The role of the sensory input intervention in recovery of the motor function in hypoxic ischemic encephalopathy rat model.

Motor disturbances predominantly characterize hypoxic-ischemic encephalopathy (HIE). Among its intervention methods, environmental enrichment (EE) is strictly considered a form of sensory intervention. However, limited research uses EE as a single sensory input intervention to validate outcomes postintervention. A Sprague-Dawley rat model subjected to left common carotid artery ligation and exposure to oxygen-hypoxic conditions is used in this study. EE was achieved by enhancing the recreational and stress-relief items within the cage, increasing the duration of sunlight, colorful items exposure, and introducing background music. JZL184 (JZL) was administered as neuroprotective drugs. EE was performed 21 days postoperatively and the rats were randomly assigned to the standard environment and EE groups, the two groups were redivided into control, JZL, and vehicle injection subgroups. The Western blotting and behavior test indicated that EE and JZL injections were efficacious in promoting cognitive function in rats following HIE. In addition, the motor function performance in the EE-alone intervention group and the JZL-alone group after HIE was significantly improved compared with the control group. The combined EE and JZL intervention group exhibited even more pronounced improvements in these performances. EE may enhance motor function through sensory input different from the direct neuroprotective effect of pharmacological treatment.NEW & NOTEWORTHY Rarely does literature assess motor function, even though it is common after hypoxia ischemic encephalopathy (HIE). Previously used environmental enrichment (EE) components have not been solely used as sensory inputs. Physical factors were minimized in our study to observe the effects of purely sensory inputs.

A cellular senescence-related genes model allows for prognosis and treatment stratification of cervical cancer: a bioinformatics analysis and external verification.

BACKGROUND: Cervical cancer (CC) is highly lethal and aggressive with an increasing trend of mortality for females. Molecular characterization-based methods hold great promise for improving the diagnostic accuracy and for predicting treatment response. METHODS: The mRNAs expression data of CC patients and cellular senescence-related genes were obtained from the Cancer Genome Atlas (TCGA) and CellAge databases, respectively. Differentially expressed genes (DEGs) of senescence related genes between tumor and normal tissues were used for Least absolute shrinkage and selection operator (LASSO) regression to construct a prognostic model. Univariate and LASSO regression analyses were applied to establish a predictive nomogram. The performance of the nomogram were evaluated by Kaplan-Meier curve, receiver operating characteristic (ROC), Harrell's concordance index (C-index), and calibration curve. GSE44001 and GSE52903 were used for external validation. RESULTS: We established a cellular senescence-related genes-based stratified model, and a multivariable-based nomogram, which could accurately predict the prognosis of CC patients in the TCGA database. The Kaplan-Meier curve indicated that patients in the low-risk group had considerably better overall survival (OS, P =2.021e-05). The area under the ROC curve (AUC) of this model was 0.743 for OS. Multivariate analysis found that the 6-gene risk signature (HR=3.166, 95%CI: 1.660-6.041, P<0.001) was an independent risk factor for CC patients. We then designed an OS-associated nomogram that included the risk signature and clinicopathological factors. The AUC reached 0.860 for predicting 5-year OS. The nomogram showed excellent consistency between the predictions and actual survival observations. Two external GEO validations were corresponding to the gene expression pattern in TCGA. CONCLUSIONS: Our results suggested a six-senescence related signature and established a prognostic nomogram that reliably predicted the overall survival for CC. These findings may be beneficial to personalized treatment and medical decision-making.

Assessment of causal association between differentiated thyroid cancer and disordered serum lipid profile: a Mendelian randomization study.

Background: Research has shown that the disordered serum lipid profile may be associated with the risk of differentiated thyroid cancer (DTC). Whether this association reflect causal effect is still unclear. The aim of this study was to evaluate the causality of circulating lipoprotein lipids on DTC. Methods: Mendelian randomization (MR) analysis was conducted to evaluate the relationship between the circulating lipoprotein lipids and DTC risk using single-nucleotide polymorphisms (SNPs) from a genome-wide association (GWA) study containing a high-incidence Italian population of 690 cases samples with DTC and 497 controls. Results: Univariate and multivariate mendelian randomization analysis demonstrated that 'total cholesterol', 'HDL cholesterol', 'apolipoprotein B' and 'ratio of apolipoprotein B to apolipoprotein A1' were correlated with DTC. According to sensitivity analysis, our results were reliable. Furthermore, multivariate analysis revealed that there is no causative association between DTC and any of the many cause factors when they interact with one another, suggesting that there was a deep interaction between the four factors, which could affect each other. Finally, the mechanism of the related effects each other as well as the target genes with significant SNP regulatory effects in DTC was explored by conducting functional enrichment analysis and constructing the regulatory networks. Conclusions: We obtained four exposure factors (total cholesterol, HDL cholesterol, apolipoprotein B and ratio of apolipoprotein B to apolipoprotein A1) closely related to DTC, which laid a theoretical foundation for the treatment of DTC.

Non-antibiotic strategies for prevention and treatment of internalized Staphylococcus aureus.

Staphylococcus aureus (S. aureus) infections are often difficult to cure completely. One of the main reasons for this difficulty is that S. aureus can be internalized into cells after infecting tissue. Because conventional antibiotics and immune cells have difficulty entering cells, the bacteria can survive long enough to cause recurrent infections, which poses a serious burden in healthcare settings because repeated infections drastically increase treatment costs. Therefore, preventing and treating S. aureus internalization is becoming a research hotspot. S. aureus internalization can essentially be divided into three phases: (1) S. aureus binds to the extracellular matrix (ECM), (2) fibronectin (Fn) receptors mediate S. aureus internalization into cells, and (3) intracellular S. aureus and persistence into cells. Different phases require different treatments. Many studies have reported on different treatments at different phases of bacterial infection. In the first and second phases, the latest research results show that the cell wall-anchored protein vaccine and some microbial agents can inhibit the adhesion of S. aureus to host cells. In the third phase, nanoparticles, photochemical internalization (PCI), cell-penetrating peptides (CPPs), antimicrobial peptides (AMPs), and bacteriophage therapy can effectively eliminate bacteria from cells. In this paper, the recent progress in the infection process and the prevention and treatment of S. aureus internalization is summarized by reviewing a large number of studies.

Multislice Spiral CT Image Analysis and Meta-Analysis of Inspiratory Muscle Training on Respiratory Muscle Function.

Respiratory muscle function has a significant effect on stroke. Stroke is one of the most common cardiovascular and cerebrovascular diseases in the clinic and has a significant impact on the quality of life of patients. Hemiplegia, cerebral hemorrhage, and even death can occur, mainly in the elderly. In this paper, we meta-analyzed the effect of inspiratory muscle training on respiratory muscle function. In this article, we used a topic search method to search for relevant literature on respiratory muscle training and obtained 58 and 32 literature studies from CNKI and Wanfang Data, respectively. As a result of the screening, 36 and 28 documents were obtained. In this paper, 64 selected articles were studied. The authors make statistics on the literature of designing serum content index and multislice spiral CT (Member of the Society of Cardiological Technicians) image of patients, so as to analyze the influence of CT image and inspiratory muscle training on respiratory muscle function. The study showed that FVC, FEV1, MIP, and diaphragm mobility of the experimental group were significantly improved after treatment in more than 85% of the studies (P < 0.05), while those of the control group were not significantly improved (P > 0.05). The comparison between the two groups after treatment showed that FVC, FEV1, MIP, and diaphragm mobility of the experimental group were higher than those of the control group (P < 0.05). The application of multislice spiral CT image analysis technology can effectively evaluate the effect of inspiratory muscle training on respiratory dysfunction in stroke patients, the mechanism of which regulates the expression of related pathways, suppresses the inflammatory response, and can reduce oxidative stress damage. Therefore, respiratory muscle training can improve the function of respiratory muscle and reduce the death rate of cerebellar hemorrhage in patients with stroke and other vascular diseases.

Exposure to mono (2-ethylhexyl) phthalate facilitates apoptosis and pyroptosis of human endometrial microvascular endothelial cells through NLRP3 inflammasome.

Mono (2-ethylhexyl) phthalate (MEHP) is a major metabolite of di (2-ethylhexyl) phthalate (DEHP). This study aimed to observe the toxic effect of MEHP on human endometrial microvascular endothelial cells (HEMECs) and its potential molecular mechanism. HEMECs were exposed to different concentrations of MEHP (0, 50, 100, and 200 nM). Cell viability and apoptosis were assessed by cell counting kit-8 (CCK-8) and flow cytometry assays. Western blot was performed to examine the expression of apoptosis-related proteins (Bcl-2, Bax, and Caspase-3). Moreover, the expression of pyroptosis-related Caspase-1 was detected by western blot and immunofluorescence assays. Lactate dehydrogenase (LDH) release levels were evaluated in HEMECs treated with MEHP and/or Caspase-1 inhibitor Ac-YVAD-CHO. After exposure to MEHP, NLRP3 expression was examined by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot. LDH release and apoptosis levels were tested in HEMECs induced by MEHP and/or siNLRP3. MEHP significantly induced cell viability and inhibited apoptosis for HEMECs, with a concentration-dependent manner. Furthermore, Bcl-2/Bax ratio was distinctly reduced and Caspase-3 expression was increased in HEMECs after exposure to MEHP. Western blot and immunofluorescence results confirmed that MEHP markedly augmented Caspase-1 expression in HEMECs. Furthermore, LDH release levels were fortified in HEMECs treated with MEHP, which were improved following cotreatment with Ac-YVAD-CHO. At the mRNA and protein levels, NLRP3 expression was prominently increased in HEMECs exposed to MEHP. NLRP3 knockdown markedly ameliorated the increase in LDH release and apoptosis induced by MEHP exposure in HEMECs. Our findings suggested that exposure to MEHP facilitates apoptosis and pyroptosis of HEMECs through NLRP3 inflammasome.

Synthesis of Surface-Modification-Oriented Nanosized Molybdenum Disulfide with High Peroxidase-Like Catalytic Activity for H2 O2 and Cholesterol Detection.

Abnormal H2 O2 and cholesterol levels are closely related to many diseases. This work reports a facile process for the synthesis of oxidized glutathione (GSSG)-modified MoS2 nanosheets (MoS2 -GSSG NSs). The biocompatible MoS2 -GSSG NSs have good dispersibility and high affinity to the substrate 3,3',5,5'-tetramethylbenzidine (TMB), which is beneficial for improving peroxidase-like catalytic activity of MoS2 . The high peroxidase-like activity of MoS2 -GSSG NSs was applied as a robust nanoplatform for low-cost, rapid, and highly effective colorimetric detection of H2 O2 and total/free cholesterol. Moreover, the peroxidase-like catalytic mechanism was studied by the steady-state kinetics method. The catalytic activity was remarkably high at a wide range of pH (2.4-7.0) and temperature values (25-70 °C). The cholesterol was catalyzed by cholesterol oxidase (ChOx) in the presence of O2 to generate H2 O2 , which oxidized TMB to generate a blue-colored product (oxTMB) under the catalysis of MoS2 -GSSG NSs. The detection limit (DL) of total cholesterol and H2 O2 was as low as 5.36 and 0.51 µm, respectively. The linear ranges for detecting cholesterol and H2 O2 were from 5.36 to 800 µm and from 0.51 to 50 µm, respectively. This method was also successfully applied to the detection of cholesterol in serum. The detection concentration of total cholesterol was consistent with that of the value detected by the blood biochemical method used in the clinic.

Protective effects of Zhuyeqing liquor on the immune function of normal and immunosuppressed mice in vivo.

BACKGROUND: Zhuyeqing Liquor (ZYQL), a well-known Chinese traditional health liquor, has various biological properties, including anti-oxidant, anti-inflammatory, immunoenhancement and cardiovascular protective effects. METHODS: The protective effects of Zhuyeqing Liquor (ZYQL) on the immune function was investigated in vivo in normal healthy mice and immunosuppressed mice treated with Cyclophosphamide (Cy, 100 mg/kg) by intraperitoneal injection on days 4, 8 and 12. ZYQL (100, 200 and 400 mg/kg) was administered via gavage daily for 14 days. The phagocytotic function of mononuclear phagocytic system was detected with carbon clearance methods, the levels of interleukin-6 (IL-6) and interferon-gamma (IFN-γ) in serum were detected with Enzyme linked immunosorbent assay (ELISA). Immune organs were weighed and organ indexes (organ weight/body weight) of thymus and spleen were calculated. Meanwhile, the activity of lysozyme (LSZ) in serum and the activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) in spleen tissue were measured. RESULTS: ZYQL significantly upgrades the K value for clearance of carbon particles in normal mice treated with ZYQL (400 mg/kg) and immunosuppressed mice treated with ZYQL (100, 200 and 400 mg/kg) together with Cy (100 mg/kg) in vivo. The treatment of ZYQL (100, 200 and 400 mg/kg) effectively increased the activity of serum lysozyme as well as promoted the serum levels of IL-6 and IFN-γ in normal mice and immunosuppressed mice. Furthermore, ZYQL (100, 200 and 400 mg/kg) had an antioxidant effects in immune system by enhancing the antioxidant enzyme activity of SOD, CAT and GSH-Px in vivo. In addition, ZYQL (100, 200 and 400 mg/kg) effectively elevated the Cy-induced decreased organ index (thymus and spleen). CONCLUSIONS: The present work shows that the dose-dependent administration of ZYQL is capable of influencing immune responses, which implying that its valuable functional health may be attributed partly to its protective effects for the immune function.

Patterned magnetic rings fabricated by dewetting of polymer-coated magnetite nanoparticles solution.

Here we present a simple and controlled method for direct fabrication of ordered 2D arrays of magnetic rings. This method utilizes polystyrene-coated magnetite nanoparticles as a solution, and the magnetic rings are fabricated on patterned self-assembled monolayers by dewetting of the solution. Polystyrene-coated magnetite nanoparticles were synthesized by atom-transfer radical polymerization, which promoted the dispersibility and stability of magnetite nanoparticles in chloroform. Magnetic rings were studied using optical photograph, SEM, and magnetic force microscopy. This approach offers a new way for patterning nanoparticulate rings with deliberate control over feature composition, size, as well as interfeature distance.