Transplantation of fibrin-thrombin encapsulated human induced neural stem cells promotes functional recovery of spinal cord injury rats through modulation of the microenvironment

Recent studies have mostly focused on engraftment of cells at the lesioned spinal cord,with the expectation that differentiated neurons facilitate recovery.Only a few studies have attempted to use transplanted cells and/or biomaterials as major modulators of the spinal cord injury microenvironment.Here,we aimed to investigate the role of microenvironment modulation by cell graft on functional recovery after spinal cord injury.Induced neural stem cells reprogrammed from human peripheral blood mononuclear cells,and/or thrombin plus fibrinogen,were transplanted into the lesion site of an immunosuppressed rat spinal cord injury model.Basso,Beattie and Bresnahan score,electrophysiological function,and immunofluorescence/histological analyses showed that transplantation facilitates motor and electrophysiological function,reduces lesion volume,and promotes axonal neurofilament expression at the lesion core.Examination of the graft and niche components revealed that although the graft only survived for a relatively short period(up to 15 days),it still had a crucial impact on the microenvironment.Altogether,induced neural stem cells and human fibrin reduced the number of infiltrated immune cells,biased microglia towards a regenerative M2 phenotype,and changed the cytokine expression profile at the lesion site.Graft-induced changes of the microenvironment during the acute and subacute stages might have disrupted the inflammatory cascade chain reactions,which may have exerted a long-term impact on the functional recovery of spinal cord injury rats.

Dietary Modulation of Glucagon-like Peptide 1 Secretion:insights and innovations

Glucagon-like peptide-1(GLP-1),a signal peptide hormone produced by enteroendocrine L cells from the distal small intestine and colon,is a crucial regulator of glycemic control,gastric emptying,satiety,and body weight.Recent advancements in understanding the dietary modulation of GLP-1 through enteroendocrine L-cells have highlighted the potential of various nutrients in enhancing its endogenous secretion.This review summarizes the current knowledge on food-derived molecules,including macronutrients,polyphenols,other chemicals,and bacterial products,that can modulate GLP-1 production.It explores the efficacy and impact of various treatments and the involved signaling pathways,aiming to contribute to developing innovative strategies for enhancing endogenous GLP-1 release.

Incidence and Associated Factors for Single and Recurrent Falls among the Elderly in an Urban Community of Beijing

Objective To investigate the incidence of falls and recurrent falls, and explore associated factors for single and recurrent falls among urban community-dwelling elderly in Beijing. Methods A cross-sectional study was conducted in 472 elderly in the Longtan community of Dongcheng district, Beijing in 2009. Data regarding the incidence of fall and recurrent falls in the previous year, as well as associated factors were collected from the elderly through face-to-face interviews. Results The incidence of falls and recurrent falls was 17.8% and 6.1%, respectively, and it increased with age （X^2for trend=21.06, 19.20, P=0.001, 0.002）. Binary logistic stepwise regression analysis showed that age （OR=2.20）, living alone （OR=4.67） and gait disturbance （OR=1.27） were risk factors, while housing with elevators （OR=0.35）, appropriate width/height of stair steps （0R=0.78）, sufficient lighting for stairway （OR=0.45） and regular exercise （OR=0.12） could lower the risk for single fall; factors such as low monthly family income （OR=1.39）, poor vision （OR=1.83）, low physical ability （OR=4.47）, abnormal static balance （OR=2.48）, and fear of falls（OR=2.23） were risk factors, while appropriate width/height of stair steps （OR=0.49） and easiness of access to daily supplies （OR=0.41） were protective factors for recurrent falls. Conclusion The incidence of falls in commun and their related injuries have been associated ty-dwelling elderly people in Beijing is common, and falls with both intrinsic and extrinsic factors.

Role of PERK/eIF2α/CHOP Endoplasmic Reticulum Stress Pathway in Oxidized Low-density Lipoprotein Mediated Induction of Endothelial Apoptosis

Objective PERK/elF2/CHOP is a major signaling pathway mediating endoplasmic reticulum （ER） stress related with atherosclerosis. Oxidized LDL （ox-LDL） also induces endothelial apoptosis and plays a vital role in the initiation and progression of atherosclerosis. The present study was conducted to explore the regulatory effect of ox-LDL on PERK/elF2a/CHOP signaling pathway in vascular endothelial cells. Methods The effects of ox-LDL on PERK and p-elF2a protein expression of primary human umbilical vein endothelial cells （HUVECs） were investigated by Western blot analysis. PERK gene silencing and selective elF2a phosphatase inhibitor, salubrinal were used to inhibit the process of ox-LDL induced endothelial cell apoptosis, caspase-3 activity, and CHOP mRNA level. Results Ox-LDL treatment significantly increased the expression of PERK, PERK-mediated inactivation of elF2a phosphorylation, and the expression of CHOP, as well as the caspase-3 activity and apoptosis. The effects of ox-LDL were markedly decreased by knocking down PERK with stable transduction of lentiviral shRNA or by selective elF2a phosphatase inhibitor, salubrinal. Conclusion This study provides the first evidence that ox-LDL induces apoptosis in vascular endothelial cells mediated largely via the PERK/elF2a/CHOP ER-stress pathway. It adds new insights into the molecular mechanisms underlying the pathogenesis and progression of atherosclerosis.

Anti-parkinsonian effects of octacosanol in 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-treated mice

Our previous research showed that octacosanol exerted its protective effects in 6-hydroxydopamine-induced Parkinsonian rats. The goal of this study was to investigate whether octacosanol would attenuate neurotoxicity in 1-methyl-4-phenyl-l,2,3,6 tetrahydropyridine （MPTP）-treated C57BL/6N mice and its potential mechanism. Behavioral tests, tyrosine hydroxylase immunohistochemistry and western blot were used to investigate the effects of octacosanol in a mouse model of Parkinson＇s disease. Oral administration of octacosanol （100 mg/kg） significantly improved behavioral impairments Jn mice treated by MPTP and markedly ameliorated morphological appearances of tyrosine hydroxylase-positive neuronal cells in the substantia nigra. Furthermore, octacosanol blocked MPTP-induced phosphorylation of p38MAPK and JNK, but not ERK1/2. These findings implicated that the protective effects afforded by octacosanol might be mediated by blocking the phosphorylation of p38MAPK and JNK on the signa transduction in vivo. Considering its excellent tolerability, octacosanol might be considered as a candidate agent for clinical application in treating Parkinson＇s disease.

Association between single nucleotide polymorphisms on chromosome 17q and the risk of prostate cancer in a Chinese population

In European populations,7 single nucleotide polymorphisms(SNPs) on chromosome 17q,3 SNPs on 17q12,and 4 SNPs on 17q24.3 were recently identified to be closely related to the risk of prostate cancer by a genome-wide association study.In Japanese populations,the correlation between 2 SNPs on 17q and the risk of prostate cancer and tumor aggressiveness was also confirmed by a large-scale experiment.However,whether 17q is associated with prostate cancer and its clinical manifestations in Chinese populations is still unknown.Therefore,we conducted a case-control study in a northern Chinese population and tested 2 SNPs,rs4430796 and rs1859962,on 17q in 124 prostate cancer patients and 111 controls using polymerase chain reaction-high resolution melting curve(PCR-HRM) combined with sequencing.We analyzed the association of the 2 SNPs with the risk of prostate cancer as well as patients' lifestyles,onset ages,Gleason scores,PSA levels,and pathologic stages.We found a significant difference in the G allele of SNP rs1859962(P = 0.035,OR = 1.51,95% CI = 1.03-2.21) but not in the rs4430796 genotype frequency or allele frequency distribution between prostate cancer patients and the controls(P > 0.05).Neither of the SNPs was significantly associated with the onset age,Gleason score,PSA level,pathologic stage,or other clinical indicators of patients with prostate cancer(P > 0.05).Our results show that polymorphism of the G allele of SNP rs1859962 is associated with the risk of prostate cancer in a Chinese population.

Adiponectin receptor 1 and small ubiquitin-like modifier 4 polymorphisms are associated with risk of coronary artery disease without diabetes

编码 adiponectin 受体 1 的基因( ADIPOR1 )和小象ubiquitin一样修饰词( SUMO4 ) 4 被连接了到 anti-atherogenic 效果，但是很少对是否被知道在二基因的多型性，独立行动或交往，没有 diabetes.MethodsWe genotyped ，影响冠的动脉疾病( CAD )的风险没有糖尿病的 200 个 CAD 病人和没有 CAD 的 200 控制，它被选择基于前一个没有 diabetes.ResultsRisk 等位基因，协会也是的潜力在 ADIPOR1 (rs7539542-G， rs7514221-C 和 rs3737884-G ) 在三 SNP 在这些 SNP 和 CAD 的临床的特征之间探索了，没有糖尿病，在在 SUMO4 的 SNP rs237025 的 G 等位基因显著地增加了 CAD 的风险，与从 1.79 ～ 4.44 的 ORs。任何这四风险等位基因的搬运人出现了类似不利 ? 临床的特征。与有 CC 或 GC 遗传型的个人相比，有在 rs3737884 的 GG 遗传型的那些在影响了左前面的下降冠的动脉的 CAD 的显著地更高的风险(或：6.77， P = 0.009 ) ，恰好冠的动脉(或：4.81， P = 0.028 ) 或容器的一个相对大的数字(P = 0.04 ) 。没有糖尿病，在 SUMO4 在 SNP 象风险等位基因一样在 ADIPOR1 在三 SNP 中的至少一个带风险等位基因的个人比不带任何风险等位基因的个人在 CAD 的显著地更高的风险(或：5.82， 95% CI：1.2327.7， P = 0.013 ) 没有糖尿病，在 ADIPOR1 和 SUMO4 的 .ConclusionsSNPs 与 CAD 的提高的风险被联系，并且在二基因的 SNP 可以交往联合影响疾病风险。

cDNA cloning, prokaryotic expression and purification of rat α-synudein

Objective To clone the cDNA of rat α-Syn gene, investigate its prokaryotic expression and produce purified recombinant rat α-Syn protein. Methods Rat α-Syn cDNA was amplified from the rat brain total RNA by RT-PCR and was cloned into pGEX-4T-1, a prokaryotic expressing vector. The recombinant plasmid containing rat α-Syn gene was transformed into E. Coli BL21 to express a fusion protein with rat α-Syn protein tagged by glutathione-S-transferase (GST). The fusion protein was then cleaved by thrombin during passing through the GST-agarose 4B column to release the recombinant rat α-Syn protein. The recombinant rat α-Syn protein was further purified using Superdex S200 gel filtration. Results DNA sequencing confirmed that the cloned cDNA contained 420 base pairs encoding 140 amino acids, which was identical to the reported amino acid sequence of rat α-Syn. After transformation, the recombinant plasmid pGEX-ra-Syn expressed a soluble protein that was inducible by IPTG. The purified recombinant protein was shown to be single band on SDS-PAGE, with a molecular size of around 18000, which was identical to the reported molecular size of rat α-Syn. Western blot analysis demonstrated that the recombinant protein was recognized by specific antibody against α-Syn. Conclusion The rat α-Syn gene was successfully expressed in prokaryotic expression system and highly purified rat α-Syn recombinant protein was produced.

Central sensibility of human cases with different body mass during oral glucose tolerance test using functional magnetic resonance imaging

BACKGROUND： Because of the limitation of technique, there are few researches on regulating function o central hypothalamus by metabolism, especially the researches on real-time function. OBJECTIVE： To evaluate the response of hypothalamus to oral glucose tolerance test （OGTT） in differen body-weighted subjects by using functional magnetic resonance imaging （fMRI） so as to investigate th relationship between the sensitivity of hypothalamus in glycoregulation and disturbance of carbohydrate metabolism. DESIGN： Paired design. SETTING： Department of Radiology and Beijing Geriatrics Institute, Beijing Hospital, National Publi Health Bureau. PARTICIPANTS： A total of twenty healthy volunteers were selected from Beijing Geriatrics Institute National Public Health Bureau, including 10 subjects with obesity （5 males and 5 females; body mass 〉 28.0 kg/m2） and 10 subjects with normal body mass （5 males and 5 females; body mass from 18.5 to 23.9 kg/m2）. All subjects gave written informed consent before participating in the study. METHODS： fMRI study was performed on GE 1.5 T Signa Twinspeed Infinity with Excite. Each voluntee was ingested of glucose during the fMRI scan. T2＊ images were acquired using a single-shot gradient echo （EPI） technique. The parameters of EPI included： TR 3 000 ms, TE 40 ms, Flip angle 90°, field of view （FOV） 24 cm × 24 cm, thickness 5 mm, gap 0 mm, matrix 64 × 64, number of excitation 1. All 10 subjects with normal body mass underwent a repeat fMRI scan after consuming an equivalent amount o water without glucose on a separate day. The procedure for the fMRI scan with water intake was the same a for glucose ingestion. fMRI data were processed with Intensity Averaging Method. MAIN OUTCOME MEASURES： The central response of hypothalamus and feedback orientation during OGTT in different body-weighted subjects. RESULTS： An acute transient decrease of fMRI intensity in posterior inferior and anterior inferior o hypothalamus was observed in all subjects within 2 minutes after oral glucose intake. This decrease wa followed by a recovery to the baseline. However, obese subjects had a delayed intensity decrease [（1.96± 1.06） minutes vs. （1.04±0.71） minutes, t =2.14, P 〈 0.05] and longer recovery time [（26.62±7.35 minutes vs. （16.29±6.42） minutes, t =3.67, P 〈 0.01] as compared with normal body-weight subjects Furthermore, decreased fMRI intensity was significant different from baseline intensity [（5.7±2.5）% vs （14.3±5.5）%, t =2.56, P 〈 0.05] in obese subjects, but not in normal body-weight subjects. The area o hypothalamus in normal body-weight volunteers demonstrated no significant signal change before and afte oral water ingestion （P 〉 0.05）. CONCLUSION： Hypothalamus response to glucose loading is different in normal body-weighted and obes subjects. This suggests that fMRI is a useful tool to evaluate the central regulation of glucose metabolism.

Some Pathological Knowledge Discovered in Large Database of Type 2 Diabetes

Taking the advantage of the nearly 14 000 items of muhi-source, multi-dimension practical dataset of type 2 diabetes, and a series of data mining experiments are designed to seek for important type 2 diabetes risk factors and their relationships with blood glucose. The valuable pathological knowledge includes, the deci- sion tree is almost identical with the list of clinical diabetic risk factors; 9 items important risk factors of type 2 diabetes were found, and the relationship between the main risk factors and the blood glucose, and the feature of critical value of the risk factors were given too in this paper. These valuable results are good to the cure and macro-control type 2 diabetes.

Mechanisms of microRNA 200a in Hepatic Insulin Resistance by Interleukin-6

Aim To explore the mechanisms of microRNA 200a in hepatic insulin resistance induced by interleukin-6(IL-6),specifically to in-vestigate the role of microRNA 200a in hepatic glucogen and insulin signal pathway transduction.Methods The cell model forhepatic insulin resistance was induced by IL-6(10μg/L) for 24 hours in NCTC1469 cell.The level of glucogen was reduced.The expression of microRNA 200a was tested by q-PCR.The level of glucogen was quantified in NCTC 1469 transfected with microRNA200a mimics.The target gene of microRNA200a was predicted by bio-information software.The protein level of the target gene wastested by Western Blotting.Results The level of glucogen and the insulin signal pathway was inhibited in NCTC 1469 cells treated by IL-6.The expression of microRNA 200a was decreased in NCTC 1469 cell induced by IL-6.The level of glucogen and theinsulin signal pathway were stimulated in NCTC 1469 cell transfected by microRNA 200a mimics.The protein level of Pten was decreased by overexpression of microRNA200a.Conclusions IL-6 downregulates the expression of microRNA200a in hepatic insulin resistant NCTC 1469 cells.The microRNA 200a stimulates biosynthesis of glucogen as well as insulin signal pathway accompanied by down-regulating the expression of Pten.

Increased systemic RNA oxidative damage and diagnostic value of RNA oxidative metabolites during Shigella flexneri-induced intestinal infection

BACKGROUND Shigella flexneri(S.flexneri)is a major pathogen causing acute intestinal infection,but the systematic oxidative damage incurred during the course of infection has not been investigated.AIM To investigate the incurred systemic RNA oxidative damage and the diagnostic value of RNA oxidative metabolites during S.flexneri-induced intestinal infection.METHODS In this study,a Sprague-Dawley rat model of acute intestinal infection was established by oral gavage with S.flexneri strains.The changes in white blood cells(WBCs)and cytokine levels in blood and the inflammatory response in the colon were investigated.We also detected the RNA and DNA oxidation in urine and tissues.RESULTS S.flexneri infection induced an increase in WBCs,C-reactive protein,interleukin(IL)-6,IL-10,IL-1β,IL-4,IL-17a,IL-10,and tumor necrosis factorα(TNF-α)in blood.Of note,a significant increase in urinary 8-oxo-7,8-dihydroguanosine(8-oxo-Gsn),an important marker of total RNA oxidation,was detected after intestinal infection(P=0.03).The urinary 8-oxo-Gsn level returned to the baseline level after recovery from infection.In addition,the results of a correlation analysis showed that urinary 8-oxo-Gsn was positively correlated with the WBC count and the cytokines IL-6,TNF-α,IL-10,IL-1β,and IL-17α.Further detection of the oxidation in different tissues showed that S.flexneri infection induced RNA oxidative damage in the colon,ileum,liver,spleen,and brain.CONCLUSION Acute infection induced by S.flexneri causes increased RNA oxidative damage in various tissues(liver,spleen,and brain)and an increase of 8-oxo-Gsn,a urinary metabolite.Urinary 8-oxo-Gsn may be useful as a biomarker for evaluating the severity and prognosis of infection.

Clinical features and risk factors of severely and critically ill patients with COVID-19

BACKGROUND As of June 1,2020,over 370000 coronavirus disease 2019(COVID-19)deaths have been reported to the World Health Organization.However,the risk factors for patients with moderate-to-severe or severe-to-critical COVID-19 remain unclear.AIM To explore the characteristics and predictive markers of severely and critically ill patients with COVID-19.METHODS A retrospective study was conducted at the B11 Zhongfaxincheng campus and E1-3 Guanggu campus of Tongji Hospital affiliated with Huazhong University of Science and Technology in Wuhan.Patients with COVID-19 admitted from 1st February 2020 to 8th March 2020 were enrolled and categorized into 3 groups:The moderate group,severe group and critically ill group.Epidemiological data,demographic data,clinical symptoms and outcomes,complications,laboratory tests and radiographic examinations were collected retrospectively from the hospital information system and then compared between groups.RESULTS A total of 126 patients were enrolled.There were 59 in the moderate group,49 in the severe group,and 18 in the critically ill group.Multivariate logistic regression analysis showed that age[odd ratio(OR)=1.055,95%(confidence interval)CI:1.099-1.104],elevated neutrophil-to-lymphocyte ratios(OR=4.019,95%CI:1.045-15.467)and elevated high-sensitivity cardiac troponin I(OR=10.126,95%CI:1.088-94.247)were high-risk factors.CONCLUSION The following indicators can help clinicians identify patients with severe COVID-19 at an early stage:age,an elevated neutrophil-to-lymphocyte ratio and high sensitivity cardiac troponin I.

LINK BETWEEN OXIDATIVE STRESS AND INSULIN RESISTANCE

Many studies on oxidative stress,insulin resistance,and antioxidant treatment have shown that increased oxidative stress may accelerate the development of diabetic complications through the excessive glucose and free fatty acids metabolism in diabetic and insulin-resistant states.Many pathogenic mechanisms such as insulin receptor substrate phosphorylation are involved in insulin resistance induced by oxidative stress.And antioxidant treatments can show benefits in animal models of diabetes mellitus and insulin resistance.However,negative evidence from large clinical trials suggests that new and more powerful antioxidants need to be studied to demonstrate whether antioxidants can be effective in treating diabetic complications.Furthermore,it appears that oxidative stress is only one of the factors contributing to diabetic complications.Thus,antioxidant treatment would most likely be more effective if it were coupled with other treatments for diabetic complications.

APOE and APOC1 gene polymorphisms are associated with cognitive impairment progression in Chinese patients with late-onset Alzheimer's disease

Current evidence shows that apolipoprotein E （APOE）, apolipoprotein CI （APOC1） and low density lipoprotein receptor-related protein （LRP） variations are related to late-onset Alzheimer＇s disease. However, it remains unclear if genetic polymorphisms in these genes are associated with cognitive decline in late-onset Alzheimer＇s disease patients. We performed a 30-month longitudi- nal cohort study to investigate the relationship between Alzheimer＇s disease and APOE, APOC1, and LRP. In this study, 78 Chinese Han patients with late-onset Alzheimer＇s disease were recruit- ed form Guangxi Zhuang Autonomous Region in China. APOE, APOC1, and LRP genotyping was performed using polymerase chain reaction-restriction fragment length polymorphisms. The Mini-Mental State Examination and Clinical Dementia Rating Scale were used to assess pa- tients＇ cognitive function. After a 30-month follow-up period, we found a significant reduction in Mini-Mental State Examination total score, a higher proportion of patients fulfilling cognitive impairment progression criteria, and a higher proportion of APOC1 H2 carriers in APOE 4 carriers compared with non-carriers. In addition, the APOE 4 allele frequency was significantly higher in the cognitive impairment progression group compared with the non-cognitive im- pairment progression group. In conclusion, APOE e4 plays an important role in augmenting cognitive decline, and APOC1 H2 may act synergistically with APOE ~4 in increasing the risk of cognitive decline in Chinese patients with late-onset Alzheimer＇s disease.