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1.
Front Immunol ; 12: 676082, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33959133

RESUMO

Lupus nephritis (LN) is a common complication of systemic lupus erythematosus (SLE) and a major risk factor for morbidity and mortality. The abundant cell-free nucleic (DNA/RNA) in SLE patients, especially dsDNA, is a key substance in the pathogenesis of SLE and LN. The deposition of DNA/RNA-immune complexes (DNA/RNA-ICs) in the glomerulus causes a series of inflammatory reactions that lead to resident renal cell disturbance and eventually renal fibrosis. Cell-free DNA/RNA is the most effective inducer of type I interferons (IFN-I). Resident renal cells (rather than infiltrating immune cells) are the main source of IFN-I in the kidney. IFN-I in turn damages resident renal cells. Not only are resident renal cells victims, but also participants in this immunity war. However, the mechanism for generation of IFN-I in resident renal cells and the pathological mechanism of IFN-I promoting renal fibrosis have not been fully elucidated. This paper reviews the latest epidemiology of LN and its development process, discusses the mechanism for generation of IFN-I in resident renal cells and the role of IFN-I in the pathogenesis of LN, and may open a new perspective for the treatment of LN.

2.
Life Sci ; : 119584, 2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-33961853

RESUMO

AIMS: Ferulic acid (FA) is a component found in plants that has free radical scavenging and liver-protective properties. Acute liver injury (ALI) is a serious complication of sepsis and is closely associated with changes in the levels of inflammatory factors. This study was taken to examine the role of FA in cecal ligation and perforation (CLP)-induced murine ALI and lipopolysaccharide (LPS)-induced cellular ALI models. MATERIALS AND METHODS: An in vivo ALI model was established by performing CLP surgery on C57BL/6 mice. After the ALI model was established, mice were examined for liver injury, including HE staining to observe tissue sections, the percentage of liver/body weight and inflammatory factor levels. Myeloperoxidase (MPO), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were measured in liver or serum using commercial kits. An in vitro ALI model was established using LPS-stimulated RAW264.7 cells. Cell viability was measured by MTT method and the intracellular levels of IL-10, IL-1ß, IL-6, IL-12 and TNF-α inflammatory factors were measured using kits. The expression of GSK-3ß, NF-κB and CREB was measured by western blot or immunofluorescence. KEY FINDINGS: FA pretreatment significantly reduced liver/body weight ratio, decreased MPO, AST and ALT activity, alleviated the inflammatory responses and improved CLP-induced histopathological changes in liver. In addition, in vitro results showed that FA could dose-dependently increase the viability of RAW264.7 cells and decrease the levels of pro-inflammatory factors. SIGNIFICANCE: In conclusion, our data suggest that FA can ameliorate ALI-induced inflammation via the GSK-3ß/NF-κB/CREB pathway, suggesting that FA can be used to protect the liver against ALI.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33973777

RESUMO

Adsorption as a desalination approach has the advantages of energy efficiency, low cost, and operational convenience, but its practical application is limited by low desalination capacity, consumption/disposal of strong acids/bases as regeneration reagents, and poor reusability. Herein, we synthesized a thermo-regenerable salt absorbent by grafting ethylenediaminetetraacetic acid (EDTA) onto a metal-organic framework (MOF), MOF-808-EDTA, which could rapidly adsorb NaCl within 30 min from saline water at 25 °C with a desalination capacity as high as 9.4 mmol/g. Moreover, the saturated adsorbent could be facilely regenerated in 80 °C water. Fourier transform infrared spectroscopy and derivative thermogravimetry revealed that temperature-regulated proton transfer between amino and carboxyl groups was the mechanism of thermo-regeneration. EDTA on MOF-808-EDTA appears in a zwitterionic state in water at room temperature, which allowed simultaneous adsorption of Na+ and Cl-. At elevated temperature, it returned to a nonionic state accompanied by the desorption of ions. A similar temperature-dependent adsorption-regeneration process was also observed for other salts, including LiCl, KCl, CaCl2, and MgCl2. Column experiments of brackish groundwater showed that 1 g of MOF-808-EDTA could produce ∼106 mL of fresh water (total dissolved solids < 600 mg/L) without significant capacity loss after 10 successive adsorption-regeneration cycles. This study is the first to propose an EDTA-based MOF for desalination and indicates the potential of MOF-808-EDTA as a green adsorbent for sustainable water desalination.

4.
Microb Cell Fact ; 20(1): 95, 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33952256

RESUMO

BACKGROUND: The global pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) highlights the need to develop safe and effective vaccines with a top priority. Multiple vaccine candidates are under development, and several vaccines are currently available. Efforts need to be undertaken to counter the threat of the global COVID-19 pandemic. RESULTS: We generated a Saccharomyces cerevisiae (S. cerevisiae)-based SARS-CoV-2 vaccine, EBY100/pYD1-RBD, in which the full-length receptor binding domain (RBD) of the spike protein of SARS-CoV-2 was expressed on the surface of yeast. Mice vaccinated orally with unadjuvanted EBY100/pYD1-RBD could produce significant humoral and mucosal responses as well as robust cellular immune responses. Notably, EBY100/pYD1-RBD elicited a mixed Th1/Th2-type cellular immune response with a Th1-biased immune response in a mouse model. CONCLUSIONS: Our findings highlight the importance of the RBD as a key target to design and develop vaccines against SARS-CoV-2 and provide evidence of oral administration of a S. cerevisiae-based SARS-CoV-2 vaccine eliciting significant immune responses. Most importantly, the S. cerevisiae surface display system can serve as a universal technology platform and be applied to develop other oral viral or bacterial vaccines.

5.
J Hand Surg Asian Pac Vol ; 26(2): 166-179, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33928864

RESUMO

Background: The Michigan Hand Outcomes Questionnaire (MHQ), a self-reported questionnaire for patients with hand disorders, has been widely used globally. It has been cross-culturally adapted into different languages across all continents. Aims of this study were to translate the MHQ into Malay language and to evaluate its reliability and validity compared with Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire in a Malay-speaking population. Methods: The MHQ was cross-culturally adapted into a Malay version based on the guidelines. A pre-testing involving thirty patients with hand disorders was performed to assess whether it was comprehensible to the target population. One hundred patients with hand disorders were recruited in this study to answer the MHQ and DASH questionnaires. The MHQ was tested twice with an interval of two weeks in between. Statistical analysis was performed to assess the reproducibility and internal consistency via the test-retest method and Cronbach's alpha calculation, respectively. The association between MHQ and DASH questionnaire was assessed with Spearman's correlation calculation. Results: In the pre-testing, twenty-six patients (86.7%) understood all the questions in the Malay version of MHQ. The test-retest analysis showed a good reliability across the duration of two weeks with the intraclass correlation coefficient of all subscales ranging from 0.925 to 0.984. Cronbach's alpha values of the Malay version MHQ ranged from 0.82 to 0.97, indicating a good internal consistency. Spearman's correlation factor of the MHQ in comparison with DASH showed a fair to moderately strong correlation with the values ranging from 0.513 to 0.757. Conclusions: The Malay version of MHQ was successfully translated and culturally-adapted with excellent reliability (reproducibility and internal consistency) and good construct validity.

6.
Sci Rep ; 11(1): 8977, 2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33903693

RESUMO

A safe and effective vaccine is the best way to control large-scale highly pathogenic avian influenza virus (HPAI) A (H5N1) outbreaks. Saccharomyces cerevisiae (S. cerevisiae) is an ideal mucosal delivery vector for vaccine development, and we have previously shown that conventional administration of a S. cerevisiae-based vaccine (EBY100/pYD1-HA) via injection led to protection against the homologous H5N1 virus in a mouse model. Because the diameter of S. cerevisiae is approximately 10 µm, which results in a severe inflammation by injection route, therefore, oral administration is a more suitable approach for EBY100/pYD1-HA conferring protection in poultry. We extended our work by evaluating the immunogenicity and protective efficacy of oral vaccination with EBY100/pYD1-HA in the chicken model. Oral immunization with EBY100/pYD1-HA could induce robust serum IgG, mucosal IgA and cellular immune responses. Importantly, EBY100/pYD1-HA provided protection against challenges with a homologous and a heterologous H5N1 viruses. These findings suggest that EBY100/pYD1-HA, a promising H5N1 oral vaccine candidate, can avoid potential reassortment of other avian influenza viruses in oral administration of live virus vaccines and overcome the limitations of conventional injection routes. Importantly, this platform will be able to provide opportunities for broader applications in poultry during HPAI A (H5N1) outbreaks.

7.
Curr Med Sci ; 41(2): 375-380, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33877556

RESUMO

Preoperative biliary drainage may increase the morbidity and mortality of pancreaticoduodenectomy. Studies on percutaneous transhepatic biliary drainage (PTBD) before laparoscopic pancreaticoduodenectomy (LPD), however, are scarce. The aim of this study was to examine the impact of PTBD on clinical outcomes of patients with malignant obstructive jaundice undergoing LPD. Clinical data of 172 patients who had malignant obstructive jaundice and underwent LPD from 2014 to 2017 in our hospital were retrospectively analyzed. Demographics, catheter-related complications, postoperative complications, and oncological outcomes were collected and analyzed. Propensity score matching was performed to minimize selection bias associated with the comparison of data between patients who underwent PTBD and then LPD (PTBD group), and those given LPD alone (LPD group). The results showed that, in the PTBD group relative to the LPD group, the operating time was significantly shortened (250.28±69.95 vs. 278.58±86.51 min, P=0.0196), the intraoperative blood loss was markedly reduced (271.96±403.47 vs. 429.72±482.47 mL, P=0.022), and overall rates of complications (16.33% vs. 36.49%, P=0.0025) including postoperative haemorrhage (2.04% vs. 12.16%, P=0.0072) and delayed gastric emptying (4.08% vs. 13.51%, P=0.0251) were greatly decreased. The propensity score-matched analysis, with 48 patients enrolled in each group, revealed no statistically significant differences in operating duration (262.71±68.64 vs. 280.25±83.52 min, P=0.264), intraoperative blood loss (290.21±407.71 vs. 373.75±422.33 mL, P=0.327) and delayed gastric emptying (4.17% vs. 12.50%, P=0.1396). PTBD group had lower incidences in overall complications (22.92% vs. 39.58%, P=0.0481) and postoperative haemorrhage (2.08% vs. 12.50%, P=0.0497) than LPD group. In conclusion, patients with malignant obstructive jaundice may benefit from PTBD procedure before LPD in terms of perioperative outcomes.

8.
Artigo em Inglês | MEDLINE | ID: mdl-33890352

RESUMO

Catalytic co-conversion of methane with carbon dioxide to produce syngas (2H2 + 2CO) involves complicated elementary steps and almost all the elementary reactions are performed at the same high temperature conditions in practical thermocatalysis. Here, we demonstrate by mass spectrometric experiments that RhTiO2- promotes the co-conversion of CH4 and CO2 to free 2H2 + CO and an adsorbed CO (COads) at room temperature; the only elementary step that requires the input of external energy is desorption of of COads from the RhTiO2CO- to reform RhTiO2-. This study not only identifies a promising active species for dry (CO2) reforming of methane to syngas, but also emphasizes the importance of temperature control over elementary steps in practical catalysis, which may significantly alleviate the carbon deposition originating from the pyrolysis of methane.

9.
Cancer ; 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33826758

RESUMO

BACKGROUND: The North Carolina Breast and Cervical Cancer Control Program (NC BCCCP) provides breast cancer screening services to underserved women to mitigate disparities in access to care. The authors sought to characterize this understudied population. METHODS: Women 21 years old or older who underwent their first breast cancer screen through NC BCCCP from 2008 to 2018 were included. Demographic factors associated with the timeline of care and odds of a breast cancer diagnosis were identified with negative binomial and logistic regression, respectively. RESULTS: Of the 88,893 women identified, 45.5% were non-Hispanic (NH) White, 30.9% were NH Black, 19.6% were Hispanic, 1.7% were American Indian, and 1.1% were Asian. Breast cancer was diagnosed in 2.5% of the women (n = 2255). Hispanic women were the least likely to be diagnosed with breast cancer (odds ratio vs NH White women, 0.40; 95% confidence interval [CI], 0.34-0.47). Among patients with breast pathology, the median time to diagnosis was 19 days (interquartile range [IQR], 10-33 days), and the time to treatment was 33 days (IQR, 19-54 days). After adjustments, a longer time to diagnosis was significantly associated with age (incidence rate ratio [IRR], 1.01; 95% CI, 1.01-1.02) and being NH Black (vs NH White; IRR, 1.17; 95% CI, 1.06-1.29). A longer time to treatment was significantly associated with age (IRR, 1.01; 95% CI, 1.01-1.01), being NH Black (vs NH White; IRR, 1.20; 95% CI, 1.10-1.31), and being Hispanic (vs NH White; IRR, 1.22; 95% CI, 1.05-1.41). CONCLUSIONS: NC BCCCP participants with breast cancer received treatment within approximately 1 month of presentation, and this finding aligns with quality care benchmarks. Nevertheless, racial/ethnic disparities in timeliness of care persist, and this suggests opportunities for improvement. LAY SUMMARY: This review of approximately 90,000 participants in a breast cancer screening program for uninsured and underinsured women highlights the importance of safety net programs in providing timely care to underserved patients. The authors found that the North Carolina Breast and Cervical Cancer Control Program met timeliness benchmarks from the Centers for Disease Control and Prevention across all racial/ethnic groups. However, non-Hispanic Black women experienced relative delays in the time to diagnosis, and both non-Hispanic Black women and Hispanic women experienced relative delays in the time to treatment. These findings demonstrate how racial/ethnic disparities in the timeliness of care can persist even within a program intended to reduce barriers to access.

10.
Front Endocrinol (Lausanne) ; 12: 651568, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33841338

RESUMO

Phyllodes tumor (PT) is a special type of breast tumors, including three types: malignant, borderline, and benign. Most of these tumors form unilateral disease and can rapidly increase in size. The occurrence of axillary lymph node metastasis is rare. Tumor-associated hypoglycemia can be divided into non-islet cell tumor and insulinoma. In non-islet cell tumor hypoglycemia (NICTH), a considerable high molecular weight form of insulin like growth factor 2 (IGF-2) is formed, which abnormally binds to insulin receptors in the tissues and causes hypoglycemia. Breast phyllodes tumors with NICTH are rare and first reported in 1983. Surgical resection is the main treatment and hypoglycemia symptoms usually resolve after surgery. Nevertheless, prior to surgery, intravenous glucose infusion is used to maintain blood glucose levels. A female patient presented with a rapidly growing breast mass and was diagnosed with a phyllodes tumor with NICTH at our hospital in August 2020; she was successfully treated through surgical resection. We reviewed the relevant literature to investigate and analyze the relationship between NICTH and phyllodes tumors, as well as optimize its diagnosis and treatment.

11.
Transplant Cell Ther ; 27(2): 181.e1-181.e9, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33830035

RESUMO

Hematopoietic stem cell transplantation (HCT) is a curative treatment option for patients with hematologic conditions but presents many complications that must be managed as a complex, chronic condition. Mobile health applications (mHealth apps) may permit tracking of symptoms in HCT. In seeking strategies to manage the complexities of HCT, our team collaborated with Sicklesoft, Inc., to develop an mHealth app specifically for HCT patients to allow for daily evaluation of patient health, Technology Recordings to better Understand Bone Marrow Transplantation (TRU-BMT). The primary value of this application is that of potentially enhancing the monitoring of symptoms and general health of patients undergoing HCT, with the ultimate goal of allowing earlier detection of adverse events, earlier intervention, and improving outcomes. To first evaluate patient interest in mHealth apps, we designed and administered an interest survey to patients at the 2017 BMT-InfoNet reunion. As a follow-up to the positive feedback received, we began testing the TRU-BMT app in a Phase 1 pilot study. Thirty patients were enrolled in this single-arm study and were given the TRU-BMT mHealth app on a smartphone device in addition to a wearable activity tracker. Patients were followed for up to 180 days, all the while receiving daily app monitoring. Adherence to TRU-BMT was approximately 30% daily and 44% weekly, and greater adherence was associated with increased meal completion, decreased heart rate, and shorter hospital stay. TRU-BMT assessments of symptom severity were significantly associated with duration of hospital stay and development of chronic graft-versus-host disease. Our findings suggest that using TRU-BMT throughout HCT is feasible for patients and established a proof-of-concept for a future randomized control trial of the TRU-BMT application in HCT. © 2021 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

12.
J Stroke Cerebrovasc Dis ; 30(7): 105790, 2021 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-33878547

RESUMO

Cognitive impairment is one of the main complications of cerebral small vessel disease (CSVD). Serum insulin-like growth factor-1 (IGF-1) might serve as a marker for the risk of cognitive decline in patients with CSVD. We investigated the association of IGF-1 with the development of cognitive impairment in patients with CSVD. We included 216 patients with CVSD (mean age, 67.57 ± 8.53 years; 31.9% female). We compared 117 (54.2%) patients who developed cognitive impairment with 99 (45.8%) patients without cognitive impairment. Patients who developed cognitive impairment had significantly lower levels of IGF-I (p < 0 .001), suggesting that altered IGF-1 signaling may be a risk factor for cognitive decline in patients with CSVD.

13.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(4): 375-380, 2021 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-33840410

RESUMO

OBJECTIVE: To study the risk factors and treatment for neutropenia of late newborns (NLN). METHODS: Related clinical data were collected from the preterm infants and critically ill neonates who were admitted to the neonatal intensive care unit from July 2019 to January 2020. A total of 46 newborns with a blood absolute neutrophil count (ANC) of < 1.5×109/L for two consecutive times at weeks 2-4 after birth were enrolled as the NLN group. A total of 92 late newborns with a blood ANC of ≥ 1.5×109/L, matched at a ratio of 1:2, were enrolled as the control group. Possible risk factors associated with NLN and the treatment process were recorded. A logistic regression analysis was performed to identify the risk factors for NLN. RESULTS: Among the 46 neonates in the NLN group, 29 had a gestational age of < 32 weeks, 14 had a gestational age of 32-37 weeks, and 3 had a gestational age of > 37 weeks. There was no significant difference between the two groups in the incidence rates of gestational hypertension, premature rupture of membranes > 18 hours and intrauterine distress, 5-minute Apgar score, the duration of positive pressure ventilation, the incidence rate of early-onset sepsis, and the type of initially used antibiotics (P > 0.05). Compared with the control group, the NLN group had a higher incidence rate of late-onset sepsis and a longer duration of antibiotic use (P < 0.05). Late-onset sepsis and prolonged duration of antibiotic use were independent risk factors for NLN (P < 0.05). With the presence of late-onset sepsis, the risk of NLN was increased by 1.537 times in neonates, and the risk of NLN was increased by 76.9% for every 3-day increase in the duration of antibiotic use. The mean age at the diagnosis of NLN was (21±6) days for the 46 neonates in the NLN group. Thirteen neonates with NLN were administered with recombinant human granulocyte colony-stimulating factor (G-CSF, 10 µg/kg) once or twice. O the 13 neonates, 6 had an ANC of < 0.5×109/L and 7 had a gestational age of < 32 weeks or severe disease conditions. After treatment the ANC returned to > 1.0×109/L in the 13 neonates. No drug-related adverse reactions were found. After the diagnosis of NLN, 2 neonates developed sepsis, and the remaining 44 neonates did not develop any common purulent infections. CONCLUSIONS: The risk of NLN increases with the presence of late-onset sepsis and the increase in the duration of antibiotic use. NLN is generally a benign process. G-CSF appears to be safe and effective for NLN with severe disease conditions or severe reduction in ANC.


Assuntos
Neutropenia , Sepse , Fator Estimulador de Colônias de Granulócitos , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Contagem de Leucócitos , Fatores de Risco
14.
Pain Ther ; 2021 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-33837931

RESUMO

INTRODUCTION: Evidence on the use of inhaled methoxyflurane in the management of trauma pain is conflicting and obfuscated. This study aimed to determine the efficacy and safety of inhaled methoxyflurane for trauma pain on the basis of published randomized controlled trials (RCTs). METHODS: RCTs assessing the efficacy of methoxyflurane in adults or adolescents with acute trauma pain published in PubMed, Web of Science, Embase, Cochrane Library, and Google Scholar were searched. The control groups were those that received placebo or standard analgesic treatment (SAT). The primary outcome was the change from baseline in pain scores during the first 30 min of treatment. Secondary outcomes included time to first pain relief, the proportion of patients experiencing pain relief, rescue analgesia rate, the treatment satisfaction of patients and investigators, and the methoxyflurane-related treatment-emergent adverse events (TEAEs). RESULTS: A total of nine RCTs (1806 patients) were identified. Results revealed that methoxyflurane provided a clinically unimportant benefit by improving the mean difference of change from baseline in pain intensity (from - 0.44 to - 1.23 cm, p < 0.001) at various time points within the first 20 min compared to control treatment. Besides, methoxyflurane decreased the time of onset of pain relief (mean difference - 5.29 min; 95% CI - 6.97 to - 3.62) and the proportion of patients who needed rescue analgesic medication (risk ratio 1.41; 95% CI 1.17-1.70) despite it increasing the risk of non-severe TEAEs (risk ratio 3.09; 95% CI 1.72-5.57). Notably, the benefit of almost all secondary pain-related outcomes was rendered clinically nonsignificant between methoxyflurane and SAT strata besides the time of onset of pain relief. The quality of evidence was low or very low in all outcomes. CONCLUSIONS: In emergency situations without effective therapy, this systematic review and meta-analysis provides low-quality evidence that methoxyflurane can be used as a rapid-acting and effective treatment for acute trauma pain, although its utilization is associated a risk of non-severe TEAEs. However, the current evidence does not support the notion that inhaled methoxyflurane offered superior analgesic efficacy to SAT. CLINICAL TRIAL NUMBER: PROSPERO registration number CRD42020223000.

15.
Ying Yong Sheng Tai Xue Bao ; 32(3): 1080-1086, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33754575

RESUMO

We analyzed the feeding ecology of Cynoglossus joyneri by carbon and nitrogen stable isotope analysis based on the samples collected from the bottom trawl surveys during spring and autumn of 2018 in Haizhou Bay, China. The results showed that the δ13C and δ15N values of C. joyneri ranged from -20.75‰ to -15.91‰ and from 5.98‰ to 12.02‰, respectively. The mean values of the δ13C and δ15N were (-17.79±1.00)‰ and (9.37±1.33)‰, respectively. There was a significantly negative correlation between the δ13C values and standard length and a positive correlation between the δ15N values and standard length. The mean trophic level of C. joyneri was (3.43±0.97). There was a significantly positive correlation between the trophic level and standard length. The dominant prey groups of C. joyneri were fish, crabs, shrimps, mollusca, polychaeta, plankton and particle organic matter (POM). The trophic contribution of shrimps was the highest among these prey groups. The trophic contribution of fish, crabs and shrimps was higher in autumn than those in spring. This study would help to understand the role of C. joyneri in the material cycling and energy flow in Haizhou Bay ecosystem, and provide scientific basis for the protection and rational utilization of this species.


Assuntos
Baías , Ecossistema , Animais , Isótopos de Carbono/análise , China , Ecologia , Cadeia Alimentar , Isótopos de Nitrogênio/análise
16.
Plant Physiol ; 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33764451

RESUMO

Nitrate acts as a vital signal molecule in the modulation of plant growth and development. The phytohormones gibberellin (GA) is also involved in this process. However, the exact molecular mechanism of how nitrate and GA signaling pathway work together in regulating plant growth remains poorly understood. In this study, we found that a nitrate-responsive BTB/TAZ protein MdBT2 participates in regulating nitrate-induced plant growth in apple (Malus × domestica). Yeast two-hybridization, protein pull-down, and bimolecular fluorescence complementation (BiFC) assays showed that MdBT2 interacts with a DELLA protein MdRGL3a, which is required for the ubiquitination and degradation of MdRGL3a proteins via a 26S proteasome-dependent pathway. Furthermore, heterologous expression of MdBT2 partially rescued growth inhibition caused by overexpression of MdRGL3a in Arabidopsis. Taken together, our findings indicate that MdBT2 promotes nitrate-induced plant growth partially through reducing the abundance of the DELLA protein MdRGL3a.

17.
Theranostics ; 11(9): 4061-4077, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33754048

RESUMO

Background: Diet manipulation is the basis for prevention of obesity and diabetes. The molecular mechanisms that mediate the diet-based prevention of insulin resistance are not well understood. Here, as proof-of-concept, ginger-derived nanoparticles (GDNP) were used for studying molecular mechanisms underlying GDNP mediated prevention of high-fat diet induced insulin resistance. Methods: Ginger-derived nanoparticles (GDNP) were isolated from ginger roots and administered orally to C57BL/6 high-fat diet mice. Fecal exosomes released from intestinal epithelial cells (IECs) of PBS or GDNP treated high-fat diet (HFD) fed mice were isolated by differential centrifugation. A micro-RNA (miRNA) polymerase chain reaction (PCR) array was used to profile the exosomal miRs and miRs of interest were further analyzed by quantitative real time (RT) PCR. miR-375 or antisense-miR375 was packed into nanoparticles made from the lipids extracted from GDNP. Nanoparticles was fluorescent labeled for monitoring their in vivo trafficking route after oral administration. The effect of these nanoparticles on glucose and insulin response of mice was determined by glucose and insulin tolerance tests. Results: We report that HFD feeding increased the expression of AhR and inhibited the expression of miR-375 and VAMP7. Treatment with orally administered ginger-derived nanoparticles (GDNP) resulted in reversing HFD mediated inhibition of the expression of miR-375 and VAMP7. miR-375 knockout mice exhibited impaired glucose homeostasis and insulin resistance. Induction of intracellular miR-375 led to inhibition of the expression of AhR and VAMP7 mediated exporting of miR-375 into intestinal epithelial exosomes where they were taken up by gut bacteria and inhibited the production of the AhR ligand indole. Intestinal exosomes can also traffic to the liver and be taken up by hepatocytes, leading to miR-375 mediated inhibition of hepatic AhR over-expression and inducing the expression of genes associated with the hepatic insulin response. Altogether, GDNP prevents high-fat diet-induced insulin resistance by miR-375 mediated inhibition of the aryl hydrocarbon receptor mediated pathways over activated by HFD feeding. Conclusion: Collectively our findings reveal that oral administration of GDNP to HFD mice improves host glucose tolerance and insulin response via regulating AhR expression by GDNP induced miR-375 and VAMP7.

18.
Elife ; 102021 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-33787496

RESUMO

The evolutionarily conserved TRanscript-EXport (TREX) complex plays central roles during mRNP (messenger ribonucleoprotein) maturation and export from the nucleus to the cytoplasm. In yeast, TREX is composed of the THO sub-complex (Tho2, Hpr1, Tex1, Mft1, and Thp2), the DEAD box ATPase Sub2, and Yra1. Here we present a 3.7 Šcryo-EM structure of the yeast THO•Sub2 complex. The structure reveals the intimate assembly of THO revolving around its largest subunit Tho2. THO stabilizes a semi-open conformation of the Sub2 ATPase via interactions with Tho2. We show that THO interacts with the serine-arginine (SR)-like protein Gbp2 through both the RS domain and RRM domains of Gbp2. Cross-linking mass spectrometry analysis supports the extensive interactions between THO and Gbp2, further revealing that RRM domains of Gbp2 are in close proximity to the C-terminal domain of Tho2. We propose that THO serves as a landing pad to configure Gbp2 to facilitate its loading onto mRNP.

19.
Medicine (Baltimore) ; 100(13): e24519, 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33787569

RESUMO

OBJECTIVES: This meta-analysis was designed to systematically evaluate whether autologous cytokine-induced killer cells (CIK) or dendritic cells and cytokine-induced killer cells (DC-CIK) immunotherapy combined with chemotherapy can improve the therapeutic effect and safety of chemotherapy in esophageal cancer (EC). MATERIALS AND METHODS: Randomized controlled trials (RCTs) were electronically searched databases including CNKI, WanFang, WeiPu, CBMDisc, PubMed, Web of Science, EMbase, the Cochrane Library, and Clinical Trials. The databases were searched for articles published until June 2019. Two researchers independently screened the literature, extracted data, and evaluated the quality of the included literature. Meta-analysis was performed using RevMan5.3. RESULTS: Seventeen studies (1416 participants) were included. The differences between CIK/DC-CIK combination chemotherapy and chemotherapy alone were significant. The results displayed that the number of CD3+, CD4+, CD4+/CD8+, and NK cells was significantly increased after 1 to 2 weeks of treatment with CIK/DC-CIK cells in the treatment group (all P < .05). In addition, the results shown that 1-year overall survival was significantly prolonged (P < .0001) and quality of life was improved (P = .001) in EC chemotherapy combined with immunotherapy groups compared with conventional treatment. Furthermore, cytokine expression levels of interleukin 2 (IL-2), tumor necrosis factor α (TNF-α), and interleukin 12 (IL-12) were significantly increased (P = .0003) as well as the levels of immunoglobulins were elevated (P < .00001). Serum levels of tumor marker molecules, carcinoembryonic antigen (CEA), carbohydrate antigen (CA)-199, and CA-125 were lower in treatment groups than that of control groups (P < .00001). No fatal adverse reactions were noted (P = .04). CONCLUSIONS: It is safe and effective for patients to use chemotherapy combined with CIK/DC-CIK immunotherapy. Immunotherapy can simultaneously improve the antitumor immune response. Specifically, DC-CIK cells can increase T lymphocyte subsets, CIK cells, NK cells, and immunoglobulins in peripheral blood to enhance antitumor immunity. Therefore, combination therapy enhances the immune function and improves the therapeutic efficacy of patients with EC.


Assuntos
Imunidade Adaptativa/imunologia , Antineoplásicos/imunologia , Células Matadoras Induzidas por Citocinas/imunologia , Células Dendríticas/imunologia , Neoplasias Esofágicas/terapia , Idoso , Terapia Combinada , Neoplasias Esofágicas/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
20.
Artigo em Inglês | MEDLINE | ID: mdl-33739920

RESUMO

Different from the conventional facial expression, micro-expression is an involuntary and transient facial expression, which can reveal a genuine emotion that people attempt to hide. The detection and recognition of micro-expressions are difficult and heavily rely on expert experiences, since micro-expressions are transient and of low intensity. Due to its intrinsic particularity and complexity, micro-expression analysis is attractive but challenging, and recently becomes an active area of research. Although there are many developments in this area, a comprehensive survey that can help researchers to systematically review them is still lacking. In this survey paper, we highlight the key differences between macro- and micro-expressions, and use these differences to guide the research survey of micro-expression analysis in a cascaded structure, including neuropsychological basis, datasets, features, detection/spotting algorithms, recognition algorithms, applications and evaluation of state of the arts. In each aspect, basic techniques, advanced developments and major challenges are addressed and discussed. Furthermore, by considering the limitations in existing micro-expression datasets, we present and release a new dataset called MMEW that has more video samples and more labeled emotion types, and perform a unified comparison of representative recognition methods on MMEW. Finally, some potential research directions are explored and outlined.

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