Circulating exosomal miR-16-5p and let-7e-5p are associated with bladder fibrosis of diabetic cystopathy.

Diabetic cystopathy (DCP) is a prevalent etiology of bladder dysfunction in individuals with longstanding diabetes, frequently leading to bladder interstitial fibrosis. Research investigating the initial pathological alterations of DCP is notably scarce. To comprehend the development of fibrosis and find effective biomarkers for its diagnosis, we prepared streptozotocin-induced long-term diabetic SD rats exhibiting a type 1 diabetes phenotype and bladder fibrosis in histology detection. After observing myofibroblast differentiation from rats' primary bladder fibroblasts with immunofluorescence, we isolated fibroblasts derived exosomes and performed exosomal miRNA sequencing. The co-differentially expressed miRNAs (DEMis) (miR-16-5p and let-7e-5p) were screened through a joint analysis of diabetic rats and long-term patients' plasma data (GES97123) downloaded from the GEO database. Then two co-DEMis were validated by quantitative PCR on exosomes derived from diabetic rats' plasma. Following with a series of analysis, including target mRNAs and transcription factors (TFs) prediction, hubgenes identification, protein-protein interaction (PPI) network construction and gene enrichment analysis, a miRNA-mediated genetic regulatory network consisting of two miRNAs, nine TFs, and thirty target mRNAs were identified in relation to fibrotic processes. Thus, circulating exosomal miR-16-5p and let-7e-5p are associated with bladder fibrosis of DCP, and the crucial genes in regulatory network might hold immense significance in studying the pathogenesis and molecular mechanisms of fibrosis, which deserves further exploration.

The effect of parecoxib sodium on postoperative delirium in elderly patients with hip arthroplasty.

Objective: This study aimed to clarify the effect of parecoxib sodium on the occurrence of postoperative delirium and to investigate its possible mechanism. Methods: A total of 80 patients who underwent elective hip arthroplasty in our hospital between December 2020 and December 2021 were selected and randomly divided into two groups: a parecoxib sodium group (group P, n = 40) and a control group (group C, n = 40). Patients in group P were intravenously injected with 40 mg of parecoxib sodium 30 min before anesthesia and at the end of the surgery. Patients in group C were intravenously injected with the same volume of normal saline at the same time points. The primary endpoint was the incidence of POD, and the secondary endpoints were the levels of inflammatory factors (tumor necrosis factor- α [TNF-α], interleukin [IL]-1ß, IL-6, and IL-10), nerve injury-related factors (brain-derived neurotrophic factor [BDNF], S-100ß protein, neuron-specific enolase [NSE], and neurofilament light chain [NfL]), and antioxidant factors (heme oxygenase-1 [HO-1]), as well as the Visual Analogue Scale (VAS) and Confusion Assessment Method-Chinese Reversion (CAM-CR) scores. Results: The incidence of POD was 10% in group P and 27.5% in group C. Intergroup comparison revealed that the levels of TNF-α, IL-1ß, S-100ß, NfL, and NSE were lower, and BDNF was higher, in group P than in group C at each postoperative time point. The levels of IL-6 were lower, and the levels of IL-10 and HO-1 were higher, in group P than in group C at 1 h and 1 day postoperatively (p < 0.05). Three days after surgery, the differences in the levels of IL-6, IL-10, and HO-1 were not statistically significant between the two groups (p > 0.05). The VAS and CAM-CR scores were lower at each postoperative time point in group P than in group C (p < 0.05). Conclusion: Parecoxib sodium could reduce postoperative pain, decrease the plasma levels of inflammatory and nerve injury-related factors, upregulate HO-1 levels, and reduce the incidence of POD. The results of this study suggest that parecoxib sodium may reduce the occurrence of POD through the effects of anti-inflammation, analgesia, and antioxidants.

Paraventricular thalamus controls consciousness transitions during propofol anaesthesia in mice.

BACKGROUND: The neuronal mechanisms underlying propofol-induced modulation of consciousness are poorly understood. Neuroimaging studies suggest a potential role for non-specific thalamic nuclei in propofol-induced loss of consciousness. We investigated the contribution of the paraventricular thalamus (PVT), a midline thalamic nucleus that has been implicated in arousal control and general anaesthesia with inhaled anaesthetics, to loss and recovery of consciousness during propofol anaesthesia. METHODS: Polysomnographic recordings and righting reflex test were used to determine the transitions of loss and recovery of righting reflex, used as a measure of consciousness in mice, during propofol anaesthesia in mice under conditions mimicking clinical propofol administration. PVT neuronal activities were monitored using fibre photometry and regulated using optogenetic and chemogenetic methods. RESULTS: Population activities of PVT glutamatergic neurones began to decrease before propofol-induced loss of consciousness and rapidly increased to a peak at the onset of recovery of consciousness. Chemogenetic inhibition of PVT calretinin-expressing (PVTCR) neurones shortened onset (from 176 [35] to 127 [26] s; P=0.001) and prolonged return (from 1568 [611] to 3126 [1616] s; P=0.002) of righting reflex. Conversely, chemogenetic activation of PVTCR neurones exerted opposite effects. Furthermore, optogenetic silencing of PVTCR neurones accelerated transitions to loss of consciousness (from 205 [35] to 158 [44] s; P=0.027) and slowed transitions to recovery of consciousness (from 230 [78] to 370 [99] s; P=0.041). During a steady period of unconsciousness maintained with continuous propofol infusion, brief optical activation of PVTCR neurones restored cortical activity and arousal with a latency of about 5 s. CONCLUSIONS: The paraventricular thalamus contributes to the control of consciousness transitions in propofol anaesthesia in mice. This provides a potential neuroanatomical target for controlling consciousness to reduce anaesthetic dose requirements and side effects.

Simultaneous Presentation of Multiple Myeloma and Lung Cancer: Case Report and Gene Bioinformatics Analysis.

Patients diagnosed with more than one cancer generally develop the individual tumors sequentially. There are a few cases of co-occurring multiple myeloma and lung cancer reported in the literature. Here, we report two cases of co-occurring multiple myeloma and lung cancer in patients who presented with the chief complaint of pain. The diagnoses of multiple myeloma and lung cancer were supported by hematologic and biochemical investigations, as well as bone marrow and lung histopathologic examination. We provided suitable interventions for both two patients. The patients are still currently undergoing treatment and followed up closely. We first performed a bioinformatic analysis to determine commonly shared genes and pathways in the two types of cancer types. Fortunately, we identified the hub gene mitochondrial trans-2-enoyl-CoA reductase (MECR), which was overexpressed in both tumors. Survival analysis correlated higher MECR expression with poorer overall survival. Signaling pathway analysis suggested possible transduction pathways implicated in the co-occurrence of both tumors. The clinical cases combined with bioinformatic analysis may provide insight for the pathogenesis of synchronous tumors.

Retraction Notice to: lncRNA MALAT1 Accelerates Wound Healing of Diabetic Mice Transfused with Modified Autologous Blood via the HIF-1α Signaling Pathway.

[This retracts the article DOI: 10.1016/j.omtn.2019.05.020.].

Treatment for CD57-negative γδ T-cell large granular lymphocytic leukemia with pure red cell aplasia: A case report.

BACKGROUND: T-cell large granular lymphocytic leukemia (T-LGLL) is a rare type of aplastic anemia with diverse clinical manifestations. Concomitant diseases are often present at the first manifestation. We describe the treatment of a patient with CD57-negative γδT-LGLL with pure red cell aplasia (PRCA). CASE SUMMARY: A 34-year-old woman with a 20-year history of anemia visited our hospital owing to severe dizziness and was admitted. Her condition was diagnosed as CD57-negative γδT-LGLL with PRCA through bone marrow cytology, bone marrow pathology, bone marrow flow cytometry, bone marrow multiplex polymerase chain reaction combined with fluorescent fragment analysis, and other tests. Treatment with prednisone, methotrexate, and subcutaneous erythropoietin did not significantly change her hemoglobin level. After treatment with oral cyclophosphamide for 3 mo, her hemoglobin level increased to approximately 100 g/L. After 5 mo of treatment, the patient could perform activities of daily living independently. CONCLUSION: The treatment of CD57-negative γδT-LGLL with PRCA with cyclophosphamide helps to improve prognosis.

Ethyl ferulate protects against lipopolysaccharide-induced acute lung injury by activating AMPK/Nrf2 signaling pathway.

Ethyl ferulate (EF) is abundant in Rhizoma Chuanxiong and grains (e.g., rice and maize) and possesses antioxidative, antiapoptotic, antirheumatic, and anti-inflammatory properties. However, its effect on lipopolysaccharide (LPS)-induced acute lung injury (ALI) is still unknown. In the present study, we found that EF significantly alleviated LPS-induced pathological damage and neutrophil infiltration and inhibited the gene expression of proinflammatory cytokines (TNF-α, IL-1ß, and IL-6) in murine lung tissues. Moreover, EF reduced the gene expression of TNF-α, IL-1ß, IL-6, and iNOS and decreased the production of NO in LPS-stimulated RAW264.7 cells and BMDMs. Mechanistic experiments revealed that EF prominently activated the AMPK/Nrf2 pathway and promoted Nrf2 nuclear translocation. AMPK inhibition (Compound C) and Nrf2 inhibition (ML385) abolished the beneficial effect of EF on the inflammatory response. Furthermore, the protective effect of EF on LPS-induced ALI was not observed in Nrf2 knockout mice. Taken together, the results of our study suggest that EF ameliorates LPS-induced ALI in an AMPK/Nrf2-dependent manner. These findings provide a foundation for developing EF as a new anti-inflammatory agent for LPS-induced ALI/ARDS therapy.

Adequate expression of neuropeptide Y is essential for the recovery of zebrafish motor function following spinal cord injury.

In strong contrast to limited repair within the mammalian central nervous system, the spinal cord of adult zebrafish is capable of almost complete recovery following injury. Understanding the mechanism underlying neural repair and functional recovery in zebrafish may lead to innovative therapies for human spinal cord injury (SCI). Since neuropeptide Y (NPY) plays a protective role in the pathogenesis of several neurological diseases, in the present study, we evaluated the effects of NPY on neuronal repair and subsequent recovery of motor function in adult zebrafish following SCI. Real-time quantitative PCR (qRT-PCR), in situ hybridization and immunostaining for NPY revealed decreased NPY expression at 12 hours (h), 6 and 21 days (d) after SCI. Double-immunostaining for NPY and islet-1, a motoneuron marker, showed that NPY was expressed in spinal cord motoneurons. Morpholino (MO) treatment for suppressing the expression of NPY inhibited supraspinal axon regrowth and locomotor recovery, in which double-staining for proliferating cell nuclear antigen (PCNA) and islet-1 showed a reduction in motoneuron proliferation. Similarly, a downregulated mRNA level of Y1 receptor of NPY (NPY1R) was also detected at 12 h, 6 and 21 d after injury. Immunostaining for NPY and in situ hybridization for NPY1R revealed that NPY1R was co-localized with NPY. Collectively, the results suggest that NPY expression in motoneurons promotes descending axon regeneration and locomotor recovery in adult zebrafish after SCI, possibly by regulating motoneuron proliferation through activation of NPY1R.

Epidemiological characteristics of hand, foot, and mouth disease in China: A meta-analysis.

BACKGROUND: To study the epidemic features of hand-foot-mouth disease (HFMD) in mainland China through systematic review and meta-analysis so as to provide evidence for the future prevention and control of HFMD. METHODS: Articles on the epidemic features of HFMD in mainland China, written in English or Chinese and released between January 1, 2015 and January 1, 2020, were searched from English literature databases including Embase, Web of Science, PubMed, Cochrane library, Google academic, and Chinese literature databases including China national knowledge infrastructure (CNKI), Wanfang, and China Biology Medicine (CBM). Papers were selected according to the inclusion and exclusion criteria, and quality scoring was performed. Meta-analysis, sensitivity analysis, and identification of publication bias were finished through STATA version 12.0 software. RESULTS: A total of 23 articles were included in this study, the total number of cases was 377,083, of which the total number of male cases was 231,798 and the total number of female cases was 145,285, the sex ratio was about 1.6:1, and the incidence of HFMD in China was 1.61‰ (95% confidence interval [CI]: 1.21‰-1.94‰). The results of the subgroup analysis showed that the incidence of HFMD in mainland China was the highest in South China, in 2014, in 1-year-old group and in other types of enteroviruses, respectively, with the rate of 3.48‰ (95% CI: 1.22‰-5.73‰), 1.81‰ (95% CI: 1.06‰-2.57‰), 15.20‰ (95% CI: 5.00‰-25.30‰), and 1.83‰ (95% CI: 1.32‰-2.33‰), respectively. The differences among the above 4 subgroups were statistically significant (P < .05). There were no publication bias in this study, and the sensitivity analysis results suggested that the meta-analysis results were robust. CONCLUSION: There were differences in the distribution of region, time, population, and etiology of HFMD in mainland China. Health departments should adopt key strategies and measures for key populations in key areas to prevent and control the development of HFMD, and improve the ability of pathogen detection and typing in laboratories.

Knockdown of lncRNA TTTY15 alleviates myocardial ischemia-reperfusion injury through the miR-374a-5p/FOXO1 axis.

Myocardial ischemia/reperfusion (I/R) injury greatly contributes to myocardial tissue damage in patients with coronary disease, which eventually leads to heart failure. Long noncoding RNAs (lncRNAs) have an emerging role in the process of myocardial I/R injury. Our previous work revealed the protective role of miR-374a-5p against myocardial I/R injury. In this study, we explored the role of lncRNA TTTY15 and its potential interaction mechanisms with miR-374a-5p in myocardial I/R injury. The expression of TTTY15 was increased both in vitro and in vivo after myocardial I/R injury models according to quantitative real-time polymerase chain reaction. Various assays were conducted to evaluate the regulatory relationship among TTTY15, miR-374a-5p, FOXO1, and autophagy in H9c2 and HL-1 cells. The results showed that TTTY15 suppresses autophagy and myocardial I/R injury by targeting miR-374a-5p. We found that TTTY15 regulates miR-374a-5p, thus affecting FOXO1 expression and autophagy in myocytes during I/R. Furthermore, in an in vivo mouse model of myocardial I/R injury, suppression of TTTY15 successfully alleviated myocardial I/R injury. Our results reveal a novel feedback mechanism in which TTTY15 regulates miRNA processing and a potential target in myocardial I/R injury. TTTY15 is a promising therapeutic target for treating myocardial I/R injury.

Sophoricoside attenuates lipopolysaccharide-induced acute lung injury by activating the AMPK/Nrf2 signaling axis.

Sophoricoside (SOP), an isoflavone glycoside isolated from seed of Sophora japonica L., has been reported to have various pharmacological activities, including anti-cancer, anti-allergy and anti-inflammation. However, the effect of SOP on lipopolysaccharides (LPS)-acute lung injury (ALI) is completely unclear. Here, we found that SOP pretreatment significantly ameliorated LPS-induced pathological damage, tissue permeability, neutrophil infiltration and the production of pro-inflammatory cytokines (TNF-α, IL-1ß and IL-6) in a murine model of ALI. Besides, SOP reduced the production of pro-inflammatory mediators such as iNOS, NO and inflammatory cytokines including TNF-α, IL-1ß and IL-6 in LPS-stimulated RAW264.7 cells and bone marrow derived macrophages. Interestingly, treatment with SOP exhibited no effect on the activation of NF-κB and MAPKs in macrophages but prominently accelerated the expression and nuclear translocation of Nrf2. By using ML385, a specific Nrf2 inhibitor, we found that inhibition of Nrf2 abolished the inhibitory effect of SOP on LPS-induced iNOS expression, NO production as well as pro-inflammatory cytokine generation. SOP also activated AMPK, an upstream protein of Nrf2, under LPS stimuli. Furthermore, we demonstrated that the accelerated expression of Nrf2 induced by SOP was reversed by interference with the AMPK inhibitor Compound C. Taken together, our results suggested that SOP attenuated LPS-induced ALI in AMPK/Nrf2 dependent manner and indicated that SOP might be a potential therapeutic candidate for treating ALI/ARDS.

Genome-Wide Analysis of the Malaria Parasite Plasmodium falciparum Isolates From Togo Reveals Selective Signals in Immune Selection-Related Antigen Genes.

Malaria is a public health concern worldwide, and Togo has proven to be no exception. Effective approaches to provide information on biological insights for disease elimination are therefore a research priority. Local selection on malaria pathogens is due to multiple factors including host immunity. We undertook genome-wide analysis of sequence variation on a sample of 10 Plasmodium falciparum (Pf) clinical isolates from Togo to identify local-specific signals of selection. Paired-end short-read sequences were mapped and aligned onto > 95% of the 3D7 Pf reference genome sequence in high fold coverage. Data on 266 963 single nucleotide polymorphisms were obtained, with average nucleotide diversity π = 1.79 × 10-3. Both principal component and neighbor-joining tree analyses showed that the Togo parasites clustered according to their geographic (Africa) origin. In addition, the average genome-wide diversity of Pf from Togo was much higher than that from other African samples. Tajima's D value of the Togo isolates was -0.56, suggesting evidence of directional selection and/or recent population expansion. Against this background, within-population analyses identifying loci of balancing and recent positive selections evidenced that host immunity has been the major selective agent. Importantly, 87 and 296 parasite antigen genes with Tajima's D values > 1 and in the top 1% haplotype scores, respectively, include a significant representation of membrane proteins at the merozoite stage that invaded red blood cells (RBCs) and parasitized RBCs surface proteins that play roles in immunoevasion, adhesion, or rosetting. This is consistent with expectations that elevated signals of selection due to allele-specific acquired immunity are likely to operate on antigenic targets. Collectively, our data suggest a recent expansion of Pf population in Togo and evidence strong host immune selection on membrane/surface antigens reflected in signals of balancing/positive selection of important gene loci. Findings from this study provide a fundamental basis to engage studies for effective malaria control in Togo.

Autologous transfusion of "old" red blood cells-induced M2 macrophage polarization through IL-10-Nrf2-HO-1 signaling complexes.

BACKGROUND: Red blood cell (RBC) transfusion is associated with systemic inflammation and immune suppression as adverse outcomes. OBJECTIVES: To investigate the immunomodulatory function of the transfused autologous RBC in altering pro-inflammatory and immunosuppressive effects. MATERIAL AND METHODS: A total of 24 Sprague Dawley male rats were randomly divided into 3 groups (n = 8 in each group). Group 1 did not receive blood transfusions, while the other 2 groups of rats separately received transfusion of RBC stored for 14 days (group 2) and 35 days (group 3). The rats were treated with HO-1 inhibitor, HO-1 inducer and nuclear factor erythroid 2-related factor 2 (Nrf2) activator after they separately received autologous transfusion of RBC that were cryopreserved for 14 days or 35 days. The blood samples of the rats were collected 12 h after the transfusion, and the macrophage phenotype of M1 and M2 were analyzed with flow cytometry (FCM). Also, the surface protein expression of CD68 and CD200R in macrophages were analyzed and the inflammatory signals in the serum were measured with enzyme-linked immunosorbent assay (ELISA). Moreover, the location and expression of proteins heme oxygenase 1 (HO-1), arginine 1 (Arg-1) and nitric oxide synthase 2 (NOS2) in macrophage were detected with immunofluorescence (IF). RESULTS: Autologous transfusion of long-time stored ("old") RBC promoted macrophage polarization to M2 phenotype and upregulated the expression of its surface proteins CD68 and CD200R. The pro-inflammatory cytokines tumor necrosis factor α (TNF-α), interleukin (IL)-6, IL-1ß, and IL-18 were inhibited, and the secretion of NOS isoforms (iNOS) in serum was reduced with blood transfusion; contrarily, the production of IL-10 and CCL22 was increased. Additionally, HO-1, Arg-1 and NOS2 proteins were located in the cytoplasm, and HO-1 and Arg-1 proteins were highly expressed in macrophage, while the expression of protein NOS2 was low. Moreover, Nrf2, HO-1 and Arg-1 proteins were upregulated in macrophage after receiving "old" RBC transfusion. CONCLUSIONS: Autologous transfusion of "old" RBC drove the macrophage phenotype toward M2 macrophages and induced immunosuppressive effects through the IL-10-NRF2-HO-1 signals.

Iron overload as a risk factor for poor graft function following allogeneic hematopoietic stem cell transplantation.

Hematological malignancies are increasingly treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT). Unfortunately, iron overload is a frequent adverse effect of allo-HSCT and is associated with poor prognosis. In the present study, we investigated hematopoiesis in iron-overloaded mice and elucidated the effects of iron overload on the bone marrow (BM) microenvironment. Iron-overloaded BALB/C mice were generated by injecting 20 mg/mL saccharated iron oxide intraperitoneally. Hematoxylin-eosin staining was performed to evaluate the effects of an iron overload in mice. BM cells obtained from C57BL/6 mice were transplanted into irradiated BALB/C mice (whole-body irradiation of 4 Gy, twice with a 4-hours interval) by tail vein injection. Two weeks after allo-HSCT, the hematopoietic reconstitution capacity was evaluated in recipients by colony-forming assays. Histopathological examinations showed brown-stained granular deposits, irregularly arranged lymphocytes in the liver tissues, and blue-stained blocks in the BM collected from mice received injections of high-dose saccharated iron oxide (20 mg/mL). Iron-overloaded mice showed more platelets, higher-hemoglobin (HGB) concentration, fewer granulocyte-macrophage colony-forming units (CFU-GM), erythrocyte colony-forming units (CFU-E), and mixed granulocyte/erythrocyte/monocyte/megakaryocyte colony-forming units (CFU-mix) than healthy mice. Iron-overloaded recipients presented with reduced erythrocytes and HGB concentration in peripheral blood, along with decreased marrow stroma cells, CFU-GM, CFU-E, and CFU-mix relative to healthy recipients. Taken together, our findings demonstrate that iron overload might alter the number of red blood cells after transplantation in mice by destroying the BM microenvironment, thereby affecting the recovery of BM hematopoietic function.

Autologous blood transfusion stimulates wound healing in diabetic mice through activation of the HIF-1α pathway by improving the blood preservation solution.

Transfusion of autologous blood is a timesaving, convenient, safe, and effective therapy from a clinical perspective, and often employed for the treatment of diabetic patients. Stabilization of HIF-1α has been widely reported to be a critical factor in the improvement of wound healing in diabetes. Therefore, our study reveals the roles of improved autologous blood in wound healing in diabetes, through autologous blood transfusion in a mouse model. Initially, BALB/c mice were subjected to streptozotocin for diabetic mouse model establishment. Diabetic mice were transfused with improved or standard autologous blood in perfusion culture system. Roles of improved autologous blood in mediating HIF-1α pathway were determined by measuring expression of VEGF, EGF, HIF-1α, and HSP-90. In order to assess the detailed regulatory mechanism of improved autologous blood in perspective of wound healing, cell proliferation, migration and cell cycle, fibroblasts isolated from diabetic mice were transfected with HIF-1α siRNA. Mice transfused with improved autologous blood exhibited increased levels of CD31 and α-SMA in skin tissues, and reduced TNF-α, IL-1ß, and IL-6 levels, indicating that improved autologous blood promoted wound healing ability and reduced the release of inflammatory factors. Diabetic mice transfused with improved autologous blood presented activated HIF-1α pathway. The survival rate, proliferation, and migration of fibroblasts were elevated via activation of the HIF-1α pathway. Taken together, improved blood preservation solution could enhance the oxygen carrying capacity of red blood cells and wound healing in mice with diabetes, which is achieved through regulation of HIF-1α pathway.

lncRNA MALAT1 Accelerates Wound Healing of Diabetic Mice Transfused with Modified Autologous Blood via the HIF-1α Signaling Pathway.

Impaired wound healing is a debilitating complication of diabetes. The long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been recognized to be differentially expressed in various diseases. However, its underlying mechanism in diabetes has not been fully understood. Notably, we aim to examine the expression of MALAT1 in diabetic mice and its role in wound healing involving the hypoxia-inducible factor-1α (HIF-1α) signaling pathway with a modified autologous blood preservative solution reported. A mouse model of diabetes was established. MALAT1 was identified to promote the activation of the HIF-1α signaling pathway and to be enriched in autologous blood through modified preservation, which might facilitate the improvement of physiological function of blood cells. Through gain- or loss-of-function approaches, viability of fibroblasts cultured in high glucose, wound healing of mice, and collagen expression in wound areas were enhanced by MALAT1 and HIF-1α. Taken together, the present study demonstrated that the physiological status of mouse blood was effectively improved by modified autologous blood preservation, which exhibited upregulated MALAT1, thereby accelerating the fibroblast activation and wound healing in diabetic mice via the activation of the HIF-1α signaling pathway. The upregulation of MALAT1 activating the HIF-1α signaling pathway provides a novel insight into drug targets against diabetes.

Autologous blood transfusion augments impaired wound healing in diabetic mice by enhancing lncRNA H19 expression via the HIF-1α signaling pathway.

BACKGROUND: Impaired wound healing frequently occurs in diabetes mellitus (DM) and is implicated in impaired angiogenesis. Long non-coding RNA (lncRNA) H19 has been reported as being reduced in DM and played a critical role in inducing angiogenesis. Thus, we hypothesized that H19 may affect impaired wound healing in streptozotocin (STZ)-induced diabetic mice transfused with autologous blood preserved in standard preservative fluid or modified preservative fluid. METHODS: Fibroblasts in injured skin were isolated and cultured in vitro. After location of H19 in fibroblasts using fluorescence in situ hybridization (FISH), RNA-pull down, RNA immunoprecipitation (RIP), chromatin immunoprecipitation (ChIP), Co immunoprecipitation (COIP) and dual luciferase reporter gene assay were used to verify the binding of H19 to HIF-1α. RESULTS: The modified preservative fluid preserved autologous blood increased the H19 expression in fibroblasts, and maintained better oxygen-carrying and oxygen release capacities as well as coagulation function. Furthermore, H19 promoted HIF-1α histone H3K4me3 methylation and increased HIF-1α expression by recruiting EZH2. H19 promoted fibroblast activation by activating HIF-1α signaling pathway in fibroblasts and enhanced wound healing in diabetic mice. CONCLUSIONS: Taken together, H19 accelerated fibroblast activation by recruiting EZH2-mediated histone methylation and modulating the HIF-1α signaling pathway, whereby augmenting the process of modified preservative fluid preserved autologous blood enhancing the postoperative wound healing in diabetic mice.

The relationship between internet-gaming experience and executive functions measured by virtual environment compared with conventional laboratory multitasks.

The aim of this study was to investigate if individuals with frequent internet gaming (IG) experience exhibited better or worse multitasking ability compared with those with infrequent IG experience. The individuals' multitasking abilities were measured using virtual environment multitasks, such as Edinburgh Virtual Errands Test (EVET), and conventional laboratory multitasks, such as the dual task and task switching. Seventy-two young healthy college students participated in this study. They were split into two groups based on the time spent on playing online games, as evaluated using the Internet Use Questionnaire. Each participant performed EVET, dual-task, and task-switching paradigms on a computer. The current results showed that the frequent IG group performed better on EVET compared with the infrequent IG group, but their performance on the dual-task and task-switching paradigms did not differ significantly. The results suggest that the frequent IG group exhibited better multitasking efficacy if measured using a more ecologically valid task, but not when measured using a conventional laboratory multitasking task. The differences in terms of the subcomponents of executive function measured by these task paradigms were discussed. The current results show the importance of the task effect while evaluating frequent internet gamers' multitasking ability.

Omega-3 free fatty acids attenuate insulin-promoted breast cancer cell proliferation.

High insulin levels in obese people are considered as a risk factor to induce breast carcinogenesis. And consumption of fish oils which mainly contain omega-3 fatty acids is associated with a reduced risk of breast cancer. However, whether omega-3 free fatty acids (FFAs) modulate insulin signaling pathway to prevent breast cancer is poorly understood. The current study tested the hypothesis that omega-3 FFAs attenuate insulin-induced breast cancer cell proliferation and regulate insulin signaling pathway. We show here that omega-3 FFAs attenuate MCF-7 cell proliferation and Akt and Erk1/2 phosphorylation levels stimulated by insulin. Knockdown Shp2 by siRNA resulted in significantly elevated omega-3 FFAs-activated Akt phosphorylation but failed to change insulin-stimulated Akt and Erk1/2 phosphorylation. And viable cell number was not affected by either downregulation of Shp2 expression or Erk1/2 inhibitor U0126 treatment. These observations indicated that omega-3 FFAs attenuate insulin-promoted breast cancer cell proliferation and insulin-activated Akt phosphorylation.