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1.
Microbiol Spectr ; : e0091321, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34756065

RESUMO

Enterococcus faecium is a clinically important pathogen that can cause significant morbidity and death. In this study, we aimed to develop a machine learning (ML) algorithm-based rapid susceptibility method to distinguish vancomycin-resistant E. faecium (VREfm) and vancomycin-susceptible E. faecium (VSEfm) strains. A predictive model was developed and validated to distinguish VREfm and VSEfm strains by analyzing the matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry (MS) spectra of unique E. faecium isolates from different specimen types. The algorithm used 5,717 mass spectra, including 2,795 VREfm and 2,922 VSEfm mass spectra, and was externally validated with 2,280 mass spectra of isolates (1,222 VREfm and 1,058 VSEfm strains). A random forest-based algorithm demonstrated overall good classification performances for the isolates from the specimens, with mean accuracy, sensitivity, and specificity of 0.78, 0.79, and 0.77, respectively, with 10-fold cross-validation, timewise validation, and external validation. Furthermore, the algorithm provided rapid results, which would allow susceptibility prediction prior to the availability of phenotypic susceptibility results. In conclusion, an ML algorithm designed using mass spectra obtained from the routine workflow may be able to rapidly differentiate VREfm strains from VSEfm strains; however, susceptibility results must be confirmed by routine methods, given the demonstrated performance of the assay. IMPORTANCE A modified binning method was incorporated to cluster MS shifting ions into a set of representative peaks based on a large-scale MS data set of clinical VREfm and VSEfm isolates, including 2,795 VREfm and 2,922 VSEfm isolates. Predictions with the algorithm were significantly more accurate than empirical antibiotic use, the accuracy of which was 0.50, based on the local epidemiology. The algorithm improved the accuracy of antibiotic administration, compared to empirical antibiotic prescription. An ML algorithm designed using MALDI-TOF MS spectra obtained from the routine workflow accurately differentiated VREfm strains from VSEfm strains, especially in blood and sterile body fluid samples, and can be applied to facilitate the rapid and accurate clinical testing of pathogens.

2.
Nanomaterials (Basel) ; 11(10)2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34685035

RESUMO

The effects of chymosin on the physicochemical and hydrolysis characteristics of casein micelles and individual caseins were investigated. Adding 0.03 units of chymosin/mL led to the casein micelles in skim milk coagulating after a 3 h incubation period at 30 °C. SDS-PAGE investigation showed that ß-CN, κ-CN, αs-CN, and a portion of ß-lactoglobulin (ß-LG) in the milk supernatant fraction (MSF) were precipitated into the milk pellet fraction (MPF). The mean particle size of the MSF with chymosin decreased from 254.4 nm to 179.2 nm after a 3 h incubation period. Mass spectrometry and SDS-PAGE analysis suggested that chymosin hydrolyzed individual ß-CN, κ-CN, and αs-CN, but not ß-LG. Chymosin hydrolysis led to a decrease in the molecular weights of the hydrolyzed ß-CN, κ-CN, and αs-CN. Particle size analysis indicated that there was no difference in the particle size distribution of hydrolyzed ß-CN and αs-CN. Moreover, our outcomes demonstrated that the hydrolysis of κ-CN by chymosin occurs before that of ß-CN and αs-CN.

3.
Front Pharmacol ; 12: 730776, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34690769

RESUMO

Aplastic Anemia (AA) is a rare but fatal hematologic disease that may occur at any age and especially higher in Asia. We investigated whether Chinese herbal medicine (CHM) is beneficial to AA patients as a complementary therapy using a nationwide population-based database in Taiwan between 2000-2016. Patient survival was estimated by Kaplan‒Meier survival analyses and Cox proportional-hazard model. CHM-users presented lower risks of overall and anemia-related mortalities when compared to non-users. The risk of overall mortality for CHM-users in AA patients was 0.70-fold [adjusted hazard ratio (aHR): 0.70, 95% confidence interval (CI): 0.66-0.74, p < 0.001). The risk of anemia-related mortality was lower in CHM-users when compared to non-users (aHR: 0.46, 95% CI: 0.32-0.67, p < 0.001). The association rule analysis revealed that CHM pairs were Ban-Zhi-Lian (BZL; Scutellaria barbata D. Don)→Bai-Hua-She-She-Cao (BHSSC; Oldenlandia diffusa (Willd.) Roxb.), followed by Dang-Gui (DG; Angelica sinensis (Oliv.) Diels)→Huang-Qi (HQi; Astragalus membranaceus (Fisch.) Bunge), and Xian-He-Cao (XHC; Agrimonia pilosa f. borealis (Kitag.) Chu)→Gui-Pi-Tang (GPT). Network analysis showed that BZL, BHSSC, DG, HQi, XHC, GPT, and Dan-Shen (DanS; Salvia miltiorrhiza var. charbonnelii (H.Lév.) C.Y.Wu) were commonly used CHMs for AA patients. Therefore, further studies for these commonly prescribed herbs are needed in functional investigations in hematopoiesis-stimulating effect and large-scale randomized controlled trials (RCT) in bone marrow failure related diseases.

4.
Molecules ; 26(19)2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34641450

RESUMO

Three new tuliposides H-J (1-3) and 11 known compounds were obtained from the methanolic extracts of the bulbs of Amana edulis for the first time. Their structures were elucidated by NMR, MS, and IR spectroscopic data, optical rotation, and Mosher's method. The melanogenesis properties of all the isolates were evaluated in B16 melanoma cells. Consequently, tributyl citrate (9) had anti-melanogenesis activity but was cytotoxic toward B16. (+)-Pyroglutamic acid (4), (+)-butyl 5-oxopyrrolidine-2-carboxylate (6), (-)-3-hydroxy-2-methylbutyrolactone (10), and 5-(hydroxymethyl)furfural (12) had increased melanin productions and tyrosinase activities. Those active components could be further studied as the candidates against melanoma and vitiligo for skin diseases or whitening/hypopigmentation for hair.


Assuntos
Glucosídeos/farmacologia , Liliaceae/química , Melanoma Experimental/tratamento farmacológico , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Animais , Melaninas/metabolismo , Camundongos , Monofenol Mono-Oxigenase/metabolismo , Células Tumorais Cultivadas
5.
J Cell Physiol ; 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34472101

RESUMO

Targeting protein kinase C (PKC) family was found to repress the migration and resistance of non-small cell lung cancer cells to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). However, none of the PKC inhibitors has been approved for anticancer therapy yet due to the limited efficacy in clinical trials, and the underlying mechanisms remain unclear. l-lactic acidosis, a common condition comprising high l-lactate concentration and acidic pH in the tumor microenvironment, has been known to induce tumor metastasis and drug resistance. In this study, l-lactic acid was found to reverse the inhibitory effects of pan-PKC inhibitors GO6983 on PKC activity, cell migration, and EGFR-TKI resistance, but these effects were not affected by the modulators of lactate receptor GPR81. Interestingly, blockade of lactate transporters, monocarboxylate transporter-1 and -4 (MCT1 and MCT4), attenuated the intracellular level of GO6983, and its inhibitory effect on PKC activity, suggesting that lactic acid promotes the resistance to PKC inhibitors by competing for the uptake through these transporters rather than by activating its receptor, GPR81. Our findings explain the underlying mechanisms of the limited response of PKC inhibitors in clinical trials.

6.
Top Stroke Rehabil ; : 1-10, 2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34340637

RESUMO

PURPOSE: The objectives are to evaluate the effects of a sequential combination of aerobic exercise and cognitive training, compared with exercise or cognitive training alone, on cognitive function, physical function, daily function, quality of life, and social participation in stroke survivors with cognitive impairment. METHODS: This is a single-blind, parallel, randomized controlled trial. Stroke patients with mild cognitive impairment (n = 56) were randomly assigned to aerobic exercise training (n = 18), computerized cognitive training (n = 18), and the sequential combination of aerobic exercise and computerized cognitive training (n = 20) group. All groups underwent training 60 min/day, 3 days/week, for a total of 12 weeks. The primary outcomes included Montreal Cognitive Assessment (MoCA), Wechsler Memory Scale-Third Edition, and the Stroop color-word test. Secondary outcomes were the Timed Up and Go test, 6-Minute Walk Test, Functional Independence Measure, Lawton Instrumental Activities of Daily Living Scale, Community Integration Questionnaire, and Stroke Impact Scale. RESULTS: 56 participants completed the trial. Compared with a single type of aerobic exercise or cognitive training, the combined training group showed significant improvement in MoCA (P < .05, η2 = 0.13), and two sub-tests in WMS-III (both P's < 0.05) following the intervention. However, no between-group differences were observed for physical functions, daily function, quality of life, and social participation measures. CONCLUSIONS: The findings provide evidence for the potential synergistic intervention in stroke survivors. Future studies investigating the transfer effects and the optimal training parameters with a larger sample is needed.

7.
Front Pharmacol ; 12: 720821, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34421615

RESUMO

Chinese herbal medicines (CHMs) are widely used in Asian countries. They show multiple pharmacological activities, including antiviral activities. The 5'-long terminal repeat (LTR) region of HIV-1, required for viral transcription, is a potential drug target for HIV-1 reactivation and intrinsic cell death induction of infected or latently infected cells. Modulation of HIV-1 reactivation requires interactions between host cell proteins and viral 5'-LTR elements. By evaluation of two CHMs- Xanthium strumarium and Pueraria montana, we found that 1) X. strumarium reactivated HIV-1 latently infected cells in J-Lat 8.4, J-Lat 9.2, U1, and ACH-2 cells in vitro; 2) 27 nuclear regulatory proteins were associated with HIV-1 5'-LTR using deoxyribonucleic acid affinity pull-down and LC-MS/MS analyses; and 3) among them, silencing of XRCC6 reactivated HIV-1 5'-LTR transcriptional activity. We found that X. strumarium inhibits the 5'-LTR associated XRCC6 nuclear regulatory proteins, increases its viral 5'-LTR promoter transcriptional activity, and reactivates HIV-1 latently infected cells in vitro. These findings may contribute to understanding the 5'-LTR activity and the host cell nuclear regulatory protein machinery for reactivating HIV-1 and for future investigations to eradicate and cure HIV-1 infection.

8.
Nat Prod Res ; : 1-5, 2021 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-34278895

RESUMO

Three glycosylated stilbenes (1-3), two anthraquinones (4, 5), one lignan (6), five tannins (7-11), two amino acids (12, 13), and one auronol (14) were isolated from the root of Ampelopsis japonica. All compounds, except for 4, 6, and 11 were obtained from this species for the first time. Compounds 6-9 could notably inhibit ROS generations in HaCaT keratinocyte cells with IC50 values of 5.28, 4.83, 0.87, and 1.66 µM, respectively. Compounds 8-10 showed potent DPPH free radical scavenging effects with IC50 values of 14.37, 16.08, and 12.11 µM, individually. In anti-melanogenesis assay, only 8 and 9 could decrease 7.93% and 11.66% melanin contents induced by α-MSH in B16F10 melanoma cells at 40 µM and moderately inhibit tyrosinase activities. By far, galloylhamameloses 8 and 9 were found to exhibit both antioxidant and anti-melanogenesis properties that could be further developed as cosmeceutical agents for skin disorders.

9.
J Ethnopharmacol ; 279: 114359, 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34174374

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Muscular dystrophies are a rare, severe, and genetically inherited group of disorders characterized by progressive loss of muscle fibers, leading to muscle weakness. The current treatment plan for muscular dystrophies includes the use of steroids to slow muscle deterioration by dampening the inflammatory response. AIM OF THE STUDY: Chinese herbal medicine (CHM) has been offered as an adjunctive therapy in Taiwan's medical healthcare plan, making it possible to track CHM usage in patients with muscular dystrophic disease. Therefore, we explored the long-term effects of CHM use on the overall mortality of patients with muscular dystrophies. MATERIALS AND METHODS: A total of 581 patients with muscular dystrophies were identified from the database of Registry for Catastrophic Illness Patients in Taiwan. Among them, 80 and 201 patients were CHM users and non-CHM users, respectively. Student's t-test, chi-squared test, Cox proportional hazard model, and Kaplan-Meier curve (log-rank test) were used for evaluation. Association rules and network analyses were performed to explore the combination of CHMs used in muscular dystrophies. RESULTS: Compared to non-CHM users, there were more female patients, more comorbidities, including chronic pulmonary disease and peptic ulcer disease in the CHM user group. Patients with prednisolone usage exhibited a lower risk of overall mortality than those who did not, after adjusting for age, sex, use of CHM, and comorbidities. CHM users showed a lower risk of overall mortality after adjusting for age, sex, prednisolone use, and comorbidities. The cumulative incidence of the overall survival was significantly higher in CHM users. Association rule and network analysis showed that one main CHM cluster was commonly used to treat patients with muscular dystrophies in Taiwan. The cluster includes Yin-Qiao-San, Ban-Xia-Bai-Zhu-Tian-Ma-Tang, Zhi-Ke (Citrus aurantium L.), Yu-Xing-Cao (Houttuynia cordata Thunb.), Che-Qian-Zi (Plantago asiatica L.), and Da-Huang (Rheum palmatum L.). CONCLUSIONS: Our data suggest that adjunctive therapy with CHM may help to reduce the overall mortality among patients with muscular dystrophies. The identification of the CHM cluster allows us to narrow down the key active compounds and may enable future therapeutic developments and clinical trial designs to improve overall survival in these patients.

10.
Front Pharmacol ; 12: 593434, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33935696

RESUMO

The survival of patients with HIV has greatly improved, due to Anti-Retroviral Therapy (ART). However, long-term HIV survivors often develop serious bone abnormalities, possibly due to the interplay of osteoblasts, osteoclasts, HIV ad ART. We evaluated in a nation-wide study in Taiwan the effect of Chinese herbal medicine (CHM) on overall mortality in HIV patients with osteoporosis or fractures. Enrollment period was between 1998 and 2011. Patients with osteoporosis or fractures before the HIV infection, and those with less than 14 days CHM use, were excluded. This left 498 patients, 160 CHM users, 338 without CHM. Univariate Kaplan-Meier and multivariate Cox regression analysis were used to compare the overall mortality in these 2 groups. Due to the nature of Chinese medicine, CHMs inevitably varied. We therefore also used rule mining and network analysis to determine which major CHM clusters were prescribed to the patients. CHM users had a much Lower mortality (hazard ratio (HR) = 0.43, 95% confidence interval (CI): 0.24-0.77, p < 0.005) and higher survival (p = 0.004, log-rank test). Although the CHMs greatly varied, network analysis identified one main cluster of strongly related CHM combinations (Chuan-Xiong-Cha-Tiao-San (CXCTS), Gan-Cao (GC; Glycyrrhiza uralensis Fisch.), Liu-He-Tang (LHT), Huang-Qin-Tang (HQT), Jia-Wei-Ping-Wei-San (JWPWS), and Dang-Gui-Long-Hui-Wan (DGLHuiW)). CHM as an additional treatment strongly improves overall survival in HIV-infected patients with osteoporosis and fractures.

11.
Sci Rep ; 11(1): 6499, 2021 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-33753796

RESUMO

The adrenal gland responds to heat stress by epinephrine and glucocorticoid release to alleviate the adverse effects. This study investigated the effect of acute heat stress on the protein profile and histone modification in the adrenal gland of layer-type country chickens. A total of 192 roosters were subject to acute heat stress and thereafter classified into a resistant or susceptible group according to body temperature change. The iTRAQ analysis identified 80 differentially expressed proteins, in which the resistant group had a higher level of somatostatin and hydroxy-δ-5-steroid dehydrogenase but a lower parathymosin expression in accordance with the change of serum glucocorticoid levels. Histone modification analysis identified 115 histone markers. The susceptible group had a higher level of tri-methylation of histone H3 lysine 27 (H3K27me3) and showed a positive crosstalk with K36me and K37me in the H3 tails. The differential changes of body temperature projected in physiological regulation at the hypothalamus-pituitary-adrenal axis suggest the genetic heterogeneity in basic metabolic rate and efficiency for heat dissipation to acclimate to thermal stress and maintain body temperature homeostasis. The alteration of adrenal H3K27me3 level was associated with the endocrine function of adrenal gland and may contribute to the thermotolerance of chickens.


Assuntos
Glândulas Suprarrenais/metabolismo , Galinhas/metabolismo , Resposta ao Choque Térmico , Código das Histonas , Animais , Proteínas Aviárias/genética , Proteínas Aviárias/metabolismo , Galinhas/genética , Hidroxiesteroide Desidrogenases/genética , Hidroxiesteroide Desidrogenases/metabolismo , Masculino , Timosina/análogos & derivados , Timosina/genética , Timosina/metabolismo
12.
J Proteome Res ; 20(5): 2953-2963, 2021 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-33780252

RESUMO

Urothelial carcinoma (UC) is the ninth most prevalent malignancy worldwide. Noninvasive and efficient biomarkers with high accuracy are imperative for the surveillance and diagnosis of UC. CKD patients were enrolled as a control group in this study for the discovery of highly specific urinary protein markers of UC. An iTRAQ-labeled quantitative proteomic approach was used to discover novel potential markers. These markers were further validated with 501 samples by ELISA assay, and their diagnostic accuracies were compared to those of other reported UC markers. BRDT, CYBP, GARS, and HDGF were identified as novel urinary UC biomarkers with a high discrimination ability in a population comprising CKD and healthy subjects. The diagnostic values of the four novel UC markers were better than that of a panel of well-known or FDA-approved urinary protein markers CYFR21.1, Midkine, and NUMA1. Three of our discovered markers (BRDT, HDGF, GARS) and one well-known marker (CYFR21.1) were finally selected and combined as a marker panel having AUC values of 0.962 (95% CI, 0.94-0.98) and 0.860 (95% CI, 0.83-0.89) for the discrimination between UC and normal groups and UC and control (healthy + CKD) groups, respectively.


Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Biomarcadores , Biomarcadores Tumorais , Proteínas de Ciclo Celular , Humanos , Proteômica
13.
Nat Prod Res ; 35(12): 2051-2055, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31359780

RESUMO

The aerial portions of Cynara scolymus commonly have been eaten as vegetables or functional foods by the people lived in Mediterranean region. In preliminary antioxidant screening, the rhizome portions (CSR) of this species showed better potential than leaves ones. However, neither phytochemical nor pharmacology studies of CSR have been reported to date. The purpose of this research was to identify the active components from CSR through bioassay-guided fractionation. The antioxidant properties of secondary metabolites 1-9 were evaluated in this investigation. Compounds 4-6, 8, and 9 showed antioxidant activities based on DPPH free radical scavenging activity with IC50 values of 22.91-147.21 µM. Besides, compound 8 significantly and dose-dependently reduced H2O2-induced ROS levels in keratinocyte HaCaT cells without cytotoxicity toward HaCaT. Overall, our studies demonstrated the rhizome of C. scolymus could be used as a new natural antioxidant like the edible aerial portions and phenolic compounds are the active components.


Assuntos
Antioxidantes/química , Antioxidantes/farmacologia , Cynara scolymus/metabolismo , Rizoma/metabolismo , Antioxidantes/administração & dosagem , Linhagem Celular , Fracionamento Químico , Cynara scolymus/química , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia , Humanos , Peróxido de Hidrogênio , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Fenóis/química , Fenóis/farmacologia , Extratos Vegetais/química , Folhas de Planta/química , Espécies Reativas de Oxigênio/metabolismo , Rizoma/química , Metabolismo Secundário
14.
J Proteome Res ; 20(1): 164-171, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33058664

RESUMO

Rapid identification of methicillin-sensitive Staphylococcus aureus (MSSA), heterogeneous vancomycin-intermediate S. aureus (hVISA), and vancomycin-intermediate S. aureus (VISA) is important for accurate treatment, timely intervention, and prevention of outbreaks. Here, 90 S. aureus isolates were analyzed for protein biomarker discovery, including MSSA, vancomycin-susceptible S. aureus (VSSA), hVISA, and VISA strains. Label-free data-independent acquisition proteomics was used to identify protein biomarkers that allow for discrimination among MSSA, hVISA, and VISA strains. There were 8786 nonredundant peptides identified, corresponding to 418 different annotated nonredundant proteins. Two VISA protein biomarkers, two hVISA protein biomarkers, and one MSSA protein biomarker with high sensitivities and specificities were discovered and verified. Data are available via MassIVE with identifier MSV000085776.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Antibacterianos/farmacologia , Humanos , Meticilina , Staphylococcus aureus Resistente à Meticilina/genética , Testes de Sensibilidade Microbiana , Proteômica , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/genética , Vancomicina/farmacologia , Resistência a Vancomicina , Staphylococcus aureus Resistente à Vancomicina
15.
J Ethnopharmacol ; 264: 113267, 2021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-32822822

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Sleep disorders affect an estimated 150 million people worldwide and result in adverse health, safety, and work performance-related outcomes that have important economic consequences. In Taiwan, Chinese herbal medicine (CHM) is a complementary natural medicine and has been widely used as an adjunctive therapy. AIM OF THE STUDY: This study aimed to investigate the effect of CHM on dementia risk in patients with sleep disorders in Taiwan. MATERIALS AND METHODS: We identified 124,605 patients with sleep disorders between the ages of 20 and 60 years. Of these, 5876 CHM users and 5876 non-CHM users were matched according to age and gender. The chi-squared test, Cox proportional hazard model, Kaplan-Meier method, and log-rank test were used for the comparisons. Association rule mining and network analysis were applied to determine a CHM pattern specialized for sleep disorders. RESULTS: More CHM users did not use sleeping pills than non-CHM users. CHM users had a lower risk of dementia than non-CHM users after adjusting for age, gender, and sleeping pill use (hazard ratio (HR): 0.469, 95% CI = 0.289-0.760; p-value = 0.002). The cumulative incidence of dementia was lower among CHM users (long-rank test, p-value < 0.001). Association rule mining and network analysis showed that Ye-Jiao-Teng (YJT; Caulis Polygoni Multiflori; Polygonum multiflorum Thunb), Suan-Zao-Ren-Tang (SZRT), Jia-Wei-Xiao-Yao-San (JWXYS), He-Huan-Pi (HHP; Cortex Albizziae; Albizia julibrissin Durazz.), and Suan-Zao-Ren (SZR; Semen Zizyphi Spinosae; Ziziphus jujuba Mill.) were important CHMs for patients with sleep disorders in Taiwan. CONCLUSIONS: A comprehensive list of herbal medicines may be useful for the clinical treatment of patients with sleep disorders, and for future scientific investigations into the prevention of dementia in these patients.


Assuntos
Demência/tratamento farmacológico , Demência/etnologia , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa/métodos , Transtornos do Sono-Vigília/tratamento farmacológico , Transtornos do Sono-Vigília/etnologia , Adulto , Estudos de Coortes , Medicamentos de Ervas Chinesas/isolamento & purificação , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Taiwan/etnologia , Resultado do Tratamento , Adulto Jovem
16.
Front Pharmacol ; 11: 594486, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33362549

RESUMO

Pemphigus is a life-threatening and skin-specific inflammatory autoimmune disease, characterized by intraepidermal blistering between the mucous membranes and skin. Chinese herbal medicine (CHM) has been used as an adjunct therapy for treating many diseases, including pemphigus. However, there are still limited studies in effects of CHM treatment in pemphigus, especially in Taiwan. To more comprehensively explore the effect of long-term CHM treatment on the overall mortality of pemphigus patients, we performed a retrospective analysis of 1,037 pemphigus patients identified from the Registry for Catastrophic Illness Patients database in Taiwan. Among them, 229 and 177 patients were defined as CHM users and non-users, respectively. CHM users were young, predominantly female, and had a lesser Charlson comorbidity index (CCI) than non-CHM users. After adjusting for age, sex, prednisolone use, and CCI, CHM users had a lower overall mortality risk than non-CHM users (multivariate model: hazard ratio (HR): 0.422, 95% confidence interval (CI): 0.242-0.735, p = 0.0023). The cumulative incidence of overall survival was significantly higher in CHM users than in non-users (p = 0.0025, log rank test). Association rule mining and network analysis showed that there was one main CHM cluster with Qi-Ju-Di-Huang-Wan (QJDHW), Dan-Shen (DanS; Radix Salviae miltiorrhizae; Salvia miltiorrhiza Bunge), Jia-Wei-Xiao-Yao--San (JWXYS), Huang-Lian (HL; Rhizoma coptidis; Coptis chinensis Franch.), and Di-Gu-Pi (DGP; Cortex lycii; Lycium barbarum L.), while the second CHM cluster included Jin-Yin-Hua (JYH; Flos lonicerae; Lonicera hypoglauca Miq.) and Lian-Qiao (LQ; Fructus forsythiae; Forsythia suspensa (Thunb.) Vahl). In Taiwan, CHMs used as an adjunctive therapy reduced the overall mortality to approximately 20% among pemphigus patients after a follow-up of more than 6 years. A comprehensive CHM list may be useful in future clinical trials and further scientific investigations to improve the overall survival in these patients.

17.
Aging Cell ; 19(11): e13236, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33029941

RESUMO

Blood-brain barrier (BBB) disruption contributes to neurodegenerative diseases. Loss of tight junction (TJ) proteins in cerebral endothelial cells (ECs) is a leading cause of BBB breakdown. We recently reported that miR-195 provides vasoprotection, which urges us to explore the role of miR-195 in BBB integrity. Here, we found cerebral miR-195 levels decreased with age, and BBB leakage was significantly increased in miR-195 knockout mice. Furthermore, exosomes from miR-195-enriched astrocytes increased endothelial TJ proteins and improved BBB integrity. To decipher how miR-195 promoted BBB integrity, we first demonstrated that TJ proteins were metabolized via autophagic-lysosomal pathway and the autophagic adaptor p62 was necessary to promote TJ protein degradation in cerebral ECs. Next, proteomic analysis of exosomes revealed miR-195-suppressed thrombospondin-1 (TSP1) as a major contributor to BBB disruption. Moreover, TSP1 was demonstrated to activate selective autophagy of TJ proteins by increasing the formation of claudin-5-p62 and ZO1-p62 complexes in cerebral ECs while TSP1 impaired general autophagy. Delivering TSP1 antibody into the circulation showed dose-dependent reduction of BBB leakage by 20%-40% in 25-month-old mice. Intravenous or intracerebroventricular injection of miR-195 rescued TSP1-induced BBB leakage. Dementia patients with BBB damage had higher levels of serum TSP1 compared to those without BBB damage (p = 0.0015), while the normal subjects had the lowest TSP1 (p < 0.0001). Taken together, the study implies that TSP1-regulated selective autophagy facilitates the degradation of TJ proteins and weakens BBB integrity. An adequate level of miR-195 can suppress the autophagy-lysosome pathway via a reduction of TSP1, which may be important for maintaining BBB function.


Assuntos
Barreira Hematoencefálica/metabolismo , MicroRNAs/metabolismo , Trombospondina 1/metabolismo , Animais , Autofagia/fisiologia , Barreira Hematoencefálica/citologia , Masculino , Camundongos , Transfecção
18.
Molecules ; 25(19)2020 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-32993192

RESUMO

Dodder (Cuscuta spp.) is a parasitic weed damaging many plants and agricultural production. The native obligate parasite Cuscuta japonica Choisy (Japanese dodder) parasitizes Dimocarpus longans Lour., Ficus septica Burm. F., Ficus microcarpa L.f., Mikania micrantha H.B.K. and Melia azedarach Linn, respectively. Five Japanese dodders growing on different plants exhibit slightly different metabolites and amounts which present different pharmacological effects. Among these plants, a significant antiviral activity against influenza A virus (IAV) was found in Japanese dodder parasitizing on D. longans Lour. (CL). To further explore methanol extract components in Japanese dodder (CL), four undescribed aromatic glycosides, cuscutasides A-D (compounds 1-4) were isolated, together with twenty-six known compounds 5-30. The chemical structures of 1-4 were elucidated using a combination of spectroscopic techniques. The eighteen isolated compounds were evaluated for antiviral activity against IAV activity. Among them, 1-monopalmitin (29) displayed potent activity against influenza A virus (A/WSN/1933(H1N1)) with EC50 2.28 ± 0.04 µM and without noteworthy cytotoxicity in MDCK cells. The interrupt step of 29 on the IAV life cycle was determined. These data provide invaluable information for new applications for this otherwise harmful weed.


Assuntos
Antivirais , Cuscuta/química , Vírus da Influenza A Subtipo H1N1/crescimento & desenvolvimento , Infecções por Orthomyxoviridae , Extratos Vegetais , Sapindaceae , Animais , Antivirais/química , Antivirais/farmacologia , Cães , Células Madin Darby de Rim Canino , Infecções por Orthomyxoviridae/tratamento farmacológico , Infecções por Orthomyxoviridae/metabolismo , Infecções por Orthomyxoviridae/patologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia
19.
BMC Complement Med Ther ; 20(1): 221, 2020 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-32664975

RESUMO

BACKGROUND: Liver cirrhosis is one of the main causes of the morbidity and mortality in liver diseases. Chinese herbal medicine (CHM) has long been used for the clinical treatment of liver diseases. This study was designed to explore the usage frequency and prescription patterns of CHM for patients with decompensated liver cirrhosis and to evaluate the long-term effects of CHM on overall mortality. METHODS: Two thousand four hundred sixty-seven patients with decompensated liver cirrhosis (ICD-9-CM code: 571.2, 571.5, and 571.6) diagnosed between 2000 and 2009 in Taiwan were identified from the registry for catastrophic illness patients. Of these, 149 CHM users and 298 CHM non-users were matched for age, gender, and Charlson comorbidity index score. The chi-squared test, paired Student's t-test, Cox proportional hazard model, and Kaplan-Meier method were applied for various comparisons between these groups of patients. RESULTS: CHM-treated patients showed a lower overall mortality risk compared with non-treated patients (Multivariable: p < 0.0001; HR: 0.54, 95% CI: 0.42-0.69). The cumulative incidence of overall mortality was lower in the CHM-treated group (stratified log-rank test, p = 0.0002). The strongest CHM co-prescription pattern- Yin-Chen-Hao-Tang (YCHT) → Long-Dan-Xie-Gan-Tang (LDXGT) had the highest support, followed by Zhi-Zi (ZZ) → Yin-Chen-Wu-Ling-San (YCWLS) and Bai-Hua-She-She-Cao (BHSSC) → Da-Huang (DaH). CONCLUSION: CHM, as adjunct therapy, might decrease the risk of overall mortality in patients with decompensated liver cirrhosis. CHM co-prescription patterns and network analysis showed that comprehensive herbal medicines have a protective role against liver fibrosis. Further studies are required to enhance the knowledge of safety and efficacy of CHM in patients with decompensated liver cirrhosis.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/mortalidade , Padrões de Prática Médica , Adulto , Idoso , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Taiwan/epidemiologia
20.
Psychoneuroendocrinology ; 120: 104800, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32688147

RESUMO

Prior studies suggest that individual differences in stress responses contribute to the pathogenesis of neuropsychiatric disorders. In the present study, we investigated the role of small ubiquitin-like modifier (SUMO) E3 ligase protein inhibitor of activated STAT1 (PIAS1) in mediating stress responses to chronic social defeat stress (CSDS). We found that mRNA and protein levels of PIAS 1 were decreased in the hippocampus of high-susceptibility (HS) mice but not in low-susceptibility (LS) mice after CSDS. Local overexpression of PIAS1 in the hippocampus followed by CSDS exposure promoted stress resilience by attenuating social avoidance and improving anxiety-like behaviors. Viral-mediated gene transfer to generate a conditional knockdown of PIAS1 in the hippocampus promoted social avoidance and stress vulnerability after subthreshold microdefeat. HS mice displayed decreased levels of glucocorticoid receptor (GR) expression, and GR SUMOylation in the hippocampus was associated with stress vulnerability. Furthermore, cytokine/chemokine levels were changed predominantly in the hippocampus of HS mice. These results suggest that hippocampal PIAS1 plays a role in the regulation of stress susceptibility by post-translational modification of GRs.


Assuntos
Proteínas Inibidoras de STAT Ativados/metabolismo , Estresse Psicológico/metabolismo , Animais , Biomarcadores , Encéfalo/metabolismo , Hipocampo/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ligação Proteica , Proteínas Inibidoras de STAT Ativados/genética , Proteínas Inibidoras de STAT Ativados/fisiologia , Receptores de Glucocorticoides/metabolismo , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/genética , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/metabolismo , Sumoilação , Ubiquitina-Proteína Ligases/metabolismo
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