Resilience and its influencing factors after emergency percutaneous coronary intervention in young and middle-aged patients with first acute myocardial infarction.

Mental health after acute myocardial infarction (AMI) influences the prognosis of patients. Resilience may contribute to improving a patient's mental health. However, no study has investigated resilience and its associated factors in young and middle-aged patients undergoing emergency percutaneous coronary intervention (PCI) after the first AMI. This study aimed to identify critical associated factors influencing resilience in these patients. This cross-sectional study recruited 161 young and middle-aged patients with first-episode AMI using a purposive sampling method. These patients were assessed 48 h after emergency PCI using the General Information Questionnaire, the Connor-Davidson Resilience Scale-10, the Perceived Social Support Scale, the General Self-Efficacy Scale, and the Post-traumatic Stress Disorder Scale Civilian Version. Stepwise and logistic regression were conducted to analyze the factors influencing resilience. Receiver operating characteristics (ROC) were used to compare the area under the curves (AUC) for each indicator. The resilience of the 161 participants was 29.50 ± 4.158. Monthly household income, self-efficacy, social support, and post-traumatic stress disorder explained 51.4% of the variance in resilience. Self-efficacy (OR 0.716, CI 0.589-0.870, P < 0.01) and social support (OR 0.772, CI 0.635-0.938, P < 0.01) were protective factors for psychological resilience, while post-traumatic stress disorder (OR 1.278, CI 1.077-1.515, P < 0.01) was a risk factor. ROC curve revealed that self-efficacy, social support, and PTSD had an AUC of 0.822, 0.855, and 0.889, respectively. Self-efficacy and social support improve, and PTSD degrades psychological resilience in young and middle-aged AMI patients undergoing emergency PCI.

Exercise-Intervened Endothelial Progenitor Cell Exosomes Protect N2a Cells by Improving Mitochondrial Function.

We have recently demonstrated that exosomal communication between endothelial progenitor cells (EPCs) and brain endothelial cells is compromised in hypertensive conditions, which might contribute to the poor outcomes of stroke subjects with hypertension. The present study investigated whether exercise intervention can regulate EPC-exosome (EPC-EX) functions in hypertensive conditions. Bone marrow EPCs from sedentary and exercised hypertensive transgenic mice were used for generating EPC-EXs, denoted as R-EPC-EXs and R-EPC-EXET. The exosomal microRNA profile was analyzed, and EX functions were determined in a co-culture system with N2a cells challenged by angiotensin II (Ang II) plus hypoxia. EX-uptake efficiency, cellular survival ability, reactive oxygen species (ROS) production, mitochondrial membrane potential, and the expressions of cytochrome c and superoxide-generating enzyme (Nox4) were assessed. We found that (1) exercise intervention improves the uptake efficiency of EPC-EXs by N2a cells. (2) exercise intervention restores miR-27a levels in R-EPC-EXs. (3) R-EPC-EXET improved the survival ability and reduced ROS overproduction in N2a cells challenged with Ang II and hypoxia. (4) R-EPC-EXET improved the mitochondrial membrane potential and decreased cytochrome c and Nox4 levels in Ang II plus hypoxia-injured N2a cells. All these effects were significantly reduced by miR-27a inhibitor. Together, these data have demonstrated that exercise-intervened EPC-EXs improved the mitochondrial function of N2a cells in hypertensive conditions, which might be ascribed to their carried miR-27a.

Comparison of rigid bronchoscopy and flexible bronchoscopy for the management of foreign body aspiration in children.

OBJECTIVE: To compare clinical outcomes of flexible and rigid bronchoscopies for the management of foreign body aspiration (FBA) in different airway locations, especially in unilateral main bronchus, in children, so as to provide some suggestions to assist clinical decisions. METHODS: The medical records of children diagnosed with FBA in Qingdao Women and Children's Hospital Affiliated to Qingdao University from January 2020 to June 2022 were retrospectively reviewed. The following information was collected: demographics, radiological findings, endoscopic findings, foreign body locations, duration of operation, operation cost, and intraoperative and postoperative complications. RESULTS: 182 children were included in the study with the median age of 1.3 years (interquatile range, 1.0-1.8). Among whom, 124 cases (68.1 %) were male and 58 cases (31.9 %) were female. 11 cases (6.0 %) had the foreign bodies located in the trachea (larynx to carina), 3 cases (1.6 %) located in the trachea and lower bronchus, 1 case (0.5 %) located in bilateral main bronchus, 135 cases (74.2 %) located in unilateral main bronchus, 4 cases (2.2 %) located in main and lobar bronchus, and 28 cases (15.4 %) located in the lobar or segmental bronchus. Among all the included children, 84 cases (46.2 %) received rigid bronchoscopy (RB) and 98 cases (53.8 %) received flexible bronchoscopy (FB). 131 cases with the foreign bodies located in unilateral main bronchus received one type of bronchoscopy (RB or FB). They were divided into two groups according to the location of foreign body relative to the midpoint of main bronchus, the proximal bronchus group and the distal bronchus group. In the proximal bronchus group, duration of operation using RB and FB was 15 (12.5-27.5) min and 15 (14.5-30.0) min, respectively (Z = 0.000, P = 1.000). The intraoperative and postoperative complication rate using RB and FB was 15.4 % and 9.1 %, respectively (χ2 = 0.008, P = 0.927). Operation cost of FB was significantly higher than that of RB (t = -13.396, P = 0.000). In the distal bronchus group, duration of operation using RB was 20 (13.5-25.0) min, which was drastically shorter than that of FB (25 (20.0-35.0) min) (Z = -2.947, P=0.003). Operation cost of FB was still found to be significantly higher than RB (t = -20.456, P=0.000). No significant difference was found in complication rate of RB (14.3%) compared to FB (8.3%) (χ2=0.251, P=0.616). CONCLUSIONS: When foreign bodies are lodged in unilateral main bronchus, RB could be chosen as the first-choice procedure with advantages in duration of operation and operation cost, especially for patients in China. Regardless of duration of operation and operation cost, FB is also a safe and efficient therapeutic procedure to remove inhaled foreign bodies in children, except for those located in the trachea and asphyxiating foreign bodies.

The miR-210 Primed Endothelial Progenitor Cell Exosomes Alleviate Acute Ischemic Brain Injury.

BACKGROUND: Stem cell-released exosomes (EXs) have shown beneficial effects on regenerative diseases. Our previous study has revealed that EXs of endothelial progenitor cells (EPC-EXs) can elicit favorable effects on endothelial function. EXs may vary greatly in size, composition, and cargo uptake rate depending on the origins and stimulus; notably, EXs are promising vehicles for delivering microRNAs (miRs). Since miR-210 is known to protect cerebral endothelial cell mitochondria by reducing oxidative stress, here we study the effects of miR-210-loaded EPC-EXs (miR210-EPC-EXs) on ischemic brain damage in acute ischemic stroke (IS). METHODS: The miR210-EPC-EXs were generated from EPCs transfected with miR-210 mimic. Middle cerebral artery occlusion (MCAO) surgery was performed to induce acute IS in C57BL/6 mice. EPC-EXs or miR210-EPC-EXs were administrated via tail vein injection 2 hrs after IS. To explore the potential mechanisms, inhibitors of the vascular endothelial growth factor receptor 2 (VEGFR2)/PI3 kinase (PI3K) or tyrosine receptor kinase B (TrkB)/PI3k pathways were used. The brain tissue was collected after treatments for infarct size, cell apoptosis, oxidative stress, and protein expression (VEGFR2, TrkB) analyses on day two. The neurological deficit score (NDS) was evaluated before collecting the samples. RESULTS: 1) As compared to EPC-EXs, miR210-EPC-EXs profoundly reduced the infarct volume and improved the NDS on day two post-IS. 2) Fewer apoptosis cells were detected in the peri-infarct brain of mice treated with miR210-EPC-EXs than in EPC-EXs-treated mice. Meanwhile, the oxidative stress was profoundly reduced by miR210-EPC-EXs. 3) The ratios of p-PI3k/PI3k, p- VEGFR2/VEGFR2, and p-TrkB/TrkB in the ipsilateral brain were raised by miR210-EPC-EXs treatment. These effects could be significantly blocked or partially inhibited by PI3k, VEGFR2, or TrkB pathway inhibitors. CONCLUSION: These findings suggest that miR210-EPC-EXs protect the brain from acute ischemia- induced cell apoptosis and oxidative stress partially through the VEGFR2/PI3k and TrkB/PI3k signal pathways.

Extracellular Vesicles in Neurodegenerative Diseases: An Update.

Neurodegenerative diseases affect millions of people worldwide. The likelihood of developing a neurodegenerative disease rises dramatically as life expectancy increases. Although it has drawn significant attention, there is still a lack of proper effective treatments for neurodegenerative disease because the mechanisms of its development and progression are largely unknown. Extracellular vesicles (EVs) are small bi-lipid layer-enclosed nanosized particles in tissues and biological fluids. EVs are emerging as novel intercellular messengers and regulate a series of biological responses. Increasing evidence suggests that EVs are involved in the pathogenesis of neurodegenerative disorders. In this review, we summarize the recent findings of EVs in neurodegenerative diseases and bring up the limitations in the field.

Predictive model for severe thrombocytopenia after transfemoral transcatheter aortic valve replacement.

The aim of this study was to develop a predictive model for severe thrombocytopenia after transfemoral transcatheter aortic valve replacement (TAVR). A total of 155 patients treated with TAVR at our center were retrospectively enrolled in this study. The incidence of severe thrombocytopenia after TAVR was 25.16%, and most patients suffered from severe thrombocytopenia on 4 days after procedure. Multivariate regression analysis showed that weight <60 kg, New York Heart Association Functional Classification (NYHAFC IV), major vascular complications, and lower first post-procedural platelet count were independent risk factors for severe thrombocytopenia after TAVR. The c-statistic for the area under the curve was 0.758, the sensitivity was 0.744, the specificity was 0.784, and the negative predictive value of the model was 91.38%. The overall predictive value was 76.77%. The predictive model developed from this cohort data could effectively identify patients at high risk of severe thrombocytopenia after TAVR, and might be applicable to patients with aortic regurgitation (AR) and severe thrombocytopenia with different definitions.

Long Non-Coding RNA LPP-AS2 Plays an Anti-Tumor Role in Thyroid Carcinoma by Regulating the miR-132-3p/OLFM1 Axis.

The cancer-promoting function of the long non-coding RNA (lncRNA) LPP-AS2 has been documented in different cancers. Nonetheless, its role in thyroid carcinoma (THCA) remains unestablished. Reverse transcription quantitative polymerase chain reaction and Western blotting were conducted to estimate the expressions of lncRNA LPP-AS2, miR-132-3p, and OLFM1. The THCA cells' functions were assessed through CCK8 assays, Transwell invasion assays, scratch wound-healing migration assays, and quantification of caspase-3 activity. The in vivo assays were also implemented to assess tumor growth. Luciferase reporter and RNA immuno-precipitation assay (RIPA) experiments were executed to elucidate the interactions of miR-132-3p with lncRNA LPP-AS2 and OLFM1. THCA tissues and cells exhibited poor lncRNA LPP-AS2 and OLFM1 expressions and a robust expression of miR-132-3p. Overexpressing lncRNA LPP-AS2 constrained THCA cell proliferation, migration, and invasion and improved caspase-3 activity. The anti-tumor function of lncRNA LPP-AS2 was also validated in vivo. miR-132-3p had an interplay with lncRNA LPP-AS2 and OLFM1. Functionally, overexpressing miR-132-3p promoted the malignant THCA cell phenotypes. However, that tumor promotion was abolished by the additional overexpression of lncRNA LPP-AS2. The in vitro experiments also demonstrated that the repressive effect of OLFM1 overexpression on THCA cell malignant action could be offset by the miR-132-3p mimic. lncRNA LPP-AS2 impedes THCA progression via the miR-132-3p/OLFM1 axis. Our findings contribute a potential strategy in interfering with THCA progression.

Relationship between Changes in Blood Glucose and Blood Lipid Levels and the Risk of Thyroid Cancer in Patients with Type 2 Diabetes Mellitus.

Objective: To investigate the relationship between changes in blood glucose and blood lipid levels and the risk of thyroid cancer in patients with type 2 diabetes mellitus. Methods: A total of 159 patients with type 2 diabetes who were treated in our hospital between June 2018 and February 2021 were recruited and assigned into the observation group, including 136 patients with type 2 diabetes without thyroid cancer (nonthyroid cancer group) and 23 patients with type 2 diabetes complicated with thyroid cancer (thyroid cancer group), and 120 healthy subjects during the same period were selected as the control group. Glycated hemoglobin (HbAlc), total cholesterol (TC), triacylglycerol (TG), high density lipoprotein cholesterol (HDL-C), and low density lipoprotein cholesterol (LDL-C) were detected and compared. Pearson's method was conducted to analyze the correlation between serum HbAlc level and TC, TG, HDL-C, and LDL-C levels in patients with type 2 diabetes mellitus; multivariate logistic regression analysis was performed to analyze the influencing factors of thyroid cancer in patients with type 2 diabetes mellitus. Results: The serum HbAlc level and the incidence of thyroid cancer in patients with type 2 diabetes mellitus in the observation group were significantly higher than those in the control group (P < 0.05). The levels of TC, TG, and LDL-C in patients with type 2 diabetes mellitus in the observation group were significantly higher than those in the control group, and the level of HDL-C was significantly lower than that in the control group (P < 0.05). The correlation analysis showed that serum HbAlc levels in patients with type 2 diabetes were positively correlated with TC and TG levels and negatively correlated with HDL-C levels (P < 0.05) and not correlated with LDL-C levels (P > 0.05). Compared with the type 2 diabetes patients without thyroid cancer, the serum HbAlc, TC, and TG levels of the patients with type 2 diabetes mellitus in the thyroid cancer group were significantly higher, and the levels of HDL-C were significantly lower (P < 0.05). There was no significant change in the level of LDL-C (P > 0.05). Multivariate logistic regression analysis showed that serum HbAlc, TC, and TC levels were all risk factors for thyroid cancer in patients with type 2 diabetes mellitus (P < 0.05), while serum HDL-C level was a protective factor for thyroid cancer in patients with type 2 diabetes mellitus (P < 0.05). Conclusion: Thyroid cancer in type 2 diabetes patients may be linked to elevated levels of blood HbAlc, TC, and TG. HbAlc may raise the risk of thyroid cancer in type 2 diabetes patients by modulating blood lipid levels, which might serve as a marker to assess the risk of thyroid cancer in type 2 diabetes mellitus patients. However, since this study did not conduct in vitro and in vivo experiments, how HbAlc affects the pathogenesis of thyroid cancer has not been described in this study, which is also our future research direction. It is expected to provide new ideas for the prevention and treatment of thyroid cancer.

Investigation of risk factors associated with impaired glucose regulation: Using the momentum equation to assess the impact of risk factors on community residents.

Objective: To identify risk factors for impaired glucose regulation (IGR) and assess their impact on community residents, this study used a questionnaire to conduct cross-sectional surveys and analysis. Methods: Overall, 774 residents of an urban community in northern China (Jian city) participated in this study. Trained investigators conducted surveys using questionnaires. Based on their medical history, respondents were divided into three glucose status groups as follows: normal (NGT), IGR, and diabetes mellitus (DM). Statistical analysis of survey data was performed using SPSS v. 22.0. Results: Age, hypertension, family history of diabetes (FHD), dyslipidemia, obesity, and cardiovascular and cerebral disease (CVD) were positively correlated with IGR in men and women. IGR was negatively correlated with a sedentary lifestyle in men and positively correlated with being overweight in women. The number of type 2 diabetes mellitus (T2D) risk factors per subject was positively correlated with age in the NGT group. Glucose status deteriorated with increasing age and the number of risk factors. FHD was the strongest risk factor in both men and women. Conclusions: Prevention of IGR includes weight control, physical activity, and prevention of hypertension and dyslipidemia, especially in subjects with FHD.

Pan-cancer analysis supports MAPK12 as a potential prognostic and immunotherapeutic target in multiple tumor types, including in THCA.

P38 mitogen-activated protein kinase (MAPK)12 (also known as P38 γ) is critical in the development and progression of various types of tumors. Despite the extensive literature on the subject, further studies are needed to elucidate its role in cancer progression. Here, a comprehensive bioinformatics analysis of a generalized cancer dataset was performed to explore the mechanism of MAPK12 regulation in tumorigenesis. Several tumor datasets and online analytical tools, including HPA, SangerBox, UALCAN, GEPIA2, STRING, ImmuCellAI, and MEXPRESS, were used to analyze the expression information on MAPK12 in several types of cancers. Western blotting and reverse transcription-quantitative PCR were used to verify the protein and mRNA expression levels of MAPK12, respectively, in human normal thyroid cells (HTORI-3) and thyroid carcinoma (THCA) cells. Cytotoxicity and EdU assays were used to verify the promoting effect of MAPK12 on cell proliferation in THCA cells. Analysis of several cancers found that MAPK12 was overexpressed in multiple cancer types. Upregulated MAPK12 mRNA expression levels were correlated with a worse prognosis in patients with several types of cancer. Cytotoxicity and EdU experiments showed that MAPK12 knockdown inhibited THCA cell proliferation. Gene Ontology-Biological Process and Kyoto Encyclopedia of Genes and Genomes analyses showed that the enrichment of MAPK12 genes was related to cell proliferation and the tumor immune microenvironment. These results showed that MAPK12 was closely related to the immune checkpoint, microsatellite instability, and tumor mutational burden and affected the sensitivity of the tumor to immunotherapy. This study showed that MAPK12 may be an immunotherapeutic and promising prognostic biomarker in certain types of tumors.

The protective effects of miR-210 modified endothelial progenitor cells released exosomes in hypoxia/reoxygenation injured neurons.

We have previously demonstrated that endothelial progenitor cells (EPCs) provide beneficial effects on ischemic stroke by reducing oxidative stress, which could be through EPCs-released exosomes (EPC-EXs). EXs are emerging as a bioagent for mediating cell-cell communications via their carried microRNAs (miR). miR-210 is shown to provide a neuroprotection effect against ischemic stroke. Here, we aimed to determine whether the combination of EPC-EXs and miR-210 would provide an enhanced protective effect on neurons. The hypoxia and reoxygenation (H/R) model were applied to neurons to mimic the ischemic injury of neurons. EPCs were transfected with miR-210 mimic to elevate the level of miR-210 in cells and EPC-EXs (miR210-EPC-EXs). For functional studies, EPC-EXs were co-incubated with H/R-injured neurons, then the cell viability and reactive oxygen species (ROS) production were determined. The results showed 1) H/R induced apoptosis and ROS overproduction in neurons; 2) miR-210 mimic increased the level of miR-210 in both EPCs and EPC-EXs; 3) EPCs cultured in serum-free medium released more exosomes in comparison with cells grown in complete growth media, suggesting serum starving induce the release of EXs; 4) After transfection, EPCs grown in complete media had almost 50 times higher miR-210 level than EPCs had in serum-free media, while the EPCs-EXs isolated from the complete media has lower miR-210 expression than from the serum-free media in a time-dependent manner, suggesting the transfer of miR-210 through EXs; 5) After co-incubation, EPC-EXs and miR210-EPC-EXs were uptaken by neurons, and the miR-210 level in neurons was elevated by miR210-EPC-EXs; 6) miR210-EPC-EXs were more effective in promoting cell viability and decreasing apoptosis and ROS production than EPC-EXs. The present study demonstrated that EPCs-carried miR-210 could be released and transferred to neurons in a time-dependent manner and that miR-210 loading can enhance the protective effects of EPC-EXs on H/R-induced neuron apoptosis, oxidative stress, and decreased viability.

Modulation of the Gut Microbiota and Glycometabolism by a Probiotic to Alleviate Amyloid Accumulation and Cognitive Impairments in AD Rats.

SCOPE: Regulating the gut microecology by probiotics is an efficient strategy to rational prevention and treatment of Alzheimer's disease (AD). However, there is currently a lack of well-known probiotic species in the protection against AD, and the involved mechanism has not been clearly interpreted. METHODS AND RESULTS: Herein, Lactobacillus plantarum MA2 (MA2), a functional probiotic isolated from traditional Chinese Tibetan kefir grains, is demonstrated to improve the cognitive deficits and anxiety-like behaviors in the d-galactose/AlCl3 induced AD rats, and attenuate the neuronal degeneration and Aß accumulation in the brain. Moreover, the study finds MA2 could alleviate the intestinal mucosal impairments, and impedes the activation of microglia and neuroinflammation through TLR4/MYD88/NLRP3 signaling pathway. 16S rRNA sequencing and metabolomic analysis indicate that MA2 reshapes the gut microbiota structure and composition, and remarkably modulates the glycometabolism. In that case, the exopolysaccharides (EPS) that derived from MA2 is furtherly proved with inhibitory effects on the Aß42 aggregation and amyloid-induced cytotoxicity. CONCLUSION: MA2 or MA2 EPS may be used as functional food and nutritional supplement for regulating the gut microbiota and metabolism disorders in AD. This study is of great significance to develop new intervention and therapeutic strategy on AD using probiotics and their metabolites.

hsa_circ_0000285 facilitates thyroid cancer progression by regulating miR-127-5p/CDH2.

Thyroid cancer (THCA) is a leading endocrine cancer and becomes the fifth most commonly diagnosed malignancy in females. It is confirmed that circular RNAs (circRNAs) perform regulatory potencies in the pathological progress of THCA. Our purpose was to certify the trait of hsa_circ_0000285 (circ_0000285) and investigate its modulatory mechanism in THCA progression. We identified the expression profile of hsa_circ_0000285 in THCA by conducting qRT-PCR assay. Therewith, the potential of hsa_circ_0000285 in THCA development was determined with a set of functional experiments, including CCK-8, wound healing assay, Western blot, and xenograft model. The molecular mechanism underlying hsa_circ_0000285 was investigated with bioinformatic analysis, RIP and dual-luciferase reporter experiments. As opposed to normal samples and cells, hsa_circ_0000285 level was overtly increased in THCA specimens and cells. The downregulation of hsa_circ_0000285 weakened the proliferative and migratory capacity of THCA cells and promoted cell apoptosis. In addition, hsa_circ_0000285 silence suppressed the tumor growth of xenograft model mice in vivo. Notably, we demonstrated that hsa_circ_0000285 might target miR-127-5p/CDH2 axis in THCA. Afterward, our findings manifested that miR-127-5p attenuation blocked the function of hsa_circ_0000285 depletion in THCA cells. In the final step, CDH2 was proven to mediate the repressive potency of miR-127-5p in the malignant behaviors of THCA. Mechanistically, hsa_circ_0000285 induced the development of THCA via functioning as a competing endogenous RNA (ceRNA) of miR-127-5p to enhance CDH2 expression, which provided a new perspective for THCA therapy.

Kombucha Reduces Hyperglycemia in Type 2 Diabetes of Mice by Regulating Gut Microbiota and Its Metabolites.

Kombucha, which is rich in tea polyphenols and organic acid, is a kind of acidic tea soup beverage fermented by acetic acid bacteria, yeasts, lactic acid bacteria. Kombucha has been reported to possess anti-diabetic activity, but the underlying mechanism was not well understood. In this study, a high-fat, high-sugar diet combined with streptozotocin (STZ) injection was used to induce T2DM model in mice. After four weeks of kombucha intervention, the physiological and biochemical index were measured to determine the diabetes-related indicators. High-throughput sequencing technology was used to analyze the changes in gut microbiota from the feces. The results showed that four weeks of kombucha intervention increased the abundance of SCFAs-producing bacteria and reduced the abundance of gram-negative bacteria and pathogenic bacteria. The improvement in gut microbiota reduced the damage of intestinal barrier, thereby reducing the displacement of lipopolysaccharide (LPS) and inhibiting the occurrence of inflammation and insulin resistance in vivo. In addition, the increased levels of SCFAs-producing bacteria, and thus increasing the SCFAs, improved islet ß cell function by promoting the secretion of gastrointestinal hormones (GLP-1/PYY). This study methodically uncovered the hypoglycemic mechanism of kombucha through gut microbiota intervention, and the result suggested that kombucha may be introduced as a new functional drink for T2DM prevention and treatment.

EPC-EXs improve astrocyte survival and oxidative stress through different uptaking pathways in diabetic hypoxia condition.

BACKGROUND: Hyperglycemia contributes to cardiovascular complications in patients with type 2 diabetes. We confirmed that high glucose (HG) induces endothelial dysfunction and cerebral ischemic injury is enlarged in diabetic mice. Stem cell-released exosomes have been shown to protect the brain from ischemic stroke. We have previously shown that endothelial progenitor cells (EPCs)-released exosomes (EPC-EXs) can protect endothelial cells from hypoxia/reoxygenation (H/R) and HG-induced injury. Here, we aim to investigate the effects of EPC-EXs on astrocytes under H/R and HG-induced injury and whether miR-126 enriched EPC-EXs (miR126-EPC-EXs) have enhanced efficacy. METHODS: EPC-EX uptake and co-localization were measured by fluorescent microscopy using PKH26 and DAPI staining. miR-126 enrichment was achieved by transfecting with miR-126 mimics and quantified with real-time PCR. After co-incubation, cell death or injury was measured by using LDH (Lactate Dehydrogenase) assay. Oxidative stress/ROS (reactive oxygen species) generation was measured by DHE (Dihydroethidium) staining and lipid peroxidation assay. RESULTS: The EPC-EXs were effectively taken up by the astrocytes in a concentration as well as time-dependent manners and were co-localized within the nucleus as well as the cytoplasm. Pathway uptake inhibitors revealed that the EPC-EXs are effectively taken up by the clathrin-mediated, caveolin-dependent, and micropinocytosis via PI3K/Akt pathway. H/R and HG-induced a cell injury which could be protected by EPC-EXs evidenced by decreased cell cytotoxicity, oxidative stress, and lipid peroxidation. Moreover, miR-126 overexpression could increase the level of miR-126 in astrocytes and enhance the protective effects of EPC-EXs. CONCLUSIONS: These results collectively indicate that the EPC-EXs could protect astrocytes against the HG plus H/R-induced damage.

Identification of a novel probiotic and its protective effects on NAFLD via modulating gut microbial community.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is becoming the most common progressive liver diseases. Therapeutic strategy based on gut-liver axis and probiotics is a promising approach for the treatment of NAFLD. However, rare probiotics have been applied in NAFLD treatment, and the involved molecular mechanism is not entirely clear. RESULTS: We initially identified a novel functional probiotic, Lactobacillus kefiranofaciens ZW3, on the lipid deposition by a simple and rapid zebrafish model. Supplementation with ZW3 to the methionine and choline deficient (MCD) diet induced NAFLD rats could improve the liver impairments and reduce inflammation through TLR4-MyD88 and JNK signaling pathways. Moreover, ZW3 modulated gut microbiota by promoting relative abundance of Firmicutes and Lactobacillus, decreasing the abundance of Escherichia-Shigella and Bacteroides. Functional prediction of microbiome showed ZW3 presented potential enhancement on carbohydrate and lipid metabolism, cell process control and signal transduction processes, and reduced several human diseases. CONCLUSION: This present study identified a novel probiotic and its protective effects on NAFLD, and interpreted the interactions of ZW3 with the immune system and gut microbiota involved in gut-liver axis. © 2022 Society of Chemical Industry.

Ultraviolet B Irradiation Alters the Level and miR Contents of Exosomes Released by Keratinocytes in Diabetic Condition.

Ultraviolet B (UVB) stimulates the generation of extracellular vesicles, which elicit systemic effects. Here, we studied whether UVB affects the release and microRNA (miR) content of keratinocyte exosomes (EXs) in diabetic conditions. In vitro, we examined the UVB effects on affecting EX release from keratinocyte HaCaT cells (HaCaT-EX) pretreated with high glucose. HaCaT-EX functions were evaluated on Schwann cells (SCs). In vivo, UVB-induced miR change in skin EXs of diabetic db/db mice was analyzed. The miRs of interest were validated in HaCaT-EXs. We found that: (1) UVB promoted HaCaT-EX generation in dose- and time-dependent manners; 100 and 1800 J m-2 of UVB had the most prominent effect and were selected as effective low- and high-fluence UVB in vitro. (2) A total of 13 miRs were differentially expressed >3-fold in skin EXs in UVB-treated db/db mice; miR-126 was the most up-regulated by low-fluence UVB. (3) Functional studies revealed that the SC viability was improved by low-fluence UVB HaCaT-EXs, while worsened by high-fluence UVB HaCaT-EXs. (4) MiR-126 inhibitor attenuated the effects induced by low-fluence UVB HaCaT-EXs. Our data have demonstrated that low- and high-fluence UVBs promote HaCaT-EX generation but differentially affect exosomal miR levels and functions under diabetic conditions.

Lactobacillus plantarum MA2 Ameliorates Methionine and Choline-Deficient Diet Induced Non-Alcoholic Fatty Liver Disease in Rats by Improving the Intestinal Microecology and Mucosal Barrier.

Non-alcoholic fatty liver disease (NAFLD) has become a highly concerned health issue in modern society. Due to the attentions of probiotics in the prevention of NAFLD, it is necessary to further clarify their roles. In this study, the methionine and choline-deficient (MCD) diet induced NAFLD rats model were constructed and treated with strain L. plantarum MA2 by intragastric administration once a day at a dose of 1 × 108 cfu/g.bw. After 56 days of the therapeutic intervention, the lipid metabolism and the liver pathological damage of the NAFLD rats were significantly improved. The content of total cholesterol (TC) and total triglyceride (TG) in serum were significantly lower than that in the NAFLD group (p < 0.05). Meanwhile, the intestinal mucosal barrier and the structure of intestinal microbiota were also improved. The villi length and the expression of claudin-1 was significantly higher than that in the NAFLD group (p < 0.05). Then, by detecting the content of LPS in the serum and the LPS-TLR4 pathway in the liver, we can conclude that Lactobacillus plantarum MA2 could reduce the LPS by regulating the gut microecology, thereby inhibit the activation of LPS-TLR4 and it downstream inflammatory signaling pathways. Therefore, our studies on rats showed that L. plantarum MA2 has the potential application in the alleviation of NAFLD. Moreover, based on the application of the strain in food industry, this study is of great significance to the development of new therapeutic strategy for NAFLD.

A Fast Bubble Detection Method in Microtubes Based on Pulsed Ultrasound.

In the process of biological microfluidic manipulation, the bubbles generated in the tube will seriously reduce the gauging accuracy. This paper introduces an improving method that can estimate the size of microbubbles in real time. Hence, the measurement data of the liquid volume can be modified according to this method. A microbubble detector based on the pulsed-ultrasound method was studied, including the device structure and the working principle. The assessment formula of the microbubbles in the tube was derived from the simulation results, which adopted the two-phase theory. The digital image processing method was applied to fulfill the microbubble calibration. This detection method was applied to measure the microbubbles in the tube and to modify the flow volume in a timely manner. The results of the experiments showed that this method is effective at improving the microflow gauging accuracy.