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1.
J Colloid Interface Sci ; 607(Pt 1): 556-567, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34520903

RESUMO

Here, we have developed a novel bilayer hollow amphiphilic biosorbent (BHAB-3) with large adsorption capacity, rapid adsorption kinetics, and cost-effective for the removal of Cr(VI) and Cu(II) from aqueous solutions. The synthesis was based on the clever use of freeze-drying to fix the structure, secondary modification of the carboxymethyl cellulose microspheres with polyethyleneimine and cross-linking by glutaraldehyde. The consequences of pH, initial concentration, contact time and temperature on adsorption were investigated. The Langmuir model fits showed that the maximum adsorption capacities of the two target heavy metal ions reached 835.91 and 294.79 mg/g, respectively. Moreover, BHAB-3 was characterized by SEM, FT-IR, TGA, and XPS synergistically, showing that it exhibits a strong complexation ability for Cu(II) and a strong electrostatic effect for Cr(VI). Adsorption and desorption experiments showed only a slight decrease in the adsorption capacity of the BHAB-3 for Cr(VI) and Cu(II) ions after 5 and 26 cycles, respectively. Given the excellent properties of this adsorbent, it is a promising candidate for heavy metal ion removal.


Assuntos
Poluentes Químicos da Água , Cátions , Cromo , Concentração de Íons de Hidrogênio , Espectroscopia de Infravermelho com Transformada de Fourier
2.
BMC Med ; 19(1): 287, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34724953

RESUMO

BACKGROUND: The 2017 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines for high blood pressure (BP) in adults came up with a new definition of hypertension with a threshold BP level of 130/80 mmHg. But the 2018 European Society of Cardiology (ESC)/European Society of Hypertension (ESH) guidelines adhered to a conventional hypertension definition as BP ≥ 140/90 mmHg. We aimed to compare the trajectories of cognitive decline between participants with BP < 130/80 mmHg in all BP measurement waves and others with all BP < 140/90 mmHg. METHODS: This pooled analysis involved middle-aged and older participants from three nationally representative ageing cohorts, including the Health and Retirement Study (HRS), the English Longitudinal Study of Ageing (ELSA), and the China Health Retirement Longitudinal Study (CHARLS). Participants were divided into the Normal (BP < 130/80 mmHg on all occasions throughout the study), the Borderline (BP < 140/90 mmHg on all occasions throughout the study but not in the Normal group), and the High (the rest of participants) BP groups. Global cognitive Z score was calculated from tests on memory, executive function, and orientation. RESULTS: A total of 17,590 participants (HRS 6964, median follow-ups 12 years; ELSA 5334, median follow-ups 16 years; CHARLS 5292, median follow-ups 7 years) were included. No significant difference in global cognitive decline rate was detected between the Normal and the borderline groups (men, pooled ß = - 0.006 standard deviation [SD]/year; 95% confidence interval [CI], - 0.020 to 0.008; P = 0.377; women, pooled ß = 0.006 SD/year; 95% CI - 0.005 to 0.018; P = 0.269). Participants in the High group had a significantly faster cognitive decline (men, pooled ß = - 0.011 SD/year; 95% CI - 0.020 to - 0.002; P = 0.013; women, pooled ß = - 0.017 SD/year; 95% CI - 0.026 to - 0.008; P < 0.001) than that in the Borderline group. CONCLUSIONS: Individuals in the Borderline group did not experience significantly faster cognitive decline compared with those in the Normal group. It might not be necessary for individuals with borderline BP (between 130/80 and 140/90 mmHg) to initiate antihypertension therapy in consideration of cognitive decline.


Assuntos
Disfunção Cognitiva , Hipertensão , Adulto , Idoso , Envelhecimento , Pressão Sanguínea , Determinação da Pressão Arterial , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/epidemiologia , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estados Unidos/epidemiologia
3.
Clin Genet ; 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34595750

RESUMO

Non-obstructive azoospermia (NOA) represents one of the most serious forms of male infertility caused by spermatogenic failure. Despite multiple genes found to be associated with human NOA, the genetic basis of this idiopathic disease remains largely unknown. FBXO43 is a direct inhibitor of the anaphase-promoting complex/cyclosome (APC/C) E3 ligase and crucially important in mouse spermatogenesis. In this study, for the first time, we identified a homozygous nonsense mutation in FBXO43 c.1747C > T:p.Gln583X in two NOA brothers from a Chinese consanguineous family via whole-exome sequencing. FBXO43 was absent from testicular tissue of the proband, and FBXO43-immunostaining signals were invisible in the affected seminiferous tubules. Furthermore, in humans, FBXO43 defects cause meiotic arrest within early diplotene of prophase I. The results here demonstrate the pathogenicity of this loss-of-function mutation and confirmed that spermatocytes were unable to complete meiotic divisions without FBXO43 in humans. In mouse testicular protein extracts, three subunits of the APC/C, including ANAPC2, ANAPC8 and ANAPC10, were validated to interact directly with FBXO43, whereas no interactions were detected for FBXO43 and SKP1. This study furthers our understanding of the genetic basis of human NOA and provides insights into FBXO43 and male infertility.

4.
Curr Med Sci ; 41(5): 869-879, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34669117

RESUMO

OBJECTIVE: To investigate the effects and mechanisms of genistein on the gene expression in the Wnt pathway in acute leukemia (AL) cells. METHODS: The expression of Wnt pathway genes and cell cycle-related genes were analyzed in two AL cell lines. Pyrophosphate sequencing was performed to determine the methylation degree. Then, the enrichment of H4K20me1 and H3K9ac was determined using ChIP-qPCR. Flow cytometry was used to analyze the cell cycle. RESULTS: The IC50 of genistein in the two AL cell lines was lower than that for the bone marrow mesenchymal stem cell line. Genistein upregulated H4K20me1, KMT5A and Wnt suppressor genes, including Wnt5a, and downregulated the downstream target genes of Wnt, such as c-myc and ß-catenin. The methylation degree and H3K9ac enrichment in the Wnt5a promoter region remained unchanged. However, the enrichment of H4K20me1 in the Wnt5a promoter and coding regions increased. In addition, genistein upregulated Phospho-cdc2, Myt1, Cyclin A, Cyclin E2, p21 and Phospho-histone H3, but downregulated Phospho-wee1. Cell cycle arrest was induced in the G2/M phase. CONCLUSION: Genistein inhibits the activation of the Wnt pathway by promoting the expression of Wnt5a through the activation of KMT5A and enrichment of H4K20me1 in the Wnt5a gene promoter and coding regions, rather than demethylation. Genistein also blocks the cell cycle in the G2/M phase. Therefore, genistein is a potential anti-leukemia drug.

5.
Front Nutr ; 8: 649422, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34692741

RESUMO

Introduction: As coronavirus Disease 2019 (COVID-19) has evolved into a global pandemic, increasing numbers of reports have linked obesity to more severe COVID-19 illness and death. However, almost all the studies focused on an increased risk of mortality or intensive care unit (ICU) admission among hospitalized obese patients with COVID-19. Is obesity also associated with the incidence of acute lung injury (ALI) in the patients with COVID-19? How about underweight patients? The answer is lacking. Therefore, our following research will answer the above two questions. Methods: We collected and analyzed epidemiologic, demographic, clinical, and laboratory data from 193 confirmed cases of COVID-19 at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology in Wuhan, China, between January 1, 2020, and March 13, 2020. They were followed up until April 15, 2020. Underweight was defined by body mass index (BMI) lower than 18.5 kg/m2, normal weight by 18.5-23.9 kg/m2, overweight by 24.0-27.9 kg/m2, and obesity as ≥28 kg/m2. Results: Among these patients, 5.70% were underweight, 58.03% were normal weight, 27.98% were overweight, and 8.29% were obese. Underweight patients were more likely to have a headache (P = 0.029). Obese patients were more likely than other groups to experience a decline in lymphocyte counts (P = 0.038), an increase in C-reactive protein (CRP; P = 0.023), bilateral multiple mottling, and ground glass opacity in the lungs (P = 0.007). Besides, the proportion of patients receiving human immunoglobulin + systematic corticosteroids treatment is the highest among the obese group compared with other BMI groups. After adjusting for potential confounders, underweight patients had a 6.483-fold higher (P = 0.012), and obese patients showed a 5.965-fold higher odds for developing ALI than normal-weight patients (P = 0.022). In addition, underweight patients were 3.255 times more likely than normal-weight patients to develop secondary infections (P = 0.041). Conclusions: Our study showed that both underweight and obese patients with COVID-19 tend to develop ALI compared with normal-weight patients. Underweight patients were more likely to develop a secondary infection than other patients.

6.
J Agric Food Chem ; 69(43): 12741-12752, 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34672194

RESUMO

Hyperuricemia is a metabolic disease caused by impaired uric acid (UA) metabolism. Ellagic acid (EA) is a natural small-molecule polyphenolic compound with known antioxidative and anti-inflammatory properties. Here, we evaluated the regulatory effects of EA on hyperuricemia and explored the underlying mechanisms. We found that EA is an effective xanthine oxidase (XOD) inhibitor (IC50 = 165.6 µmol/L) and superoxide anion scavenger (IC50 = 27.66 µmol/L). EA (5 and 10 µmol/L) treatment significantly and dose-dependently reduced UA levels in L-O2 cells; meanwhile, intraperitoneal EA administration (50 and 100 mg/kg) also significantly reduced serum XOD activity and UA levels in hyperuricemic mice and markedly improved their liver and kidney histopathology. EA treatment significantly reduced the degree of foot edema and inhibited the expression of NLPR3 pathway-related proteins in foot tissue of monosodium urate (MSU)-treated mice. The anti-inflammatory effect was also observed in lipopolysaccharide-stimulated RAW-264.7 cells. Furthermore, EA significantly inhibited the expressions of XOD and NLRP3 pathway-related proteins (TLR4, p-p65, caspase-1, TNF-α, and IL-18) in vitro and in vivo. Our results indicated that EA exerts ameliorative effects in experimental hyperuricemia and foot edema via regulating the NLRP3 signaling pathway and represents a promising therapeutic option for the management of hyperuricemia.


Assuntos
Hiperuricemia , Animais , Ácido Elágico , Hiperuricemia/tratamento farmacológico , Hiperuricemia/genética , Inflamassomos , Camundongos , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Xantina Oxidase
7.
Front Endocrinol (Lausanne) ; 12: 721198, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34552561

RESUMO

GLP-1 is derived from intestinal L cells, which takes effect through binding to GLP-1R and is inactivated by the enzyme dipeptidyl peptidase-4 (DPP-4). Since its discovery, GLP-1 has emerged as an incretin hormone for its facilitation in insulin release and reduction of insulin resistance (IR). However, GLP-1 possesses broader pharmacological effects including anti-inflammation, neuro-protection, regulating blood pressure (BP), and reducing lipotoxicity. These effects are interconnected to the physiological and pathological processes of Alzheimer's disease (AD), hypertension, and non-alcoholic steatohepatitis (NASH). Currently, the underlying mechanism of these effects is still not fully illustrated and a better understanding of them may help identify promising therapeutic targets of AD, hypertension, and NASH. Therefore, we focus on the biological characteristics of GLP-1, render an overview of the mechanism of GLP-1 effects in diseases, and investigate the potential of GLP-1 analogues for the treatment of related diseases in this review.

8.
Int J Biol Macromol ; 190: 919-926, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34530036

RESUMO

Novel millimeter hollow microspheres were fabricated from carboxymethyl cellulose microspheres and polyethyleneimine using glutaraldehyde as a crosslinking agent. The hollow microspheres prepared with different polyethyleneimine usages and different polyethyleneimine treatment time were investigated deeply and characterized via SEM-EDX, FT-IR, and BET surface area analysis. It was shown that polyethyleneimine could break the coordination bonds between the carboxyl and Al (III) in carboxymethyl cellulose microspheres, leading to the formation of hollow structures. Most importantly, the usage and treatment time of polyethyleneimine can distinctly tailor the structure of the carboxymethyl cellulose microspheres, resulting in the formation of different hollow microspheres with varied shell thickness and size. Most importantly, we found that the prepared hollow microspheres have excellent adsorption performance toward targeted methyl blue under testing conditions. By virtue of the large accessible amount of -NH2 groups and its unique hollow structure, this type of millimeter hollow microspheres have broad application prospects in the treatment of emerging contaminants in wastewater.

9.
Ann Transl Med ; 9(15): 1245, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34532382

RESUMO

Background: Caffeine is broadly present in tea, coffee, and cocoa, and is commonly consumed. The bone microenvironment might be damaged by excessive caffeine, which has been shown to exert negative effects on human health. In this study, we sought to determine whether excessive caffeine could damage the biological functions of bone marrow mesenchymal stem cells (BMSCs) and induce bone loss in mice, and further investigate effective therapeutic methods. Methods: BMSCs were treated with different concentrations of caffeine (0.01, 0.05, 0.1, 0.5, and 1.0 mM) for 48 h. Cell counting kit-8 (CCK-8) assay, colony formation assay, wound healing assay, and quantitative real-time polymerase chain reaction (qRT-PCR) analysis were performed to detect the cell viability, proliferation, migration, and pluripotency of BMSCs, respectively. Alizarin red S (ARS) staining, alkaline phosphatase (ALP) staining, oil red O (ORO) staining, and qRT-PCR assay were applied to assess the osteogenic and adipogenic differentiation of BMSCs. BMSCs were treated with caffeine and further exposed to different concentrations of psoralidin (PL) (0.01, 0.1, 1, and 10 µM) for 48 h. Micro-computed tomography (µCT) scanning was used to evaluate the bone mass of mice. 7α-(7-((4,4,5,5,5-Pentafluoropentyl)-sulfiny)nonyl)estra-1,3,5(10)-triene-3,17ß-diol (ICI 182,780, ICI) was applied to examine whether the classical estrogen receptor (ER) pathway was involved. Results: The CCK-8 assay, colony formation assay, wound healing assay, and qRT-PCR analysis indicated that caffeine (0.01, 0.05, 0.1, 0.5, 1.0 mM) attenuated the cell viability, proliferation, migration and pluripotency of BMSCs, respectively, in a concentration-dependent manner. Caffeine treatment inhibited osteogenic differentiation but promoted adipogenic differentiation of BMSCs in a dose-dependent manner. Furthermore, ARS staining, ALP staining, ORO staining, and qRT-PCR assay showed that excessive caffeine induced bone loss and osteoporosis (OP) in mice by regulating the osteogenesis and adipogenesis of BMSCs. Also, PL treatment could reverse the caffeine-induced dysfunctions and aberrant differentiation of BMSCs via the ER pathway. Conclusions: Our results revealed a novel molecular mechanism for the therapeutic effects of PL in treating excessive caffeine-induced OP, which might shed new light on the clinical application of PL for caffeine-related OP.

10.
Autophagy ; : 1-13, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34524948

RESUMO

ABBREVIATIONS: BioID: proximity-dependent biotin identification; GO: gene ontology; OSBPL: oxysterol binding protein like; VAPA: VAMP associated protein A; VAPB: VAMP associated protein B and C.

11.
Front Oncol ; 11: 600557, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34367938

RESUMO

Artificial intelligence (AI) has invaded our daily lives, and in the last decade, there have been very promising applications of AI in the field of medicine, including medical imaging, in vitro diagnosis, intelligent rehabilitation, and prognosis. Breast cancer is one of the common malignant tumors in women and seriously threatens women's physical and mental health. Early screening for breast cancer via mammography, ultrasound and magnetic resonance imaging (MRI) can significantly improve the prognosis of patients. AI has shown excellent performance in image recognition tasks and has been widely studied in breast cancer screening. This paper introduces the background of AI and its application in breast medical imaging (mammography, ultrasound and MRI), such as in the identification, segmentation and classification of lesions; breast density assessment; and breast cancer risk assessment. In addition, we also discuss the challenges and future perspectives of the application of AI in medical imaging of the breast.

13.
J Cancer Res Ther ; 17(3): 695-701, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34269301

RESUMO

Objectives: The aim of the study was to compare the relative diagnostic utility of low-dose computed tomography (LDCT) and standard-dose computed tomography (SDCT)-guided lung biopsy approaches. Materials and Methods: The PubMed, Embase, and Cochrane Library databases were searched for relevant studies published through August 2020. Data pertaining to endpoints including technical success, diagnostic performance, operative time, radiation dose, and complications, were extracted, and meta-analysis was performed using RevMan v5.3. Results: Three retrospective analyses and three randomized controlled trials, were included. The studies included 1977 lung lesions across 1927 patients who underwent LDCT-guided lung biopsy, and 887 lung lesions across 879 patients who underwent SDCT-guided lung biopsy. No significant differences were observed between these LDCT and SDCT groups with respect to the rates of technical success (99.0% vs. 99.5%, odds ratio [OR]: 1.82, P = 0.35,), diagnostic yield (79.6% vs. 76.2%, OR: 0.93, P = 0.47), diagnostic accuracy (96.1% vs. 96.1%, OR: 0.93, P = 0.69), operative time (mean difference [MD]: 1.04, P = 0.30), pneumothorax (19.9% vs. 21.3%, OR: 0.92, P = 0.43) or hemoptysis (4.6% vs. 5.8%, OR: 1.14, P = 0.54). Patients in the LDCT group received a significantly lower radiation dose (MD: ‒209.87, P < 0.00001) than patients in the SDCT group. Significant heterogeneity was observed with respect to the operative duration and radiation dose endpoints (I2 = 84% and 100%, respectively). Conclusions: Relative to SDCT-guided lung biopsy, an LDCT-guided approach is equally safe and can achieve comparable diagnostic efficacy while exposing patients to lower doses of radiation.

14.
Psychiatr Q ; 92(4): 1645-1656, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34159503

RESUMO

The efficacy and safety of adjunctive nonconvulsive electrotherapy (NET) for patients with depression are undetermined. This systematic review was conducted to examine the efficacy and safety of adjunctive NET for patients with depression. Chinese (WanFang and Chinese Journal Net) and English (PubMed, EMBASE, PsycINFO and the Cochrane Library) databases were systematically searched from their inception until Jan 27, 2021 by three independent investigators. One randomized controlled trial (RCT) with 3 treatment arms (n = 108) and two observational studies (single-group, before-after design, n = 31) were included. In the RCT, the antidepressant efficacy of NET on depression was similar to that of electroconvulsive therapy (ECT) (P > 0.05) but with significantly fewer neurocognitive impairments as measured by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) (P < 0.05). In two observational studies, the 17-item Hamilton Depression Rating Scale (HAMD-17) scores decreased significantly from baseline to post-NET (all Ps < 0.05), without adverse neurocognitive effects. In the RCT, adverse drug reactions (ADRs) were not separately reported among the 3 treatment arms but a similar rate of discontinuation was reported. The currently available limited evidence from 3 studies suggests that NET as an adjunctive treatment may be a safe, well-tolerated, effective therapy for depression without serious neurocognitive impairments.

15.
Hum Mol Genet ; 30(21): 1996-2011, 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34169321

RESUMO

Motile cilia and flagellar defects can result in primary ciliary dyskinesia, which is a multisystemic genetic disorder that affects roughly 1:10 000 individuals. The nexin-dynein regulatory complex (N-DRC) links neighboring doublet microtubules within flagella, serving as a central regulatory hub for motility in Chlamydomonas. Herein, we identified two homozygous DRC1 variants in human patients that were associated with multiple morphological abnormalities of the sperm flagella (MMAF) and male infertility. Drc1-/-, Drc1R554X/R554X and Drc1W244X/W244X mice on the C57BL/6 background suffered from pre-pubertal mortality. However, when the ICR background was introduced, some of these mice were able to survive and recapitulate the MMAF phenotypes detected in human patients. By analyzing these animals, we determined that DRC1 is an essential regulator of N-DRC assembly in cilia and flagella. When DRC1 is absent, this results in the shortening of cilia and consequent impairment of their motility. Damage associated with DRC1 deficiency in sperm flagella was more pronounced than in cilia, as manifested by complete axoneme structural disorder in addition to the loss of the DRC structure. Altogether, these findings suggest that DRC1 is required for the structural stability of flagella but not cilia, emphasizing the key role of this protein in mammalian species.

17.
J Leukoc Biol ; 110(2): 293-300, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34184320

RESUMO

Chronic pancreatitis (CP) is a continuing or relapsing inflammatory disease of the pancreas, characterized by fibrosis of the whole tissue. The regulatory mechanisms of the immune microenvironment in the pathogenesis of CP are still not clear. Immune cells, especially myeloid cells, play an important role in the pathogenesis of pancreatitis. Understanding the regulatory mechanisms of immune infiltration has a significant impact on CP intervention. Here, we demonstrated that transcription factor STAT5 was involved in and critical for the progression of CP. Inflammatory stress could significantly increase the expression and activation of STAT5 during CP. STAT5 deficiency or inhibition contributed to alleviating pancreatic inflammation and fibrosis in CP mice. The increased neutrophil infiltration, mediated by up-regulated GM-CSF, was responsible for the pancreatitis-promoting activity of STAT5. Our investigation highlighted the importance of STAT5 in regulating the immune microenvironment of CP. Targeting STAT5 may hold distinct promise for clinical treatment to alleviate CP.


Assuntos
Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Neutrófilos/imunologia , Neutrófilos/metabolismo , Pancreatite Crônica/etiologia , Pancreatite Crônica/metabolismo , Fator de Transcrição STAT5/metabolismo , Animais , Biomarcadores , Suscetibilidade a Doenças , Fibrose , Humanos , Pancreatite Crônica/patologia , Estresse Fisiológico
18.
PeerJ ; 9: e11545, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34141486

RESUMO

Background: The CCT complex is an important mediator of microtubule assembly and intracellular protein folding. Owing to its high expression in spermatids, CCT knockdown can disrupt spermatogenesis. In the present report, we therefore evaluated the in vivo functionality of the testis-specific CCT complex component CCT6B using a murine knockout model system. Methods: A CRISPR/Cas9 approach was used to generate Cct6b-/- mice, after which candidate gene expression in these animals was evaluated via qPCR and Western blotting. Testicular and epididymal phenotypes were assessed through histological and immunofluorescent staining assays, while a computer-assisted sperm analyzer was employed to assess semen quality. Results: Cct6b-/- mice were successfully generated, and exhibited no differences in development, fertility, appearance, testis weight, or sperm counts relative to control littermates. In addition, no differences in spermatogenesis were detected when comparingCct6b+/+ and Cct6b-/- testes. However, when progressive motility was analyzed, the ratio of normal sperm was significantly decreased in Cct6b-/- male mice, with nuclear base bending being the primary detected abnormality. In addition, slight decreases in Cct4 and Cct7 expression were detected. Conclusion: These data indicated that CCT6B is an important regulator of murine spermatogenesis, with the loss of this protein resulting in CCT complex dysfunction, providing a foundation for further studies.

19.
Minerva Surg ; 2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34160171

RESUMO

INTRODUCTION: Postoperative pancreatic fistula (POPF) remains a major cause of morbidity following pancreaticoduodenectomy (PD). This network meta-analysis (NMA) compared techniques of pancreatic anastomosis following PD to determine the technique with the best outcome profile. EVIDENCE ACQUISITION: A systematic literature search was performed on the Scopus, EMBASE, Medline and Cochrane databases to identify RCTs employing the international study group of pancreatic fistula(ISGPF) definition of POPF. The main outcomes were POPF and clinically relevant POPF. RESULTS: Three techniques of pancreatic anastomosis following PD were directly compared in 16 RCTs comprising 2365 patients. EVIDENCE SYNTHESIS: Overall, 929 patients underwent duct-to-mucosa pancreaticojejunostomy(PJ DTM), 760 patients invagination pancreaticojejunostomy(PJ Inv), and 676 patients underwent pancreatogastrostomy(PG). The results of comparisons of POPF, clinically relevant POPF, biliary leakage, delayed gastric emptying(DGE), in hospital mortality, internal hemorrhage, reoperation in our network meta-analysis suggested there were no significant differences among the 3 procedures. CONCLUSIONS: There are no significant differences among PJ DTM, PJ Inv and PG in the prevention of POPF, clinically relevant POPF, biliary leakage, DGE, internal hemorrhage and reoperation. However, further randomized controlled trials should be undertaken to ascertain these findings.

20.
J Virol ; 95(17): e0074721, 2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34133897

RESUMO

The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is bringing an unprecedented health crisis to the world. To date, our understanding of the interaction between SARS-CoV-2 and host innate immunity is still limited. Previous studies reported that SARS-CoV-2 nonstructural protein 12 (NSP12) was able to suppress interferon-ß (IFN-ß) activation in IFN-ß promoter luciferase reporter assays, which provided insights into the pathogenesis of COVID-19. In this study, we demonstrated that IFN-ß promoter-mediated luciferase activity was reduced during coexpression of NSP12. However, we could show NSP12 did not affect IRF3 or NF-κB activation. Moreover, IFN-ß production induced by Sendai virus (SeV) infection or other stimulus was not affected by NSP12 at mRNA or protein level. Additionally, the type I IFN signaling pathway was not affected by NSP12, as demonstrated by the expression of interferon-stimulated genes (ISGs). Further experiments revealed that different experiment systems, including protein tags and plasmid backbones, could affect the readouts of IFN-ß promoter luciferase assays. In conclusion, unlike as previously reported, our study showed SARS-CoV-2 NSP12 protein is not an IFN-ß antagonist. It also rings the alarm on the general usage of luciferase reporter assays in studying SARS-CoV-2. IMPORTANCE Previous studies investigated the interaction between SARS-CoV-2 viral proteins and interferon signaling and proposed that several SARS-CoV-2 viral proteins, including NSP12, could suppress IFN-ß activation. However, most of these results were generated from IFN-ß promoter luciferase reporter assay and have not been validated functionally. In our study, we found that, although NSP12 could suppress IFN-ß promoter luciferase activity, it showed no inhibitory effect on IFN-ß production or its downstream signaling. Further study revealed that contradictory results could be generated from different experiment systems. On one hand, we demonstrated that SARS-CoV-2 NSP12 could not suppress IFN-ß signaling. On the other hand, our study suggests that caution needs to be taken with the interpretation of SARS-CoV-2-related luciferase assays.


Assuntos
RNA-Polimerase RNA-Dependente de Coronavírus , Interferon beta , Regiões Promotoras Genéticas , SARS-CoV-2 , RNA-Polimerase RNA-Dependente de Coronavírus/genética , RNA-Polimerase RNA-Dependente de Coronavírus/metabolismo , Células HEK293 , Humanos , Fator Regulador 3 de Interferon/genética , Fator Regulador 3 de Interferon/metabolismo , Interferon beta/antagonistas & inibidores , Interferon beta/biossíntese , Interferon beta/genética , NF-kappa B/genética , NF-kappa B/metabolismo , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , SARS-CoV-2/genética , SARS-CoV-2/metabolismo
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