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1.
Signal Transduct Target Ther ; 6(1): 136, 2021 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-33790236

RESUMO

Epidemiological studies of the COVID-19 patients have suggested the male bias in outcomes of lung illness. To experimentally demonstrate the epidemiological results, we performed animal studies to infect male and female Syrian hamsters with SARS-CoV-2. Remarkably, high viral titer in nasal washings was detectable in male hamsters who presented symptoms of weight loss, weakness, piloerection, hunched back and abdominal respiration, as well as severe pneumonia, pulmonary edema, consolidation, and fibrosis. In contrast with the males, the female hamsters showed much lower shedding viral titers, moderate symptoms, and relatively mild lung pathogenesis. The obvious differences in the susceptibility to SARS-CoV-2 and severity of lung pathogenesis between male and female hamsters provided experimental evidence that SARS-CoV-2 infection and the severity of COVID-19 are associated with gender.

2.
Nat Commun ; 12(1): 1383, 2021 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-33654063

RESUMO

In this study, we investigate the seroprevalence of SARS-CoV-2 antibodies among blood donors in the cities of Wuhan, Shenzhen, and Shijiazhuang in China. From January to April 2020, 38,144 healthy blood donors in the three cities were tested for total antibody against SARS-CoV-2 followed by pseudotype SARS-CoV-2 neutralization tests, IgG, and IgM antibody testing. Finally, a total of 398 donors were confirmed positive. The age- and sex-standardized SARS-CoV-2 seroprevalence among 18-60 year-old adults (18-65 year-old in Shenzhen) was 2.66% (95% CI: 2.24%-3.07%) in Wuhan, 0.033% (95% CI: 0.0029%-0.267%) in Shenzhen, and 0.0028% (95% CI: 0.0001%-0.158%) in Shijiazhuang, respectively. Female sex and older-age were identified to be independent risk factors for SARS-CoV-2 seropositivity among blood donors in Wuhan. As most of the population of China remained uninfected during the early wave of the COVID-19 pandemic, effective public health measures are still certainly required to block viral spread before a vaccine is widely available.


Assuntos
/patogenicidade , Anticorpos Antivirais/sangue , Doadores de Sangue/estatística & dados numéricos , /epidemiologia , China/epidemiologia , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Testes de Neutralização , Prevalência , Fatores de Risco , /imunologia
3.
J Vis Exp ; (168)2021 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-33645577

RESUMO

To select food with nutritional value while avoiding the consumption of harmful agents, animals need a sophisticated and robust taste system to evaluate their food environment. The fruit fly, Drosophila melanogaster, is a genetically tractable model organism that is widely used to decipher the molecular, cellular, and neural underpinnings of food preference. To analyze fly food preference, a robust feeding method is needed. Described here is a two-choice feeding assay, which is rigorous, cost-saving, and fast. The assay is Petri-dish-based and involves the addition of two different foods supplemented with blue or red dye to the two halves of the dish. Then, ~70 prestarved, 2-4-day-old flies are placed in the dish and allowed to choose between blue and red foods in the dark for about 90 min. Examination of the abdomen of each fly is followed by the calculation of the preference index. In contrast to multiwell plates, each Petri dish takes only ~20 s to fill and saves time and effort. This feeding assay can be employed to quickly determine whether flies like or dislike a particular food.


Assuntos
Bioensaio/métodos , Drosophila melanogaster/fisiologia , Preferências Alimentares , Animais , Corantes , Comportamento Alimentar , Indicadores e Reagentes , Inanição
4.
Cancer Sci ; 2021 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-33675124

RESUMO

Ribosomal proteins (RPs) are important components of ribosomes and related to the occurrence and development of tumors. However, little is known about the effects of the RP network on cervical cancer (CC). In this study, we screened differentially expressed RPL34 in CC by high-throughput quantitative proteome assay. We found that RPL34 acted as a tumor suppressor and was downregulated in CC and inhibited the proliferation, migration, and invasion abilities of CC cells. Next, we verified that RPL34 regulated the CC through the MDM2-P53 pathway by using Act D medicine, MDM2 inhibitor, and a series of western blotting(WB)assays. Moreover, an antisense lncRNA, RPL34-AS1, regulated the expression of RPL34 and participated in the tumorigenesis of CC. RPL34 can reverse the effect of RPL34-AS1 in CC cells. Finally, by RNA-binding protein immunoprecipitation (RIP) assay we found that eukaryotic initiation factor 4A3 (EIF4A3), which binds to RPL34-AS1, regulated RPL34-AS1 expression in CC. Therefore, our findings indicate that RPL34-AS1-induced RPL34 inhibits CC cell proliferation, invasion, and metastasis through modulation of the MDM2-P53 signaling pathway, which provides a meaningful target for the early diagnosis and treatment of CC.

5.
Chem Res Toxicol ; 34(3): 684-694, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33663212

RESUMO

Compounds containing hexavalent chromium [Cr(VI)] have been classified as Group I human carcinogens in 1990 by the International Agency for Research on Cancer, known to induce human lung cancers. To determine the nature of Cr(VI) carcinogenesis, much has been learned about genetic damage and epigenetic alterations. On the basis of bibliometric analysis of the available literature found between 1966 and 2020, the present study investigated the evolution of author keywords; provided a summary of relevant studies focused on populations, animals/plants, or cells; and depicted the co-operation among countries or institutions and research group development. Additionally, multiomics technology and bioinformatics analysis can be a valuable tool for figuring out new biomarkers from different molecular levels like gene, RNA, protein, and metabolite and ascertaining the mechanism pathways of Cr(VI) genotoxicity and carcinogenesis.

6.
J Colloid Interface Sci ; 592: 358-370, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33677196

RESUMO

To improve advanced oxidation processes (AOPs), bio-inspired iron-encapsulated biochar (bio-inspired Fe⨀BC) catalysts with superior performance were prepared from iron-rich biomass of Iris sibirica L. using a pyrolysis method under anaerobic condition. The obtained compounds were used as catalysts to activate perdisulfate (PDS) and then degradate 2,4-dichlorophenol (2,4-DCP), and synthetic iron-laden biochar (synthetic Fe-BC) was used for comparison. The highest removal rate of 2,4-DCP was 98.35%, with 37.03% of this being distinguished as the contribution of micro-electrolysis, greater than the contribution of adsorption (32.81%) or advanced oxidation (28.51%). The high performance of micro-electrolysis could be attributable to the formation of Fe (Iron, syn) and austenite (CFe15.1) with strong electron carrier at 700 °C. During micro-electrolysis, Fe2+ and electrons were gradually released and then used as essential active components to enhance the AOPs. The slow-releasing Fe2+ (K = 0.0048) also inhibited the overconsumption of PDS (K = -0.00056). Furthermore, the electrons donated from Fe⨀BC-4 were able to activate PDS directly. The electrons were enriched by the porous structure of Fe⨀BC-4, and the formation of the COFe bond in the π-electron system could also accelerate the electron transfer to activate PDS. Similar reactive oxygen species (ROS) were identified during the micro-electrolysis and AOPs, leading to similar degradation pathways. The higher does concentration of O2- generated during micro-electrolysis than during the AOPs also led to a greater dechlorination effect.

7.
Plant J ; 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33547682

RESUMO

Nitrogen (N) is an essential major nutrient for food crops. Although ammonium (NH4 + ) is the primary N source of rice (Oryza sativa), nitrate (NO3 - ) can also be absorbed and utilized. Rice responds to NO3 - application by altering its root morphology, such as root elongation. Strigolactones (SLs) are important modulators of root length. However, the roles of SLs and their downstream genes in NO3 - -induced root elongation remain unclear. Here, the levels of total N and SL (4-deoxyorobanchol) and the responses of seminal root (SR) lengths to NH4 + and NO3 - were investigated in rice plants. NO3 - promoted SR elongation, possibly due to short-term signal perception and long-term nutrient function. Compared with NH4 + conditions, higher SL signalling/levels and less D53 protein were recorded in roots of NO3 - -treated rice plants. In contrast to wild-type plants, SR lengths of d mutants were less responsive to NO3 - conditions, and application of rac-GR24 (SL analogue) restored SR length in d10 (SL biosynthesis mutant) but not in d3, d14, and d53 (SL-responsive mutants), suggesting that higher SL signalling/levels participate in NO3 - -induced root elongation. D53 interacted with SPL17 and inhibited SPL17-mediated transactivation from the PIN1b promoter. Mutation of SPL14/17 and PIN1b caused insensitivity of the root elongation response to NO3 - and rac-GR24 applications. Therefore, we conclude that perception of SLs by D14 leads to degradation of D53 via the proteasome system, which releases the suppression of SPL14/17-modulated transcription of PIN1b, resulting in root elongation under NO3 - supply.

8.
Sci Rep ; 11(1): 3255, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33547368

RESUMO

Rituximab combined with chemotherapy is the first-line induction therapy of CD20 positive B-cell non-Hodgkin lymphomas (CD20+ B-NHL). Recently new anti-CD20 monoclonal antibodies (mAbs) have been developed, but their efficacy and safety compared with rituximab are still controversial. We searched MEDLINE, Embase, and Cochrane Library for eligible randomized controlled trials (RCTs) that compared new anti-CD20 mAbs with rituximab in induction therapy of B-NHL. The primary outcomes are progression-free survival (PFS) and overall survival (OS), additional outcomes include event-free survival (EFS), disease-free survival (DFS), overall response rate (ORR), complete response rate (CRR) and incidences of adverse events (AEs). Time-to-event data were pooled as hazard ratios (HRs) using the generic inverse-variance method and dichotomous outcomes were pooled as odds ratios (ORs) using the Mantel-Haenszel method with their respective 95% confidence interval (CI). Eleven RCTs comprising 5261 patients with CD20+ B-NHL were included. Compared with rituximab, obinutuzumab significantly prolonged PFS (HR 0.84, 95% CI 0.73-0.96, P = 0.01), had no improvement on OS, ORR, and CRR, but increased the incidences of serious AEs (OR 1.29, 95% CI 1.13-1.48, P < 0.001). Ofatumumab was inferior to rituximab in consideration of ORR (OR 0.73, 95% CI 0.55-0.96, P = 0.02), and had no significant differences with rituximab in regard to PFS, OS and CRR. 131I-tositumomab yielded similar PFS, OS, ORR and CRR with rituximab. 90Y-ibritumomab tiuxetan increased ORR (OR 3.07, 95% CI 1.47-6.43, P = 0.003), but did not improve PFS, DFS, OS and CRR compared with rituximab. In conclusion, compared with rituximab in induction therapy of CD20+ B-NHL, obinutuzumab significantly improves PFS but with higher incidence of AEs, ofatumumab decreases ORR, 90Y-ibritumomab tiuxetan increases ORR.

9.
Matern Child Nutr ; : e13157, 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33594802

RESUMO

In this secondary analysis of data from a double-blind randomized controlled trial (clinicaltrials.gov identifier: NCT00133744) of micronutrient supplementation (multiple micronutrients [MMN], iron-folic acid [IFA] and folic acid [FA] alone), we examined the potential modifying effect of gestational age at enrolment on the association of antenatal supplementation and pregnancy-induced hypertension (PIH). We included 18,775 nulliparous pregnant women with mild or no anaemia who were enrolled at 20 weeks of gestation or earlier from five counties of northern China. Women were randomly assigned to receive daily FA, IFA or MMN from enrolment until delivery. We used logistic regression to evaluate the association between PIH and timing of micronutrient supplementation. The incidence of PIH was statistically significantly lower among women who began MMN supplementation before 12 gestational weeks compared with women who began MMN supplementation at 12 weeks or later (RR = 0.74, 95% CI: 0.60-0.91). A similar protective effect was observed for both early-onset (<28 weeks, RR 0.45, 0.21-0.96) and late-onset of PIH (≥28 weeks, RR 0.77, 0.63-0.96). No statistically significant association was observed between PIH occurrence and timing of supplementation for FA or IFA. Maternal MMN supplementation and antenatal enrolment during the first trimester of pregnancy appeared to be of importance in preventing both early- and late-onset of PIH.

10.
Medicine (Baltimore) ; 100(7): e24845, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33607855

RESUMO

ABSTRACT: Despite the establishment of the links between ulcerative colitis (UC) and depression, between UC and gut microbiota, few correlations between depression and gut microbiota have yet been demonstrated especially in ulcerative colitis patients. The objective of our study was therefore to determine whether the comorbidity of depressive disorder in ulcerative colitis patients correlate with alterations in the gut microbiota and to identify the specific microbiota signatures associated with depression.Between March 2017 and February 2018, 31 healthy volunteers, 31 UC patients without depression, and 31 UC patients with depression from Longhua Hospital were enrolled. Clinical data and fecal samples were collected for each patient. Fecal bacteria were identified using 16 s rRNA sequencing. We compared microbial composition among the 3 groups using bioinformatic analysis.Patients with UC with depression had higher disease severity (P < .05). The UC without depression group had moderate reduction of microbial abundance and uniformity compared to the control group. The UC with depression group had the lowest microbial abundance. With regard to the vital bacteria in the microbiota-gut-brain axis, patients with UC and depression had the lowest abundance of Firmicutes, Clostridia, and Clostridiales but the highest abundance of Proteobacteria, Gammaproteobacteria, and Bacilli.The presence of depression in UC patients presented significant differences in the composition of gut microbiota compared with UC patients without depression, with increased abundance of Firmicutes and reduced abundance of Proteobacteria.


Assuntos
Colite Ulcerativa/microbiologia , Depressão/microbiologia , Fezes/microbiologia , Microbioma Gastrointestinal/genética , Adulto , Bactérias/classificação , Bactérias/genética , Bactérias/crescimento & desenvolvimento , Estudos de Casos e Controles , Clostridiales/crescimento & desenvolvimento , Colite Ulcerativa/psicologia , Comorbidade , Biologia Computacional/métodos , Depressão/complicações , Feminino , Firmicutes/crescimento & desenvolvimento , Gammaproteobacteria/crescimento & desenvolvimento , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Proteobactérias/crescimento & desenvolvimento , RNA Ribossômico 16S/genética , Índice de Gravidade de Doença
11.
Plant Signal Behav ; 16(4): 1885888, 2021 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-33570443

RESUMO

Shoot branching is determined by axillary bud formation and outgrowth and remains one of the most variable determinants of yield in many crops. Plant nitrogen (N) acquired mainly in the forms of nitrate and ammonium from soil, dominates plant development, and high-yield crop production relies heavily on N fertilization. In this review, the regulation of axillary bud outgrowth by N availability and forms is summarized in plant species. The mechanisms of auxin function in this process have been well characterized and reviewed, while recent literature has highlighted that auxin export from a bud plays a critical role in N-modulating this process.

12.
Sci Total Environ ; 770: 145284, 2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-33515890

RESUMO

Neural tube defects (NTDs) are among the most common and disabling fetal congenital defects. Organochlorine pesticides (OCPs) are ubiquitous in the environment. In this study, 119 women who had NTD-affected pregnancies (cases) and 119 women who delivered healthy neonates (controls) were recruited in a rural area of Northern China. We used concentrations of OCPs in umbilical cord tissue as markers of prenatal exposure to investigate the association between in utero exposure to OCPs and NTD risk. Concentrations of 20 OCPs were quantified by gas chromatography-mass spectrometry, and 16 of the 20 OCPs were included in the analyses. Odds ratios and 95% confidence intervals (95% CIs) for the associations between levels of individual OCPs and NTD risk were estimated separately with logistic regression adjusting for potential confounders. The combined effects of exposure to the 16 OCPs as a mixture were analyzed with Bayesian kernel machine regression (BKMR). Logistic regression showed that the risk for NTDs increased 5.44-fold (95% CI, 2.21-13.41) for ß-hexachlorocyclohexane, 2.51-fold (95% CI, 1.07-5.86) for endosulfan I, 3.78-fold (95% CI, 1.60-8.89) for endosulfan II, 3.42-fold (95% CI, 1.44-8.12) for ο,ρ'-dichlorodiphenyldichloroethane, and 2.89-fold (95% CI, 1.22-6.86) for ρ,ρ'-dichlorodiphenyltrichloroethane when the concentration of each of these OCPs was above its median (exposed) compared to below its median (non-exposed). Other OCPs were not associated with NTD risk in multivariate models. In BKMR, NTD risk increased almost linearly with concentrations of the 16 OCPs as a mixture, which suggests joint effects on NTD risk. Exposure to α-hexachlorocyclohexane, ß-hexachlorocyclohexane, endosulfan II, ο,ρ'-dichlorodiphenyldichloroethane, and ρ,ρ'-dichlorodiphenyldichloroethane was associated with an increased risk for NTDs when levels of the remaining 15 OCPs were taken into account. Taken together, these findings show that prenatal exposure to OCPs is associated with increased risk for NTDs.


Assuntos
Hidrocarbonetos Clorados , Defeitos do Tubo Neural , Praguicidas , Efeitos Tardios da Exposição Pré-Natal , Teorema de Bayes , China/epidemiologia , Feminino , Humanos , Hidrocarbonetos Clorados/análise , Recém-Nascido , Defeitos do Tubo Neural/induzido quimicamente , Defeitos do Tubo Neural/epidemiologia , Gravidez
13.
J Cell Physiol ; 2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33438203

RESUMO

Intensive use of methotrexate (MTX) and/or dexamethasone (DEX) for treating childhood malignancies is known to cause chondrocyte apoptosis and growth plate dysfunction leading to bone growth impairments. However, mechanisms remain vague and it is unclear whether MTX and DEX combination treatment could have additive effects in the growth plate defects. In this study, significant cell apoptosis was induced in mature ATDC5 chondrocytes after treatment for 48 h with 10-5 M MTX and/or 10-6 M DEX treatment. PCR array assays with treated cells plus messenger RNA and protein expression confirmation analyses identified chemokine CXCL12 having the most prominent induction in each treatment group. Conditioned medium from treated chondrocytes stimulated migration of RAW264.7 osteoclast precursor cells and formation of osteoclasts, and these stimulating effects were inhibited by the neutralizing antibody for CXCL12. Additionally, while MTX and DEX combination treatment showed some additive effects on apoptosis induction, it did not have additive or counteractive effects on CXCL12 expression and its functions in enhancing osteoclastic recruitment and formation. In young rats treated acutely with MTX, there was increased expression of CXCL12 in the tibial growth plate, and more resorbing chondroclasts were found present at the border between the hypertrophic growth plate and metaphysis bone. Thus, the present study showed an association between induced chondrocyte apoptosis and stimulated osteoclastic migration and formation following MTX and/or DEX treatment, which could be potentially or at least partially linked molecularly by CXCL12 induction. This finding may contribute to an enhanced mechanistic understanding of bone growth impairments following MTX and/or DEX therapy.

14.
Ecotoxicol Environ Saf ; 208: 111632, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33396152

RESUMO

Titanium (Ti) is commonly used in additives in the form of titanium dioxide (TiO2). However, our understanding of the effect of Ti on reproductive health remains limited. This nested case-control study, performed in a Ti mining exposure field, investigated the association between maternal blood Ti concentration and the risk of low birth weight (LBW), as well as the potential biological mechanism. A total of 45 women who delivered LBW infants (cases) and 352 women with normal birth weight infants (controls) were included. We collected maternal peripheral blood samples in the first or early second trimester to measure Ti concentration in serum (Tisr) and blood cells (Tibc), as well as inflammatory, lipid, and oxidative stress biomarkers thereof. The demographic characteristics of the women included in the study were also obtained. The results showed that the median total blood Ti concentration (Titb) in the case group was significantly higher than that in the control group (134 vs. 129 ng/mL, P = 0.039). A higher Titb level was associated with a greater risk of LBW [odds ratio = 2.62; 95% confidence interval (CI): 1.16-5.90], but no such association was observed for Tisr or Tibc after adjusting for potential confounders. The serum lipid biomarkers TC, TG, and total lipids (TL) were all negatively associated with Tisr and Titb. Serum 8-OHdG was positively associated with Tibc. We concluded that a high Titb during early pregnancy may increase the risk of LBW. Lipid metabolism and oxidative stress may play an important role in the adverse health effects associated with Ti exposure. Thus, our results merit more attention to the probable adverse effects of titanium exposure during pregnancy.


Assuntos
Recém-Nascido de Baixo Peso , Exposição Materna/efeitos adversos , Saúde Reprodutiva , Titânio/toxicidade , Adulto , Estudos de Casos e Controles , China , Feminino , Humanos , Recém-Nascido , Metabolismo dos Lipídeos/efeitos dos fármacos , Razão de Chances , Estresse Oxidativo/efeitos dos fármacos , Gravidez , Titânio/sangue
15.
J Clin Hypertens (Greenwich) ; 23(4): 835-842, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33507600

RESUMO

Studies have shown that maternal blood pressure level is associated with neonatal birthweight, but the results are not exactly consistent. As the most common hypertensive disorders during pregnancy, the mechanism of gestational hypertension and pre-eclampsia that affect fetal growth remain unclear. Our objective was to examine the association of gestational hypertension and pre-eclampsia with the risk of low birthweight (LBW) and small-for-gestational-age (SGA). Data were obtained from the China-US Collaborative Project for Neural Tube Defects Prevention, a large population-based cohort study. We selected participants who were registered in two southern provinces, had exact information on gestational blood pressure and pregnancy outcomes, and were not affected by chronic hypertension. Logistic regression was used to adjust for the effects of the main potential confounders, including age, body mass index, education, occupation, ethnicity, folic acid use, and parity. The overall incidences of LBW and SGA were 2.25% and 5.86%, respectively. The incidences of LBW/SGA were 3.58%/7.58% and 6.02%/10.67% for gestational hypertension and pre-eclampsia group, relative to 2.11%/5.68% and 2.16%/5.74% for normal group. The adjusted odds ratios associated with gestational hypertension/pre-eclampsia were 1.77 (95% CI: 1.63, 1.92)/3.01 (95% CI: 2.67, 3.40) for LBW and 1.40 (95% CI: 1.32, 1.48)/2.02 (95% CI: 1.84, 2.22) for SGA, respectively. The early onset of gestational hypertension/pre-eclampsia appeared to be a relatively more detrimental exposure window for both LBW and SGA. Our results support an association between gestational hypertension or pre-eclampsia and the increased risk of LBW and SGA.

16.
J Matern Fetal Neonatal Med ; 34(2): 274-280, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31006286

RESUMO

Background: Case-control studies have consistently suggested an association between pre- or periconceptional maternal obesity and an increased risk for neural tube defects (NTDs). Few studies have examined the association between body mass index (BMI) and NTDs using measured weight and height. We examined this association in a large cohort study in China.Methods: We used data from a large population-based cohort study established to evaluate the effectiveness of folic acid supplementation to prevent NTDs in China. BMI was computed using maternal weight and height measured before pregnancy or during early pregnancy. External birth defects were identified through a unique birth defects surveillance system. We estimated the birth prevalence and prevalence odds ratios (POR) for NTDs by Chinese BMI categories, controlling for potential confounders.Results: Our study population included a total of 194,844 women. We observed significantly elevated risk for spina bifida (adjusted POR = 5.4, 95% CI: 1.3-22.5) among children born to obese compared to normal weight women. Among women who took folic acid supplements, the adjusted POR for spina bifida among obese women was 10.0 (95% CI: 2.3-42.6) compared to pill users who were of normal weight. Borderline significantly elevated risk was observed for anencephaly (adjusted POR = 1.8; 95% CI: 1.0-3.2) among children born to underweight compared to normal weight women.Conclusions: Our findings suggest that maternal periconceptional obesity may be associated with an increased risk for spina bifida. Maternal underweight may be associated with increased risk for anencephaly.

17.
Proc Natl Acad Sci U S A ; 118(2)2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33372138

RESUMO

Precise regulation of coinhibitory receptors is essential for maintaining immune tolerance without interfering with protective immunity, yet the mechanism underlying such a balanced act remains poorly understood. In response to protein immunization, T follicular helper (TFH) cells lacking Tcf1 and Lef1 transcription factors were phenotypically normal but failed to promote germinal center formation and antibody production. Transcriptomic profiling revealed that Tcf1/Lef1-deficient TFH cells aberrantly up-regulated CTLA4 and LAG3 expression, and treatment with anti-CTLA4 alone or combined with anti-LAG3 substantially rectified B-cell help defects by Tcf1/Lef1-deficient TFH cells. Mechanistically, Tcf1 and Lef1 restrain chromatin accessibility at the Ctla4 and Lag3 loci. Groucho/Tle corepressors, which are known to cooperate with Tcf/Lef factors, were essential for TFH cell expansion but dispensable for repressing coinhibitory receptors. In contrast, mutating key amino acids in histone deacetylase (HDAC) domain in Tcf1 resulted in CTLA4 derepression in TFH cells. These findings demonstrate that Tcf1-instrinsic HDAC activity is necessary for preventing excessive CTLA4 induction in protein immunization-elicited TFH cells and hence guarding their B-cell help function.

18.
Sci Total Environ ; 752: 141824, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-32896789

RESUMO

Chromium (Cr) can coexist with other heavy metals in the blood of chronically chromate-exposed individuals. However, few studies have explored the health impacts of other hazardous metals after exposure to hexavalent chromium [Cr(VI)]. This study aimed to assess the modification effects of blood lead (Pb) on the genetic damage induced by Cr(VI). During 2010-2019, 1000 blood samples were collected from 455 workers exposed to chromate and 545 workers not exposed to chromate from the same factory with similar labor intensity. The levels of Cr and Pb were measured in whole blood samples. Micronucleus frequency (MNF) and urinary 8-hydroxydeoxyguanosine (8-OHdG) were measured to reflect different types of genetic damage. Multivariate linear regression analyses were performed to evaluate the associations between hazardous metals and the modification effects of Pb on genetic damage. The geometric mean levels of Cr and Pb in the exposure group were significantly higher than those in the control group [Cr: 6.42 (6.08- 6.79) vs. 1.29 (1.22- 1.36) µg/L; Pb: 38.82 (37.22- 40.50) vs. 34.47 (33.15- 35.85) µg/L]. The geometric means of urinary 8-OHdG and MNF in exposure group were 4.00 (3.64- 4.40) µg/g and 5.40 (4.89- 5.97) ‰, respectively, significantly higher than the 3.20 (2.94- 3.48) µg/g and 4.57 (4.15- 5.03) ‰, respectively, in control group. log2Cr was independently and positively associated with urinary 8-OHdG (ß-adjusted = 0.143, 95% CI: 0.082- 0.204) and MNF (ß-adjusted = 0.303, 95%CI: 0.020- 0.587). With the change in circulating Pb levels, the types of genetic damage induced by Cr(VI) were different. At low levels of circulating Pb (<30.80 µg/L), chromate mainly caused changes in 8-OHdG, while at high circulating Pb levels (≥44.88 µg/L), chromate induced alterations in MNF. The findings suggested that chromate exposure could cause multiple types of genetic damage, and circulating Pb might modify the association between circulating Cr and the form of genetic damage.


Assuntos
Cromatos , Exposição Ocupacional , Cromatos/toxicidade , Cromo/toxicidade , Estudos Epidemiológicos , Humanos , Chumbo/toxicidade , Exposição Ocupacional/análise
19.
Medicine (Baltimore) ; 99(49): e23518, 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33285764

RESUMO

BACKGROUND: Chronic kidney disease (CKD) as a disease that poses a great threat to human health, which has become a public health issue of great concern. Studies have found that exercise training has a positive effect on improving the condition of chronic kidney disease. We will conduct a network meta-analysis to assess the effects of aerobic training, resistance training and combined aerobic and resistance training in treating CKD patients. METHODS: We will search PubMed, EMBASE, Medline, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of science to identify randomized control trails (RCTs) that assessed the effect of different exercise training for CKD patients. Cochrane Handbook will be used to evaluate the risk of bias of included articles. We will use Stata or R software to perform data analysis. RESULTS AND CONCLUSION: Our systematic review and network meta-analysis will be the first study that investigates the effect of different exercise training for CKD patients, and will provide evidence for management of chronic kidney disease. ETHICS AND DISSEMINATION: The data involved in this study are from published articles. For this reason, there is no need for ethical approval or patient consent. TRIAL REGISTRATION: the registration number was: CRD42020157280.

20.
Emerg Microbes Infect ; : 1-22, 2020 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-33296295

RESUMO

Hepatitis B e antigen (HBeAg) is a widely-used marker both for chronic hepatitis B (CHB) clinical management and HBV-related basic research. However, due to its high amino acid sequence homology to hepatitis B core antigen (HBcAg), most of available anti-HBe antibodies are cross-reactive with HBcAg resulting in high interference against accurate measurement of the status and level of HBeAg. In the study, we generated several monoclonal antibodies (mAbs) targeting various epitopes on HBeAg and HBcAg. Among these mAbs, a novel mAb 16D9, which recognizes the SKLCLG (aa -10 to -5) motif on the N-terminal residues of HBeAg that is absent on HBcAg, exhibited excellent detection sensitivity and specificity in pairing with another 14A7 mAb targeting the HBeAg C-terminus (STLPETTVVRRRGR, aa141 to 154). Based on these two mAbs, we developed a novel chemiluminescent HBeAg immunoassay (NTR-HBeAg). By using HBV cell culture samples and sera from patients with chronic HBV infection, we demonstrated the new assay could detect HBeAg derived from various HBV genotypes. In contrast to widely-used commercial assays, the NTR-HBeAg completely eliminated the cross-reactivity with secreted HBcAg from precore mutant (G1896A) virus in either cell culture or patient sera. The improved specificity of the NTR-HBeAg assay enables its applicability in cccDNA-targeting drug screening in cell culture systems, and also provides an accurate tool for clinical HBeAg detection. Trial registration: Netherlands National Trial Register identifier: NTR-..

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