Sirtuin 6 regulates macrophage polarization to alleviate sepsis-induced acute respiratory distress syndrome via dual mechanisms dependent on and independent of autophagy.

BACKGROUND AIMS: Sepsis-induced acute respiratory distress syndrome (ARDS) can be mediated by an imbalance in macrophage polarization; however, the underlying mechanisms remain poorly understood. This study aimed to investigate the modulatory role of sirtuin 6 (SIRT6) in macrophage polarization during sepsis-induced ARDS. METHODS: A mouse ARDS model was established using cecal ligation and puncture. Isolated alveolar macrophages (AMs) and lipopolysaccharide (LPS)-stimulated bone marrow-derived macrophages (BMDMs) were adopted as in vitro models. Macrophage polarization was evaluated by measuring M1 and M2 macrophage percentages via flow cytometry and expression of specific markers. The expression of microtubule-associated light chain protein 3I/II and beclin-1 was detected for assessing macrophage autophagy. Binding between specificity protein 1 (SP1) and the target gene promoter was evaluated using a chromatin immunoprecipitation assay. RNA expression was analyzed by quantitative reverse transcription polymerase chain reaction and western blotting. RESULTS: Treatment with the SIRT6 activator UBCS039 significantly alleviated lung injury in the mouse ARDS model and enhanced autophagy and M2 polarization in isolated AMs. M2 polarization and autophagy in LPS-challenged BMDMs were also effectively promoted by UBCS039 treatment or SIRT6 overexpression. An adenosine monophosphate-activated protein kinase inhibitor (Compound C) or autophagy inhibitor (3-methyladenine) partially abrogated M2 polarization mediated by SIRT6 overexpression upon LPS exposure. SIRT6 induced autophagy and M2 polarization of BMDMs partially via its deacetylase activity. SIRT6 inhibited mammalian target of rapamycin transcription by modulating SP1 to promote BMDM M2 polarization, which was independent of autophagy. CONCLUSIONS: SIRT6 promotes M2 polarization of macrophages to alleviate sepsis-induced ARDS in an autophagy-dependent and -independent manner.

Inhibition of ANXA2 regulated by SRF attenuates the development of severe acute pancreatitis by inhibiting the NF-κB signaling pathway.

BACKGROUND: Acute pancreatitis (AP) is an inflammatory process of the pancreas resulting from biliary obstruction or alcohol consumption. Approximately, 10-20% of AP can evolve into severe AP (SAP). In this study, we sought to explore the physiological roles of the transcription factor serum response factor (SRF), annexin A2 (ANXA2), and nuclear factor-kappaB (NF-κB) in SAP. METHODS: C57BL/6 mice and rat pancreatic acinar cells (AR42J) were used to establish an AP model in vivo and in vitro by cerulein with or without lipopolysaccharide (LPS). Production of pro-inflammatory cytokines (IL-1ß and TNF-α) were examined by ELISA and immunoblotting analysis. Hematoxylin and eosin (HE) staining and TUNEL staining were performed to evaluate pathological changes in the course of AP. Apoptosis was examined by flow cytometric and immunoblotting analysis. Molecular interactions were tested by dual luciferase reporter, ChIP, and Co-IP assays. RESULTS: ANXA2 was overexpressed in AP and correlated to the severity of AP. ANXA2 knockdown rescued pancreatic acinar cells against inflammation and apoptosis induced by cerulein with or without LPS. Mechanistic investigations revealed that SRF bound with the ANXA2 promoter region and repressed its expression. ANXA2 could activate the NF-κB signaling pathway by inducing the nuclear translocation of p50. SRF-mediated transcriptional repression of ANXA2-protected pancreatic acinar cells against AP-like injury through repressing the NF-κB signaling pathway. CONCLUSION: Our study highlighted a regulatory network consisting of SRF, ANXA2, and NF-κB that was involved in AP progression, possibly providing some novel targets for treating SAP.

Dynorphin/KOR inhibits neuronal autophagy by activating mTOR signaling pathway to prevent acute seizure epilepsy.

In previous studies, we found that dynorphin exerts antiepileptic effect by activating the kappa opioid receptor (KOR). However, the role of neuronal autophagy in dynorphin/KOR-mediated antiepileptic is still unclear. This study aimed to investigate the molecular mechanism of dynorphin's antiepileptic effect by inhibiting autophagy and reducing neuronal apoptosis. Here, a pilocarpine-induced rat model of epilepsy was established and hippocampal neurons were treated with Mg2+ -free exposed for epileptiform activity induction. The real-time polymerase chain reaction and Western blot analysis were used to evaluate messenger RNA and protein expression. The TdT-mediated dUTP-biotin nick end labeling staining and flow cytometry were used to analyze cell apoptosis in vivo and in vitro. Neuron cells viability was detected by Cell Counting Kit-8 assay. Immunofluorescent staining and green fluorescent protein-light chain 3 immunofluorescence were used to measure autophagy in vivo and in vitro. Results showed that overexpression of prodynorphin alleviated neuronal apoptosis, activated the mammalian target of rapamycin (mTOR) signaling pathway, and inhibited neuronal autophagy in epileptic rats. Dynorphin inhibited Mg2+ -free-induced seizure-like neuron apoptosis, partially reversing the effect of Mg2+ -free on the mTOR signaling pathway and seizure-like neuron autophagy. Further, using rapamycin, we found that dynorphin inhibited Mg2+ -free-induced seizure-like neuron autophagy and apoptosis by activating the mTOR signaling pathway. In conclusion, dynorphin inhibits autophagy by activating the mTOR signaling pathway and has a protective effect on epilepsy acute seizure and epilepsy-induced brain injury.

Expression and prognostic significance of CBX2 in colorectal cancer: database mining for CBX family members in malignancies and vitro analyses.

BACKGROUND: The Chromobox (CBX) domain protein family, a core component of polycomb repressive complexes 1, is involved in transcriptional repression, cell differentiation, and program development by binding to methylated histone tails. Each CBX family member plays a distinct role in various biological processes through their own specific chromatin domains, due to differences in conserved sequences of the CBX proteins. It has been demonstrated that colorectal cancer (CRC) is a multiple-step biological evolutionary process, whereas the roles of the CBX family in CRC remain largely unclear. METHODS: In the present study, the expression and prognostic significance of the CBX family in CRC were systematically analyzed through a series of online databases, including Cancer Cell Line Encyclopedia (CCLE), Oncomine, Human Protein Atlas (HPA), and Gene Expression Profiling Interactive Analysis (GEPIA). For in vitro verification, we performed cell cloning, flow cytometry and transwell experiments to verify the proliferation and invasion ability of CRC cells after knocking down CBX2. RESULTS: Most CBX proteins were found to be highly expressed in CRC, but only the elevated expression of CBX2 could be associated with poor prognosis in patients with CRC. Further examination of the role of CBX2 in CRC was performed through several in vitro experiments. CBX2 was overexpressed in CRC cell lines via the CCLE database and the results were verified by RT-qPCR. Moreover, the knockdown of CBX2 significantly suppressed CRC cell proliferation and invasion. Furthermore, the downregulation of CBX2 was found to promote CRC cell apoptosis. CONCLUSIONS: Based on these findings, CBX2 may function as an oncogene and potential prognostic biomarker. Thus, the association between the abnormal expression of CBX2 and the initiation of CRC deserves further exploration.

Influence of heel design on lower extremity biomechanics and comfort perception in overground running.

The study investigated whether an alteration of the shoe heel curvature would influence lower extremity biomechanics and comfort perception in running. Twenty recreational habitual rearfoot strikers performed five running trials in running shoes with three different heel curvature designs (short-parallel, long-parallel and oblique curvatures). Synchronised force plate and motion capturing systems were used to collect three-dimensional lower extremity joint kinetics and kinematics, followed by subjective comfort perception on the 15 cm Visual Analogue Scale. The results showed that participants wearing oblique and long-parallel curvature shoes exhibited larger initial frontal shoe-ground angle (p= 0.003, p= 0.016) and ankle inversion angle (p= 0.008, p= 0.032) as well as higher maximum sagittal foot slap velocity (p= 0.041, p = 0.011) compared with a short-parallel curvature shoe. When wearing the short-parallel curvature shoe, participants had better rearfoot stability perception than the oblique curvature shoes (p = 0.028). These results suggest that the short parallel curvature shoes had better motion control and stability perception than the other two curvature conditions. However, the design of heel curvature seems to have minimal influence on the cushioning related variables in running.

Downregulated microRNA-150 upregulates IRX1 to depress proliferation, migration, and invasion, but boost apoptosis of gastric cancer cells.

OBJECTIVE: Many studies have reported the correlation of microRNAs (miRNAs) with cancers, yet few have proposed the function of miR-150 in gastric cancer. This study intends to discuss the role of miR-150 in gastric cancer development by regulating IRX1. METHODS: Gastric cancer tissues and adjacent tissues were collected. MiR-150-3p, IRX1, CXCL14, and NF-κB (p65) expressions were detected. Gastric cancer cell lines SNU-1 and MKN-45 were used for subsequent cellular experiments. Cell proliferation, colony formation, migration and invasion, apoptosis, and cell cycle distribution in SNU-1 and MKN-45 cells were determined via gain-of and loss-of-function assays. The tumor growth in nude mice was also detected. RESULTS: MiR-150, CXCL14, and NF-κB (p65) were upregulated and IRX1 was downregulated in gastric cancer tissues and cells. CXCL14 and NF-κB (p65) expression was positively related to miR-150 expression and negatively to IRX1 expression. MiR-150 inhibition and IRX1 overexpression in SNU-1 cells restricted viability, colony formation, migration, and invasion abilities, but boosted apoptosis of gastric cancer cells in vitro, and also repressed tumor growth in vivo. These results could be reversed by miR-150 elevation and IRX1 silencing, and the results from in vivo and in vitro experiments were consistent. CONCLUSION: Our study reveals that miR-150 downregulation restrains proliferation, migration, and invasion, while facilitating apoptosis of gastric cancer cells by upregulating IRX1.

Relation between blood glucose and the prognosis of severe coronavirus disease 2019. / 血糖与重型2019å† çŠ¶ç— æ¯’ç— é¢„åŽçš„å ³ç³».

OBJECTIVES: To describe the clinical characteristics and outcomes of severely ill patients with coronavirus disease 2019, and to investigate the relationship between plasma glucose level and the prognosis of severely ill patients with coronavirus disease 2019. METHODS: We enrolled 52 severely ill patients with coronavirus disease 2019. Among them, 12 cases progressed to critical illness. The clinical and biochemical characteristics of severely and critically ill patients were compared. RESULTS: Compared with the severely ill patients, critically ill patients had higher white blood cell and neutrophil counts, as well as higher levels of D-dimer, IL-6 and C-reactive protein (all P<0.05). Before treatment, the fasting plasma glucose (FPG) levels were significantly higher in the critically ill patient's group [(10.23±3.71) mmol/L] compared to those in the severely ill patients [(7.12±3.35) mmol/L, P<0.05]. After adjusting for age, gender, and course of the disease, fasting blood glucose at admission (OR=1.308, 95% CI 1.066 to 1.606, P=0.01) and hyperglycemia at admission (OR=29.198, 95% CI 2.903 to 293.639, P=0.004) were closely related to whether severely ill patients progressed to critical patients with coronavirus disease 2019. In our study, 15 (34.8%) of the severely ill and 10 (83.3%) critically ill patients received the steroid treatment. Compared with the severely ill patients, the FPG levels in critically ill patients were higher (P<0.05). CONCLUSIONS: Fasting hyperglycemia at admission is a significant predictor for the prognosis of severely ill patients with coronavirus disease 2019. Closely monitoring and the optimal management of hyperglycemia may improve the prognosis of patients with coronavirus disease 2019.

Effect of shoe wearing time and midsole hardness on ground reaction forces, ankle stability and perceived comfort in basketball landing.

This study examined the effect of wearing time on comfort perception and landing biomechanics of basketball shoes with different midsole hardness. Fifteen basketball players performed drop landing and layup first step while wearing shoes of different wearing time (new, 2-, 4-, 6- and 8-week) and hardness (soft, medium and hard). Two-way ANOVA with repeated measures was performed on GRF, ankle kinematic and comfort perception variables. Increased wearing time was associated with poorer force attenuation and comfort perception during landing activities (p < 0.05). The new shoes had significantly smaller forefoot (2- and 4-week) and rearfoot peak GRF impacts (all time conditions) in drop landing and smaller rearfoot peak GRF impact (6- and 8-week) in layup; shoes with 4-week of wearing time had significantly better perceptions of forefoot cushioning, forefoot stability, rearfoot cushioning, rearfoot stability and overall comfort than the new shoes (p < 0.05). Compared with hard shoes, the soft shoes had better rearfoot cushioning but poorer forefoot cushioning (p < 0.05). Shoe hardness and wearing time would play an influential role in GRF and comfort perception, but not in ankle kinematics. Although shoe cushioning performance would decrease even after a short wearing period, the best comfort perception was found at 4-week wearing time.

Reducing the occurrence rate of catheter dysfunction in peritoneal dialysis: a single-center experience about CQI.

To reduce the occurrence rate of peritoneal dialysis (PD) catheter dysfunction caused by catheter displacement or plugging, this study screened all patients with peritoneal dialysis catheterization from 2002 to 2015 from the Third Xiangya Hospital of Central South University. There were 256 patients before continuous quality improvement (CQI) (from 2002 to 2007) and 813 patients after CQI (from 2008 to 2015). The occurrence rate of catheter dysfunction was 5.9% in the preCQI group: seven cases were associated with peritonitis, six cases were involved in omentum wrapping, one case was blocked by oviduct, and one case was blocked by blood clot. Through PDCA (plan-do-check-act) four-step of CQI, the following measures were adopted: (1) Preoperative: treat complications, enema and urine catheterization (2) Intraoperative: strengthen analgesia, Lower the insert position of catheter to 7.5 ∼ 8.5 cm above the pubic symphysis, extending the straight distance of catheter in rectus abdominis and decrease the times of peritoneal dialysis catheter implantation. (3) Postoperative: strengthen the training of nurses, patients and their families. (4) strengthen anticoagulation therapy during peritonitis treatment. (5) use laparoscopic technology for refractory patients, and so on. The occurrence of catheter dysfunction was 1.5% in the postCQI group (p < 0.05): two cases were associated with peritonitis, ten cases were involved in omentum wrapping. The measures we adopted in CQI reduce the occurrence rate of catheter displacement or plugging in peritoneal dialysis.

[Role of local citrate anticoagulation in continuous blood purification to patients at high risk of bleeding in ICU].

OBJECTIVE: To evaluate the safety and efficiency of citrate anticoagulant-based continuous blood purification in patients at high risk of bleeding. 
 Methods: One hundred and fifty-two patients at high risk of bleeding were divided into local citrate group (group A, n=68) and heparin group (group B, n=84). Clotting function, change of pH, ionized sodium, bicarbonate ion, ionized calcium, activated clotting time (ACT) and complications were monitored before and during treatment. 
 Results: Compared to the group A, the incidence of clotting in filter and chamber, the degree of bleeding or fresh bleeding were significantly reduced in the group B (P<0.05). ACT of post-filter at 4, 8 and 12 h during the treatment in the group A was significantly extended compared with that without treatment (P<0.05), while there was no significant change in group B (P>0.05). The pH value, the levels of ionized sodium, bicarbonate ion and ionized calcium during the treatment were maintained in normal range in both group A and group B.
 Conclusion: Local citrate-based continuous blood purification can achieve effective anticoagulation and decrease the incidence of bleeding. It is an ideal choice for patients at high risk of bleeding.

CGRP mediate the isosorbide-5-mononitrate cardiovascular response in healthy Chinese male volunteers through a XOR-independent pathway.

OBJECTIVES: This study was designed to determine whether xanthine oxidoreductase (XOR) is involved in Isosorbide- 5-mononitrate (IS-5-MN) metabolism, and to elucidate the role of the neuropeptide calcitonin gene-related peptide (CGRP) in the IS-5-MN response. METHODS: In 15 Chinese volunteers, we observed the relationship between baseline XOR-mRNA expression in peripheral blood mononuclear cells (PBMCs) and the response to 20 mg IS-5-MN. IS-5-MN pharmacokinetics profiles, changes in plasma concentrations of CGRP, and CGRPmRNA expression in PBMCs were assessed in vivo and in vitro. RESULTS: Individuals with a lower baseline XOR-mRNA expression showed lower plasma XOR activity and significantly greater changes in SBP (ΔSBP) after IS-5-MN administration. Individuals with a lower baseline XOR-mRNA expression also showed significantly greater increases in plasma concentrations of CGRP. There were no differences in IS-5-MN AUC between the two groups. IS-5-MN significantly up-regulated the expression of CGRP α- and CGRP ß-mRNA in PBMCs, which were not affected by the XOR inhibitor allopurinol. CONCLUSIONS: Our study suggests that CGRP may contribute to the response to IS-5 MN in a XOR-independent pathway.

Synchrotron radiation techniques for nanotoxicology.

Nanotoxicology studies the interactions of engineered nanomaterials with biological systems. Traditional in vitro and in vivo toxicological assays have been successfully employed. However, the toxicological mechanisms of nanoparticles might not be the same as those incurred in traditional molecular toxicology. Furthermore, how to realize in situ and real time measurements especially in the biological microenvironment is still a challenge. Synchrotron radiation, which is highly polarized and tunable, has been proved to play an indispensible role for nanotoxicology studies. In this review, the role of synchrotron radiation techniques is summarized in screening physicochemical characteristics, in vitro and in vivo behaviors, and ecotoxicological effects of engineered nanomaterials. FROM THE CLINICAL EDITOR: The rapid gain in popularity of nanomaterials has also raised the concern of nanotoxicity, which needs to be assessed and addressed. In this comprehensive review, the authors outlined the underlying principles of using synchrotron radiation techniques for nanotoxicology studies and also in other scientific fields.

MicroRNA-92a functions as an oncogene in colorectal cancer by targeting PTEN.

BACKGROUND: Our previous studies show that microRNA-92a (miR-92a) is overexpressed in colorectal cancer (CRC) and is thought to be correlated with the development of the cancer. However, its biological role in CRC remains poorly understood. AIMS: The aim of the study was to determine the role of miR-92a and to elucidate its regulatory mechanism in CRC. METHODS: The expression levels of miR-92a and phosphatase and tensin homologue (PTEN) were detected by qRT-PCR and western blot. MTT, migration and invasion assays were used to examine the proliferation, migration and invasion of pre-miR-92a transfected SW480 cells, and a mouse model was used to investigate tumorigenesis. In addition, the regulation of PTEN by miR-92a was evaluated by qRT-PCR, western blot and luciferase reporter assays. RESULTS: The expression of miR-92a was significantly up-regulated in the tissues of CRC patients with lymph node metastasis. The ectopic expression of miR-92a enhanced CRC cell proliferation, migration and invasion. Similar results were found in xenograft assay performed in nude mice. Up-regulation of miR-92a induced EMT in CRC cells. There was an inverse correlation between the levels of miR-92a and PTEN in CRC tissues. The overexpression of miR-92a in CRC cells decreased PTEN expression at the translational level, and decreased PTEN-driven luciferase-reporter activity. CONCLUSIONS: Our results demonstrated that miR-92a induced EMT and regulated cell growth, migration and invasion in the SW480 cells, at least partially, via suppression of PTEN expression. MiR-92a may serve as a novel therapeutic target in colorectal cancer.

Influence of shoe upper structure on shoe microclimate and human physiological characteristics during running.

BACKGROUND: Shoes upper has been shown to affect the shoe microclimate (temperature and humidity). However, the existing data on the correlation between the microclimate inside footwear and the body's physical factors is still quite limited. OBJECTIVE: This study examined whether shoes air permeability would influence foot microclimate and spatial characteristics of lower limb and body. METHODS: Twelve recreational male habitual runners were instructed to finish an 80 min experimental protocol, wearing two running shoes with different air permeability. RESULTS: Participants wearing CLOSED upper structure shoe exhibited higher in-shoe temperature and relative humidity. Although there was no significant difference, shank temperature and metabolism in OPEN upper structure shoes were lower. CONCLUSIONS: This indicates that the air permeability of shoes can modify the microclimate of the feet, potentially affecting the lower limb temperature. This study provides relevant information for the design and evaluation of footwear.

The triacylglycerol structures are key factors influencing lipid digestion in preterm formulas during in vitro digestion.

Preterm formulas are usually supplemented with medium-chain triacylglycerols (MCT) whereas breast milk contains more medium and long-chain triacylglycerols (MLCT). Different types of triacylglycerol (TAG) containing medium-chain fatty acids may influence lipid digestion. In this study, the digestive characteristics of breast milk and preterm formulas with different MCT contents were evaluated using a dynamic in vitro system simulating the gastrointestinal tract of preterm infants. The lipolysis products, including diacylglycerols, monoacylglycerols (MAGs), free fatty acids, and undigested TAGs, were analyzed. Formulas with MCT addition has significantly (P < 0.05) lower lipolysis degree (LD, 69.35%-71.28%) than breast milk (76.93%). Higher amounts of C8:0 and C10:0 were released in the formulas with MCT addition. Breast milk released more C18:1n-9, C18:2n-6, and MAG containing C16:0, whereas formulas released more free C16:0. The Pearson correlation heatmap showed that the LD value was significantly and positively (P < 0.05) related to the MLCT and sn-2 C16:0 content.

Overexpression of miR-92a correlates with tumor metastasis and poor prognosis in patients with colorectal cancer.

OBJECTIVES: MicroRNAs regulate gene expression at the post-transcriptional level and play important roles in cancer development, progression, and metastasis. The aim of this study was to investigate the expression of miR-92a in colorectal cancer and the normal adjacent mucosa and its potential relevance to clinicopathological characteristics and patient survival. METHODS: Surgical specimens of cancer tissue and adjacent normal mucosa were obtained from 82 patients with colorectal carcinomas. The relative expression levels of miR-92a mRNA in the cancer and the normal adjacent mucosa were measured by quantitative real-time reverse transcriptase polymerase chain reaction. We analyzed their correlation with tumor metastasis, clinicopathologic parameters, and clinical outcome. RESULTS: The relative expression levels of miR-92a were significantly higher in colorectal cancer tissues than in the normal adjacent mucosa (p < 0.001), and a high expression of miR-92a correlated with advanced clinical stage (p = 0.025), lymph node metastases (p = 0.015), and distant metastases (p = 0.046). Kaplan-Meier analysis indicated that patients with high miR-92a expression had a poor overall survival (p = 0.001). Moreover, multivariate analysis showed that increased expression of miR-92a was an independent predictor of overall survival. CONCLUSION: This study revealed that miR-92a overexpression was correlated with specific colorectal cancer biopathologic features, such as TNM stage, lymph node and distant metastases, and poor survival of the patients, indicating that miR-92a may serve as a molecular prognostic marker for colorectal cancer and disease progression.

[Accuracy of endorectal ultrasonography in preoperative staging of rectal cancer].

OBJECTIVE: To evaluate the accuracy of endorectal ultrasonography in preoperative staging of rectal carcinoma. METHODS: The 319 patients with rectal adenocarcinoma underwent endorectal ultrasonography evaluation from January 2007 to March 2010. There were 175 males and 144 females, and the age of patients were 22-82 year old (median 59 years). According their visiting time, 319 patients were divided into 3 groups (period A: January to December 2007; period B: January to December 2008; and period C: January 2009 to March 2010). All patients underwent endorectal ultrasonography, and the 3 doctors had finished evaluations with 272 cases (Doctor 1, 2, 3 had finished evaluations with 162, 64 and 46 cases respectively). The endorectal ultrasonography staging was compared with the pathology findings based on the surgical specimens in 319 patients who had surgery. RESULTS: Overall accuracy in assessing the level of rectal wall invasion was 67%. The accuracy of uT2 and uT3 were 43% and 81% respectively, and the difference was statistically significant (χ(2) = 30.54, P < 0.01), and the accuracy of uT4a was 59%, which was lower than uT3 (81%,χ(2) = 13.77, P < 0.01). Overall accuracy in assessing nodal involvement in the 311 patients treated with radical surgery was 66%. Staging accuracy tends to improve with experience, the accuracy with Doctor 1 in period C(staging accuracy of T and N were 84% and 81% respectively) were higher than period A(staging accuracy of T and N were 55% and 41% respectively) (χ(2) = 6.65 and 13.27, P < 0.01). CONCLUSIONS: Transrectal ultrasound for preoperative staging of rectal has higher accuracy with mastered ultrasound doctor.

Effect of Implantable Electrical Nerve Stimulation on Cortical Dynamics in Patients With Herpes Zoster-Related Pain: A Prospective Pilot Study.

Implantable electrical nerve stimulation (ENS) can be used to treat neuropathic pain caused by herpes zoster. However, little is known about the cortical mechanism underlying neuromodulation therapy. Here, we recorded a 16-channel resting-state electroencephalogram after the application of spinal cord stimulation (n = 5) or peripheral nerve stimulation (n = 3). The neuromodulatory effect was compared between specific conditions (active ENS versus rest). To capture the cortical responses of ENS, spectral power and coherence analysis were performed. ENS therapy achieved satisfactory relief from pain with a mean visual analog scale score reduction of 5.9 ± 1.1. The spectral analysis indicated that theta and alpha oscillations increased significantly during active neuromodulation compared with the resting state. Furthermore, ENS administration significantly increased frontal-frontal coherence in the alpha band. Our findings demonstrate that, despite methodological differences, both spinal cord and peripheral nerve stimulation can induce cortical alpha oscillation changes in patients with zoster-related pain. The dynamic change may, in part, mediate the analgesic effect of ENS on herpes zoster-related pain.

Adiponectin reduces apoptosis of diabetic cardiomyocytes by regulating miR-711/TLR4 axis.

OBJECTIVE: To investigate the regulation of adiponectin/miR-711 on TLR4/NF-κB-mediated inflammatory response and diabetic cardiomyocyte apoptosis. METHODS: Diabetes models were established using rats and H9c2 cardiomyocytes. qRT-PCR was used to detect adiponectin, miR-711, and TLR4. MTT, ß-galactosidase staining, and flow cytometry were utilized to assess cell viability, senescence, and apoptosis, respectively. The colorimetric method was used to measure caspase-3 activity, DCFH-DA probes to detect ROS, and western blotting to determine the protein levels of Bax, Bcl-2, TLR4, and p-NF-κB p65. ELISA was performed to measure the levels of adiponectin, ICAM-1, MCP-1, and IL-1ß. Dual-luciferase reporter system examined the targeting relationship between miR-711 and TLR4. H&E and TUNEL staining revealed myocardial structure and apoptosis, respectively. RESULTS: Adiponectin and miR-711 were underexpressed and TLR4/NF-κB signaling pathway was activated in high glucose-treated H9c2 cells. High glucose treatment reduced viability, provoked inflammatory response, and accelerated senescence and apoptosis in H9c2 cells. miR-711 could bind TLR4 mRNA and inactivate TLR4/NF-κB signaling. Adiponectin treatment increased miR-711 expression and blocked TLR4/NF-κB signaling. Adiponectin/miR-711 reduced myocardial inflammation and apoptosis in diabetic rats. CONCLUSION: Adiponectin inhibits inflammation and alleviates high glucose-induced cardiomyocyte apoptosis by blocking TLR4/NF-κB signaling pathway through miR-711.