Association between serum branched chain amino acids, mammalian target of rapamycin levels and the risk of gestational diabetes mellitus: a 1:1 matched case control study.

BACKGROUND: To investigate the association between serum branched chain amino acids (BCAAs), mammalian target of rapamycin (mTOR) levels and the risk of gestational diabetes mellitus (GDM) in pregnant women. METHODS: 1:1 matched case-control study was conducted including 66 GDM patients and 66 matched healthy pregnant women (± 3 years) in 2019, in China. Fasting bloods of pregnant women were collected in pregnancy at 24 ~ 28 weeks gestation. And the serum levels of valine (Val), leucine (Leu), isoleucine (Ile) and mTOR were determined. Conditional logistic regressions models were used to estimate the associations of BCAAs and mTOR concentrations with the risk of GDM. RESULTS: Concentrations of serum Val and mTOR in cases were significantly higher than that in controls (P < 0.05). After adjusted for the confounded factors, both the second tertile and the third tertile of mTOR increased the risk of GDM (OR = 11.771, 95%CI: 3.949-35.083; OR = 4.869 95%CI: 1.742-13.611, respectively) compared to the first tertile of mTOR. However, the second tertile of serum Val (OR = 0.377, 95%CI:0.149-0.954) and the second tertile of serum Leu (OR = 0.322, 95%CI: 0.129-0.811) decreased the risk of GDM compared to the first tertile of serum Val and Leu, respectively. The restricted cubic spline indicated a significant nonlinear association between the serum levels of mTOR and the risk of GDM (P values for non-linearity = 0.0058). CONCLUSION: We confirmed the association of higher mTOR with the increased risk of GDM in pregnant women. Pregnant women who were in the certain range level of Val and Leu were at lower risk of GDM. Our findings provided epidemiological evidence for the relation of serum BCAAs and mTOR with risk of GDM.

Resistant Dextrin Protects Rats Against Streptozotocin Induced Gestational Diabetes Mellitus via Alteration of TLR4/MyD88/NF-κB Signaling Pathway.

Objective: Gestational diabetes mellitus (GDM) is a metabolic disorder that occurs in 3-5% of pregnancies. The inflammatory response is essential to the development of GDM. Resistant dextrin is a natural fiber and exhibits an antidiabetic effect against diabetes. We investigate resistant dextrin's preventive role and underlying mechanism against STZ-induced GDM. Material and method: Female Wistar rats were utilized, and GDM was induced in pregnant rats using STZ. The levels of glycated hemoglobin (HbA1c), resistin, serum-c-peptide, free fatty acid, antioxidant, hepatic glycogen, lipid, inflammatory cytokines, apoptosis, and inflammatory parameters were estimated. mRNA expression of Toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), nuclear factor kappa B (NF-κB) and NOD-like receptor protein 3 (NLRP3) was estimated. We also estimated the histopathology of pancreatic and liver tissue. Result: Body weight, plasma insulin, fetal body weight, and blood glucose levels were all considerably (P < .001) improved by resistant dextrin, while placental weight and blood sugar levels were also decreased. Resistant dextrin significantly (P < .001) suppressed the levels of HbA1c, resistin, serum-c-peptide, and hepatic glycogen and improved the free fatty acid (FFA) level. Resistant dextrin significantly (P < .001) altered the level of adiponectin, leptin, intercellular Adhesion Molecule 1 (ICAM-1), and visfatin; antioxidant parameters such as malonaldehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione peroxidase (GPx), glutathione S-transferase GST, inflammatory cytokines like tumor necrosis factor- α (TNF-α), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-2 (IL-2), interferon- γ (INF-γ), interleukin-10 (IL-10); apoptosis parameters include Bcl-2, caspase-3, and Bax, respectively. Resistant dextrin significantly (P < .001) suppressed the mRNA expression of NF-κB, MyD88, NLRP3, and TLR4. Resistant dextrin altered the histopathological changes in the pancreas and hepatic tissue. Discussion and Conclusion: In short, resistant dextrin demonstrated a protective effect against STZ-induced GDM by modulating the TLR4/MyD88/NF-κB signaling pathway.

Spatiotemporal distribution, interactions and toxic effect of microorganisms and ARGs/MGEs from the bioreaction tank in hospital sewage treatment facility.

Antibiotic resistance genes (ARGs) can be emitted from wastewater to ambient air and impose unignorable inhalable hazards, which could be exacerbated in antibiotic-concentrated hospital sewage. However, whether the ARG-carrying pathogens are more likely to infect cells remains largely unknown. Here, this study investigated and analyzed the spatiotemporal distribution, interaction, and toxicity of airborne microorganisms and their hosting ARGs in a hospital sewage treatment facility. The average concentration of ARGs/MGEs in sewage of bioreaction tank (BRT-W) was 2.27 × 104 gene copies/L. In the air of bioreaction tank (BRT-A), the average concentration of ARGs/MGEs was 15.86 gene copies/m3. In the four seasons, the ARGs concentration of sewage gradually decreased over time; The concentration of ARGs in the air first decreased and then increased. In spring, the concentration of ARGs/MGEs (qacedelta1-01) in BRT-W was highest (1.05 × 105 gene copies/L); The concentration of ARGs/MGEs (strB) in BRT-A in winter was higher than other seasons (26.18 gene copies/m3). Different from the past, this study also paid attention to the pathogenic potential of ARGs/MGEs in the air. The results of cell experiments showed that the cytotoxicity of drug-resistant Escherichia coli could reach Grade V. This suggested that the longer the drug-resistant E. coli were exposed to cells, the greater the cytotoxicity. Moreover, the cytotoxicity of bacteria increased with the increase in exposure time. In spring, the toxic effect of ARGs/MGEs in sewage of BRT-W was highest. Traceability analysis proved that BRT-W was an essential source of microorganisms and ARGs/MGEs in BRT-A. Furthermore, the combined risk of people exposed to the air of BRT in spring was higher than that in other seasons.

Change characteristics, bacteria host, and spread risks of bioaerosol ARGs/MGEs from different stages in sewage and sludge treatment process.

The spread of antibiotic resistance genes (ARGs) in the atmospheric environment has seriously threatened human health. Wastewater treatment plants (WWTPs) are an important source of aerosol ARGs. A large WWTP, including sewage treatment process (SWP) and sludge treatment process (SDP), was selected in North China for sampling in this study. The content of ARGs, mobile genetic elements (MGEs), and bacterial genera in sewage/sludge and aerosols from different process stages was detected. The possible correlation between ARGs/ MGEs and bacteria was analyzed. The risk of antibiotic-resistant bacteria was evaluated and the diffusion of ARGs/MGEs was simulated. The results showed that the concentration of ARGs/MGEs varied as the process progressed, and which in the aeration tank was relatively high. The ARGs/MGEs content in SWP aerosol (8.35-163.27 copies/m3) was higher than that in SDP (5.52-16.36 copies/m3). The main ARGs/MGEs detected in SWP aerosol were tnpA-05, tnpA-04, and ermF, while the main ARGs/MGEs detected in SDP aerosol were sul1, ermF, and blaPAO. ARGs were positively correlated with most bacteria and Escherichia coli with ARGs carries higher cytotoxicity. ARGs/MGEs mainly diffused towards the southeast, which may cause harm to urban residents with the diffusion of aerosols. This study provides clues and theoretical basis for preventing the hazards of ARGs from WWTP sources.

Mediating Effect of Insulin-Like Growth Factor-I Underlying the Link Between Vitamin D and Gestational Diabetes Mellitus.

Vitamin D was well-known to be associated with gestational diabetes mellitus (GDM). Insulin-like growth factor-I (IGF-I) has been linked to vitamin D and GDM, respectively. We hypothesize that changes in IGF-I metabolism induced by 25(OH)D3 might contribute to GDM. Therefore, we investigated the independent and combined relationships of serum 25(OH)D3 and IGF-I concentrations with GDM risk, and the mediation effect of IGF-I on 25(OH)D3. A total of 278 pregnant women (including 125 cases and 153 controls) were recruited in our current study. Maternal serum 25(OH)D3 and IGF-I were measured in the second trimester. Logistic regression models were used to estimate the associations of 25(OH)D3 and IGF-I concentrations with the risk of GDM. Mediation analyses were used to explore the mediation effect of IGF-I on the association between 25(OH)D3 and the risk of GDM. After adjusted for the confounded factors, both the third and fourth quartile of 25(OH)D3 decreased the risk of GDM (OR = 0.226; 95% CI, 0.103-0.494; OR = 0.109; 95% CI, 0.045-0.265, respectively) compared to the first quartile of 25(OH)D3. However, the third and fourth quartile of serum IGF-I (OR = 5.174; 95% CI, 2.287-11.705; OR = 12.784; 95% CI, 5.292-30.879, respectively) increased the risk of GDM compared to the first quartile of serum IGF-I. Mediation analyses suggested that 19.62% of the associations between 25(OH)D3 and GDM might be mediated by IGF-I. The lower concentration of serum 25(OH)D3 or higher IGF-I in the second trimester was associated with an increased risk of GDM. The serum IGF-I level might be a potential mediator between 25(OH)D3 and GDM.

Bioaerosols in deodorization covers of wastewater treatment plants: Emission characteristics and health risks.

Wastewater treatment plants (WWTPs) are the main source of bioaerosol emissions. The cover of deodorization within WWTPs serves not only to manage odors but also to limit the dispersion of bioaerosols. This study investigated the emission characteristics and exposure risks of bioaerosols inside deodorization covers from a WWTP in Northern China. The results revealed that the concentration of bacteria in bioaerosols ranged from 96 ± 8 to 706 ± 45 CFU/m3, with the highest concentration observed in the biochemical reaction tank. The predominant bacterial genera in bioaerosols within the odor control covers were Cetobacterium, Romboutsia, Bacteroides, Lactobacillus, and Tubricibacter, while the dominant fungal genera included Aspergillus, Alternaria, Fusarium, and Cladosporium. The main water-soluble ions in the air were NH4+, Ca2+, SO42-, and Cl-. SO42- was found to promote the survival of Cetobacterium, Brevibacterium, Fusarium, Penicillium, and Filobasidium, while Cl- exhibited inhibitory effects on most microorganisms in bioaerosols. Source tracker analysis indicated that wastewater was the primary source of bioaerosols in the biochemical reaction tank. The non-carcinogenic risk associated with bioaerosols within deodorization covers was less than 1 (2.34 × 10-9 to 3.08 × 10-2). FunGuild fungal functional prediction suggested that the abundance of animal pathogens was highest in the bioaerosols from the anaerobic sedimentation tank. BugBase phenotypic prediction showed that the abundance of potential pathogens in secondary sedimentation tank bioaerosols was the highest. This study effectively revealed the characteristics and sources of bioaerosols in the sewage and sludge treatment area under the deodorization cover, which provided a theoretical basis for enhancing the management and control of bioaerosols.

Airborne ARGs/MGEs from two sewage types during the COVID-21: Population, microbe interactions, cytotoxicity, formation mechanism, and dispersion.

During the COVID-2021 epidemic, a large number of antibiotics were used for clinical treatment in hospitals or daily prevention. Sewage from hospital sewage treatment centers (HSTC) and wastewater treatment plants (WWTP) produced a lot of antibiotic-resistance genes/mobile genetic elements (ARGs/MGEs). In this study, the sewage and bioaerosol in the biochemical tank (BT) of an HSTC and a WWTP were sampled throughout the year. The results showed that the average absolute abundance of sewage in BT of WWTP (BTW-W) was higher than sewage in BT of HSTC (BTW-H). Sewage was an important source of microorganisms and ARGs/MGEs in the air of BT. Microorganisms and MGEs were the factors affecting the differences in ARGs/MGEs. Cytotoxicity experiment proved that the cytotoxicity changed from Grade III to Grade IV with the increase in drug-resistant Escherichia coli concentration. According to the formation mechanism formula, the average generation rate of ARGs/MGEs in BT of HSTC was lower than that in WWTP. The diffusion range of ARGs/MGEs of HSTC was larger than that of WWTP. According to the above results, this study found that when people were far away from BT, the health risk of HSTC caused by the diffusion of bioaerosol was higher than WWTP; When people were close to BT, the health risk of WWTP was higher than HSTC due to the aeration of BT. This study provided a basis for public protection of ARGs. In the future, the elimination of airborne ARGs and crowd protection can be further studied in detail.

Protective effect of soy isolate protein against streptozotocin induced gestational diabetes mellitus via TLR4/MyD88/NF-κB signaling pathway.

BACKGROUND: Gestational diabetes mellitus (GDM) is a serious complication of pregnancy that is characterized by high blood sugar levels that occur due to insulin resistance and dysfunction in glucose metabolism during pregnancy. It usually develops in the second or third trimester of pregnancy and affects about 7 % of all pregnancies worldwide. In this experimental study, we scrutinized the GDM protective effect of soy isolate protein against streptozotocin (STZ) induced GDM in rats and explore the underlying mechanism. MATERIAL AND METHODS: Sprague-Dawley (SD) rats were used in this experimental study. A 55 mg/kg intraperitoneal injection of streptozotocin (STZ) was administered to induce diabetes in female rats, followed by oral administration of soy isolate protein for 18 days. Body weight, glucose levels, and insulin were measured at different time intervals (0, 9, and 18 days). Lipid profiles, antioxidant levels, inflammatory cytokines, apoptosis parameters, and mRNA expression were also assessed. Pancreatic and liver tissues were collected for histopathological examination during the experimental study. RESULTS: Soy isolate protein significantly (P < 0.001) reduced the glucose level and enhanced the insulin level and body weight. Soy isolate protein remarkably decreased the placental weight and increased the fetal weight. Soy isolate protein significantly (P < 0.001) decreased the HbA1c, hepatic glycogen, serum C-peptide and increased the level of free fatty acid. Soy isolate protein significantly (P < 0.001) altered the level of lipid, antioxidant and inflammatory cytokines. Soy isolate protein significantly (P < 0.001) improved the level of adiponectin, visfatin and suppressed the level of leptin and ICAM-1. Soy isolate protein significantly (P < 0.001) altered the mRNA expression and also restored the alteration of histopathology. CONCLUSION: Based on the result, soy isolate protein exhibited the GDM protective effect against the STZ induced GDM in rats via alteration of TLR4/MyD88/NF-κB signaling pathway.

Curcumin prevents Alzheimer's disease progression by upregulating JMJD3.

The main purpose of this research was to explore the molecular mechanisms of Jumonji Domain-Containing Protein 3 (JMJD3) in Alzheimer's disease (AD) and to analyze its role in the anti-AD mechanism of curcumin (CUR). In the in vitro study of AD, JMJD3 overexpression promoted the trimethylation of histone H3 lysine 27 (H3K27me3), downregulated brain-derived neurotrophic factor (BDNF ), improved the abnormality of mitochondrial stress response (MSR) markers, Aß accumulation, increased cell proliferation and inhibited apoptosis. Upregulating BDNF also achieved above similar results. Knockout of JMJD3 could downregulate BDNF, upregulate the level of H3K27me3 methylation and inhibit MSR markers, while transfection of JMJD3 RNAi could counteract the upregulated effect of BDNF. Then, MSR activator could also improve AD. In addition, JMJD3 in AD in vitro models was obviously upregulated under CUR stimulation, and it triggered a series of reactions as mentioned above. In the in vivo study, the levels of JMJD3, the mRNA and protein levels of BDNF in the right brain tissues of AD mice were downregulated, the methylation of H3K27me3 increased, and the MSR markers (ClpP, HSP6, HSP-60, ATFS-1, etc.) were downregulated; the above indexes were improved in varying degrees with the intervention of CUR. Thus, we conclude that CUR can induce the upregulation of JMJD3 and improve BDNF expression by promoting the demethylation of H3K27me3, thereby maintaining the balance of MSR and thus, preventing AD development.

Changes in adverse pregnancy outcomes in women with advanced maternal age (AMA) after the enactment of China's universal two-child policy.

The universal two-child policy (TCP; 2016) in China has affected many aspects of maternal-neonatal health. A tertiary hospital-based retrospective study (2011-2019) was used to find the association of these policy changes with maternal age and pregnancy outcomes in women with AMA (≥ 35 years) in the Hubei Province, China. The proportion of neonatal births to women with AMA increased by 68.8% from 12.5% in the one-child policy (OCP) period to 21.1% in the universal TCP period [aOR 1.76 (95% CI: 1.60, 1.93)]. In the univariate analysis, the proportion of preterm births (29.4% to 24.1%), low birth weight (LBW) (20.9% to 15.9%), and hypertensive disorders of pregnancy (HDP) (11.5% to 9.2%) significantly (p < 0.05) decreased in women with AMA from the OCP period to universal TCP period. However, the proportion of intrauterine growth restriction (IUGR) (0.2% to 0.7%) and gestational diabetes mellitus (GDM) (1.7% to 15.6%) was significantly (p < 0.05) increased over the policy changes. After adjusting for confounding factors, only the risk of GDM increased [aOR 10.91 (95% CI: 6.05, 19.67)] in women with AMA from the OCP period to the universal TCP period. In conclusion, the risk of GDM increased in women with AMA from the OCP period to the universal TCP period.

The COVID-19 infection in children and its association with the immune system, prenatal stress, and neurological complications.

The Coronavirus disease 2019 (COVID-19)" caused by the "severe acute respiratory syndrome corona virus 2 (SARS-CoV-2)" has caused huge losses to the world due to the unavailability of effective treatment options. It is now a serious threat to humans as it causes severe respiratory disease, neurological complications, and other associated problems. Although COVID-19 generally causes mild and recoverable symptoms in children, it can cause serious severe symptoms and death causing complications. Most importantly, SARS-CoV-2 can cause neurological complications in children, such as shortness of breath, myalgia, stroke, and encephalopathy. These problems are highly linked with cytokine storm and proinflammatory responses, which can alter the physiology of the blood-brain barrier and allow the virus to enter the brain. Despite the direct infection caused by the virus entry into the brain, these neurological complications can result from indirect means such as severe immune responses. This review discusses viral transmission, transport to the brain, the associated prenatal stress, and neurological and/or immunological complications in children.

A review of the berberine natural polysaccharide nanostructures as potential anticancer and antibacterial agents.

Despite the promising medicinal properties, berberine (BBR), due to its relatively poor solubility in plasma, low bio-stability and limited bioavailability is not used broadly in clinical stages. Due to these drawbacks, drug delivery systems (DDSs) based on nanoscale natural polysaccharides, are applied to address these concerns. Natural polymers are biodegradable, non-immunogenic, biocompatible, and non-toxic agents that are capable of trapping large amounts of hydrophobic compounds in relatively small volumes. The use of nanoscale natural polysaccharide improves the stability and pharmacokinetics of the small molecules and, consequently, increases the therapeutic effects and reduces the side effects of the small molecules. Therefore, this paper presents an overview of the different methods used for increasing the BBR solubility and bioavailability. Afterwards, the pharmacodynamic and pharmacokinetic of BBR nanostructures were discussed followed by the introduction of natural polysaccharides of plant (cyclodextrines, glucomannan), the shells of crustaceans (chitosan), and the cell wall of brown marine algae (alginate)-based origins used to improve the dissolution rate of poorly soluble BBR and their anticancer and antibacterial properties. Finally, the anticancer and antibacterial mechanisms of free BBR and BBR nanostructures were surveyed. In conclusion, this review may pave the way for providing some useful data in the development of BBR-based platforms for clinical applications.

Lighting up Individual Organelles With Fluorescent Carbon Dots.

Cell organelles play crucial roles in the normal functioning of an organism, therefore the disruption of their operation is associated with diseases and in some cases death. Thus, the detection and monitoring of the activities within these organelles are of great importance. Several probes based on graphene oxide, small molecules, and other nanomaterials have been developed for targeting specific organelles. Among these materials, organelle-targeted fluorescent probes based on carbon dots have attracted substantial attention in recent years owing to their superior characteristics, which include facile synthesis, good photostability, low cytotoxicity, and high selectivity. The ability of these probes to target specific organelles enables researchers to obtain valuable information for understanding the processes involved in their functions and/or malfunctions and may also aid in effective targeted drug delivery. This review highlights recently reported organelle-specific fluorescent probes based on carbon dots. The precursors of these carbon dots are also discussed because studies have shown that many of the intrinsic properties of these probes originate from the precursor used. An overview of the functions of the discussed organelles, the types of probes used, and their advantages and limitations are also provided. Organelles such as the mitochondria, nucleus, lysosomes, and endoplasmic reticulum have been the central focus of research to date, whereas the Golgi body, centrosome, vesicles, and others have received comparatively little attention. It is therefore the hope of the authors that further studies will be conducted in an effort to design probes with the ability to localize within these less studied organelles so as to fully elucidate the mechanisms underlying their function.

Global Research Trends in Pediatric Trauma From 1968 to 2021: A Bibliometric Analysis.

Introduction: Every year, millions of children die from preventable causes worldwide. According to World Health Organization, injuries are the leading cause of disability and death among all age groups below 60 years. Aim: This study aimed to evaluate the global research outcomes and trends, and some key bibliometric indicators in pediatric trauma. Methods: A descriptive bibliometric analysis study was designed. On June 14, 2021, an electronic search was performed in the Web of Science Core Collection database using the potential searching keywords "Pediatric AND Trauma" in the title field without any limitations. The search was performed using the Boolean search query method. The data were downloaded in plaintext and comma-separated values format. The required graphs were generated using OriginPro 2018. Furthermore, the data were transferred to HistCite™ software for bibliometric analysis. In addition, the obtained data were plotted for network visualization mapping using VOSviewer software version 1.6.15 for windows. Results: A total of 2,269 documents were included in the final analysis. The included documents were authored by 7,894 authors and published in 395 research and academic journals, mainly in the English language (n = 2,222). The main document types were articles (n = 1,276, citations = 18,244), and meeting abstracts (n = 331, citations = 19). Pediatric (n = 2,269) and trauma (n = 2,257) were the most widely used keywords. The most productive year was 2019 (n = 184, citations = 527). The most prolific author was Upperman JS (n = 29, citations = 202). The most attractive journals in pediatric trauma research were The Journal of Trauma and Acute Care Surgery (n = 290, citations = 5,199) and the Journal of Pediatric Surgery (n = 256, citations = 5,088). The most active institute was the University of California System (n = 110). The most dominant country was the United States of America (USA) (n = 1,620, citations = 22,983). The USA and Canada had the highest total link strength, 103 and 70, respectively. Conclusion: This study provides a comprehensive overview of research output in pediatric trauma. The USA continues to dominate scientific research and funding in pediatric trauma. Findings of the current study will help the researchers and clinicians to understand the recent achievements and research frontiers. Collaborative research initiative needs to be established between institutions in developed and developing countries and among researchers.

Down-regulated long non-coding RNA RMST ameliorates dopaminergic neuron damage in Parkinson's disease rats via regulation of TLR/NF-κB signaling pathway.

OBJECTIVE: Current treatment and prognosis of Parkinson's disease (PD) are not ideal. This study explored the mechanism of long non-coding RNA (lncRNA) rhabdomyosarcoma 2-associated transcript (RMST) in dopaminergic (DA) neuron damage in PD rats. METHODS: PD rats were modeled and injected with RMST silence or overexpression vectors to figure out its roles in oxidative stress, the apoptosis of DA neurons in brain substantia nigra (SN), and neurobehavioral activities of PD rats. Tyrosine hydroxylase (TH), synaptophysin (SYN), glial fibrillary acidic protein (GFAP) and ionized calcium-binding adaptor molecule (Iba-1) in SN were detected. RMST and Toll-like receptor (TLR)/nuclear factor kappa B (NF-κB) pathway-related factors were detected. RESULTS: RMST expression in brain SN of rats, TLR2, TLR4 expression in neurons and NF-κB expression in cell nucleus were increased. Silenced RMST improved the neurobehavioral activities, depressed oxidative stress and neuronal apoptosis, increased TH and SYN expression, and reduced the activation degree of glial cells in SN and the inflammatory response via reducing GFAP and Iba-1. Moreover, reduced RMST reduced TLR2 and TLR4 expression in neurons and NF-κB expression in cell nucleus in PD rats. CONCLUSION: Inhibited RMST attenuates DA neuron damage in PD rats, which may be implicated with TLR/NF-κB signaling pathway.

Dynamics of binding ability prediction between spike protein and human ACE2 reveals the adaptive strategy of SARS-CoV-2 in humans.

SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is a novel coronavirus causing the COVID-19 pandemic in 2020. High adaptive plasticity on the spike protein of SASR-CoV-2 enables it to transmit across different host species. In the present study, we collected 2092 high-quality genome sequences of SARS-CoV-2 from 160 regions in over 50 countries and reconstructed their phylogeny. We also analyzed the polymorphic interaction between spike protein and human ACE2 (hACE2). Phylogenetic analysis of SARS-CoV-2 suggests that SARS-CoV-2 is probably originated from a recombination event on the spike protein between a bat coronavirus and a pangolin coronavirus that endows it humans infectivity. Compared with other regions in the S gene of SARS-CoV-2, the direct-binding sites of the receptor-binding domain (RBD) is more conserved. We focused on 3,860 amino acid mutations in spike protein RBD (T333-C525) of SARS-CoV-2 and simulated their differential stability and binding affinity to hACE2 (S19-D615). The results indicate no preference for SARS-CoV-2 infectivity on people of different ethnic groups. The variants in the spike protein of SARS-CoV-2 may also be a good indicator demonstrating the transmission route of SARS-CoV-2 from its natural reservoir to human hosts.

Interaction between SNCA gene polymorphisms and T2DM with Parkinson's disease.

AIMS: To investigate the association of several single nucleotide polymorphisms (SNPs) within alpha-synuclein (SNCA) gene and additional gene-environment interaction with Parkinson's disease (PD) risk. METHODS: Hardy-Weinberg equilibrium (HWE) is tested for controls using SNPstats (http://bioinfo.iconcologia.net/SNPstats). Logistic regression is used to calculate the ORs (95% CI) for relations between the four SNPs and PD risk. The generalized multifactor dimensionality reduction (GMDR) model is used to evaluate the synergy between gene and environment. RESULTS: A total of 1161 people were included in this study, including 386 cases of PD and 775 normal controls. In this study, the genotype frequency of the control group was consistent with HWE distribution. Rs356219-G allele frequency was 30.0% in patients and 19.8% in control group. The rs356221-T allele frequency was 29.7% in the patients and 20.8% in the control group. Rs356219-G and rs356221-T alleles were associated with increased PD risk, with adjusted ORs (95% CI) of 1.92 (1.28-2.52) and 1.52 (1.05-2.02), respectively. We also found no significant correlation between rs2301134 and rs2301135 and susceptibility to PD. The best gene-environment interaction models were determined by GMDR analysis, which shown a significant gene-T2DM interaction combinations, but the gene-alcohol drinking interaction combinations were all not significant. We also conducted stratified analysis for interaction effect using logistic regression. We found that T2DM patients with rs356221-AT/ TT genotype have the highest PD risk, compared to subjects with rs356219-AA genotype, OR (95%CI) = 2.67 (1.83-3.46). CONCLUSIONS: The rs356219-G and rs356221-T, gene-environment interaction between rs356221 and T2DM were all associated with increased PD risk.

Curcumin-Activated Mesenchymal Stem Cells Derived from Human Umbilical Cord and Their Effects on MPTP-Mouse Model of Parkinson's Disease: A New Biological Therapy for Parkinson's Disease.

BACKGROUND: The aim of this study was to investigate the effects of human umbilical cord mesenchymal stem cell activated by curcumin (hUC-MSCs-CUR) on Parkinson's disease (PD). hUC-MSCs can differentiate into many types of adult tissue cells including dopaminergic (DA) neurons. CUR could protect DA neurons from apoptosis induced by 6-hydroxydopamine (6-OHDA). Therefore, we used the hUC-MSCs activated by CUR for the treatment of PD in an animal model. METHODS: The hUC-MSCs-CUR was transplanted into the MPTP-induced PD mouse models via the tail vein. We found that hUC-MSCs-CUR significantly improved the motor ability, increased the tyrosine hydroxylase (TH), dopamine (DA), and Bcl-2 levels, and reduced nitric oxide synthase, Bax, and cleaved caspase 3 expression in PD mice. The supernatant of hUC-MSCs-CUR (CM-CUR) was used to stimulate the SH-SY5Y cellular model of PD; cell proliferation, differentiation, TH, and neuronal-specific marker microtubular-associated protein 2 (MAP2) expressions were examined. RESULTS: Our data showed that CM-CUR significantly promoted cell proliferation and gradually increased TH and MAP2 expression in SH-SY5Y PD cells. The beneficial effects could be associated with significant increase of rough endoplasmic reticulum in the hUC-MSCs-CUR, which secretes many cytokines and growth factors beneficial for PD treatment. CONCLUSIONS: Transplantation of hUC-MSCs-CUR could show promise for improving the motor recovery of PD.

Haplotype analysis on association between variants of interleukin 6 (IL-6) and late-onset Alzheimer's disease in a Chinese Han population.

OBJECTIVE: The aim of this study was to evaluate the influence of single nucleotide polymorphisms (SNPs) in interleukin-6 (IL-6) gene and the haplotype on late-onset Alzheimer's disease (LOAD). METHODS: A total of 896 participants were enrolled, including 446 LOAD patients and 450 controls. Total genomic DNA was extracted from the blood of participants and genotyping was then performed. Hardy-Weinberg equilibrium test was conducted in controls. Multivariate analysis was performed to determine the association between 4 SNPs (rs1800796, rs7802308, rs1800795 and rs13447446) in IL-6 gene and LOAD. Pairwise LD analysis was employed to identify the association between haplotype and LOAD. RESULTS: Multivariate logistic analysis showed that T allele of rs7802308 and G allele of rs1800796 were correlated with decreased risk of LOAD, adjusted ORs were 0.68 (95% CI: 0.50-0.91) and 0.71 (95% CI: 0.51-0.92), respectively. However, rs1800795 and rs13447446 were not associated with LOAD. Pairwise LD analysis among the 4 SNPs showed that only rs1800796 and rs1800795 in IL-6 gene was in heavy LD, the D' value was >0.75 (0.825). In all samples, the haplotype C-G was observed most frequently in two groups, with 55.79% and 49.46% in the LOAD patients and controls, respectively. The results also indicated that haplotype G-C was significantly associated with decreased LOAG risk. CONCLUSIONS: T allele of rs7802308 and G allele of rs1800796 were correlated with decreased risk of LOAD. The haplotype G-C were also correlated with decreased risk of LOAD.

MicroRNA-129-5p alleviates nerve injury and inflammatory response of Alzheimer's disease via downregulating SOX6.

There is growing evidence of the position of microRNAs (miRs) in Alzheimer's disease (AD), thus our objective was to discuss the impact of miR-129-5p regulating nerve injury and inflammatory response in AD rats by modulating SOX6 expression. The AD rat model was established by injecting Aß25-35 into the brain. The pathological changes, ultrastructure, number of neurons, cell degeneration and apoptosis of hippocampal tissue were observed in vivo. MiR-129-5p, SOX6, IL-1ß, TNF-α, Bcl-2 and Bax expression in serum and hippocampal tissues were detected by ELISA, RT-qPCR or western blot analysis. The successfully modeled hippocampal neuronal cells of AD were transfected with miR-129-5p mimic, SOX6-siRNA or their controls to figure out their roles in proliferation, apoptosis and inflammatory reaction in vitro. Low expression of SOX6 and high expression of miR-129-5p in vivo of rats would shorten the escape latent period and increase the times of crossing platforms, alleviate the pathological injury, inhibit neuronal apoptosis and reduce the inflammatory reaction. Up-regulation of miR-129-5p and down-regulation of SOX6 promoted proliferation, suppressed apoptosis and degraded the inflammatory reaction of neuronal cells in vitro. Up-regulation of SOX6 reversed the expression of miR-129-5p to reduce the damage and inflammatory response of the cell model of AD. Our study presents that up-regulation of miR-129-5p or down-regulation of SOX6 can reduce nerve injury and inflammatory response in rats with AD. Thus, miR-129-5p may be a potential candidate for the treatment of AD.