Exosomes and microRNAs: insights into their roles in thermal-induced skin injury, wound healing and scarring.

A burn is a type of injury to the skin or other tissues caused by heat, chemicals, electricity, sunlight, or radiation. Burn injuries have been proven to have the potential for long-term detrimental effects on the human body. The conventional therapeutic approaches are not able to effectively and easily heal these burn wounds completely. The main potential drawbacks of these treatments include hypertrophic scarring, contracture, infection, necrosis, allergic reactions, prolonged healing times, and unsatisfactory cosmetic results. The existence of these drawbacks and limitations in current treatment approaches necessitates the need to search for and develop better, more efficient therapies. The regenerative potential of microRNAs (miRNAs) and the exosomal miRNAs derived from various cell types, especially stem cells, offer advantages that outweigh traditional burn wound healing treatment procedures. The use of multiple types of stem cells is gaining interest due to their improved healing efficiency for various applications. Stem cells have several key distinguishing characteristics, including the ability to promote more effective and rapid healing of burn wounds, reduced inflammation levels at the wound site, and less scar tissue formation and fibrosis. In this review, we have discussed the stages of wound healing, the role of exosomes and miRNAs in improving thermal-induced wounds, and the impact of miRNAs in preventing the formation of hypertrophic scars. Research studies, pre-clinical and clinical, on the use of different cell-derived exosomal miRNAs and miRNAs for the treatment of thermal burns have been documented from the year 2000 up to the current time. Studies show that the use of different cell-derived exosomal miRNAs and miRNAs can improve the healing of burn wounds. The migration of exosomal miRNAs to the site of a wound leads to inhibition of apoptosis, induction of autophagy, re-epithelialization, granulation, regeneration of skin appendages, and angiogenesis. In conclusion, this study underscores the importance of integrating miRNA and exosome research into treatment strategies for burn injuries, paving the way for novel therapeutic approaches that could significantly improve patient outcomes and recovery times.

Degradation-Sensitive Health Indicator Construction for Precise Insulation Degradation Monitoring of Electromagnetic Coils.

Electromagnetic coils are indispensable components for energy conversion and transformation in various systems across industries. However, electromagnetic coil insulation failure occurs frequently, which can lead to serious consequences. To facilitate predictive maintenance for industrial systems, it is essential to monitor insulation degradation prior to the formation of turn-to-turn shorts. This paper experimentally investigates coil insulation degradation from both macro and micro perspectives. At the macro level, an evaluation index based on a weighted linear combination of trend, monotonicity and robustness is proposed to construct a degradation-sensitive health indicator (DSHI) based on high-frequency electrical response parameters for precise insulation degradation monitoring. While at the micro level, a coil finite element analysis and twisted pair accelerated degradation test are conducted to obtain the actual turn-to-turn insulation status. The correlation analysis between macroscopic and microscopic effects of insulation degradation is used to verify the proposed DSHI-based method. Further, it helps to determine the threshold of DSHI. This breakthrough opens new possibilities for predictive maintenance for industrial equipment that incorporates coils.

Intelligent Fault Diagnosis of Industrial Robot Based on Multiclass Mahalanobis-Taguchi System for Imbalanced Data.

One of the biggest challenges for the fault diagnosis research of industrial robots is that the normal data is far more than the fault data; that is, the data is imbalanced. The traditional diagnosis approaches of industrial robots are more biased toward the majority categories, which makes the diagnosis accuracy of the minority categories decrease. To solve the imbalanced problem, the traditional algorithm is improved by using cost-sensitive learning, single-class learning and other approaches. However, these algorithms also have a series of problems. For instance, it is difficult to estimate the true misclassification cost, overfitting, and long computation time. Therefore, a fault diagnosis approach for industrial robots, based on the Multiclass Mahalanobis-Taguchi system (MMTS), is proposed in this article. It can be classified the categories by measuring the deviation degree from the sample to the reference space, which is more suitable for classifying imbalanced data. The accuracy, G-mean and F-measure are used to verify the effectiveness of the proposed approach on an industrial robot platform. The experimental results show that the proposed approach's accuracy, F-measure and G-mean improves by an average of 20.74%, 12.85% and 21.68%, compared with the other five traditional approaches when the imbalance ratio is 9. With the increase in the imbalance ratio, the proposed approach has better stability than the traditional algorithms.

Sensory plasticity of carotid body is correlated with oxidative stress in paraventricular nucleus during chronic intermittent hypoxia.

Chronic intermittent hypoxia (CIH) is known to induce hypertension, but the mechanism is not well understood. We hypothesized that sensory plasticity of the carotid body (CB) and oxidative stress in the paraventricular nucleus (PVN) are involved in CIH-induced hypertension. In this study, rats were exposed to CIH for 28 days (intermittent hypoxia of 21% O2 for 60 s and 5% O2 for 30 s, cyclically repeated for 8 hr/day) and then randomly grouped for intracerebroventricular injection of 5-HT2 receptor antagonist ritanserin, Rho-associated protein kinase (ROCK) inhibitor Y-27632, and NADPH oxidase (NOX) inhibitor diphenyleneiodonium (DPI), respectively. We found that CIH increased blood pressure (BP), elevated carotid sinus nerve (CSN) and renal sympathetic nerve (RSN) activities, oxidative stress, and cell apoptosis in PVN. NOX-derived reactive oxygen species (ROS) production and cell apoptosis decreased when CIH-induced activation of 5-HT/5-HT2AR/PKC signaling was inhibited by ritanserin. In addition, RhoA expression was downregulated when oxidative stress was attenuated by DPI, while Y-27632 decreased the expression of endothelin-1, which is overexpressed in the vascular wall during hypertension. Moreover, treatment with ritanserin, DPI or Y-27632 attenuated the sensory plasticity and sympathetic hyperactivity as well as CIH-induced elevation of BP. In conclusion, CIH-induced activation of 5-HT/5-HT2AR/PKC signaling contributes to NOX-derived oxidative stress in PVN, which may cause sensory plasticity of CB, RSN hyperactivity, and elevated BP.

DL-Propargylglycine protects against myocardial injury induced by chronic intermittent hypoxia through inhibition of endoplasmic reticulum stress.

BACKGROUND: Chronic intermittent hypoxia (CIH), an important basis of the pathogenesis of organ damage induced by obstructive sleep apnea syndrome (OSAS), is associated with myocardial injury, such as left ventricular dysfunction, apoptosis, and oxidative stress. Endogenous hydrogen sulfide (H2S) plays an important role in maintaining cardiovascular functions. Many studies have demonstrated that exogenous H2S has protective effects against myocardial injury induced by various cardiovascular diseases, and inhibiting the generation of endogenous H2S has opposite effects. However, the effect of DL-propargylglycine (PAG), an effective inhibitor of cystathionine γ-lyase (CSE)-synthesized H2S, on the regulation myocardial injury remains controversial. PURPOSE: The present study was aimed to explore the influence of PAG on myocardial injury induced in rats by CIH. METHODS: Sprague-Dawley rats were randomly divided into a normal control (NC) group, a CIH group, a NC + PAG group, and a CIH + PAG group. After establishing the CIH model in rats, blood pressure, left ventricular function, oxidative stress, apoptosis, and the level of endoplasmic reticulum (ER) stress were detected. RESULTS: In NC rats, PAG had no effect on blood pressure, but induced myocardial dysfunction and up-regulated oxidative stress and apoptosis of the myocardium. In the CIH + PAG group, pretreatment with PAG significantly reduced blood pressure and improved the left ventricular ejection fraction (LVEF) and the left ventricular fractional shortening (LVFS) compared to the CIH group. Significantly lower levels of oxidative stress, apoptosis, and the ER stress were detected in the CIH + PAG group than in the CIH group. CONCLUSION: These results suggest that PAG can protect the myocardium against CIH-induced injury through inhibition of endoplasmic reticulum stress.

The role of the Nox4-derived ROS-mediated RhoA/Rho kinase pathway in rat hypertension induced by chronic intermittent hypoxia.

BACKGROUND: Obstructive sleep apnea syndrome, which is a risk factor for resistant hypertension, is characterized by chronic intermittent hypoxia (CIH) and is associated with many cardiovascular diseases. CIH elicits systemic oxidative stress and sympathetic hyperactivity, which lead to hypertension. Rho kinases (ROCKs) are considered to be major effectors of the small GTPase RhoA and have been extensively studied in the cardiovascular field. Upregulation of the RhoA/ROCK signaling cascade is observed in various cardiovascular disorders, such as atherosclerosis, pulmonary hypertension, and stroke. However, the exact molecular function of RhoA/ROCK in CIH remains unclear and requires further study. OBJECTIVE: This study aimed to investigate the role of the NADPH oxidase 4 (Nox4)-induced ROS/RhoA/ROCK pathway in CIH-induced hypertension in rats. METHODS: Male Sprague-Dawley rats were exposed to CIH for 21 days (intermittent hypoxia of 21% O2 for 60 s and 5% O2 for 30 s, cyclically repeated for 8 h/day). We randomly assigned 56 male rats to groups of normoxia (RA) or vertically implemented CIH together with vehicle (CIH-V), GKT137831 (CIH-G), N-acetyl cysteine (NAC) (CIH-N), or Y27632 (CIH-Y). The rats in the RA group were continuously exposed to room air, whereas the rats in the other groups were exposed to CIH. Systolic blood pressure (BP) was monitored at the beginning of each week. After the experiment, renal sympathetic nerve activity (RSNA) was recorded, and serum and renal tissues were subjected to molecular biological and biochemical analyses. RESULTS: Compared with the BP of RA rats, the BP of CIH-V rats started to increase 2 weeks after the beginning of the experiment, subsequently stabilizing at a high level at the end of the third week. CIH increased both RSNA and oxidative stress. This response was attenuated by treatment of the rats with GKT137831 or NAC. Inhibiting Nox4 activity or ROS production reduced RhoA/ROCK expression. Treatment with Y27632 reduced both BP and RSNA in rats exposed to CIH. CONCLUSION: Hypertension can be induced by CIH in SD rats. The CIH-induced elevation of BP is at least partially mediated via the Nox4-induced ROS/RhoA/ROCK pathway.

The role of gonadal hormones in the hypoglossal discharge activity of rats exposed to chronic intermittent hypoxia.

OBJECTIVE: The role of gonadal hormones in chronic intermittent hypoxia (CIH)-evoked hypoglossal nerve (XII) neuroplasticity has not been thoroughly studied. The purpose of this study was to reveal the effects of gonadal hormone concentration variations on the XII discharge activity of rats exposed to CIH and the corresponding relationship with 5-hydroxytryptamine (5-HT). METHODS: This study employed five groups of female rats and six groups of male rats. Gonadal hormone levels were modified through gonadal resection and daily supplementation with gonadal hormones in rats of both sexes. Rats in the CIH groups were exposed to an additional 4 weeks of CIH once the operative incision for gonadectomy had healed. Finally, XII spontaneous discharge activities were recorded, and serum estradiol, testosterone and 5-HT concentrations were detected by ELISA. RESULTS: Among the female rats, the normal estradiol level groups expressed XII neuroplasticity, while the low estradiol level group failed to express this phenomenon. XII neuroplasticity was related to the serum estradiol concentration. In the male rats, XII neuroplasticity was successfully evoked in the normal testosterone level group but was suppressed in the low testosterone level group and aromatase inhibitor group. XII neuroplasticity was not significantly related to serum testosterone concentrations. Both estradiol and testosterone concentrations were related to 5-HT concentrations. CONCLUSIONS: This is the first study to analyze the effects of gonadal hormones on XII neuroplasticity in both female and male rats. The results suggest that the estradiol level is related to XII neuroplasticity rather than the testosterone level, and testosterone may indirectly adjust XII neuroplasticity by converting to estradiol. Estradiol and testosterone levels are related to 5-HT levels in the respective genders.

Effects of early postoperative enteral nutrition versus usual care on serum albumin, prealbumin, transferrin, time to first flatus and postoperative hospital stay for patients with colorectal cancer: A systematic review and meta-analysis.

BACKGROUND: Early enteral nutrition (EEN) after surgery had been reported to decrease morbidity and mortality. However, no meta-analysis performed on nutrition status and recovery after surgery to Colorectal cancer (CRC). AIM: We aimed to estimate effect of EEN for postoperative CRC. METHODS: Electronic databases were searched for randomized controlled trials published prior to September 2017. Papers comparing EEN after surgery to traditional nutritional regimen in CRC patients were selected. The chosen articles should containe one or more of the following outcome measures: serum albumin, prealbumin, transferrin, time to first flatus and postoperative hospital stay. RESULTS: 2307 cases from 26 studies were included. The analysis showed that EEN was more effective in increasing serum albumin and prealbumin, promoting the recovery of gastrointestinal function, and decreasing the time of postoperative hospital stay, especially for colon cancer. CONCLUSION: EEN can improve nutritional status and promote intestinal function recovery for patients undergoing CRC surgery.

Diabetes mellitus carries a risk of esophageal cancer: A meta-analysis.

BACKGROUND: Many studies have showed that diabetes mellitus (DM) might be a risk factor for certain types of cancers. However, there are still inconsistent results on the effects of DM on the risk of esophageal cancer (EC). The objective of this study is to investigate the association and to quantify the correlation between DM and EC by a meta-analysis. METHODS: The initial search identified 339 articles. Those publications that did not report the exact number of EC cases were removed. Finally, 13 meaningful studies were extracted from the databases of PubMed, MEDLINE, and Web of Science. All pooled analyses of risk ratios (RRs) and 95% confidence intervals (CIs) were assessed by a random-effect or fixed-effect model. Subgroup analysis was implemented on the basis of the sex or ethnicity. I value was used to assess heterogeneity, and funnel plot analysis was for publication bias. RESULTS: The result showed that there was a positive correlation between type 2 diabetes mellitus (T2DM) and EC risk (RR = 1.28, 95% CI: 1.12-1.47, P < .001). Subgroup analysis based on gender showed that male was an important risk factor for EC (RR = 1.53, 95% CI: 1.44-1.62, P < .001), but female was not (RR = 1.23, 95% CI: 0.41-3.69, P = .71). In addition, subgroup analysis based on ethnicity showed that DM was significantly correlated to EC in North America subjects (RR = 1.39, 95% CI: 1.31-1.47, P < .001), and in Europe subjects (RR = 1.37, 95% CI: 1.02-1.83, P = .04), whereas no correlation was found in Asian subjects (RR = 0.98, 95% CI: 0.50-1.95, P = .96). Furthermore, DM had a correlation to an increased risk of esophageal adenocarcinoma (EAC) (RR = 1.43, 95% CI: 1.35-1.51, P < .001). CONCLUSION: This meta-analysis indicates that DM is positively correlated to EC. However, the results should be interpreted with caution because of the limitations on potential clinical confounding factors in each study included in this meta-analysis.

Establishment of a Rabbit Model of Chronic Obstructive Sleep Apnea and Application in Cardiovascular Consequences.

BACKGROUND: Although obstructive sleep apnea (OSA) has been recognized as a major risk factor for cardiovascular complications and its clinical features are well characterized, it is difficult to replicate the OSA hypoxic model in humans. We aimed to establish an experimental rabbit model for chronic OSA and to explore its application to measure blood pressure (BP), myocardial systolic function, and oxidative stress. METHODS: The rabbit model for OSA was established by repeatedly closing the airway and then reopening it. A tube specially designed with a bag that could be alternately inflated and deflated according to a predetermined time schedule, resulting in recurrent airway occlusions and chronic intermittent hypoxia (CIH) imitating OSA patterns in humans, was used. Twenty-four rabbits were randomly divided into obstruction, sham, and control groups, and their upper airways were alternately closed for 15 s and then reopened for 105 s in a 120-s-long cycle, for 8 h each day over 12 consecutive weeks. Before and after the experiment, the BP of each rabbit was monitored. Levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the serum, superoxide dismutase (SOD) activity, malondialdehyde (MDA) and reactive oxygen species (ROS) contents, as well as Na+-K+-ATPase/Ca2+-ATPase activities in cardiac muscle were examined. In addition, cardiac functional parameters were measured using echocardiography. RESULTS: After 3 months, all rabbits in the obstruction group manifested sleepiness performance similar to that observed in OSA patients. Traces of airflow and SpO2showed that this model mimicked the respiratory events involved in OSA, including increased respiratory effort and decreased oxygen saturation. Gradually, the BP rose each month. CIH led to obvious oxidative stress and injured myocardial systolic performance. The serum levels of IL-6 and TNF-α increased significantly (64.75 ± 9.05 pg/ml vs. 147.00 ± 19.24 pg/ml and 59.38 ± 8.21 pg/ml vs. 264.75 ± 25.54 pg/ml, respectively, both P < 0.001). Compared with the sham and the control groups, myocardial activities of Na+-K+-ATPase/Ca2+-ATPase and SOD in the obstruction group decreased markedly, while ROS and MDA content increased. CONCLUSIONS: These results show that the rabbit model for OSA simulates the pathophysiological characteristics of OSA in humans, which implies that this animal model is feasible and useful to study the mechanisms involved in the cardiovascular consequences of OSA.

Association between polymorphisms of the HSPB7 gene and Cheyne-Stokes respiration with central sleep apnea in patients with dilated cardiomyopathy and congestive heart failure.

BACKGROUND: CSR-CSA is frequent in patients with CHF. Dilated cardiomyopathy (DCM) is a structural heart disease with strong genetic background, yet one of the leading etiological causes of CHF. Studies have showed that the HSPB7 gene is associated with DCM. OBJECTIVES: We aimed to explore the prevalence of polymorphisms of the HSPB7 gene in the Chinese Han population with CSR-CSA and CHF caused by DCM. METHODS: A total of 503 unrelated subjects of the Chinese Han population, including 283 CHF patients caused by DCM and 220 healthy controls, were involved in the study. The CHF patients were classified as the CSA-CHF group and the non-CSA-CHF group according to the PSG parameters. The rs1739843 polymorphisms of the HSPB7 gene were identified by real-time quantitative polymerase chain reaction. RESULTS: In the present study, 35.8% of CHF patients caused by DCM had CSR-CSA. Comparison demonstrated that the CSA-CHF group had significantly higher TT genotype and T allele frequencies in the rs1739843 single nucleotide polymorphism (SNP) of the HSPB7 gene. There were no significant differences among the CC genotype distribution of the CSA-CHF group and the non-CSA-CHF group or the control group. CONCLUSIONS: The rs1739843 polymorphism of the HSPB7 gene might be involved in the pathogenesis of CSR-CSA and CHF subjects caused by DCM in the Chinese Han population. This finding was from a genetic search for the role of the HSPB7 gene in CSR-CSA of CHF patients caused by DCM.

Chronic intermittent hypoxia versus continuous hypoxia: Same effects on hemorheology?

Although both chronic intermittent hypoxia (CIH) and chronic continuous hypoxia (CCH) have effects on hemorheology, we do not know whether their roles are the same. In this study, we explored the effect of simulated-apnea CIH on hemorheology in experimental rats and compared with the effect of CCH. 45 adult SD rats were randomly divided into the normoxic control group, CCH and CIH groups. CIH rats were given nitrogen and air alternately for 8 hours per day and the experiment lasted for 5 weeks. The control group were placed in the normoxia animal chambers, and the CCH rats were housed in the same chambers which were continuously given normobaric hypoxia (FiO2 = 10%). After the preparations, the blood samples were taken and the hemorheology were determined. Compared with control group, the whole blood apparent viscosity, plasma viscosity, hematocrit, erythrocyte aggregation index and electrophoresis index, platelet aggregation rate and fibrinogen significantly increased in CIH group and CCH group. The whole blood viscosity, plasma viscosity, hematocrit and fibrinogen values were much higher in CCH group than in CIH group. However, there was not significantly difference in RBC deformation index or rigidity index among the three groups and no significantly differences were found in the effects on RBC rheological property between CIH and CCH. Our results suggest that intermittent hypoxia and continuous hypoxia increase whole blood viscosity, impair the functions of red blood cells and promote the platelet aggregation in model rats. Moreover, CCH had a greater effect on blood rheology than CIH.

[Impacts of acupuncture at twelve meridians acupoints on brain waves of patients with general anxiety disorder].

OBJECTIVE: To observe the clinical efficacy of acupuncture at twelve meridians acupoints on general anxiety disorder and explore its mechanism. METHODS: Eighty patients were randomized into an acupuncture group and a clonazepam group, 40 cases in each one. In the acupuncture group, acupuncture at twelve meridians acupoints was applied, meaning quick needling at the specific acupoints of each meridian, such as Lieque (LU 7) of the Lung Meridian, Hegu (LI 4) of the Large Intestine Meridian and Shenmen (HT 7) of the Heart Meridian. After arrival of qi, the reinforcing or reducing technique was applied accordingly and the needles were not retained. In the clonazepam group, clonazepam was prescribed for oral administration. The course of treatment was 6 weeks. Before treatment and in 2, 4 and 6 weeks of treatment, respectively, Hamilton Anxiety Scale (HAMA) was evaluated in two groups and the changes in the basic electrical activity of brain waves before and after treatment were observed. RESULTS: HAMA score was reduced apparently after treatment as compared with that before treatment in two groups (all P < 0.01). The improvements of the total HAMA scores in 2, 4 and 6 weeks of treatment in the acupuncture group were superior obviously to those in the clonazepam group (all P < 0.05). After treatment, the activity of brain waves was improved remarkably, manifested as reducing of wave a frequency, increasing of wave alpha rhythm and reducing of wave theta (all P < 0.05). The efficacy was similar in comparison between the two groups (all P > 0.05). CONCLUSION: Acupuncture at the twelve meridians acupoints achieves the superior and quick effect on general anxiety disorder as compared with clonazepam and the efficacy mechanism is related to the improvements of brain waves in the patients.