotide-3'-phosphodiesterase (CNPase) were measured by immunohistochemistry, western blot and quantitative real-time polymerase chain reaction. The protein expressions of semaphorins (Sema) 3A, Neuropilin (NRP) - 1, leukemia inhibitory factor (LIF), LIF receptor (LIFR) and Nkx6.2 were further investigated by western blot. RESULTS: BSYSC treatment improved the body weight and clinical score of EAE mice, alleviated inflammatory infiltration and nerve fiber injuries. It also protected the ultrastructural integrity of myelin sheath. BSYSC significantly increased expressions of PDGFRα and CNPase in mice with EAE on 40 dpi. Furthermore, BSYSC treatment increased the expressions of LIF, LIFR and Nkx6.2 and reduced Sema3A and NRP-1 in EAE mice on 40 dpi. CONCLUSIONS: The data demonstrated that BSYSC exhibited the neuroprotective effect against EAE by promoting oligodendrocyte progenitor cells (OPCs) proliferation and differentiation, thus facilitating remyelination. Sema3A/NRP-1, LIF/LIFR and Nkx6.2 are likely contributed to the effects of BSYSC on OPCs.

A thymosin repeated protein1 reduces white spot syndrome virus replication in red claw crayfish Cherax quadricarinatus.

The ß-thymosins are a group of structurally related, highly conserved intracellular small peptides in vertebrates with various biological functions, including cytoskeletal remodeling, neuronal development, cell migration, cell survival, tissue repair and inhibition of inflammation. In contrast to vertebrates, the function of ß-thymosin is not fully understood in crustaceans. Previously, we found that a thymosin-repeated protein1 (CqTRP1) gene was up-regulated after white spot syndrome virus (WSSV) challenge in hematopoietic tissue (Hpt) cells from the red claw crayfish Cherax quadricarinatus. To further identify the effect of CqTRP1 on WSSV infection, a full length cDNA sequence of ß-thymosin homologue was cloned and analyzed from red claw crayfish followed by functional study. The CqTRP1 cDNA contains an open reading frame of 387 nucleotides encoding a protein of 129 amino acids with a putative molecular mass of 14.3 kDa. The amino acid sequence showed high identity with other ß-thymosins and contained three characteristic thymosin ß actin-binding motifs, suggesting that CqTRP1 was a member of the ß-thymosin family. Tissue distribution analysis revealed a ubiquitous presence of CqTRP1 in all the examined tissues with the highest expression in hemocytes, Hpt and gonad at the transcriptional level. Interestingly, the gene silencing of endogenous CqTRP1 by RNAi enhanced the WSSV replication in Hpt cells. Meanwhile, the WSSV replication was significantly reduced in the Hpt cell cultures if overloaded with a recombinant CqTRP1. Taken together, these data clearly indicated that CqTRP1 was likely to be associated with the anti-WSSV response in a crustacean C. quadricarinatus, which provides new strategy against white spot disease in crustacean aquaculture.

MicroRNA-322 attenuates aluminum maltolate-induced apoptosis in the human SH-SY5Y neuroblastoma cell line.

Aluminum-maltolate (Al­Malt) is a potent apoptosis inductor, which has been widely reported as an etiologic factor in Alzheimer's disease (AD). MicroRNA-322 (miR­322) is a vital regulator in various biological processes. The aim of the current study was to identify the role and possible underlying mechanism of miR­322 in Al­Malt­induced apoptosis. Eight concentrations of Al­Malt were prepared and used for treating the human neuroblastoma cell line, SH­SY5Y. Subsequent to treatment with Al­Malt for 3 days, cell viability, apoptosis and the expression levels of apoptosis­associated factors were measured. In addition, the mRNA expression level of miR­322 was monitored. Furthermore, cells were transfected with an miR­322 mimic and/or treated with Al­Malt, and cell viability, apoptosis and the expression levels of apoptosis­associated factors were measured again. Al­Malt significantly inhibited cell viability, but promoted apoptosis. The apoptosis­associated factors, V­Myc avian myelocytomatosis viral oncogene homolog (c­Myc), Bcl-2-associated X protein, caspase­3 and cleaved caspase­3 were markedly upregulated by Al­Malt. The mRNA expression level of miR­322 was negatively regulated by Al­Malt. Furthermore, miR­322 attenuated the apoptosis induced by Al­Malt and recovered the expression changes of these four factors. Thus, miR­322 may attenuate Al­Malt­induced apoptosis by recovering the expression change of c­Myc. Furthermore, miR­322 may be involved in the pathogenesis of Al­Malt­associated AD.