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1.
J Immunol ; 213(3): 373-383, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38884660

RESUMO

Conventionally, immune responses are studied in the context of inflamed tissues and their corresponding draining lymph nodes (LNs). However, little is known about the effects of systemic inflammatory signals generated during local inflammation on distal tissues and nondraining LNs. Using a mouse model of cutaneous immunization, we found that systemic inflammatory stimuli triggered a rapid and selective distal response in the small intestine and the mesenteric LN (mesLN). This consisted of increased permeability of intestinal blood vessels and lymphatic drainage of bloodborne solutes into the mesLN, enhanced activation and migration of intestinal dendritic cells, as well as amplified T cell responses in the mesLNs to systemic but not orally derived Ags. Mechanistically, we found that the small intestine endothelial cells preferentially expressed molecules involved in TNF-α signaling and that TNF-α blockade markedly diminished distal intestinal responses to cutaneous immunization. Together, these findings reveal that the intestinal immune system is rapidly and selectively activated in response to inflammatory cues regardless of their origin, thus identifying an additional layer of defense and enhanced surveillance of a key barrier organ at constant risk of pathogen encounter.


Assuntos
Imunização , Linfonodos , Animais , Camundongos , Linfonodos/imunologia , Imunização/métodos , Camundongos Endogâmicos C57BL , Citocinas/imunologia , Citocinas/metabolismo , Intestino Delgado/imunologia , Células Dendríticas/imunologia , Inflamação/imunologia , Fator de Necrose Tumoral alfa/imunologia , Fator de Necrose Tumoral alfa/metabolismo , Linfócitos T/imunologia , Mucosa Intestinal/imunologia
2.
J Am Chem Soc ; 146(8): 5051-5055, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38373353

RESUMO

The construction of quaternary carbon centers via C-C coupling protocols remains challenging. The coupling of tertiary C(sp3) with secondary or tertiary C(sp3) counterparts has been hindered by pronounced steric clashes and many side reactions. Herein, we have successfully developed a type of bisphosphine ligand iron complex-catalyzed coupling reactions of tertiary alkyl halides with secondary alkyl zinc reagents and efficiently realized the coupling reaction between tertiary C(sp3) and secondary C(sp3) with high selectivity for the initial instance, which provided an efficient method for the construction of quaternary carbon centers with high steric hindrance. The combination of an iron catalyst and directing group of the substrate makes the great challenging transformation possible.

3.
J Am Chem Soc ; 146(14): 9871-9879, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38547318

RESUMO

Carbenes, recognized as potent intermediates, enable unique chemical transformations, and organoborons are pivotal in diverse chemical applications. As a hybrid of carbene and the boryl group, α-boryl carbenes are promising intermediates for the construction of organoborons; unfortunately, such carbenes are hard to access and have low structural diversity with their asymmetric transformations largely uncharted. In this research, we utilized boryl cyclopropenes as precursors for the swift synthesis of α-boryl metal carbenes, a powerful category of intermediates for chiral organoboron synthesis. These α-boryl carbenes undergo a series of highly enantioselective transfer reactions, including B-H and Si-H insertion, cyclopropanation, and cyclopropanation/Cope rearrangement, catalyzed by a singular chiral copper complex. This approach opens paths to previously unattainable but easily transformable chiral organoborons, expanding both carbene and organoboron chemistry.

4.
BMC Microbiol ; 24(1): 139, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38658841

RESUMO

BACKGROUND: Gastric cancer is one of the global health concerns. A series of studies on the stomach have confirmed the role of the microbiome in shaping gastrointestinal diseases. Delineation of microbiome signatures to distinguish chronic gastritis from gastric cancer will provide a non-invasive preventative and treatment strategy. In this study, we performed whole metagenome shotgun sequencing of fecal samples to enhance the detection of rare bacterial species and increase genome sequence coverage. Additionally, we employed multiple bioinformatics approaches to investigate the potential targets of the microbiome as an indicator of differentiating gastric cancer from chronic gastritis. RESULTS: A total of 65 patients were enrolled, comprising 33 individuals with chronic gastritis and 32 with gastric cancer. Within each group, the chronic gastritis group was sub-grouped into intestinal metaplasia (n = 15) and non-intestinal metaplasia (n = 18); the gastric cancer group, early stage (stages 1 and 2, n = 13) and late stage (stages 3 and 4, n = 19) cancer. No significant differences in alpha and beta diversities were detected among the patient groups. However, in a two-group univariate comparison, higher Fusobacteria abundance was identified in phylum; Fusobacteria presented higher abundance in gastric cancer (LDA scored 4.27, q = 0.041 in LEfSe). Age and sex-adjusted MaAsLin and Random Forest variable of importance (VIMP) analysis in species provided meaningful features; Bacteria_caccae was the most contributing species toward gastric cancer and late-stage cancer (beta:2.43, se:0.891, p:0.008, VIMP score:2.543). In contrast, Bifidobacterium_longum significantly contributed to chronic gastritis (beta:-1.8, se:0.699, p:0.009, VIMP score:1.988). Age, sex, and BMI-adjusted MasAsLin on metabolic pathway analysis showed that GLCMANNANAUT-PWY degradation was higher in gastric cancer and one of the contributing species was Fusobacterium_varium. CONCLUSION: Microbiomes belonging to the pathogenic phylum Fusobacteria and species Bacteroides_caccae and Streptococcus_anginosus can be significant targets for monitoring the progression of gastric cancer. Whereas Bifidobacterium_longum and Lachnospiraceae_bacterium_5_1_63FAA might be protection biomarkers against gastric cancer.


Assuntos
Bactérias , Fezes , Gastrite , Metagenoma , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/microbiologia , Masculino , Feminino , Pessoa de Meia-Idade , Gastrite/microbiologia , Fezes/microbiologia , Bactérias/genética , Bactérias/classificação , Bactérias/isolamento & purificação , Idoso , Microbioma Gastrointestinal/genética , Adulto
5.
J Org Chem ; 89(14): 10299-10310, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-38954507

RESUMO

A three-component strategy was developed to enable hydrodefluoroamination of ß-trifluoromethyl enones by selectively activating two C(sp3)-F bonds in the trifluoromethyl group. The method involved a sequence of carbonyl reduction, hydrodefluorination, and defluoroamination under transition-metal-free conditions. Synthetically useful (E)-stereospecific α-fluoroenamides were obtained in good yields with diverse functional group tolerance, which could be easily transformed into valuable organofluorides and heterocycles. The carbonyl auxiliary exerts both electronic and steric impacts on the CF3-alkenes, allowing for controllable and selective defluorination.

6.
Dig Dis Sci ; 69(9): 3172-3179, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38949750

RESUMO

BACKGROUND: There are scanty population-based studies investigating the incidence and prevalence rates of inflammatory bowel disease (IBD) in Taiwan. AIMS: This study aimed to estimate the nationwide prevalence and incidence of IBD and identify its noticeable trends in Taiwan between 2016 and 2020. METHODS: A retrospective study by analyzing the data from the National Health Insurance Research Database of Taiwan. RESULTS: A total of 2595 patients with catastrophic IBD illness were registered from 2016 to 2020 in Taiwan (CD, 880; UC, 1715). The male-to-female ratio in the study sample was 1.83:1 for CD and 1.69:1 for UC. The median age of those registered with CD and UC was 37 and 47 years, respectively. The incidence rate of CD was 0.65 per 100,000 persons in 2016 and it was increased to 0.81 per 100,000 persons in 2020. The incidence rate of UC was 1.16 per 100,000 persons in 2016 and it was increased to 1.53 in 2020. Overall, the incidence of IBD was increase from 1.81 per 100,000 persons to 2.34 per 100,000 persons between 2016 and 2020. Overall, the prevalence rates of IBD was increase from 14.95 per 100,000 persons to 20.02 per 100,000 persons between 2016 and 2020. CONCLUSION: The epidemiological stages of IBD in Taiwan was considered in the acceleration in incidence stage, during which incidence rises and prevalence is relatively low. Understanding these geographical differences is important for the rising global burden of IBD.


Assuntos
Colite Ulcerativa , Humanos , Taiwan/epidemiologia , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Incidência , Estudos Retrospectivos , Prevalência , Adulto Jovem , Adolescente , Idoso , Colite Ulcerativa/epidemiologia , Doenças Inflamatórias Intestinais/epidemiologia , Criança , Doença de Crohn/epidemiologia , Bases de Dados Factuais , Pré-Escolar , Fatores de Tempo
7.
Dig Dis Sci ; 69(9): 3382-3391, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39090445

RESUMO

BACKGROUND/AIMS: Crohn's Disease (CD) can affect the entire gastrointestinal tract, including the upper sections (UGI), which is often overlooked, especially in Asian populations. There's a notable gap in research regarding the impact of UGI involvement on the intricate landscape of ensuing complications. This study aims to address this gap. METHODS: Conducting a retrospective study at Chang Gung Memorial Hospital from January 2001 to September 2023, we compared CD patients with UGI (Montreal L4) involvement against non-L4 counterparts, focusing on baseline characteristics, post-diagnosis complications, and overall outcomes. Routine UGI endoscopy was performed around the time of diagnosis in all patients followed in our inflammatory bowel disease (IBD) center, and all CD patients with adequate follow-up were included in this study. RESULTS: The study included 212 CD patients, 111 in the L4 group and 101 in the non-L4 group, with an average follow-up of 40.8 ± 15.1 months. At baseline, individuals in the L4 category demonstrated elevated smoking rates, increased Crohn's Disease Activity Index scores, a higher prevalence of strictures, and a more prevalent usage of biologics and proton pump inhibitors. Moreover, this group was characterized by reduced albumin levels. Upon concluding the follow-up, those with L4 involvement continued to show escalated CDAI scores and hospitalization frequencies, alongside heightened C-reactive protein levels and diminished albumin concentrations. Additionally, the occurrence of UGI involvement, stricturing disease at the time of diagnosis, and a younger age at the onset of CD were pinpointed as independent predictors for the development of new-onset strictures. CONCLUSIONS: CD patients with UGI involvement exhibit elevated disease activity and serve as independent predictors for the development of intestinal strictures. Thorough UGI evaluations at the time of diagnosis, coupled with assertive treatment strategies, are essential for managing these patients effectively.


Assuntos
Doença de Crohn , Humanos , Doença de Crohn/complicações , Doença de Crohn/epidemiologia , Doença de Crohn/diagnóstico , Estudos Retrospectivos , Masculino , Feminino , Adulto , Constrição Patológica , Pessoa de Meia-Idade , Trato Gastrointestinal Superior/patologia , Endoscopia Gastrointestinal , Adulto Jovem , Fatores de Risco
8.
Neurosurg Rev ; 47(1): 763, 2024 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-39382734

RESUMO

Epithelioid glioblastoma (Ep-GBM) is a rare variant of glioblastoma characterized by a high recurrence rate and poor prognosis. Currently, there is no established standard treatment for Ep-GBM. Therefore, we identified 58 Ep-GBM cases to investigate these characteristics and identify the possible prognostic factors of survival. There were 30 male and 28 female patients with a median age of 39 years. Headaches and dizziness were the most common clinical symptom. The tumor is most frequently located in the temporal lobe (36.2%). The positivity rate for BRAF-V600E is 56.9% (33/58), for MGMT is 56.9% (33/58), and for INI-1 is 75% (30/40). Tumor recurrence was observed in 39 patients. The median progression-free survival (PFS) of all patients was 12.7 months, while the median overall survival (OS) was 29.1 months. Additionally, the median survival time after recurrence was 14.3 months. Both univariate and multivariate COX regression analyses revealed that individuals who received more than six cycles of adjuvant oral temozolomide experienced a longer median PFS compared to those who received fewer cycles. Characteristics associated with poorer PFS included tumor dissemination prior to initial surgery. Additionally, both analyses identified tumor dissemination, radiotherapy and adjuvant oral temozolomide as predictors of OS. Notably, for patients with recurrent Ep-GBM, reoperation was shown to significantly increase survival time after recurrence. In conclusion, the standard Stupp regimen is also applicable to patients with Ep-GBM, extending adjuvant oral temozolomide could further improve survival for Ep-GBM patients, reoperation may also prolong survival for recurrent Ep-GBM.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Humanos , Masculino , Feminino , Glioblastoma/terapia , Glioblastoma/mortalidade , Glioblastoma/patologia , Adulto , Pessoa de Meia-Idade , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Idoso , Adulto Jovem , Recidiva Local de Neoplasia , Temozolomida/uso terapêutico , Adolescente , Antineoplásicos Alquilantes/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/genética , Prognóstico
9.
BMC Med Educ ; 24(1): 292, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38491363

RESUMO

BACKGROUND: Narrative medicine demonstrated positive impact on empathy in medicine and nursing students. However, this pedagogical approach had not been evaluated in pharmacy education. This study sought to apply and evaluate the narrative medicine approach in extending empathy in Asian undergraduate pharmacy students. METHODS: Narrative medicine was applied through workshops which used narratives of people with different experiences and perspectives. First-year undergraduate pharmacy students who volunteered and attended these workshops formed the intervention group (N = 31) and the remaining first-year cohort formed the control group (N = 112). A sequential explanatory mixed methods approach was adopted in which quantitative methods were first used to measure impact on pharmacy students' empathy using the Jefferson Scale of Empathy- Health Professions Student (JSE-HPS), and qualitative methods (i.e. group interviews) were then used to assess pharmacy students' emotional responses to narratives, and the perspectives of pharmacy students and faculty of this pedagogical approach. RESULTS: There was no difference in JSE-HPS scores between intervention and control groups across baseline (i.e. upon matriculation), pre-intervention, and post-intervention timepoints. Pharmacy students in the intervention group had lower scores in Factor 3 ("Standing in People's Shoes") following the intervention. Five themes, guided by internal and external factors in cognition, emerged from the Group Interviews: (1) incongruence between students' motivation and faculty's perception, (2) learning context, (3) academic context, (4) cognitive system, and (5) affective system. Themes 1, 4 and 5 referred to internal factors such as students' motivation, perceived learnings, and feelings. Themes 2 and 3 referred to external factors including workshop materials, activities, content, and facilitation. CONCLUSION: This study is the first to demonstrate that pharmacy students engaged with the narrative medicine approach as narratives elicited emotional responses, exposed them to diverse perspectives, and deepened their appreciation of the importance of empathy and complexities of understanding patients' perspectives. Scaffolded educational interventions using narratives and real-life patient encounters, alongside longitudinal measurements of empathy, are necessary to bring about meaningful and sustained improvements in empathy.


Assuntos
Educação em Farmácia , Medicina Narrativa , Estudantes de Medicina , Humanos , Singapura , Estudantes de Medicina/psicologia , Empatia , Pessoal de Saúde
10.
Comput Inform Nurs ; 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39194408

RESUMO

Patient education and self-management are essential for patients with liver cirrhosis. Based on Fisher and Fisher's Information-Motivation-Behavior Skills model, a Cirrhosis Care App was developed to support the education and self-management of these patients. To evaluate the effectiveness of the application, a randomized controlled trial was conducted with patients having liver cirrhosis who were being followed up in the outpatient area of ​​a medical center in Taiwan. The experimental group used the app for 1 month, whereas a control group continued to receive conventional patient education. A pretest and posttest questionnaire was used to evaluate the app's effectiveness in improving the knowledge and practice of self-care. In addition, a questionnaire was developed based on the Technology Acceptance Model to understand satisfaction with the app. Results showed that following the implementation of the Cirrhosis Care App, patients' self-care knowledge and ability to promote self-care practice improved. User satisfaction with the app was measured and reflected in its frequency of use. This study confirmed that the Cirrhosis Care App, based on the Information-Motivation-Behavior Skills model, can improve patient knowledge and self-care practice and be actively promoted to benefit patients with cirrhosis.

11.
Angew Chem Int Ed Engl ; 63(21): e202402044, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38469657

RESUMO

The nuanced role of spin effects remains a critical gap in designing proficient open-shell catalysts. This study elucidates an iron-catalyzed allylic C(sp3)-H silylation/alkyne hydrosilylation reaction, in which the spin state of the open-shell iron catalyst dictates the reaction kinetics and pathway. Specifically, spin crossover led to alkyne hydrosilylation, whereas spin conservation resulted in a novel allylic C(sp3)-H silylation reaction. This chemoselectivity, governed by the spin-crossover efficiency, reveals an unexpected dimension in spin effects and a first in the realm of transition-metal-catalyzed in situ silylation of allylic C(sp3)-H bonds, which had been previously inhibited by the heightened reactivity of alkenes in hydrosilylation reactions. Furthermore, this spin crossover can either accelerate or hinder the reaction at different stages within a single catalytic reaction, a phenomenon scarcely documented. Moreover, we identify a substrate-assisted C-H activation mechanism, a departure from known ligand-assisted processes, offering a fresh perspective on C-H activation strategies.

12.
Mol Pain ; 19: 17448069231170072, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37002193

RESUMO

BACKGROUND: Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder, and its specific pathogenesis is still unclear. We have previously reported that TTX-resistant (TTX-R) sodium channels in colon-specific dorsal root ganglion (DRG) neurons were sensitized in a rat model of visceral hypersensitivity induced by neonatal colonic inflammation (NCI). However, the detailed molecular mechanism for activation of sodium channels remains unknown. This study was designed to examine roles for melatonin (MT) in sensitization of sodium channels in NCI rats. METHODS: Colorectal distention (CRD) in adult male rats as a measure of visceral hypersensitivity. Colon-specific dorsal root ganglion (DRG) neurons were labeled with DiI and acutely dissociated for measuring excitability and sodium channel current under whole-cell patch clamp configurations. Western blot and Immunofluorescence were employed to detect changes in expression of Nav1.8 and MT2. RESULTS: The results showed that rats exhibited visceral hypersensitivity after NCI treatment. Intrathecal application of melatonin significantly increased the threshold of CRD in NCI rats with a dose-dependent manner, but has no role in the control group. Whole-cell patch clamp recording showed that melatonin remarkably decreased the excitability and the density of TTX-R sodium channel in DRG neurons from NCI rats. The expression of MT2 receptor at the protein level was markedly lower in NCI rats. 8MP, an agonist of MT2 receptor, enhanced the distention threshold in NCI rats. Application of 8MP reversed the enhanced hypersensitivity of DRG neurons from NCI rats. 8MP also reduced TTX-R sodium current density and modulated dynamics of TTX-R sodium current activation. CONCLUSIONS: These data suggest that sensitization of sodium channels of colon DRG neurons in NCI rats is most likely mediated by MT2 receptor, thus identifying a potential target for treatment for chronic visceral pain in patients with IBS.


Assuntos
Síndrome do Intestino Irritável , Melatonina , Dor Visceral , Ratos , Animais , Masculino , Síndrome do Intestino Irritável/complicações , Síndrome do Intestino Irritável/tratamento farmacológico , Síndrome do Intestino Irritável/metabolismo , Ratos Sprague-Dawley , Melatonina/farmacologia , Melatonina/uso terapêutico , Melatonina/metabolismo , Dor Visceral/metabolismo , Nociceptividade , Receptor MT2 de Melatonina/metabolismo , Gânglios Espinais/metabolismo , Tetrodotoxina , Canal de Sódio Disparado por Voltagem NAV1.8/metabolismo
13.
BMC Cardiovasc Disord ; 23(1): 86, 2023 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-36782127

RESUMO

BACKGROUND: Aortic pseudoaneurysm is a life-threatening clinical condition, and thoracic endovascular aortic repair (TEVAR) has been reported to have a relatively satisfactory effect in aortic pathologies. We summarized our single-centre experience using chimney TEVAR for aortic arch pseudoaneurysms with inadequate landing zones. METHODS: A retrospective study was conducted from October 2015 to August 2020, 32 patients with aortic arch pseudoaneurysms underwent chimney TEVAR to exclude an aortic lesion and reconstruct the supra-aortic branches, including 3 innominate artery, 12 left common carotid arteries and 29 left subclavian arteries. Follow-up computed tomography was suggested before discharge; at 3, 6, 12 months and yearly thereafter. RESULTS: The median age of 32 patients was 68.0 years (range, 28-81) with the mean max diameter of aneurysm of 47.9 ± 12.0 mm. Forty-four related supra-aortic branches were well preserved, and the technical success rate was 100%. The Type Ia endoleaks occurred in 3 (9%) patients. Two patients were lost to follow-up and 4 patients died during the follow-up period. The mean follow-up times was 46.5 ± 14.3 months. One patient died due to acute myocardial infarction just 10 days after chimney TEVAR and the other 3 patients passed away at 1.5 months, 20 months, and 31 months with non-aortic reasons. The 4.5-year survival estimate was 84.4%. The primary patency rate of the target supra-arch branch vessels was 97.7% (43/44), and no other aorta-related reinterventions and severe complications occurred. CONCLUSION: For aortic arch pseudoaneurysms with inadequate landing zones for TEVAR, the chimney technique seems to be feasible, with acceptable mid-term outcomes, and it could serve as an alternative minimally invasive approach to extend the landing zone. Slow flow type Ia endoleak could be treated conservatively after chimney TEVAR. Additional experience is needed, and the long-term durability of chimney TEVAR requires further follow-up.


Assuntos
Falso Aneurisma , Implante de Prótese Vascular , Procedimentos Endovasculares , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Aorta Torácica/diagnóstico por imagem , Aorta Torácica/cirurgia , Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/efeitos adversos , Falso Aneurisma/diagnóstico por imagem , Falso Aneurisma/cirurgia , Falso Aneurisma/complicações , Estudos Retrospectivos , Resultado do Tratamento , Fatores de Risco , Procedimentos Endovasculares/efeitos adversos , Aortografia/métodos , Fatores de Tempo , Endoleak/diagnóstico por imagem , Endoleak/etiologia , Endoleak/cirurgia , Stents/efeitos adversos
14.
Int J Mol Sci ; 24(4)2023 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-36835095

RESUMO

The prevalence of nonalcoholic fatty liver disease (NAFLD) is estimated to be approximately about 25.24% of the population worldwide. NAFLD is a complex syndrome and is characterized by a simple benign hepatocyte steatosis to more severe steatohepatitis in the liver pathology. Phellinus linteus (PL) is traditionally used as a hepatoprotective supplement. Styrylpyrone-enriched extract (SPEE) obtained from the PL mycelia has been shown to have potential inhibition effects on high-fat- and high-fructose-diet-induced NAFLD. In the continuous study, we aimed to explore the inhibitory effects of SPEE on free fatty acid mixture O/P [oleic acid (OA): palmitic acid (PA); 2:1, molar ratio]-induced lipid accumulation in HepG2 cells. Results showed that SPEE presented the highest free radical scavenging ability on DPPH and ABTS, and reducing power on ferric ions, better than that of partitions obtained from n-hexane, n-butanol and distilled water. In free-fatty-acid-induced lipid accumulation in HepG2 cells, SPEE showed an inhibition effect on O/P-induced lipid accumulation of 27% at a dosage of 500 µg/mL. As compared to the O/P induction group, the antioxidant activities of superoxide dismutase, glutathione peroxidase and catalase were enhanced by 73%, 67% and 35%, respectively, in the SPEE group. In addition, the inflammatory factors (TNF-α, IL-6 and IL-1ß) were significantly down-regulated by the SPEE treatment. The expressions of anti-adipogenic genes involved in hepatic lipid metabolism of 5' adenosine monophosphate (AMP)-activated protein kinase (AMPK), sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) were enhanced in the SPEE supplemented HepG2 cells. In the protein expression study, p-AMPK, SIRT1 and PGC1-α were significantly increased to 121, 72 and 62%, respectively, after the treatment of SPEE. Conclusively, the styrylpyrone-enriched extract SPEE can ameliorate lipid accumulation and decrease inflammation and oxidative stress through the activation of SIRT1/AMPK/PGC1-α pathways.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Phellinus , Humanos , Proteínas Quinases Ativadas por AMP/metabolismo , Ácidos Graxos não Esterificados/metabolismo , Células Hep G2/efeitos dos fármacos , Células Hep G2/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Sirtuína 1/metabolismo , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Pironas/química , Pironas/farmacologia , Phellinus/química
15.
Angew Chem Int Ed Engl ; 62(51): e202315473, 2023 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-37934194

RESUMO

Stereoconvergent transformation of E/Z mixtures of olefins to products with a single steric configuration is of great practical importance but hard to achieve. Herein, we report an iron-catalyzed stereoconvergent 1,4-hydrosilylation reactions of E/Z mixtures of readily available conjugated dienes for the synthesis of Z-allylsilanes with high regioselectivity and exclusive stereoselectivity. Mechanistic studies suggest that the reactions most likely proceed through a two-electron redox mechanism. The stereoselectivity of the reactions is ultimately determined by the crowded reaction cavity of the α-diimine ligand-modified iron catalyst, which forces the conjugated diene to coordinate with the iron center in a cis conformation, which in turn results in generation of an anti-π-allyl iron intermediate. The mechanism of this stereoconvergent transformation differs from previously reported mechanisms of other related reactions involving radicals or metal-hydride species.

16.
Endoscopy ; 54(3): 290-298, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-33271603

RESUMO

BACKGROUND: The likelihood of advanced or synchronous neoplasms is significantly higher in fecal immunochemical test (FIT)-positive individuals than in the general population. The magnitude of the colonoscopy-related complication rate in FIT-positive individuals remains unknown. This study aimed to elucidate the colonoscopy-related complication rate after a positive FIT result and compare it with the rate when colonoscopy was performed for other purposes. METHODS: Information regarding colonoscopy-related severe complications after a positive FIT result (FIT-colonoscopy) and ordinary colonoscopy during 2010-2014 was collected from the Taiwanese Colorectal Cancer Screening Program Database and National Health Insurance Research Database. Severe complications included significant bleeding, perforation, and cardiopulmonary events ≤ 14 days after colonoscopy. The number of events per 1000 procedures was used to quantify complication rates. Multivariate analysis was conducted to assess the association of various factors with severe complications associated with FIT-colonoscopy compared with ordinary colonoscopy. RESULTS: 319 114 FIT-colonoscopies (214 955 patients) were identified, 51 242 (16.1 %) of which included biopsy and 94 172 (29.5 %) included polypectomy. Overall, 2125 significant bleedings (6.7 ‰) and 277 perforations (0.9 ‰) occurred ≤ 14 days after FIT-colonoscopy. Polypectomy, antiplatelet use, and anticoagulant use were associated with higher risk of complications (adjusted odds ratio [aOR] 4.41, 95 % confidence interval [CI] 4.05-4.81); aOR 1.35, 95 %CI 1.12-1.53; aOR 1.88, 95 %CI 0.61-5.84, respectively). Compared with ordinary colonoscopy, FIT-colonoscopy involved significantly higher risk of significant bleeding (aOR 3.10, 95 %CI 2.90-3.32). CONCLUSIONS: FIT-colonoscopy was associated with a more than two-fold risk of significant bleeding, especially when polypectomy was performed.


Assuntos
Neoplasias Colorretais , Detecção Precoce de Câncer , Biópsia , Colonoscopia/efeitos adversos , Colonoscopia/métodos , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Detecção Precoce de Câncer/efeitos adversos , Detecção Precoce de Câncer/métodos , Fezes , Humanos , Programas de Rastreamento/métodos , Sangue Oculto
17.
J Endovasc Ther ; 29(4): 525-535, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-34836467

RESUMO

PURPOSE: The optimal treatment for isolated abdominal aortic dissection (IAAD) is currently unknown. We compared the effects of straight and bifurcated aortic stent grafts on postoperative aortic remodeling in patients with IAAD. MATERIALS AND METHODS: From February 2012 to December 2019, 57 patients with IAAD were treated using endovascular methods, including either a bifurcated or a straight aortic stent graft. The clinical features, risk factors, computed tomography angiograms, midterm follow-up results, and aortic remodeling of these patients were reviewed and analyzed. RESULTS: In total, 44 (77%) patients were treated with a bifurcated graft and 13 (23%) patients were treated with a straight graft. Patients treated with straight grafts had fewer common iliac arteries involved (38% vs 73%, p=0.023), the dissection length was shorter (76.3 ± 40.0 vs 116.2 ± 56.7 mm, p=0.011), and the preoperative aortic diameter (26.0 ± 5.6 vs 35.2 ± 12.1 mm) and the false lumen diameter (13.1 ± 5.2 vs 21.2 ± 11.3 mm) were smaller. During the procedure, there were 3 (5.3%) type I endoleaks, 1 (1.8%) surgical conversion and 1 (1.8%) partial renal artery coverage without perioperative mortality. Patients with straight grafts had shorter operative time (96.5 ± 24.4 vs 144.2 ± 49.0 minutes, p<0.0001). The median follow-up duration was 37.6 ± 21.0 (range = 3-89) months with 1 (1.8%) aortic-related death. Type A aortic dissection occurred in 1 (1.8%) patient. New descending aortic dissection occurred in 3 (5.3%) patients, and 1 patient advanced to type A aortic dissection 3 months later. Two (3.5%) patients had limb occlusion. There was no significant difference in aortic remodeling, survival, and freedom from all adverse events between the 2 treatment strategies. CONCLUSIONS: Endovascular treatment provides a safe, minimally invasive treatment for IAAD in midterm follow-up. Compression of the true lumen at the aortic bifurcation is the main concern after treatment with a bifurcated graft. Straight grafts are an excellent alternative for some patients, with the benefit of reduced procedural time, effective aortic remodeling, and excellent clinical prognosis. More experience is needed to offer clear recommendations for making treatment decisions as well as determine long-term effectiveness and durability.


Assuntos
Dissecção Aórtica , Implante de Prótese Vascular , Procedimentos Endovasculares , Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/etiologia , Dissecção Aórtica/cirurgia , Aortografia/métodos , Prótese Vascular , Implante de Prótese Vascular/efeitos adversos , Procedimentos Endovasculares/efeitos adversos , Humanos , Desenho de Prótese , Stents , Fatores de Tempo , Resultado do Tratamento
18.
Arch Virol ; 167(12): 2519-2528, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36083350

RESUMO

The wide spread of coronavirus disease 2019 (COVID-19) has significantly threatened public health. Human herd immunity induced by vaccination is essential to fight the epidemic. Therefore, highly immunogenic and safe vaccines are necessary to control SARS-CoV-2, whose S protein is the antigenic determinant responsible for eliciting antibodies that prevent viral entry and fusion. In this study, we developed a SARS-CoV-2 DNA vaccine expressing the S protein, named pVAX-S-OP, which was optimized according to the human-origin codon preference and using polyinosinic-polycytidylic acid as an adjuvant. pVAX-S-OP induced specific antibodies and neutralizing antibodies in BALB/c and hACE2 transgenic mice. Furthermore, we observed 1.43-fold higher antibody titers in mice receiving pVAX-S-OP plus adjuvant than in those receiving pVAX-S-OP alone. Interferon gamma production in the pVAX-S-OP-immunized group was 1.58 times (CD3+CD4+IFN-gamma+) and 2.29 times (CD3+CD8+IFN-gamma+) lower than that in the pVAX-S-OP plus adjuvant group but higher than that in the control group. The pVAX-S-OP vaccine was also observed to stimulate a Th1-type immune response. When, hACE2 transgenic mice were challenged with SARS-CoV-2, qPCR detection of N and E genes showed that the viral RNA loads in pVAX-S-OP-immunized mice lung tissues were 104 times and 106 times lower than those of the PBS control group, which shows that the vaccine could reduce the amount of live virus in the lungs of hACE2 mice. In addition, pathological sections showed less lung damage in the pVAX-S-OP-immunized group. Taken together, our results demonstrated that pVAX-S-OP has significant immunogenicity, which provides support for developing SARS-CoV-2 DNA candidate vaccines.


Assuntos
COVID-19 , Vacinas de DNA , Animais , Humanos , Camundongos , Adjuvantes Imunológicos , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/prevenção & controle , Imunidade Celular , Camundongos Transgênicos , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/genética , Vacinas de DNA/genética
19.
BMC Gastroenterol ; 22(1): 475, 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36404314

RESUMO

BACKGROUND: The influence of alcoholic liver disease (ALD) on the postoperative outcomes is not completely understood. Our purpose is to evaluate the complications and mortality after nonhepatic surgeries in patients with ALD. METHODS: We conducted a retrospective cohort study included adults aged 20 years and older who underwent nonhepatic elective surgeries using data of Taiwan's National Health Insurance, 2008-2013. Using a propensity-score matching procedure, we selected surgical patients with ALD (n = 26,802); or surgical patients without ALD (n = 26,802) for comparison. Logistic regression was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) of postoperative complications and in-hospital mortality associated with ALD. RESULTS: Patients with ALD had higher risks of acute renal failure (OR 2.74, 95% CI 2.28-3.28), postoperative bleeding (OR 1.64, 95% CI 1.34-2.01), stroke (OR 1.51, 95% CI 1.34-1.70) septicemia (OR 1.47, 95% CI 1.36-1.58), pneumonia (OR 1.43, 95% CI 1.29-1.58), and in-hospital mortality (OR 2.64, 95% CI 2.24-3.11) than non-ALD patients. Patients with ALD also had longer hospital stays and higher medical expenditures after nonhepatic surgical procedures than the non-ALD patients. Compared with patients without ALD, patients with ALD who had jaundice (OR 4.82, 95% CI 3.68-6.32), ascites (OR 4.57, 95% CI 3.64-5.74), hepatic coma (OR 4.41, 95% CI 3.44-5.67), gastrointestinal hemorrhage (OR 3.84, 95% CI 3.09-4.79), and alcohol dependence syndrome (OR 3.07, 95% CI 2.39-3.94) were more likely to have increased postoperative mortality. CONCLUSION: Surgical patients with ALD had more adverse events and a risk of in-hospital mortality after nonhepatic surgeries that was approximately 2.6-fold higher than that for non-ALD patients. These findings suggest the urgent need to revise the protocols for peri-operative care for this population.


Assuntos
Hepatopatias Alcoólicas , Humanos , Adulto , Estudos Retrospectivos , Pontuação de Propensão , Razão de Chances , Mortalidade Hospitalar , Hepatopatias Alcoólicas/complicações , Hepatopatias Alcoólicas/cirurgia
20.
Environ Res ; 205: 112455, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-34863688

RESUMO

The loss of soil organic phosphorus can easily cause water eutrophication. In order to effectively reduce the loss of soil organic phosphorus, this manuscript investigated the adsorption of soil organic phosphorus by lanthanum modified biochar (BC), traditional adsorbent gypsum (GY) and zeolite (ZE) by taking phytic acid as the representative. The adsorption isotherm model and kinetic models were used to fit the phosphorus absorption characteristics of the adsorbents. The effects of initial pH and temperature on the adsorption capacity were discussed, and the adsorption mechanism of each adsorbent was explained by means of FTIR and XRD. The results showed that the adsorption capacity of phytate phosphorus followed the trend of BCTS > GYTS > ZETS > TS (soil), and the maximum phosphorus adsorption capacity obtained from Langmuir isotherm for treatment with BCTS was 2.836 mg g-1, and the treatment had the strongest affinity for phytate phosphorus and also the ability to store phosphorus. The adsorption process fits well with Langmuir isotherm equation and pseudo-second-order kinetic equation, and the adsorption behavior of phytate phosphorus was mainly controlled by the chemisorption of monolayer. When the concentration of phytate phosphorus was 100 mg L-1, percentage of modified biochar added to the soil was 3% and the pH was 6, the adsorption capacity reached the maximum, and the maximum adsorption capacity was 2.000 mg g-1. The results of FTIR and XRD characterization showed that complexation was the main adsorption mechanism. In this study, the combination of modified biochar and soil phytate phosphorus can provide a good theoretical basis for reducing the loss of soil organic phosphorus.


Assuntos
Fósforo , Poluentes Químicos da Água , Adsorção , Carvão Vegetal , Concentração de Íons de Hidrogênio , Cinética , Fósforo/química , Solo , Poluentes Químicos da Água/análise
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