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1.
Nanomaterials (Basel) ; 14(9)2024 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-38727396

RESUMEN

A series of quaternary ammonium or phosphonium salts were applied as zeolite growth modifiers in the synthesis of hierarchical ZSM-5 zeolite. The results showed that the use of methyltriphenylphosphonium bromide (MTBBP) could yield nano-sized hierarchical ZSM-5 zeolite with a "rice crust" morphology feature, which demonstrates a better catalytic performance than other disinfect candidates. It was confirmed that the addition of MTBBP did not cause discernable adverse effects on the microstructures or acidities of ZSM-5, but it led to the creation of abundant meso- to marco- pores as a result of aligned tiny particle aggregations. Moreover, the generation of the special morphology was believed to be a result of the coordination and competition between MTBBP and Na+ cations. The as-synthesized hierarchical zeolite was loaded with Zn and utilized in the propane aromatization reaction, which displayed a prolonged lifetime (1430 min vs. 290 min compared with conventional ZSM-5) and an enhanced total turnover number that is four folds of the traditional one, owing to the attenuated hydride transfer reaction and slow coking rate. This work provides a new method to alter the morphological properties of zeolites with low-cost disinfectants, which is of great potential for industrial applications.

2.
Int J Drug Policy ; 118: 104118, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37422985

RESUMEN

BACKGROUND: The North American overdose crisis has continued at unprecedented rates with more than 100,000 overdose deaths estimated to have occurred in the United States in 2022. Regional variations in overdose rates signify differences in local drug supplies. State-level drug supply surveillance systems have been limited in their ability to document and communicate the rapidly changing drug supplies which can hinder harm reduction efforts at the community level. We sought to address by piloting a two-year, community-engaged local drug supply surveillance program in Rhode Island (RI). METHODS: The first set of samples (n = 125) were collected from May 2022 to January 2023 across RI and included used paraphernalia (e.g., cookers), refuse (e.g., baggies), and product. Samples were tested using comprehensive toxicology testing approaches via liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS). Results were disseminated to participants and the broader public across platforms. RESULTS: Fentanyl was detected in 67.2% of all samples tested. 39.2% (n = 49) of samples were expected to be fentanyl. Xylazine was detected in 41.6% of all samples-always in combination with fentanyl-and no samples were expected to contain xylazine. In expected stimulant samples (n = 39), 10% contained fentanyl and/or analogues as major substances and 30.8% contained trace amounts of fentanyl and/or analogues. In expected stimulant samples, 15.4% contained xylazine with fentanyl. No opioids or benzodiazepines were detected in expected hallucinogen or dissociative samples (n = 7). In expected benzodiazepine samples (n = 8), no opioids were detected. CONCLUSIONS: Our results describe part of the local drug supply in Rhode Island, including a presence of NPS and adulterants (e.g., designer benzodiazepines, xylazine). Importantly, our findings underscore the feasibility of developing a community-driven drug supply surveillance database. Expanding drug supply surveillance initiatives is imperative for improving the health and safety of people who use drugs and informing public health approaches to addressing the overdose crisis.


Asunto(s)
Sobredosis de Droga , Xilazina , Humanos , Estados Unidos , Rhode Island/epidemiología , Xilazina/uso terapéutico , Analgésicos Opioides/uso terapéutico , Fentanilo/análisis , Sobredosis de Droga/epidemiología
3.
Zhongguo Zhong Yao Za Zhi ; 48(3): 847-852, 2023 Feb.
Artículo en Chino | MEDLINE | ID: mdl-36872250

RESUMEN

The concept of ethnic medicine is divided into a broad sense and a narrow sense. The broad concept refers to the traditional medicine of the Chinese nation, and the narrow concept refers to the traditional medicine of Chinese ethnic minorities. The external medicine is one of the main forms of ethnic medicine, and it is also the important content of ethnic medicine for external use, which is widely used in clinical practice. As the theory of ethnic medicine is unique, the application methods have certain characteristics, which are the key technical parts of clinical practice. However, the existing traditional Chinese medicine consensus formulation me-thods cannot meet the needs of the consensus formulation of the external ethnic medicine. Therefore, the methods suitable for expert consensus on external ethnic medicine are required. This article took Expert opinion on clinical application of Baimai Ointment as an exa-mple, and explorde a reasonable, effective, multi-dimensional, and multi-stage method to formulate expert consensus on the external ethnic medicine. In this research, three-dimensional sources of information, including ancient classics, clinical research evidence, and expert application experiences, were systematically and scientifically collected. After organization and analysis, the information was formed into comprehensive evidence. In a formal consensus meeting, part of the recommendations reached consensus. As to the issues that did not reach agreement, in-depth interviews were used to explore the reasons for the differences and resolve the disagreements. Finally, unanimous recommendations were reached. There are common problems during the formulation process of Expert opinion on clinical application of Baimai Ointment. This study is expected to provide references for the formulation of expert consensus on other external ethnic medicine.


Asunto(s)
Productos Biológicos , Medicamentos Herbarios Chinos , Humanos , Consenso
4.
FASEB J ; 37(1): e22712, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36527439

RESUMEN

Mixed lineage leukemia 1 (MLL1), a histone H3 lysine 4 (H3K4) methyltransferase, exerts its enzymatic activity by interacting with menin and other proteins. It is unclear whether inhibition of the MLL1-menin interaction influences epithelial-mesenchymal transition (EMT), renal fibroblast activation, and renal fibrosis. In this study, we investigated the effect of disrupting MLL1-menin interaction on those events and mechanisms involved in a murine model of renal fibrosis induced by unilateral ureteral obstruction (UUO), in cultured mouse proximal tubular cells and renal interstitial fibroblasts. Injury to the kidney increased the expression of MLL1 and menin and H3K4 monomethylation (H3K4me1); MLL1 and menin were expressed in renal epithelial cells and renal interstitial fibroblasts. Inhibition of the MLL1-menin interaction by MI-503 administration or siRNA-mediated silencing of MLL1 attenuated UUO-induced renal fibrosis, and reduced expression of α-smooth muscle actin (α-SMA) and fibronectin. These treatments also inhibited UUO-induced expression of transcription factors Snail and Twist and transforming growth factor ß1 (TGF-ß1) while expression of E-cadherin was preserved. Moreover, treatment with MI-503 and transfection with either MLL siRNA or menin siRNA inhibited TGF-ß1-induced upregulation of α-SMA, fibronectin and Snail, phosphorylation of Smad3 and AKT, and downregulation of E-cadherin in cultured renal epithelial cells. Finally, MI-503 was effective in abrogating serum or TGFß1-induced transformation of renal interstitial fibroblasts to myofibroblasts in vitro. Taken together, these results suggest that targeting disruption of the MLL1-menin interaction attenuates renal fibrosis through inhibition of partial EMT and renal fibroblast activation.


Asunto(s)
Enfermedades Renales , Leucemia , Obstrucción Ureteral , Ratones , Animales , Factor de Crecimiento Transformador beta1/metabolismo , Fibronectinas/metabolismo , Fibrosis , Enfermedades Renales/etiología , Enfermedades Renales/prevención & control , Enfermedades Renales/metabolismo , Obstrucción Ureteral/metabolismo , Riñón/metabolismo , Transición Epitelial-Mesenquimal , Cadherinas/metabolismo , ARN Interferente Pequeño/metabolismo
5.
Cell Death Dis ; 13(9): 770, 2022 09 06.
Artículo en Inglés | MEDLINE | ID: mdl-36068197

RESUMEN

Mixed lineage leukemia 1 (MLL1) is a histone H3 lysine 4 (H3K4) methyltransferase that interacts with WD repeat domain 5 (WDR5) to regulate cell survival, proliferation, and senescence. The role of MLL1 in the pathogenesis of acute kidney injury (AKI) is unknown. In this study, we demonstrate that MLL1, WDR5, and trimethylated H3K4 (H3K4me3) were upregulated in renal tubular cells of cisplatin-induced AKI in mice, along with increased phosphorylation of p53 and decreased expression of E-cadherin. Administration of MM102, a selective MLL1/WDR5 complex inhibitor, improved renal function and attenuated tubular injury and apoptosis, while repressing MLL1, WDR5, and H3K4me3, dephosphorylating p53 and preserving E-cadherin. In cultured mouse renal proximal tubular cells (RPTCs) exposed to cisplatin, treatment with MM102 or transfection with siRNAs for either MLL1 or WDR5 also inhibited apoptosis and p53 phosphorylation while preserving E-cadherin expression; p53 inhibition with Pifithrin-α lowered cisplatin-induced apoptosis without affecting expression of MLL1, WDR5, and H3K4me3. Interestingly, silencing of E-cadherin offset MM102's cytoprotective effects, but had no effect on p53 phosphorylation. These findings suggest that MLL1/WDR5 activates p53, which, in turn, represses E-cadherin, leading to apoptosis during cisplatin-induced AKI. Further studies showed that MM102 effectively inhibited cisplatin-triggered DNA damage response (DDR), as indicated by dephosphorylation of ataxia telangiectasia mutated (ATM) and ATM and Rad-3 related (ATR) proteins, dephosphorylation of checkpoint kinase 1 and 2 (Chk1 and Chk2); depression of γ-H2AX; and restrained cell cycle arrest, as evidenced by decreased expression of p21 and phospho-histone H3 at serine 10 in vitro and in vivo. Overall, we identify MLL1 as a novel DDR regulator that drives cisplatin-induced RPTC apoptosis and AKI by modulating the MLL1/WDR5-/ATR/ATM-Chk-p53-E-cadherin axis. Targeting the MLL1/WDR5 complex may have a therapeutic potential for the treatment of AKI.


Asunto(s)
Lesión Renal Aguda , Leucemia , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/genética , Lesión Renal Aguda/metabolismo , Animales , Apoptosis , Cadherinas/genética , Cadherinas/metabolismo , Cisplatino/farmacología , Histona Metiltransferasas/metabolismo , Histonas/metabolismo , Riñón/metabolismo , Leucemia/tratamiento farmacológico , Ratones , Proteína de la Leucemia Mieloide-Linfoide/genética , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo
6.
Int J Biol Sci ; 18(10): 3944-3960, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35844799

RESUMEN

Our understanding of coding gene functions in lung cancer leads to the development of multiple generations of targeted drugs. Noncoding RNAs, including circular RNAs (circRNAs), have been demonstrated to play a vital role in tumorigenesis. Uncovering the functions of circRNAs in tumorigenesis and their underlying regulatory mechanisms may shed new light on the development of novel diagnostic and therapeutic strategies for human cancer. Here we report the important role of circFAT1 in lung adenocarcinoma (LUAD) progression and the potential impact of circFAT1 on LUAD treatment. We found that circFAT1 was one of the top expressed circRNAs in A549 cells by circRNA-seq and was significantly upregulated in human LUAD tissues. Multiple cellular assays with A549 and PC9 LAUD cell lines under both gain-of-function and loss-of-function conditions demonstrated that circFAT1 promoted proliferation of LUAD cells in vitro and in vivo. At molecular level, circFAT1 sequestered miR-7 to upregulate IRS2, which in turn regulated downstream ERK1/2 phosphorylation and CCND1 expression, ultimately promoting tumor progression. In addition, we showed that DDP treatment was much more effective in circFAT1 knockdown tumor cells in vitro and in a xenograft tumor model. Our results indicate that circFAT1 promote tumorigenesis in LUAD through sequestering miR-7, consequently upregulating IRS2-ERK1/2-mediated CCND1 expression, and can be a valuable therapeutic target and an important parameter for precision treatment in LUAD patients.


Asunto(s)
Adenocarcinoma del Pulmón , Neoplasias Pulmonares , MicroARNs , Adenocarcinoma del Pulmón/metabolismo , Carcinogénesis/genética , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Transformación Celular Neoplásica , Ciclina D1/genética , Ciclina D1/metabolismo , Regulación Neoplásica de la Expresión Génica , Humanos , Proteínas Sustrato del Receptor de Insulina/genética , Proteínas Sustrato del Receptor de Insulina/metabolismo , Neoplasias Pulmonares/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , ARN Circular/genética
7.
Eur J Nutr ; 61(7): 3531-3543, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35618921

RESUMEN

PURPOSE: Inflammatory bowel disease (IBD) is a multifactorial chronic disease of the gastrointestinal tract. Dietary intervention in the treatment of IBD has gradually attracted more attention. In this study, amino acid-balanced diets (AABD) based on grains were developed and their influences on the regulation of IBD were investigated. METHODS: Dextran sodium sulfate (DSS)-induced acute colitis mice model was employed to evaluate the effects of AABD. Pathological symptoms, intestinal inflammation, gut barrier proteins and gut microbiota were determined after AABD intake. RESULTS: It was shown that AABD alleviated the symptoms of colitis by reducing the histological scores of mice colon, suppressing the expression of pro-inflammatory cytokines (IL-1ß, IL-6 and TNF-α) and upregulating the expression of tight junction proteins. Analysis of gut microbiota revealed that AABD altered the structure of gut microbiota by decreasing the abundance and richness of harmful bacteria induced by DSS (Escherichia-Shigella, Parasutterella, etc.) and increasing that of beneficial bacteria (Akkermansia, etc.). Correlation analysis indicated that the alterations of pro-inflammatory factors were related with the change of microbiota, suggesting that the inhibitory effects of AABD on inflammation might be due to its regulation gut microbiota. CONCLUSION: The AABD could efficiently mitigate colitis, and this study indicated that AABD could be applied as a promising dietary regulation strategy of IBD.


Asunto(s)
Colitis , Microbioma Gastrointestinal , Enfermedades Inflamatorias del Intestino , Aminoácidos/farmacología , Animales , Colitis/inducido químicamente , Colitis/patología , Colon/metabolismo , Citocinas/metabolismo , Sulfato de Dextran/efectos adversos , Dieta , Modelos Animales de Enfermedad , Inflamación/patología , Ratones , Ratones Endogámicos C57BL
8.
Aesthet Surg J ; 42(2): NP125-NP129, 2022 01 12.
Artículo en Inglés | MEDLINE | ID: mdl-33944901

RESUMEN

CD30 lymphocyte activation antigen and phosphorylated STAT3 (pSTAT3) are consistent markers of tumor cells in breast implant-associated anaplastic large cell lymphoma (BIA-ALCL). We present a case of BIA-ALCL in a breast implant capsule containing clustered tumor cells expressing CD30, pSTAT3, pSTAT6, interleukin 9, and granzyme B tumor cell biomarkers. Remarkably, the contralateral breast contained many scattered large, atypical CD30+ cells surrounded by inflammatory cells, raising a suspicion of bilateral BIA-ALCL, known to occur in some patients. To clarify the diagnosis, immunohistochemistry and multilabel immunofluorescence were performed. Unlike the tumor cells, the atypical CD30+ cells of the contralateral breast lacked pSTAT3, pSTAT6, interleukin 9, and granzyme B, eliminating a diagnosis of bilateral BIA-ALCL. This case highlights the importance of interpreting CD30 staining in the context of other tumor cell biomarkers and histopathology to avoid an incorrect diagnosis of BIA-ALCL. We believe the findings also suggest the possibility of CD30 expression as an early event in the multistep pathogenesis of BIA-ALCL.


Asunto(s)
Implantación de Mama , Implantes de Mama , Neoplasias de la Mama , Linfoma Anaplásico de Células Grandes , Mama , Implantación de Mama/efectos adversos , Implantes de Mama/efectos adversos , Neoplasias de la Mama/etiología , Femenino , Humanos , Antígeno Ki-1 , Linfoma Anaplásico de Células Grandes/diagnóstico , Linfoma Anaplásico de Células Grandes/etiología
9.
Zhongguo Zhong Yao Za Zhi ; 46(22): 5977-5986, 2021 Nov.
Artículo en Chino | MEDLINE | ID: mdl-34951189

RESUMEN

The present study aimed to systematically evaluate the efficacy and safety of Ginkgo biloba extract 50(GBE50) in the treatment of ischemic stroke. The databases including CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, and Cochrane Library were searched for randomized controlled trial(RCT) of GBE50 for the treatment of ischemic stroke reported between database inception and May 2020. The methodological quality of the included RCTs was evaluated via the Cochrane risk of bias tool. The RevMan 5.4 was used for Meta-analysis. Sixteen RCTs were included, involving 1 615 patients with acute ischemic stroke. Most of the included RCTs reported the methods of random sequence generation, but only two performed the concealment of random sequence. All RCTs failed in blinding. Two RCTs reported the information of cases lost to follow-up and drop-outs. Since the number was small, the baselines of groups remained balanced. All RCTs reported key outcomes of ischemic stroke, which made selective reporting bias in a low risk. Meta-analysis results revealed that GBE50 combined with routine therapies could effectively lower the score of the National Institutes of Health stroke scale(NIHSS) and restore cognitive function and daily activity in ischemic stroke patients. Compared with routine therapies, the combination is advantageous in treating patients with ischemic stroke. However, high-quality multicenter RCTs with large sample sizes are still required for verification.


Asunto(s)
Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Isquemia Encefálica/tratamiento farmacológico , Ginkgo biloba , Humanos , Estudios Multicéntricos como Asunto , Extractos Vegetales , Accidente Cerebrovascular/tratamiento farmacológico
10.
Integr Cancer Ther ; 20: 15347354211031650, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34261372

RESUMEN

BACKGROUND: Traditional Chinese medicine (TCM) is widely integrated into cancer care in China. An overview in 2011 identified 2384 randomized and non-randomized controlled trials (RCTs, non-RCTs) on TCM for cancer published in the Chinese literature. This article summarizes updated evidence of RCTs on TCM for cancer care. METHODS: We searched 4 main Chinese databases: China National Knowledge Infrastructure, Chinese Scientific Journal Database, SinoMed, and Wanfang. RCTs on TCM used in cancer care were analyzed in this bibliometric study. RESULTS: Of 5834 RCTs (477 157 cancer patients), only 62 RCTs were indexed in MEDLINE. The top 3 cancers treated were lung, stomach, and breast cancer. About 4752 RCTs (81.45%) tested TCM combined with conventional treatment, and 1082 RCTs (18.55%) used TCM alone for treating symptoms and side-effects. Herbal medicine was the most frequently used TCM modality (5087 RCTs; 87.20%). The most frequently reported outcome was symptom improvement (3712 RCTs; 63.63%) followed by quality of life (2725 RCTs; 46.71%), and biomarkers (2384 RCTs; 40.86%). The majority of RCTs (4051; 69.44%) concluded there were beneficial effects using either TCM alone or TCM plus conventional treatment compared with conventional treatment. CONCLUSION: Substantial randomized trials demonstrated different types/stages of cancer were treated by various TCM modalities, alone or in combination with conventional medicine. Further evaluation on the effects and safety of TCM modalities focusing on outcomes such as quality of life is required.


Asunto(s)
Neoplasias de la Mama , Medicamentos Herbarios Chinos , China , Medicamentos Herbarios Chinos/uso terapéutico , Femenino , Humanos , Medicina Tradicional China , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto
11.
FASEB J ; 35(7): e21715, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-34143514

RESUMEN

SET and MYND domain protein 2 (SMYD2) is a lysine methyltransferase that mediates histone H3 lysine 36 trimethylation (H3K36me3) and acts as a regulator of tumorgenesis and cystic growth. However, its role in renal fibrosis remains unknown. In this study, we found that SMYD2 was highly expressed in the murine kidney of renal fibrosis induced by unilateral ureteral obstruction, and primarily located in interstitial fibroblasts and renal tubular epithelial cells. Pharmacological inhibition of SMYD2 with AZ505, a highly selective inhibitor of SMYD2, protected against renal fibrosis and inhibited activation/proliferation of renal interstitial fibroblasts and conversion of epithelial cells to a profibrotic phenotype in this model. In cultured renal interstitial fibroblasts, treatment with AZ505 or silencing of SMYD2 by specific siRNA also inhibited serum- or TGF-ß1-induced activation and proliferation of renal interstitial fibroblasts. Mechanistic studies showed that SMYD2 inhibition reduced phosphorylation of several profibrotic signaling molecules, including Smad3, extracellular signal-regulated kinase 1/2, AKT, signal transducer and activator of transcription-3 and nuclear factor-κB in both injured kidney and cultured renal fibroblasts. AZ505 was also effective in suppressing renal expression of Snail and Twist, two transcriptional factors that mediate renal partial epithelial-mesenchymal transition and fibrosis. Conversely, AZ505 treatment prevented downregulation of Smad7, a renoprotective factor in vivo and in vitro. These results indicate that SMYD2 plays a critical role in mediating conversion of epithelial cells to a profibrotic phenotype, renal fibroblast activation and renal fibrogenesis, and suggest that SMYD2 may be a potential target for the treatment of chronic fibrosis in kidney disease.


Asunto(s)
Fibroblastos/metabolismo , Fibrosis/metabolismo , N-Metiltransferasa de Histona-Lisina/metabolismo , Enfermedades Renales/metabolismo , Riñón/metabolismo , Lisina/metabolismo , Metiltransferasas/metabolismo , Animales , Benzoxazinas , Proliferación Celular/fisiología , Células Epiteliales/metabolismo , Transición Epitelial-Mesenquimal/fisiología , Masculino , Ratones , Ratones Endogámicos C57BL , Fosforilación/fisiología , ARN Interferente Pequeño/metabolismo , Ratas , Factor de Transcripción STAT3/metabolismo , Transducción de Señal/fisiología , Obstrucción Ureteral/metabolismo , beta-Alanina/análogos & derivados
12.
Medicine (Baltimore) ; 99(47): e23218, 2020 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-33217834

RESUMEN

BACKGROUND: Cardiovascular disease is the main cause of death in patients with chronic kidney disease (CKD). Studies have found that hypothyroidism can significantly increase cardiovascular risk. Meanwhile, hypothyroidism is a common complication of CKD, but the correlation between hypothyroidism and cardiovascular risk in CKD patients has not been verified and paid enough attention. We therefore plan to conduct a systematic review and meta-analysis to explore whether hypothyroidism was independently predictive for the cardiovascular risk in patients with CKD. METHODS: We will search in PubMed, Embase Database, Web of Science, China National Knowledge Infrastructure (CNKI), China Biology Medicine Database (CBM), and Wanfang Database, and include the cross-sectional studies, case--control studies, and cohort studies that explore the association between hypothyroidism and cardiovascular risk in CKD patients. According to the eligibility criteria, two researchers will independently screen the retrieved literature, evaluate the methodological quality, and extract data. We will combine the extracted data based on STATA and TSA software. RESULTS: This systematic review will assess the association between hypothyroidism and cardiovascular risk in CKD patients based on the incidence of cardiovascular events in CKD people with hypothyroidism. CONCLUSIONS: This study will provide more evidence for the correlation between hypothyroidism and cardiovascular risk in CKD patients, which will contribute to the management and clinical practice of CKD population. ETHICS AND DISSEMINATION: This protocol is based on available literatures so that the ethical approval and informed consent are not applicable. The results of this study will be published in a peer-reviewed journals or relevant conferences. PROTOCOL REGISTRATION NUMBER: INPLASY2020100022.


Asunto(s)
Enfermedades Cardiovasculares/epidemiología , Hipotiroidismo/complicaciones , Hipotiroidismo/epidemiología , Insuficiencia Renal Crónica/complicaciones , Humanos , Incidencia , Metaanálisis como Asunto , Proyectos de Investigación , Factores de Riesgo , Revisiones Sistemáticas como Asunto
13.
FASEB J ; 34(12): 16552-16566, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33118211

RESUMEN

Human osteoarthritis cartilage contains chondrocytes (OAC) and mesenchymal stromal cells (OA-MSC). Here, we found that TGF-ß had different effects on OA-MSC and OAC, and revealed its lateral signaling mechanism in OA. RNAseq analysis indicated that OA-MSC expressed the same level of Bone Morphogenetic Protein (BMP) Receptor-1A as OAC but only 1/12 of Transforming Growth Factor beta (TGF-ß) Receptor-1. While TGF-ß specifically activated SMAD2 in OAC, it also activated BMP signaling-associated SMAD1 in OA-MSC. While TGF-ß stimulated chondrogenesis in OAC, it induced hypertrophy, mineralization, and MMP-13 in OA-MSC. Inhibiting TGF-ßR1 suppressed MMP-13 in OA-MSC but stimulated it in OAC. In contrast, by specifically targeting BMPR1A/ACVR1 in both cell types, LDN193189 inhibits cartilage degeneration through suppressing hypertrophy and MMP-13 in a mouse osteoarthritis model. Thus, LDN193189, a drug under development to inhibit constitutive BMP signaling during heterotopic ossification, may be re-purposed for OA treatment.


Asunto(s)
Cartílago Articular/metabolismo , Células Madre Mesenquimatosas/metabolismo , Osteoartritis/metabolismo , Transducción de Señal/fisiología , Factor de Crecimiento Transformador beta/metabolismo , Animales , Células Cultivadas , Condrocitos/metabolismo , Condrogénesis/fisiología , Humanos , Hipertrofia/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Receptor Tipo I de Factor de Crecimiento Transformador beta/metabolismo , Proteína Smad2/metabolismo
14.
Medicine (Baltimore) ; 99(35): e21558, 2020 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-32871871

RESUMEN

BACKGROUND: As indicated by numerous studies, there exists a relationship between the polymorphism of methylenetetrahydrofolate reductase (MTHFR) and susceptibility to diabetic nephropathy (DN) in various populations; nonetheless, the findings remain inconsistent. Therefore, we carried out a meta-analysis to determine the relationship between the MTHFR gene polymorphism and DN susceptibility. MATERIALS AND METHOD: Related studies were identified from PubMed, Cochrane Library, EMBASE, and the China National Knowledge Infrastructure database (time period: from building the library to October 2019). The strength of the association was examined using odds ratios (ORs) with 95% confidence intervals (95% CIs). RESULTS: The findings illustrated that the C677T gene polymorphism was significantly associated with an enhanced susceptibility to DN compared to that with diabetes mellitus in allelic (OR = 1.64, 95% CI = 1.34-2.00, P < .001), dominant (OR = 1.85, 95% CI = 1.40-2.46, P < .001), codominant (heterozygote: OR = 1.67, 95% CI = 1.27-2.21, P < .001; homozygote: OR = 2.55, 95% CI = 1.82-3.57, P < .001), and recessive (OR = 1.89, 95% CI = 1.50-2.38, P < .001) models of the overall population. Moreover, as compared with the healthy controls, a significantly augmented susceptibility to DN was found in all 5 genetic comparison models (allelic: OR = 2.06, 95% CI = 1.58-2.67, P < .001; dominant: OR = 2.52, 95% CI = 1.73-3.69, P < .001; codominant: OR = 3.78, 95% CI = 2.50-5.70, P < .001; recessive: OR = 2.41, 95% CI = 1.96-2.97, P < .001). Furthermore, stratifying data by ethnicity revealed substantially augmented vulnerability to DN in not only Caucasian but also Asian populations. CONCLUSION: The present study suggests that the C677T polymorphism was associated with an augmented susceptibility to DN.


Asunto(s)
Diabetes Mellitus Tipo 2/complicaciones , Nefropatías Diabéticas/epidemiología , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Polimorfismo de Nucleótido Simple/genética , Alelos , Pueblo Asiatico/genética , Estudios de Casos y Controles , China/epidemiología , Diabetes Mellitus Tipo 2/genética , Nefropatías Diabéticas/etiología , Nefropatías Diabéticas/genética , Predisposición Genética a la Enfermedad , Humanos , Factores de Riesgo , Población Blanca/genética
15.
Zhongguo Zhong Yao Za Zhi ; 45(7): 1596-1599, 2020 Apr.
Artículo en Chino | MEDLINE | ID: mdl-32489037

RESUMEN

Standardization is the technical support for the development of traditional Chinese medicine(TCM), and the guidelines have become the main component of the core standards of TCM technology. With the rise and development of evidence-based medicine in China, more than 500 guidelines have been issued in China, and the number is still increasing, but the quality of guidelines still lags far behind the international level. Similarly, the formulation of evidence-based clinical practice guidelines for TCM has gradually attracted the attention of the industry, but the quality is not so good, and most guidelines are not really evidence-based guidelines. Only reliable guidelines can fully and effectively play the role of clinical guidance. In order to comprehensively improve the scientificity and credibility of the guidelines, guideline evaluation can be used as a means to improve the quality of the guidelines. For the development of traditional Chinese medicine, it has become an urgent task to establish a complete evaluation standard system of guidelines, especially the evaluation standard system that conforms to the technical characteristics of traditional Chinese medicine. In this paper, the advantages and limitations of a series of domestic and foreign guideline evaluation tools were systematically analyzed, and the thinking and difficulties to establish the evaluation system of TCM guidelines were put forward, with a purpose to further improve the quality of TCM clinical practice guidelines, so that they can be better applied in clinical practice to enhance the clinical efficacy of TCM and ensure the quality of medical services.


Asunto(s)
Medicamentos Herbarios Chinos , Medicina Tradicional China , China , Medicina Basada en la Evidencia , Internacionalidad , Estándares de Referencia
16.
Zhongguo Zhong Yao Za Zhi ; 45(7): 1600-1605, 2020 Apr.
Artículo en Chino | MEDLINE | ID: mdl-32489038

RESUMEN

Based on the idea of establishing a complete guideline evaluation system applicable to the field of traditional Chinese medicine(TCM), the author believes that a complete guideline evaluation system of traditional Chinese medicine clinical practice should be divided into three parts: quality evaluation, clinical applicability evaluation and clinical application investigation. According to the different purposes, different evaluators, different evaluation methods and different evaluation time points in the guideline evaluation, the quality evaluation recommendation list, the clinical applicability evaluation recommendation list and the clinical application questionnaire were formed. Among them, the purpose of quality evaluation is to evaluate the methodological quality in the guideline development process, in order to measure whether the entire guideline development process is scientifically rigorous. The evaluators must be the methodologists with an evidence-based medicine background. Therefore, a logical, detailed and comprehensive guideline quality evaluation list will provide good evaluation tools for the TCM guideline formulation team and play an important role in promoting the quality and application of the guidelines. By referring to the internationally recognized development process and methods of evaluation tools, as well as the proof by authoritative TCM clinical experts and methodologists, the author worked out the quality evaluation list of clinical practice guidelines applicable to the field of TCM by considering the characteristics of TCM field. In this paper, the author introduces the whole list of quality evaluation recommendations, and interprets each item in details, hoping to provide reference for the standardization of TCM clinical practice guidelines in the future.


Asunto(s)
Medicina Basada en la Evidencia , Medicina Tradicional China , Encuestas y Cuestionarios
17.
Zhongguo Zhong Yao Za Zhi ; 45(7): 1606-1610, 2020 Apr.
Artículo en Chino | MEDLINE | ID: mdl-32489039

RESUMEN

The development of the guidelines should not only meet the rigorous methodological requirements, but also ensure the credibility or enforceability of the guideline recommendations when they are applied in clinical practice. Based on the idea of establi-shing a perfect guideline evaluation system applicable to the field of traditional Chinese medicine(TCM), the author believed that a complete evaluation system of clinical practice guidelines in the field of TCM shall be divided into three parts: quality evaluation, applicability evaluation and clinical application investigation. Among them, applicability evaluation refers to the evaluation of the degree of fit between the guideline and clinical practice, that is, whether the guidelines have good readability and clinical applicability to promote clinical application. The evaluators are clinical experts in the related fields of TCM. Therefore, a logical, detailed and comprehensive guideline quality evaluation list will provide good evaluation tools for the TCM guideline formulation team and play an important role in promoting the quality and application of the guidelines. Based on the internationally recognized development process and methods of evaluation tools, as well as the proof by authoritative TCM clinical experts and methodologists, the author worked out the quality evaluation list of clinical practice guidelines applicable to the field of TCM. In this paper, the author introduces the whole list of quality evaluation, and interprets each item in details, hoping to provide reference for the standardization of TCM clinical practice guidelines in the future.


Asunto(s)
Medicina Tradicional China , Estándares de Referencia
18.
Zhongguo Zhong Yao Za Zhi ; 45(5): 1167-1173, 2020 Mar.
Artículo en Chino | MEDLINE | ID: mdl-32237461

RESUMEN

To systematically evaluate the clinical efficacy and safety of Cheezheng Pain Relieving Plaster in the treatment of soft tissue injury. Four Chinese databases(namely CNKI, WanFang, VIP, CBM) and 2 English databases(namely PubMed, Cochrane Library) were retrieved from the establishment of each database to March 2019. The randomized controlled trials of Cheezheng Pain Relieving Plaster compared with routine therapy in treatment of soft tissue injury were included. The quality of the included studies was assessed using the Cochrane Risk Assessment Tool. Five studies were included, and 367 patients were enrolled. None of the included studies reported randomized concealment, blinding, follow-up and dropping off. The results showed that Cheezheng Pain Relieving Plaster may have advantages in alleviating joint pain, swelling, tenderness and dysfunction and other symptoms, with no serious adverse reaction. Compared with routine therapy, Cheezheng Pain Relieving Plaster may have advantages in the treatment of soft tissue injury. However, due to the quality of the included RCTs, the conclusions of this study were limited. In addition, to produce high-quality evidences for the clinical application of Cheezheng Pain Relieving Plaster, the conclusions of this study shall be further verified with large-sample, scientifically designed and strictly implemented clinical trials.


Asunto(s)
Medicamentos Herbarios Chinos/uso terapéutico , Dolor/tratamiento farmacológico , Traumatismos de los Tejidos Blandos/tratamiento farmacológico , Artralgia/tratamiento farmacológico , Edema/tratamiento farmacológico , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento
19.
J Hazard Mater ; 393: 122362, 2020 07 05.
Artículo en Inglés | MEDLINE | ID: mdl-32114133

RESUMEN

Source tracking for heavy metals contained in road deposited sediments (RDS) is essential for pollution control and human health risk management. Previous studies on tracking sources for heavy metals have mostly been qualitative or semi-quantitative. This study quantitatively assessed the relative contributions of eight sources to five typical heavy metals in the urban environment using a chemical mass-balance based stochastic method. The results indicated that tire wear contributed the most masses to RDS (33 ± 26 %) while brake lining dusts contributed the least. Urban soil, tire wear, and brake lining dusts contributed the most to Pb (41 ± 32 %), Zn (28 ± 25 %), and Cu (59 ± 30 %), respectively, while gasoline engine exhaust was the main source of both Cr (29 ± 28 %) and Ni (20 ± 23 %). The outcomes also showed that tire wear and diesel engine exhaust have higher potential to threaten human health risk because they generate high amounts of heavy metals with high bioaccessibility. The research results can also provide a quantitative guidance for taking remediation actions of heavy metal control on urban road surfaces and measuring the effectiveness of those actions.

20.
Chemosphere ; 245: 125634, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31864047

RESUMEN

Road deposited sediments (RDS) is the key carrier of pollutants in the urban road stormwater processes and hence has been seen as an important pollutant source of urban road stormwater. Although many research studies have focused on RDS and pollutants attached to RDS, the investigation on RDS toxicity is very limited. Toxicity test can permit an overall assessment on whether the RDS polluted stormwater can be safely reused. This paper used two living organisms, namely Chinese hamster ovary (CHO) cells, (mammalian cells to indicate human health related toxicity) and Chlorella Pyrenoidosa (algae to indicate ecological health related toxicity) to test RDS toxicity by using an innovative "equivalent toxicity area (ETA)" approach. The outcomes showed that mammalian cells are more sensitive than algae in terms of RDS toxicity. Pb, Cd and Cr primarily contributed to mammalian cell-based toxicity while Zn, Ni, Cu and TOC are primarily toxic to algae. It is also found that road site characteristics such as land uses exerted an important influence on RDS toxicity. Commercial areas tended to generate RDS with higher human health risk related toxicity while industrial areas had a potential to produce RDS with high ecological health risk related toxicity. The research outcomes also showed that solely focusing on pollutant themselves on RDS can not accurately indicate RDS pollution. An approach to considering both pollutant loads and toxicity is preferred. These results were expected to provide a useful insight to enhancing effectiveness of RDS polluted urban road stormwater management and ensuring their reuse safety.


Asunto(s)
Monitoreo del Ambiente/métodos , Contaminantes Ambientales/toxicidad , Animales , Células CHO , Chlorella , Cricetinae , Cricetulus , Contaminación Ambiental , Sedimentos Geológicos , Humanos , Metales Pesados/análisis , Pruebas de Toxicidad/métodos
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