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1.
Magn Reson Imaging ; 75: 134-140, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33127411

RESUMO

OBJECTIVE: Alfaxalone has been used increasingly in biomedical research and veterinary medicine of large animals in recent years. However, its effects on the cerebral blood flow (CBF) physiology and intrinsic neuronal activity of anesthetized brains remain poorly understood. METHODS: Four healthy adult rhesus monkeys were anesthetized initially with alfaxalone (0.125 mg/kg/min) or ketamine (1.6 mg/kg/min) for 50 min, then administrated with 0.8% isoflurane for 60 min. Heart rates, breathing beats, and blood pressures were continuously monitored. CBF data were collected using pseudo-continuous arterial spin-labeling (pCASL) MRI technique and rsfMRI data were collected using single-shot EPI sequence for each anesthetic. RESULTS: Both the heart rates and mean arterial pressure (MAP) remained more stable during alfaxalone infusion than those during ketamine administration. Alfaxalone reduced CBF substantially compared to ketamine anesthesia (grey matter, 65 ± 22 vs. 179 ± 38 ml/100g/min, p<0.001; white matter, 14 ± 7 vs. 26 ± 6 ml/100g/min, p < 0.05); In addition, CBF increase was seen in all selected cortical and subcortical regions of alfaxalone-pretreated monkey brains during isoflurane exposure, very different from the findings in isoflurane-exposed monkeys pretreated with ketamine. Also, alfaxalone showed suppression effects on functional connectivity of the monkey brain similar to ketamine. CONCLUSION: Alfaxalone showed strong suppression effects on CBF of the monkey brain.The residual effect of alfaxalone on CBF of isoflurane-exposed brains was evident and monotonous in all the examined brain regions when used as induction agent for inhalational anesthesia. In particular, alfaxalone showed similar suppression effect on intrinsic neuronal activity of the brain in comparison with ketamine. These findings suggest alfaxalone can be a good alternative to veterinary anesthesia in neuroimaging examination of large animal models. However, its effects on CBF and functional connectivity should be considered.

2.
Neural Regen Res ; 16(1): 172-178, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32788473

RESUMO

Stem cells have been confirmed to be involved in the occurrence and development of diabetic retinopathy; however, the underlying mechanisms remain unclear. In this study, we used Citespace software to visually analyze 552 articles exploring the stem cell-based treatment of diabetic retinopathy over the past 20 years, which were included in the Web of Science Core Collection. We found the following: (1) a co-citation analysis of the references cited by all 552 articles indicated 15 clusters. In cluster #0, representing the stem cell field, some highly cited landmark studies emerged between 2009-2013. For example, endothelial progenitor cells and diabetic retinopathy gradually received the full attention of scholars, in terms of their relationship and therapeutic prospects. Some researchers also verified the potential of adipose-derived stem cells to differentiate into stable retinal perivascular cells, using a variety of animal models of retinal vascular disease. All of these achievements provided references for the subsequent stem cell research. (2) An analysis of popular keywords among the 552 articles revealed that, during the past 20 years, a relative increase in basic research articles examining stem cells and endothelial progenitor cells for the treatment of diabetic retinopathy was observed. The contents of these articles primarily involved the expression of vascular endothelial growth factor, vascular regeneration, oxidative stress, and inflammatory response. (3) A burst analysis of keywords used in the 552 articles indicated that genetic and cytological research regarding the promotion of angiogenesis was an issue of concern from 2001 to 2012, including several studies addressing the expression of various growth factor genes; from 2014 to 2020, mouse models of diabetic retinopathy were recognized as mature animal models, and the most recent research has focused on macular degeneration, macular edema, neurodegeneration, and inflammatory changes in diabetic animal models. (4) Globally, the current authoritative studies have focused on basic research towards the stem cell treatment of diabetic retinopathy. Existing clinical studies are of low quality and have insufficient evidence levels, and their findings have not yet been widely accepted in clinical practice. Major challenges during stem cell transplantation remain, including stem cell heterogeneity, cell delivery, and the effective homing of stem cells to damaged tissue. However, clinical trials examining potential stem cell-based treatments of diabetic retinopathy, including the use of pluripotent stem cells, retinal pigment epithelial cells, bone marrow mesenchymal stem cells, and endothelial progenitor cells, are currently ongoing, and high-quality clinical evidence is likely to appear in the future, to promote clinical transformation.

3.
Life Sci ; : 118748, 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33189827

RESUMO

AIMS: Radiotherapy has become a basic treatment modality for head and neck cancer. However, radiotherapy results in inevitable side effects, particularly radiation sialadenitis, that significantly impairs quality of life. A previous study indicated that nerve growth factor (NGF) has a radio-protective effect, but the mechanism was not determined in salivary glands. In this study, we explored the functional role and mechanism regarding how NGF protects salivary glands against IR-induced damage. MAIN METHODS: Human salivary gland (HSG) cells and C57BL/6 mice were selected to establish an IR-induced salivary gland damage model in vitro and in vivo. Recombinant NGF protein and NGF siRNA and over-expression plasmids were applied to manipulate NGF expression in vitro. AAV-NGF was retrogradely perfused into the submandibular gland (SMG) through the SMG duct to manipulate NGF expression in vitro. Small-molecule inhibitors and siRNAs were applied to inhibit AKT and JNK. Western blotting, quantitative PCR, flow cytometry and histology assays were performed to analyse the functional role and mechanism of NGF. KEY FINDINGS: Our study demonstrated that NGF expression was upregulated following radiotherapy both in human HSG cells and mouse SMG tissues. NGF could reduce IR-induced HSG cell apoptosis, and AAV-mediated gene therapy could restore the salivary flow rate and protect the salivary gland against IR-induced apoptosis in vivo. Mechanistically, NGF protects salivary glands from IR-induced apoptosis by de-phosphorylating JNK kinase rather than promoting AKT phosphorylation. SIGNIFICANCE: The current study findings indicated that the modulation of the NGF pathway might prevent IR-induced salivary hypo-function.

4.
J Biol Chem ; 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33199371

RESUMO

Monomethylamine (MMA) is an important climate-active oceanic trace gas and ubiquitous in the oceans. The γ-glutamylmethylamide synthetase (GmaS) catalyzes the conversion of MMA to γ-glutamylmethylamide (GMA), the first step in MMA metabolism in many marine bacteria. The gmaS gene occurs in ~23% of microbial genomes in the surface ocean and is a validated biomarker to detect MMA-utilizing bacteria. However, the catalytic mechanism of GmaS has not been studied due to the lack of structural information. Here, the GmaS from Rhodovulum sp. 12E13 (RhGmaS) was characterized, and the crystal structures of apo-RhGmaS and RhGmaS with different ligands in five states were solved. Based on structural and biochemical analyses, the catalytic mechanism of RhGmaS was explained. ATP is first bound in RhGmaS, leading to a conformational change of a flexible loop (Lys287-Ile305), which is essential for the subsequent binding of glutamate. During the catalysis of RhGmaS, the residue Arg312 participates in polarizing the γ-phosphate of ATP and in stabilizing the γ-glutamyl phosphate intermediate; Asp177 is responsible for the deprotonation of MMA, assisting the attack of MMA on γ-glutamyl phosphate to produce a tetrahedral intermediate; and Glu186 acts as a catalytic base to abstract a proton from the tetrahedral intermediate to finally generate GMA. Sequence analysis suggested that the catalytic mechanism of RhGmaS proposed in this study has universal significance in bacteria containing GmaS. Our results provide novel insights into MMA metabolism, contributing to a better understanding of MMA catabolism in global carbon and nitrogen cycles.

5.
Mol Divers ; 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33200293

RESUMO

Here, two series of novel ursolic acid-based 1,2,4-triazolo[1,5-a]pyrimidines derivatives were synthesized and screened for their anti-inflammatory activity by evaluating their inhibition effect of using LPS-induced inflammatory response in RAW 264.7 macrophages in vitro; the effects of different concentrations of the compounds on the secretion of nitric oxide (NO) and inflammatory cytokines including TNF-α and IL-6 were evaluated. Their toxicity was also assessed in vitro. Results showed that the most prominent compound 3 could significantly decrease production of the above inflammatory factors. Docking study was performed for the representative compounds 3, UA, and Celecoxib to explain their interaction with cyclooxygenase-2 (COX-2) receptor active site. In vitro enzyme study implied that compound 3 exerted its anti-inflammatory activity through COX-2 inhibition.

6.
Hepatol Res ; 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33227168

RESUMO

AIM: The aim of this study was to use a metabonomics approach to identify potential biomarkers of exhaled breath condensate (EBC) for predicting the prognosis of acute-on-chronic liver failure (ACLF). METHODS: Using liquid chromatography mass spectrometry, EBC metabolites of ACLF patients surviving without liver transplantation (n=57) and those with worse outcomes (n=45), and controls (n=16) were profiled from a specialized liver disease center in Beijing. The metabolites were used to identify candidate biomarkers, and the predicted performance of potential biomarkers was tested. RESULTS: 41 metabolites, involving glycerophospholipid metabolism, sphingolipid metabolism, arachidonic acid metabolism and amino acid metabolism, as candidate biomarkers for discriminating the different outcomes of ACLF were selected. A prognostic model was constructed by a panel of four metabolites including phosphatidylinositol [20:4(5Z,8Z,11Z,14Z)/13:0], phosphatidyl ethanolamine (12:0/22:0), l-metanephrine and ethylbenzene, which could predict the worse prognosis in ACLF patients with sensitivity (84.4%) and specificity (89.5%) (area under the receiver operating characteristic curve [AUC] = 0.859, 95% confidence interval [CI] = 0.787-0.931). Compared with MELD score (AUC = 0.639, 95% CI = 0.526-0.753) and MELD-Na score (AUC = 0.692, 95% CI = 0.582-0.803), EBC-associated metabolite signature model could better predict worse outcomes in patients with ACLF (p<0.05). Using the MELD-Na score and EBC metabolite signatures, a decision tree model was built for predicting the prognosis of ACLF identified on logistic regression analyses (AUC = 0.906, 95% CI = 0.846-0.965). CONCLUSION: EBC metabolic signatures show promise as potential biomarkers for predicting worse prognosis of ACLF.

7.
Immunol Lett ; 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33186635

RESUMO

In abnormal glycosylation, molecules of glucose or other carbohydrates in living organisms are inappropriately attached to proteins, which causes protein denaturation. Abnormal glycosylation modification is known to directly or indirectly affect the tumor escape process, but very few studies have been performed on whether protein glycosylation changes the structure and function of immune cells and immune molecules and thereby regulates the occurrence and development of tumor escape. Therefore, this article summarizes the effect of the immune system on tumor escape in association with the abnormal glycosylation process from an immunological perspective.

8.
Zhongguo Zhong Yao Za Zhi ; 45(18): 4510-4518, 2020 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-33164382

RESUMO

The names, basic sources, medicinal parts, efficacy and standards of the medicinal materials in Euphorbiaceae were systematically collated and analyzed by the textual research for Yao medicine monographs in this paper. The results showed that there were great differences in the names, basic sources, medicinal parts and efficacy of some medicinal materials recorded in different literatures. There were 19 genera and 60 species(including varieties) of Euphorbiaceae of Yao medicine, involving 50 kinds of medicinal materials. Among them, there were 42 kinds of single basic sources medicine, 8 kinds of multi basic sources medicine, 28 kinds of root medicine, 26 kinds of whole plant medicine, 25 kinds of unique Yao medicine, accounting for 50%, 11 kinds of cross with Chinese medicinal materials, accounting for 22%. There were 21 kinds of Yao medicine standards at all levels, but only 1 kind of Laoban medicine and 2 kinds of Yao medicine standards. The Yao medicine in Euphorbiaceae could be named by means of transliteration of Yao language/Yao language transliteration/Chinese medicine name, Laoban medicine, plant morphology, medicinal properties, color and smell of medicine, while the medicinal parts and efficacy of the same medicinal name were different from those of traditional Chinese medicine. Therefore, the name and basic sources of the medicinal materials in Euphorbiaceae were not standardized, and the quality standard is not perfect. The above results provided a reference for the construction and improvement of quality standard system, the promotion of the production of medicinal materials and clinical medication standards, and the further development and utilization of Euphorbiaceae.


Assuntos
Medicamentos de Ervas Chinesas , Euphorbiaceae , Plantas Medicinais , Humanos , Medicina Tradicional Chinesa , Registros , Padrões de Referência
9.
J Phys Chem A ; 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33226240

RESUMO

We report several novel thermometers resulting from the temperature-induced aggregation of difluoroboron ß-diketonate chromophores. These thermometers exhibit a much wider temperature-dependent fluorescence emission from 445 to 592 nm along with the color change from blue to red in a dilute chloroform solution. Spectroscopy measurements and theoretical calculations confirm that the thermochromic luminescence originates from the reversible change in the noncovalent intermolecular interactions and the abrupt volume shrinkage of the solvent at its melting point. The present work provides a new strategy for rationally designing high-performance thermometers having a wide emission property.

10.
Crit Rev Food Sci Nutr ; : 1-19, 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33226273

RESUMO

Traditional fermented soybean food has emerged as an important part of people's dietary structure because of the unique flavors and improved health benefit. During fermentation, the nutrients in soybean undergo a series of biochemical reactions catalyzed naturally by microorganism secreted enzymes. Thereafter, many functional and bioactive substances such as bioactive peptides, unsaturated fatty acids, free soy isoflavones, vitamins and minerals are produced, making fermented soy products more advantageous in nutrition and health. This review comprehensively discusses the historical evolution, distribution, traditional fermentation processing, main sources and characteristics of fermented strains, flavor components, nutritional properties, and biological activities of four traditional fermented soybean foods including douchi, sufu, dajiang, and soy sauce. In the end, we introduce four major challenges encountered by traditional fermented soybean foods including high salt content, formation of biogenic amine, the presence of pathogenic microorganisms and mycotoxins, and quality inconsistency. We conclude that the establishment of scientific quality standard and innovated fermentation processing is the potential solutions to combat the issues and improve the safety of traditional fermented soybean products.

11.
J Formos Med Assoc ; 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33214033

RESUMO

BACKGROUND: Epileptic surgery is the potentially curative treatment for children with refractory seizures. The study aimed to quantify and analyze high frequency oscillation (HFO) ripples and interictal epileptiform discharges (EDs) in intraoperative electrocorticography (ECoG) between malformation of cortical dysplasia (MCD) and non-MCD children with MRI-lesional focal epilepsy, and evaluate of seizure outcomes after epileptic surgery. METHODS: The intraoperative ECoG was performed before and after lesionectomy. Quantifications of HFO ripples and interictal EDs of ECoG by frequency, amplitude, and foci of intraoperative ECoG were performed based on electrode location, and the characteristics of ECoG recordings were analyzed in each patient based on their histopathology. Seizure outcome after surgery according to their quantitative ECoG findings was analyzed. RESULTS: Frequency of EDs and HFO ripple rates in preresection ECoG were significantly higher in children with MCD compared with non-MCD (p = 0.018 and p = 0.002, respectively). Higher frequencies of EDs and ripple rates in preresection ECoG were observed in residual seizures than in seizure-free children (p = 0.045 and p = 0.005, respectively). Clinically, children with residual seizures after surgery were significantly younger at the onset, had a trend of higher seizure frequency and higher spike frequency of presurgical videoEEG. CONCLUSION: Our results suggested that quantification of intraoperative ECoG predicted seizure outcomes and reflected different ED pattern and frequencies between MCD and non-dysplastic histopathology among children who underwent resective epileptic surgery. The results of our study were encouraging and indicated that intraoperative ECoG improved the outcomes of surgery in children with epilepsy.

12.
Medicine (Baltimore) ; 99(46): e23243, 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33181713

RESUMO

BACKGROUND: This study uses a method of systematic evaluation to evaluate the safety and effectiveness of heated humidified high-flow nasal cannula (HHHFNC) as an initial ventilation method in the treatment of neonatal respiratory distress syndrome (NRDS) scientifically. In the field of evidence-based medicine, this study provides a theoretical reference and basis for choosing appropriate initial non-invasive ventilation methods in the treatment of NRDS, thereby providing assistance for clinical treatment. METHODS: The main electronic network databases were searched by computer, including 4 Chinese databases: CNKI, WangFang Data, CQVIP, SinoMed and 3 English databases: PubMed, The Cochrane Library and EMBASE, the time range of retrieval from the beginning of each database to September 1, 2020. The content involves all the published randomized controlled trials on the effectiveness of HHHFNC compared with NCPAP as an initial ventilation method in the treatment of NRDS. Using a search method that combines medical subject words and free words. Based on the Cochrane risk bias assessment tool, 2 researchers independently screen the literature, and then extract the data we needed in the literature, and cross-check. If it is difficult to decide whether to include literature, then turning to a third researcher for help and making a final decision after discussion, and using RevMan 5.3 and STATA 13.0 to analyze the relative data. RESULTS: Based on the method of meta-analysis, this study analyzes the pre-determined outcome indicators through scientific statistical analysis, and compares the effectiveness and safety of HHHFNC compared with NCPAP as an initial ventilation method in the treatment of NRDS. All results will be published in peer-reviewed high-quality professional academic journals. CONCLUSION: Based on evidence-based medicine, this study will obtain the establishing evidence of comparison that the clinical effectiveness and safety of HHHFNC compared with NCPAP as an initial ventilation method in the treatment of NRDS through the existing data and data, which provides the evidence support of evidence-based medicine in the treatment of NRDS. OSF REGISTRATION NUMBER: September 17, 2020. osf.io/f6at4 (https://osf.io/f6at4).

13.
Artigo em Inglês | MEDLINE | ID: mdl-33217055

RESUMO

BACKGROUND AND AIM: During this COVID-19 pandemic, Taiwan is one of the few countries where fecal immunochemical test (FIT) and endoscopic activity for colorectal cancer (CRC) screening keeps ongoing. We aimed to investigate how screening uptake and colonoscopy rate were affected in one of the biggest screening hubs in Northern Taiwan. METHODS: We conducted a prospective observational study tracing and analyzing the screening uptake and the trend of compliance to diagnostic colonoscopy in FIT positive subjects in the National Taiwan University Hospital screening hub since the outbreak of COVID-19 and compared it with that of the corresponding periods in the past three years. Cancellation and rescheduling rates of colonoscopy, and related reasons were also explored. RESULTS: Screening uptake during December 2019 to April 2020 was 88.8 %, which was significantly lower than that in the corresponding period of the past three years (91.2-92.7%, p for trend <0.0001) Colonoscopy rate in this period was 66.1%, which was also significantly lower than that in the past three years (70.2%-77.5%; p for trend =0.017). Rescheduling or cancellation rate was up to 10.9%, which was significantly higher than that in the past 3 years. (p for trend=0.023) and half of them was due to the fear of being infected. DISCUSSION: FIT screening was significantly affected by COVID-19 pandemic. In order to resume the practice in COVID-19 era, screening organizers should consider various approaches to secure timely diagnosis of CRC.

14.
ISA Trans ; 2020 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-33158549

RESUMO

Machine learning techniques have been successfully applied for the intelligent fault diagnosis of rolling bearings in recent years. This study has developed an Improved Multi-Scale Convolutional Neural Network integrated with a Feature Attention mechanism (IMS-FACNN) model to address the poor performance of traditional CNN-based models under unsteady and complex working environments. The proposed IMS-FACNN has a good extrapolation performance because of the novel IMS coarse grained procedure with training interference and the introduced the feature attention mechanism, which improves the model's generalization ability. The proposed IMS-FACNN model has a better performance than existing methods in all the examined scenarios including diagnosing the bearing fault of a real wind turbine. The results show that the reliability and superiority of the IMS-FACNN model in diagnosing faults of rolling bearings.

15.
BMC Musculoskelet Disord ; 21(1): 752, 2020 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-33189156

RESUMO

BACKGROUND: Two parallel cannulated screws along with an anterior wire to construct a tension band is a popular approach in transverse patellar fractures. However, the optimal screw proximity, either deep or superficial screw placements, remains controversial. Hence, a new concept of the addition of a third screw to form a triangular configuration along with the original two parallel screws was proposed in this study. Therefore, the biomechanical effect of the additional third screw on the stability of the fractured patella was investigated with finite element (FE) simulation. METHODS: An FE knee model including the distal femur, proximal tibia, and fractured patella (type AT/OTA 34-C) was developed in this study. Four different screw configurations, including two parallel cannulated screws with superficial (5-mm proximity) and deep (10-mm proximity) placements and two parallel superficial screws plus a third deep screw, and two parallel deep screws plus a third superficial screw, with or without the anterior wire, were considered for the simulation. RESULTS: Results indicated that the addition of a third screw increased stability by reducing the dorsal gap opening when two parallel screws were deeply placed, particularly on the fractured patella without an anterior wire. However, the third screw was of little value when two parallel screws were superficially placed. In the existence of two deep parallel screws and the anterior wire, the third screw reduced the gap opening by 23.5% (from 1.15 mm to 0.88 mm) and 53.6% (from 1.21 mm to 0.61 mm) in knee flexion 45° and full extension, respectively. Furthermore, in the absence of the anterior wire, the third screw reduced the gap opening by 73.5% (from 2 mm to 0.53 mm) and 72.2% (from 1.33 mm to 0.37 mm) in knee flexion 45° and full extension, respectively. CONCLUSION: Based on the results, a third cannulated screw superficially placed (5-mm proximity) is recommended to increase stability and maintain contact of the fractured patella, fixed with two parallel cannulated screws deeply placed (10-mm proximity), particularly when an anterior wire was not used. Furthermore, the third screw deeply placed is not recommended in a fractured patella with two parallel superficial screws.

16.
Cell Rep ; 33(7): 108398, 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33207193

RESUMO

To understand how neural-immune-associated genes and pathways contribute to neurodegenerative disease pathophysiology, we performed a systematic functional genomic analysis in purified microglia and bulk tissue from mouse and human AD, FTD, and PSP. We uncover a complex temporal trajectory of microglial-immune pathways involving the type 1 interferon response associated with tau pathology in the early stages, followed by later signatures of partial immune suppression and, subsequently, the type 2 interferon response. We find that genetic risk for dementias shows disease-specific patterns of pathway enrichment. We identify drivers of two gene co-expression modules conserved from mouse to human, representing competing arms of microglial-immune activation (NAct) and suppression (NSupp) in neurodegeneration. We validate our findings by using chemogenetics, experimental perturbation data, and single-cell sequencing in post-mortem brains. Our results refine the understanding of stage- and disease-specific microglial responses, implicate microglial viral defense pathways in dementia pathophysiology, and highlight therapeutic windows.

17.
Int Arch Allergy Immunol ; : 1-10, 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33207352

RESUMO

INTRODUCTION: Nasal inverted papilloma (NIP) is a benign tumour with multiple inflammatory cell infiltration. Tertiary lymphoid organs (TLOs) support local antibody production and play important roles in airway inflammation. However, the evidence of TLOs and local immunoglobulins in NIP has not been reported yet. We investigated the presence of TLOs and immunoglobulins in NIP tissues and their association with the clinical-pathological characteristics of NIPs. METHODS: We analyzed the occurrence and composition of TLOs and local immunoglobulins by immunohistochemistry and evaluated the lymph organogenesis associated genes and cytokines by quantitative qPCR and Luminex assays, respectively, in papilloma tissues from 84 NIP cases. RESULTS: TLOs were present in 54% (45/84) of the NIP patients but not in control subjects. TLOs were composed of T cells, B cells, follicular dendritic cells, macrophages, and natural killer cells. Compared to NIP tissues without TLOs, tissues with TLOs showed significantly higher eosinophil infiltration levels (3.5-fold), elevation of lymphorganogenic genes (CXCL12, CXCL13, CCL20, CCL21, CD21L, and lymphotoxin alpha and beta), and increased Th17 (IL-21, IL-22, and GM-CSF) and Th2 (IL-5 and IL-13) cytokine production. Moreover, NIP with TLOs demonstrated a higher number of follicular T helper cells and immunoglobulin-producing plasma cells (CD138+ IgA+, CD138+ IgM+, CD138+ IgE+, and CD138+ IgG+) than those without TLOs, and these antibody-producing cells were positively correlated with the eosinophil number. CONCLUSION: The high frequency of TLOs and excess local immunoglobulin production are associated with an eosinophilic and Th2 skew microenvironment in the NIP mucosa, which would contribute to an important immunopathogenic response during NIP pathogenesis.

18.
Artigo em Inglês | MEDLINE | ID: mdl-33202564

RESUMO

Patients with dementia are predisposed to multiple physiological abnormalities. It is uncertain if dementia associates with higher rates of perioperative mortality and morbidity. We used reimbursement claims data of Taiwan's National Health Insurance and conducted propensity score matching analyses to evaluate the risk of mortality and major complications in patients with or without dementia undergoing major surgery between 2004 and 2013. We applied multivariable logistic regressions to calculate adjusted odds ratios (aORs) with 95% confidence intervals (CIs) for the outcome of interest. After matching to demographic and clinical covariates, 7863 matched pairs were selected for analysis. Dementia was significantly associated with greater risks of 30-day in-hospital mortality (aOR: 1.71, 95% CI: 1.09-2.70), pneumonia (aOR: 1.48, 95% CI: 1.16-1.88), urinary tract infection (aOR: 1.59, 95% CI: 1.30-1.96), and sepsis (OR: 1.77, 95% CI: 1.34-2.34) compared to non-dementia controls. The mortality risk in dementia patients was attenuated but persisted over time, 180 days (aOR: 1.49, 95% CI: 1.23-1.81) and 365 days (aOR: 1.52, 95% CI: 1.30-1.78) after surgery. Additionally, patients with dementia were more likely to receive blood transfusion (aOR: 1.32, 95% CI: 1.11-1.58) and to need intensive care (aOR: 1.40, 95% CI: 1.12-1.76) compared to non-dementia controls. Senile dementia and Alzheimer's disease were independently associated with higher rates of perioperative mortality and complications, but vascular dementia was not affected. We found that preexisting dementia was associated with mortality and morbidity after major surgery.

19.
New Microbes New Infect ; : 100814, 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33204428

RESUMO

The coronavirus disease 2019 (COVID-19) is still global epidemic. Several studies of severe COVID-19 patients regard convalescent plasma (CP) transfusion as an effective therapy. However, there are no significant improvements in the randomized clinical trial of CP treatment. Until now, the data of mild COVID-19 patients transfused CP were lack. This study recruited 8 mild COVID-19 patients received at least one dose of CP transfusion. After CP therapy, all patients improved the clinical symptoms. The level of lymphocyte counts tended to increase, meanwhile LDH, CK and AST tended to decrease. However, CRP of 3 patients increased transiently. The median time that SARS-CoV-2 nucleic acid of the patients turned to negative was 2.5d after CP transfusion. The study shows the potential benefits of CP. Meanwhile, CP probably enhances the inflammatory response to SARS-CoV-2 temporarily in the patients with insufficient antiviral immunity. However, the effects of CP are not permanent.

20.
Chembiochem ; 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33205522

RESUMO

Baeyer-Villiger monooxygenases (BVMOs) are remarkable biocatalysts for the Baeyer-Villiger oxidation of ketones to generate esters or lactones. The regioselectivity of BVMOs is essential for determining the ratio of the two regioisomeric products ("normal" and "abnormal") when catalyzing asymmetric ketone substrates. Starting from a known normal-preferring BVMO sequence from Pseudomonas putida KT2440 ( Pp BVMO), a novel BVMO from Gordonia sihwensis ( Gs BVMO) with higher normal regioselectivity (up to 97/3) was identified. Furthermore, protein engineering increased the specificity constant ( k cat / K M ) 8.9-fold to 484 s -1 mM -1 for 10-ketostearic acid derived from oleic acid. Consequently, by using the variant Gs BVMO C308L as an efficient biocatalyst, 10-ketostearic acid was efficiently transformed into  9-(nonanoyloxy)nonanoic acid, with a space-time yield of 60.5 g L -1 d -1 . This study showed that the mutant with higher regioselectivity and catalytic efficiency could be applied to prepare medium-chain ω-hydroxy fatty acids through biotransformation of long-chain aliphatic keto acids derived from renewable plant oils.

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