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1.
Food Funct ; 2021 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-33903876

RESUMO

Maternal vitamin supplementation has been demonstrated to reduce the risks of a number of neurodevelopmental diseases in children. Autism spectrum disorder (ASD) is a group of neurodevelopment defects with high prevalence but without satisfactory therapy. The present work detected the effects of pregnancy supplementation with folic acid (FA) at different doses on rat models of ASD induced by prenatal exposure to valproic acid (VPA), an anti-epileptic increasing the risk of ASD when administered during pregnancy. The results show that maternal FA supplementation at a high dose (4 mg kg-1) prevented the delay in growth and development, and the deficits in social communicative behaviors and repetitive behaviors, possibly by restoring the increased dendritic spine density and rectifying the over-expression of synaptic proteins associated with excitatory neurons and the lower expression with inhibitory ones. The results provided experimental evidence suggesting a possible role of maternal FA supplementation in preventing ASD.

2.
Sci Rep ; 11(1): 8394, 2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33863942

RESUMO

Schizotypy, a subclinical group at risk for schizophrenia, has been found to show impairments in response inhibition. However, it remains unclear whether this impairment is accompanied by outright stopping (reactive inhibition) or preparation for stopping (proactive inhibition). We recruited 20 schizotypy and 24 non-schizotypy individuals to perform a modified stop-signal task with electroencephalographic (EEG) data recorded. This task consists of three conditions based on the probability of stop signal: 0% (no stop trials, only go trials), 17% (17% stop trials), and 33% (33% stop trials), the conditions were indicated by the colour of go stimuli. For proactive inhibition (go trials), individuals with schizotypy exhibited significantly lesser increase in go response time (RT) as the stop signal probability increasing compared to non-schizotypy individuals. Individuals with schizotypy also exhibited significantly increased N1 amplitude on all levels of stop signal probability and increased P3 amplitude in the 17% stop condition compared with non-schizotypy individuals. For reactive inhibition (stop trials), individuals with schizotypy exhibited significantly longer stop signal reaction time (SSRT) in both 17% and 33% stop conditions and smaller N2 amplitude on stop trials in the 17% stop condition than non-schizotypy individuals. These findings suggest that individuals with schizotypy were impaired in both proactive and reactive response inhibition at behavioural and neural levels.

3.
Chin J Nat Med ; 19(4): 241-254, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33875165

RESUMO

Angelicae Sinensis Radix (Danggui) and Ligusticum Chuanxiong Rhizoma (Chuan Xiong) herb-pair (DC) have been frequently used in Traditional Chinese medicine (TCM) prescriptions for hundreds of years to prevent vascular diseases and alleviate pain. However, the mechanism of DC herb-pair in the prevention of liver fibrosis development was still unclear. In the present study, the effects and mechanisms of DC herb-pair on liver fibrosis were examined using network pharmacology and mouse fibrotic model. Based on the network pharmacological analysis of 13 bioactive ingredients found in DC, a total of 46 targets and 71 pathways related to anti-fibrosis effects were obtained, which was associated with mitogen-activated protein kinase (MAPK) signal pathway, hepatic inflammation and fibrotic response. Furthermore, this hypothesis was verified using carbon tetrachloride (CCl4)-induced fibrosis model. Measurement of liver functional enzyme activities and histopathological examination showed that DC dramatically reduced bile acid levels, inflammatory cell infiltration and collagen deposition caused by CCl4. The increased expression of liver fibrosis markers, such as collagen 1, fibronectin, α-smooth muscle actin (α-SMA) and transforming growth factor-ß (TGF-ß), and inflammatory factors, such as chemokine (C-C motif) ligand 2 (MCP-1), interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α) and IL-6 in fibrotic mice were significantly downregulated by DC herb-pair through regulation of extracellular signal-regulated kinase 1/2 (ERK1/2)-protein kinase B (AKT) signaling pathways. Collectively, these results suggest that DC prevents the development of liver fibrosis by inhibiting collagen deposition, decreasing inflammatory reactions and bile acid accumulation, which provides insights into the mechanisms of herb-pair in improving liver fibrosis.

4.
Theor Appl Genet ; 134(5): 1587-1599, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33677639

RESUMO

KEY MESSAGE: A novel Ug99-resistant wheat-Thinopyrum ponticum translocation line was produced, its chromosomal composition was analyzed and specific markers were developed. Stem rust caused by Puccinia graminis f. sp. tritici Eriks. & E. Henn (Pgt) has seriously threatened global wheat production since Ug99 race TTKSK was first detected in Uganda in 1998. Thinopyrum ponticum is near immune to Ug99 races and may be useful for enhancing wheat disease resistance. Therefore, developing new wheat-Th. ponticum translocation lines that are resistant to Ug99 is crucial. In this study, a novel wheat-Th. ponticum translocation line, WTT34, was produced. Seedling and field evaluation revealed that WTT34 is resistant to Ug99 race PTKST. The resistance was derived from the alien parent Th. ponticum. Screening WTT34 with markers linked to Sr24, Sr25, Sr26, Sr43, and SrB resulted in the amplification of different DNA fragments from Th. ponticum, implying WTT34 carries at least one novel stem rust resistance gene. Genomic in situ hybridization (GISH), multicolor fluorescence in situ hybridization (mc-FISH), and multi-color GISH (mc-GISH) analyses indicated that WTT34 carries a T5DS·5DL-Th translocation, which was consistent with wheat660K single-nucleotide polymorphism (SNP) array results. The SNP array also uncovered a deletion event in the terminal region of chromosome 1D. Additionally, the homeology between alien segments and the wheat chromosomes 2A and 5D was confirmed. Furthermore, 51 PCR-based markers derived from the alien segments of WTT34 were developed based on specific-locus amplified fragment sequencing (SLAF-seq). These markers may enable wheat breeders to rapidly trace Th. ponticum chromosomal segments carrying Ug99 resistance gene(s).

5.
Asia Pac J Clin Nutr ; 30(1): 7-14, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33787035

RESUMO

BACKGROUND AND OBJECTIVES: Little is known about nutritional status in patients with hepatocellular carcinoma (HCC) after multiple rounds of transarterial chemoembolization (TACE). We established a comprehensive nutritional index (CNI) and evaluated its prognostic value for overall survival (OS) and time to progression (TTP). METHODS AND STUDY DESIGN: HCC patients (N=282) who underwent multiple TACE treatments were enrolled. CNI was established by principal component analysis based on body mass index, usual body weight percentage, hemoglobin, total lymphocyte count, and albumin; the cutoff value was determined by receiver operating characteristic curve and Youden index analysis. The correlation between CNI and treatment-related complications was analyzed with Spearman's method. The Kaplan-Meier method with log-rank test and Cox proportional hazards model were used to compare the prognostic values of CNI, prognostic nutritional index (PNI), and nutrition risk index (NRI) for OS and TTP. RESULTS: Nutritional status declined after repeated TACE (p<0.001). CNI (cutoff= 0.251) varied according to albumin-bilirubin grade, tumor size, and number of TACE treatments (p<0.001 or 0.025) and was negatively correlated with rate of serious complications (r=-0.185, p=0.002). Patients with low CNI had shorter OS (p=0.014) and TTP (p=0.007); high CNI predicted longer OS (hazard ratio [HR], 0.72; 95% confidence interval [CI]: 0.52-1.00, p=0.048) and TTP (HR, 0.69; 95% CI: 0.50-0.94, p=0.019). Post-treatment PNI and NRI were unrelated to prognosis (p>0.05). CONCLUSIONS: HCC patients have poor nutritional status after multiple TACE treatments, which predicts shorter OS and TTP. The prognostic performance of CNI is superior to those of PNI and NRI.

6.
Mol Immunol ; 133: 184-193, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33744653

RESUMO

Natural killer enhancing factor (NKEF)-A/B is a member of Peroxiredoxin (Prxs) family, which is named for the function of enhancing NK cells activity. NKEF also plays essential roles in multiple physiology/pathology processes including inflammation regulation, cancer development and redox reactions. However, the regulatory effects of fish NKEF on immune cells remain largely unknown. In this study, the full-length cDNA of NKEF-A (Accession No. MK584553, designated as On-NKEF-A) was identified from Nile tilapia (Oreochromis niloticus). On-NKEF-A encoded a 198 amino acid peptide with molecular mass of 22.085 kDa. On-NKEF-A protein contained a typical 2-Cys family domain, two active sites (51aa and 172aa) that were conserved in mammals, birds, amphibians and fish. Phylogenetic analysis showed that On-NKEF-A had the closest relationship with Zebra mbuna (Maylandia zebra) NKEF. The On-NKEF-A transcription was present in all examined tissues or organs. And the relative high expression levels of On-NKEF-A was found in head kidney leucocytes and nonspecific cytotoxic cells (NCC). After Streptococcus agalactiae stimulation, On-NKEF-A was significantly up-regulated in head kidney, spleen, gill and skin. Also, On-NKEF-A was markedly induced post S. agalactiae, LPS and poly I:C stimulation in head kidney-derived NCC. Moreover, On-NKEF-A was mainly distributed in cytoplasm of fathead minnow cells (FHM cells). The further in vitro analysis found that the recombinant protein of On-NKEF-A (rOn-NKEF-A) could induce the expression of various molecular markers of B cells, macrophages and NCC, enhanced the cytotoxicity of NCC via increasing the effectors expression. The present data collectively indicate that On-NKEF-A participates in anti-bacterial immune response via regulating NCC activity, which will provide new ideas to further explore the defense mechanism of fish against bacteria.

7.
Hear Res ; 404: 108211, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33684887

RESUMO

The cochlear implant (CI) has an effective habilitation modality for hearing-impaired children by promoting sound perception, vocalization, and language ability. However, the major challenge that remained was the lack of assessment standards for pediatric CI users, especially prelingually deaf children, to evaluate hearing rehabilitation effectiveness. In the present study, we conducted an oddball paradigm with stimuli varying in pure-tone, syllable, and tonal sounds. After implantation, we utilized cortical auditory evoked potential (CAEP) and mismatch negativity (MMN) to obtain time-domain analysis; meanwhile, the source localization was investigated to obtain spatial accuracy of the plasticity in the auditory cortex. P1 started to emerge at the third month after implantation, but its peak level was not significant until the sixth month. The temporal lobe was activated between the third and sixth months after implantation. The MMN waveform was basically normal approximately after 12 months. These results suggest that the auditory system goes through a critical period of rapid development between three and six months and enters a maturation period after 12 months. This work indicates that CAEPs are more suitable for assessing the early auditory system reconstruction, while MMN performs better in evaluating the advanced auditory function. Furthermore, source localization has proven to be an efficient tool in exploring auditory cortex plasticity, especially for pediatric CI users.

8.
Nucl Med Biol ; 96-97: 27-34, 2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33725499

RESUMO

INTRODUCTION: Due to individual deviations in tumor tissue uptake, the role of [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography (PET) in hepatocellular carcinoma (HCC) diagnosis is limited. ß-Hydroxy ß-methylglutaryl-CoA reductase degradation 1 (HRD1) plays a key role in clearing misfolded proteins. This study is aimed to investigate the role and mechanism of HRD1 in [18F]FDG uptake for the diagnosis of HCC. METHODS: HRD1 expression level was detected using immunohistochemical (IHC) staining in 9 HCC patients. [18F]FDG PET/CT scans were conducted before treatment. [18F]FDG uptakes in HRD1 overexpressed and knockdown transgenic models were measured by γ-counter and microPET imaging. The GLUT1-HRD1 complex was examined by co-immunoprecipitation and IHC assays. GLUT1 expression in different cell lines, xenograft models and HCC patients was evaluated by Western blot and IHC assays. RESULTS: HRD1 was highly expressed in the HCC tumors of patients with low [18F]FDG uptake, while the HRD1 expression was obviously low in the higher [18F]FDG uptake group. Both in vitro and in vivo studies found that HRD1 significantly inhibited [18F]FDG uptake in HCC Huh7 cell lines and animal models. Furthermore, the co-location and interaction of HRD1 with GLUT1 were detected, and the results also indicate that HRD1 could induce the degradation of GLUT1 in vitro and in vivo. CONCLUSION: HRD1 inhibits the high uptake of [18F]FDG in HCC tumor cells by inducing degradation of GLUT1, which leads to decreased diagnostic efficiency of [18F]FDG PET imaging for HCC. ADVANCES IN KNOWLEDGE: This study suggests that HRD1 inhibits the high uptake of [18F]FDG in HCC tumor by inducing degradation of GLUT1. IMPLICATIONS FOR PATIENT CARE: HCC diagnosis with [18F]FDG PET should be accompanied by determination of HRD1 expression, and patients with high tumor HRD1 expression might be unsuitable for [18F]FDG PET.

9.
Theriogenology ; 165: 92-98, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33647740

RESUMO

MicroRNAs (miRNAs) are key epigenomic regulators of proliferation, differentiation, and secretion in cells involved in follicular development. We here studied the functional role of one such molecule, miR-130a-3p, in goat ovarian granulosa cells (GCs). High expression of this miRNA was evident in goat GCs by fluorescence in situ hybridization and suppressed estradiol and progesterone secretion from these cells, as determined by ELISA. miR-130a-3p was predicted to have a binding site for the 3' UTR of the prostate transmembrane protein androgen induced 1 gene (PMEPA1), and this was verified by a dual-luciferase reporter assay. PMEPA1 mRNA and protein expression were both found to be regulated by miR-130a-3p in GCs. Moreover, the overexpression or knockdown of PMEPA1 enhanced or suppressed estradiol and progesterone secretion from these cells, respectively. Furthermore, the secretion of estradiol and progesterone did not change significantly after the offsetting of PMEPA1 overexpression in GCs by miR-130a-3p. In summary, our present data indicate that miR-130a-3p inhibits the secretion of estradiol and progesterone in GCs by targeting PMEPA1. Our study thus provides seminal data and important new insights into the regulation of reproductive mechanisms in the nanny goat and other female mammals.

10.
Oncol Rep ; 45(4)2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33649843

RESUMO

Triggering receptor expressed on myeloid cells­1 (TREM1) is a cell­surface protein expressed on tumor­associated macrophages (TAMs), the predominant inflammatory cells in the tumor microenvironment; however, the mechanisms for the influence of TREM1 on TAM polarization during liver cancer progression have not been investigated. In the present study, 20 patients diagnosed with hepatocellular carcinoma (HCC) who underwent surgery were enrolled, and TREM1 expression on M1/M2 macrophages and on M2 macrophages was assessed by immunohistochemical staining. Human leukemia monocytic cells (THP­1) were differentiated into M2 macrophages using phorbol 12­myristate 13­acetate, IL­4 and IL­13. A specific short hairpin RNA was used to knockdown TREM1 expression. To investigate the effects of TREM1 downregulation in macrophages on the migration and invasion of liver cancer cells, HepG2 and MHCC97H cell lines were co­cultured with specific conditioned media. Reverse transcription­quantitative PCR and western blot analyses were used to detect M1 and M2 macrophage marker expression. The expression levels of proteins of the PI3K/AKT/mTOR signaling pathway were analyzed by western blotting, revealing that TREM1 expression in HCC tissues was significantly elevated compared with that in adjacent normal tissues, and TREM1 was highly expressed on the cell membranes of M2 macrophages in tumor tissues compared with in adjacent normal tissues. The present results demonstrated that TREM1 downregulation in macrophages shifted M2 macrophages towards an M1 phenotype, as defined by higher expression levels of M1­associated markers and decreased expression levels of M2­associated markers. In addition, TREM1 downregulation in macrophages suppressed migration and invasion of HepG2 and MHCC97H cells. Furthermore, TREM1­knockdown in macrophages inhibited PI3K/AKT/mTOR activation in the polarization of M2 macrophages. In conclusion, downregulation of TREM1 expression in macrophages shifted M2 macrophages towards a M1 phenotype via inhibiting PI3K/AKT signaling. In addition, migration and invasion of HepG2 and MHCC97H cells were inhibited when this signaling pathway was blocked. The present findings suggest TREM1 as a novel potential therapeutic target for liver cancer management.

11.
Math Biosci ; 335: 108572, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33662405

RESUMO

For nearly eight decades the Luria-Delbrück protocol remains the preferred method for experimentally determining microbial mutation rates. However, earnest development and rigorous applications of statistical methods for mutation rate comparison using fluctuation assay data are a relatively recent phenomenon. While likelihood ratio tests tailored for the fluctuation protocol give investigators appropriate tools, researchers sometimes may prefer to view the comparison of two mutation rates through the lens of the ratio of the two mutation rates. The idea of using the bootstrap technique to construct intervals for mutation rate fold change was proposed nearly a decade ago, but it failed to gain traction partly due to a failure to incorporate likelihood-based estimation. In addition to extending the bootstrap method, this paper proposes two new methods of constructing intervals for mutation rate fold change: a profile likelihood method and a Bayesian method utilizing Monte Carlo Markov chain. All three methods are assessed by large-scale simulations.

12.
Zhongguo Gu Shang ; 34(1): 73-80, 2021 Jan 25.
Artigo em Chinês | MEDLINE | ID: mdl-33666024

RESUMO

OBJECTIVE: To compare the clinical effects of three different methods of binding multi-fold rib graft, iliac bone graft and titanium mesh graft in tuberculosis of thoracic vertebra by approach of transverse rib process. METHODS: A hundred and seven patients with tuberculosis of thoracic vertebra received surgical treatment from January 2010 to December 2016 were retrospectively analyzed. The patients were divided into three groups according different methods of bone graft. The surgical approach of the transverse rib process was used in all 107 patients, after thoroughly remove the necrotic tissue of tuberculosis, three different bone grafts were used respectively including iliac bone graft (36 cases, group A), binding multi-fold rib graft (35 cases, group B), titanium mesh bone graft (36 cases, group C). Perioperative indexes, the time required for bone graft during operation, intraoperation blood loss, the loss rate of the anterior edge of the lesion, Cobb angle, postoperative bone graft fusion time, spinal nerve recovery and Oswestry Disability Index were compared among three groups. RESULTS: All the patients were followed up for 13 to 24 months, and the operation time required for bone graft was (23.2±4.1) min in group A, (23.8± 4.4)min in group B, and (25.5±4.2) min in group C, with no statistically significant difference among three groups (P>0.05). Intraoperative blood loss was (541.6±35.3) ml in group A, (546.8±27.8) ml in group B, and (540.1±34.5) ml in group C, withno statistically significant difference among three groups(P>0.05). Preoperative anterior vertebral height loss rate was (46.0± 3.1)% in group A, (46.4±3.3)% in group B, and (45.3±3.6)% in group B;at the final follow up, the loss rate of anterior vertebral height among three groups was (8.6±5.0)%, (8.1±4.2)%, (9.4±4.3)%, respectively. There were no statistically significant differences before operation and final follow-up among three groups (P>0.05). Preoperative Cobb angle was (35.1±4.8)° in group A, (35.2±4.5)° in group B and (35.2±4.5)° in group C, with no statistically significant difference among three groups (P>0.05);postoperative at 3 days, Cobb angle in three groups was (15.1±3.6)°, (15.3±3.1)° and (15.2±3.4)°, respectively, there was no statistically significant difference among three groups (P>0.05);at the final follow-up, the Cobb angle among three groups was (17.7±3.3)°, (17.9±3.9)°, (18.6±3.6)°, respectively, with no statistically significant difference among three groups (P>0.05). The time of bone graft fusion was (5.6±0.5) months in group A, (5.6±0.6) months in group B and (5.8±0.6)months in group C, with no statistically significant difference among three groups (P>0.05). Frankel classification at the final follow up, 4 cases were grade B, 7 cases were grade C, 10 cases were grade D, and 86 cases were grade E. Spinal nerve function in all three groups recovered to a certain extent after treatment, with no statistically significant difference among three groups (P> 0.05). Oswestry Disability Index at the final follow-up showed no statistically significant difference among three groups (P> 0.05). CONCLUSION: The approach of transverse rib process for debridement of lesions can effectively treat tuberculosis of thoracic vertebra by binding multi-fold rib graft, iliac bone graft and titanium mesh graft, but binding multi-fold rib graft can effectively avoid iliac bone donor complications, and is an effective alternative to iliac bone graft, which is worth popularizing.


Assuntos
Fusão Vertebral , Tuberculose da Coluna Vertebral , Transplante Ósseo , Humanos , Vértebras Lombares , Estudos Retrospectivos , Costelas/cirurgia , Telas Cirúrgicas , Vértebras Torácicas/cirurgia , Titânio , Resultado do Tratamento , Tuberculose da Coluna Vertebral/cirurgia
14.
Orthop Surg ; 2021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33686801

RESUMO

OBJECTIVE: To evaluate whether it is safe and effective for orthopaedic medical staff to provide support to the work against COVID-19. METHODS: One hundred and twenty-two orthopaedic medical staff from the orthopaedic center of Zhongnan Hospital of Wuhan University were included in this retrospective investigation. A total of 43 surgeons and 69 nurses provided medical support in the treatment of COVID-19 patients from 1 January 2020 to 8 April 2020 in four different hospitals in Wuhan. We collected data on the age, gender, and body temperature of orthopaedic medical staff, as well as the results for their chest CT scans, SARS-CoV-2 RNA, SARS-CoV-2 IgM and SARS-CoV-2 IgG tests, and training and examinations on COVID-19 knowledge. We also collected data on the time span of work, the number of infected staff during the support period, the number of COVID-19 patients the surgeons treated and the cure rate, the performance of the surgeons as assessed by the specialists and patients, and the number of infected staff during the pandemic. RESULTS: Among the 49 surgeons and 73 nurses, 43 surgeons and 69 nurses provided support against COVID-19. A total of 12 surgeons and 11 nurses provided support in the fields of respiration, intensive care, and emergency. A total of 34 surgeons and 58 nurses worked in the designated wards restructured for COVID-19 in the orthopaedic building. The average time span of work for the surgeons and nurses was 14.78 ± 3.64 days and 24.77 ± 7.58 days, respectively. No staff were infected during the support period. Over 1000 patients were received in the fever clinic by orthopaedic surgeons. The overall number of the treated hospitalized patients was 622. Among these patients, 226 cases were mild, 318 were mild to moderate, and 58 were severe or critical. The cure rate was 96.01%, 99.37%, and 52.00% respectively. The performance of the surgeons was scored 87.02 ± 3.17 and 90.69 ± 3.58 by the specialists and the patients, respectively. During the whole pandemic, 3 surgeons and 3 nurses who did not participate in the support work were infected in the early stages. The morbidity of all the orthopaedic staff was 4.92% during the whole pandemic, while no one was infected during the support work. CONCLUSION: Our investigation indicated that although they worked outside their specialty, it was safe and effective for the orthopaedic staff to provide medical support in the work against COVID-19 with adequate precautions and proper training.

15.
Phytomedicine ; 84: 153495, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33611210

RESUMO

BACKGROUND: Ulcerative colitis (UC) is a chronic relapsing inflammatory disease that markedly elevates the risk of colon cancers and results in disability. The disrupted immune homeostasis has been recognized as a predominant player in the pathogenesis of UC. However, the overall remission rate of current therapies based on immunoregulation is still unsatisfactory. Si-Ni-San (SNS) has been found effective in relieving UC through thousands of years of clinical practice, yet the specific mechanisms of the protective effect of SNS were not fully elucidated. PURPOSE: We aim to investigate the therapeutic effects of SNS against the development of chronic colitis and the underlying mechanisms. METHODS: We established a DSS-induced chronic experimental colitis mouse model to evaluate the effect of SNS. RNA-sequencing, bioinformatic analysis, and in vitro studies were performed to investigate the underlying mechanisms. RESULTS: Our data demonstrated that SNS significantly ameliorated chronic experimental colitis via inhibiting the expression of genes associated with inflammatory responses. Interestingly, SNS significantly suppressed DSS-induced type I interferon (IFN) responses instead of directly downregulating the production of pro-inflammatory cytokines, such as Il-6. In vitro study further found that SNS selectively inhibited STING and RIG-I pathway-induced type I IFN responses by modulating TBK1- and IRF3-dependent signaling transduction. SNS also suppressed the expression of IFN-stimulated genes by directly inhibiting STAT1 and STAT2 activation. CONCLUSION: Our study not only provides novel insights into the pathogenic role of type I IFN responses in colitis but also suggested that SNS or bioactive compounds derived from SNS may serve as novel therapeutic strategies for the treatment of UC via interfering type I IFN-mediated inflammation.

16.
Medicine (Baltimore) ; 100(6): e24593, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33578559

RESUMO

BACKGROUND: The goals of improving quality of life and increasing longevity are receiving growing amounts of attention. Body weight and lipid metabolism are closely related to various complications of diabetes. The aim of this study was to rank SGLT inhibitors according to their efficacy with regard to weight and evaluate the effect of SGLT inhibitors on lipid metabolism at 24 weeks of treatment. METHODS: The Web of Science, PubMed, Cochrane Library, Embase, and Clinical Trials databases were electronically searched to collect randomized controlled trials involving patients with type 2 diabetes mellitus through June 2020. Two researchers independently screened and evaluated the selected studies and extracted the outcome indexes. ADDIS 1.16.5 and STATA 16 software were used to perform the network meta-analysis and draw the plots. RESULTS: Ultimately, 36 studies were selected and included in this study. We found that all SGLT inhibitors were effective at reducing weight; canagliflozin was the most effective. SGLT inhibitors and placebo were not associated with significantly different serum cholesterol levels. SGLT inhibitors lowered serum triglyceride levels and increased serum high-density and low-density lipoprotein cholesterol levels. SGLT inhibitors also reduced the level of alanine aminotransferase. CONCLUSIONS: SGLT inhibitors can bring about weight loss in patients with T2DM and can also improve lipid metabolism. Therefore, patients with hyperlipidemia who have been unsuccessful at losing weight should consider taking SGLT inhibitors. In addition, SGLT inhibitors are hepatoprotective and appear to be safe for patients with mild to moderate liver dysfunction. TRIAL REGISTRATION: CRD42020198516.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Metabolismo dos Lipídeos/efeitos dos fármacos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Peso Corporal/efeitos dos fármacos , Humanos , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia
17.
Medicine (Baltimore) ; 100(6): e24636, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33578582

RESUMO

BACKGROUND: To explore the accuracy and security of 3-dimensional (3D) printing technology combined with guide plates in the preoperative planning of thoracic tuberculosis and the auxiliary placement of pedicle screws during the operation. METHODS: Retrospective analysis was performed on the data of 60 cases of thoracic tuberculosis patients treated with 1-stage posterior debridement, bone graft fusion, and pedicle screw internal fixation in the Department of Orthopedics, Zhejiang Chinese Medicine and Western Medicine Integrated Hospital from March 2017 to February 2019. There were 31 males and 29 females; age: 41 to 52 years old, with an average of (46.6 ±â€Š2.0) years old. According to whether 3D printing personalized external guide plates are used or not, they are divided into 2 groups: 30 cases in 3D printing group (observation group), and 30 cases in pedicle screw placement group (control group). A 1:1 solid model of thoracic spinal tuberculosis and personalized pedicle guide plates was created using the 3D printing technology combined with guide plates in the observation group. Stability and accuracy tests were carried out in vitro and in vivo. 30 patients in the control group used conventional nail placement with bare hands. The amount of blood loss, the number of fluoroscopy, the operation time, and the occurrence of adverse reactions related to nail placement were recorded. After the operation, the patients were scanned by computed tomography to observe the screw position and grade the screw position to evaluate the accuracy of the navigation template. All patients were followed up for more than 1 year. Visual Analogue Scale scores, erythrocyte sedimentation rate, and C-reactive protein were evaluated before surgery, 6 months after surgery, and 12 months after surgery. RESULTS: Sixty patients were followed up for 6 to 12 months after surgery. One hundred seventy-five and 177 screws were placed in the 3D printing group and the free-hand placement group, respectively. The rate of screw penetration was only 1.14% in the 3D-printed group (all 3 screws were grade 1) and 6.78% in the free-hand nail placement group (12 screws, 9 screws were grade 1 and 3 screws were grade 2). The difference was statistically significant (P = .047). The operation time of the 3D printing group ([137.67 ±â€Š9.39] minutes), the cumulative number of intraoperative fluoroscopy ([4.67 ±â€Š1.03] times), and the amount of intraoperative blood loss ([599.33 ±â€Š83.37] mL) were significantly less than those in the manual nail placement group ([170.00 ±â€Š20.48] minutes, [9.38 ±â€Š1.76] times, [674.6 ±â€Š83.61] mL). The differences were statistically significant (P < .05). There was no significant difference in VAS score and Oswestry disability index score between the 2 groups of patients before operation, 3 and 6 months after operation (P > .05). CONCLUSION: The 3D printing technology combined with guide plate is used in thoracic spinal tuberculosis surgery to effectively reduce the amount of bleeding, shorten the operation time, and increase the safety and accuracy of nail placement.


Assuntos
Parafusos Ósseos , Fusão Vertebral , Vértebras Torácicas , Tuberculose da Coluna Vertebral/cirurgia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Impressão Tridimensional , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Tuberculose da Coluna Vertebral/diagnóstico por imagem
18.
Mol Plant Pathol ; 22(4): 422-439, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33559339

RESUMO

Histone-3-lysine-4 (H3K4) methylation is catalysed by the multiprotein complex known as the Set1/COMPASS or MLL/COMPASS-like complex, an element that is highly evolutionarily conserved from yeast to humans. However, the components and mechanisms by which the COMPASS-like complex targets the H3K4 methylation of plant-pathogenic genes in fungi remain elusive. Here we present a comprehensive analysis combining biochemical, molecular, and genome-wide approaches to characterize the roles of the COMPASS-like family in the rice blast fungus Magnaporthe oryzae, a model plant pathogen. We purified and identified six conserved subunits of COMPASS from M. oryzae: MoBre2 (Cps60/ASH2L), MoSpp1 (Cps40/Cfp1), MoSwd2 (Cps35), MoSdc1 (Cps25/DPY30), MoSet1 (MLL/ALL), and MoRbBP5 (Cps50), using an affinity tag on MoBre2. We determined the sequence repeat in dual-specificity kinase splA and ryanodine receptors domain of MoBre2 can interact directly with the DPY30 domain of MoSdc1 in vitro. Furthermore, we found that deletion of the genes encoding COMPASS subunits of MoBre2, MoSPP1, and MoSwd2 caused similar defects regarding invasive hyphal development and pathogenicity. Genome-wide profiling of H3K4me3 revealed that it has remarkable co-occupancy at the transcription start site regions of target genes. Significantly, these target genes are often involved in spore germination and pathogenesis. Decreased gene expression caused by the deletion of MoBre2, MoSwd2, or MoSpp1 was highly correlated with a decrease in H3K4me3. These results suggest that MoBre2, MoSpp1, and MoSwd2 function as a whole COMPASS complex, contributing to fungal development and pathogenesis by regulating H3K4me3-targeted genes in M. oryzae.

19.
J Pediatr ; 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33581106

RESUMO

OBJECTIVE: To identify clinical and laboratory predictors for early macrophage activation syndrome (MAS) associated with systemic juvenile idiopathic arthritis (sJIA). STUDY DESIGN: This is a retrospective cohort study of 149 sJIA patients, of which 27 patients had 31 episodes of MAS. We evaluated the clinical and laboratory features of sJIA patients with MAS and compared them with those without MAS. We focused our analysis on the overall process of MAS development, especially MAS onset. RESULTS: As shown in previous studies, we found a high percentage of fever, absence of arthritis, and central nervous system dysfunction at MAS onset in our study cohort. We also found that 35% MAS patients had hypotension although not shock, and 22.6% MAS patients had gastrointestinal involvement at MAS onset. Compared with MAS patients without hypotension, MAS patients with hypotension had higher ICU admission, presented with more arthritis, serositis, pneumonia, and gastrointestinal involvement, and had higher white blood cell and absolute neutrophil counts and serum bilirubin levels, and lower serum total protein. We confirmed laboratory markers such as platelet counts, lactate dehydrogenase, and aspartate aminotransferase can help to identify early MAS and that ferritin: ESR ratio of around 20.0 had a high diagnostic sensitivity and specificity for MAS. In addition, we discovered that the combination of interferon (IFN)-γ >17.1 pg/mL and interleukin (IL)-10 >7.8 pg/mL appeared to be a good cytokine pattern for the recognition of MAS onset. CONCLUSION: Sudden hypotension, elevated ferritin: ESR ratio, and the cytokine pattern of significantly increased IFN-γ and IL-10 levels are important markers for early identification of MAS in addition to the traditional characteristics of sJIA-associated MAS.

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