Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 66
Filtrar
1.
EMBO J ; : e108544, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34850409

RESUMO

Since numerous RNAs and RBPs prevalently localize to active chromatin regions, many RNA-binding proteins (RBPs) may be potential transcriptional regulators. RBPs are generally thought to regulate transcription via noncoding RNAs. Here, we describe a distinct, dual mechanism of transcriptional regulation by the previously uncharacterized tRNA-modifying enzyme, hTrmt13. On one hand, hTrmt13 acts in the cytoplasm to catalyze 2'-O-methylation of tRNAs, thus regulating translation in a manner depending on its tRNA-modification activity. On the other hand, nucleus-localized hTrmt13 directly binds DNA as a transcriptional co-activator of key epithelial-mesenchymal transition factors, thereby promoting cell migration independent of tRNA-modification activity. These dual functions of hTrmt13 are mutually exclusive, as it can bind either DNA or tRNA through its CHHC zinc finger domain. Finally, we find that hTrmt13 expression is tightly associated with poor prognosis and survival in diverse cancer patients. Our discovery of the noncatalytic roles of an RNA-modifying enzyme provides a new perspective for understanding epitranscriptomic regulation.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34819981

RESUMO

Traditional Chinese medicine has shown promising results in treating the symptoms of hypertension, a major global health concern not yet fully managed by modern medicine. It is, therefore, of high priority to clarify the altered pathophysiology of hypertension in individuals with liver Yang hyperactivity syndrome (HLYH) in response to effective treatments to better understand this disorder. The primary aim of this study was to construct a personalized syndrome discriminant system based on data capable of informing management strategies prior to the initiation of antihypertensive therapy or the implementation of screening strategies in at-risk HLYH. Based on the successful replication of HLYH rat models, we extracted the core discriminant factors of the disorder through the integration of physical signs, biochemical indicators, and metabolic markers. Macro and micro information was correlated to construct a syndrome discriminant system. At the macroscopic level, HLYH rat models characterized by elevated blood pressure were found to be associated with significant changes in water intake, pain threshold, retention time on a rotating platform, and body surface temperature. A total of 27 potential biomarkers and 14 metabolic pathways appeared to reflect the primary metabolic characteristics. Through the integration of these data, we successfully constructed a combined macro-micro personalized syndrome discriminant system, which provides a foundation for research regarding the risk loci of HLYH. Our findings also broaden our understanding of the biological pathways involved in HLYH.

3.
Hum Cell ; 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34606042

RESUMO

The vascular endothelium plays a key role in the pathobiology of atherosclerotic cardiovascular disease. Endothelial cell Piezo1 mediates blood vessel formation, angiogenesis and regulation of blood pressure. However, changes of Piezo1 expression in atherosclerosis (AS) and the role of Piezo1 in the progression of atherosclerotic diseases remains obscure. Thus, the current study is to elucidate the role and mechanism of which Piezo1 mediates vascular inflammation in atherosclerotic mice and vascular endothelial inflammation induced by oxidized low density lipoprotein (ox-LDL) in vitro. Here, we have shown that the expression of Piezo1 was significantly increased in the stenotic carotid artery of ApoE-/- mice fed by high-fat diet (HFD). Pharmacological inhibition of Piezo1 (GsMTx-4) attenuated plaque formation, decreased the level of inflammation related factors (JNK, TNF-α, NF-κB, VCAM-1) of carotid plaque in atherosclerotic mice. Meanwhile, ox-LDL also upregulates Piezo1 and inflammation proteins (NF-κB, JNK and TNF-α) in endothelium cells (ECs). YAP/TAZ is activated accompanied by the enhanced Piezo1 activity in ECs induced by ox-LDL. Interference by siRNA of Piezo1 abolished the expression of YAP/TAZ and inflammation proteins (JNK, NF-κB and TNF-α). In addition, Ca2+ influx in ECs induced by ox-LDL was increased than control group, Piezo1 siRNA can reduce the calcium content. Piezo1 agonist Yoda1 increased Ca2+ influx and promote YAP nucleus translocation in ECs, genetic deletion of Piezo1 reversed it. Our results indicate that Piezo1 could mediate endothelial atherogenic inflammatory responses via regulation of YAP/TAZ activation and nuclear localization. Piezo1 may be a potential therapeutic target for atherosclerotic diseases in the future.

4.
BMC Cancer ; 21(1): 1134, 2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34686154

RESUMO

BACKGROUND: Signaling through VEGF/VEGFR induces cancer angiogenesis and affects immune cells. An increasing number of studies have recently focused on combining anti-VEGF/VEGFR agents and immune checkpoint inhibitors (ICIs) to treat cancer in preclinical and clinical settings. BD0801 is a humanized rabbit anti-VEGF monoclonal antibody in the clinical development stage. METHODS: In this study, the anti-cancer activities of BD0801 and its potential synergistic anti-tumor effects when combined with different immunotherapies were assessed by using in vitro assays and in vivo tumor models. Ex vivo studies were conducted to reveal the possible mechanisms of actions (MOA) underlying the tumor microenvironment modification. RESULTS: BD0801 showed more potent antitumor activity than bevacizumab, reflected by stronger blockade of VEGF/VEGFR binding and enhanced inhibitory effects on human umbilical vein endothelial cells (HUVECs). BD0801 exhibited dose-dependent tumor growth inhibitory activities in xenograft and murine syngeneic tumor models. Notably, combining BD0801 with either anti-PD-1 or anti-PD-L1 antibodies showed synergistic antitumor efficacy in both lung and colorectal cancer mouse models. Furthermore, the mechanistic studies suggested that the MOA of the antitumor synergy involves improved tumor vasculature normalization and enhanced T-cell mediated immunity, including increased tumor infiltration of CD8+ and CD4+ T cells and reduced double-positive CD8+PD-1+ T cells. CONCLUSIONS: These data provide a solid rationale for combining antiangiogenic agents with immunotherapy for cancer treatment and support further clinical development of BD0801 in combination with ICIs.

5.
Nucleic Acids Res ; 49(20): 11900-11919, 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34669960

RESUMO

Post-transcriptional modifications affect tRNA biology and are closely associated with human diseases. However, progress on the functional analysis of tRNA modifications in metazoans has been slow because of the difficulty in identifying modifying enzymes. For example, the biogenesis and function of the prevalent N2-methylguanosine (m2G) at the sixth position of tRNAs in eukaryotes has long remained enigmatic. Herein, using a reverse genetics approach coupled with RNA-mass spectrometry, we identified that THUMP domain-containing protein 3 (THUMPD3) is responsible for tRNA: m2G6 formation in human cells. However, THUMPD3 alone could not modify tRNAs. Instead, multifunctional methyltransferase subunit TRM112-like protein (TRMT112) interacts with THUMPD3 to activate its methyltransferase activity. In the in vitro enzymatic assay system, THUMPD3-TRMT112 could methylate all the 26 tested G6-containing human cytoplasmic tRNAs by recognizing the characteristic 3'-CCA of mature tRNAs. We also showed that m2G7 of tRNATrp was introduced by THUMPD3-TRMT112. Furthermore, THUMPD3 is widely expressed in mouse tissues, with an extremely high level in the testis. THUMPD3-knockout cells exhibited impaired global protein synthesis and reduced growth. Our data highlight the significance of the tRNA: m2G6/7 modification and pave a way for further studies of the role of m2G in sperm tRNA derived fragments.

6.
Zhongguo Zhong Yao Za Zhi ; 46(11): 2881-2888, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34296589

RESUMO

In this study, patients with prehypertensive liver-fire hyperactivity syndrome(LFHS) were selected as the research objects. The plasma samples of healthy volunteers and patients with prehypertensive LFHS were analyzed by non-targeted metabolomics based on UPLC-Q-Exactive MS. The differential biomarkers and metabolic pathways were screened out by multivariate statistics and metabolic pathway analysis, which revealed the characteristics of metabolic patterns of the syndrome. Thirty-three potential biomarkers such as androsterone and lysophosphatidylcholine and 16 related metabolic pathways such as steroid hormone metabolism and lipid metabolism were identified, and a partial least squares-discriminant analysis(PLS-DA) model of traditional Chinese medicine(TCM) syndromes was preliminarily constructed: Y =-0.070X_(13)-0.006X_8+ 0.040X_5-0.152X_1+0.131X_(10)+0.036X_(11)+0.043X_(23)+0.076X_(16)+0.132X_(20)+0.081X_(19)-0.101X_(31)+0.082X_(15)-0.038X_9+0.079X_(24). The predictive value of the model was 88.1%, and the explanatory power was 88.4%. In this study, the characteristic metabolic pattern of the prehypertensive LFHS was distinguished and revealed by metabolomics. The constructed PLS-DA model is expected to provide an objective basis for the identification of TCM syndromes in prehypertension, and inspiration for exploring the biological basis of TCM syndromes at small-molecular and overall levels.


Assuntos
Fígado , Metabolômica , Biomarcadores , Cromatografia Líquida de Alta Pressão , Humanos , Síndrome , Tecnologia
7.
Food Chem ; 364: 130426, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34175616

RESUMO

Present work investigated the effects of processing (homogenization, sterilization) and cold storage on physicochemical properties, in vitro digestion and Caco-2 cellular uptake of bovine milk. Extreme heat sterilization and low temperature storage have significant impact on particle size and phospholipidome of bovine milk. In addition, cold storage of bovine milks led to formation of ß' polymorphs crystals and endothermic peak with Toffset higher than body temperature. Processing and cold storage also increased the initial digestibility but reduced the overall digestibility of bovine milk. This might be related to the decreased particle size of the milk fat globules, changed in the phospholipidome of the MFGM and formation of ß' polymorphs crystals in frozen milk. It is interesting to note that PE has relatively faster digestion meanwhile SM has relatively slower digestion. HTST milk which demonstrated lesser changed in terms of phospholipidome demonstrated highest cellular uptakes of most fatty acids.


Assuntos
Digestão , Leite , Animais , Células CACO-2 , Bovinos , Ácidos Graxos , Humanos , Tamanho da Partícula
8.
Sci Rep ; 11(1): 10265, 2021 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-33986411

RESUMO

The successful implementation of heterosis in rice has significantly enhanced rice productivity, but the genetic basis of heterosis in rice remains unclear. To understand the genetic basis of heterosis in rice, main-effect and epistatic quantitative trait loci (QTLs) associated with heterosis for grain yield-related traits in the four related rice mapping populations derived from Xiushui09 (XS09) (japonica) and IR2061 (indica), were dissected using single nucleotide polymorphism bin maps and replicated phenotyping experiments under two locations. Most mid-parent heterosis of testcross F1s (TCF1s) of XS09 background introgression lines (XSILs) with Peiai64S were significantly higher than those of TCF1s of recombinant inbred lines (RILs) with PA64S at two locations, suggesting that the effects of heterosis was influenced by the proportion of introgression of IR2061's genome into XS09 background. A total of 81 main-effect QTLs (M-QTLs) and 41 epistatic QTLs were identified for the phenotypic variations of four traits of RILs and XSILs, TCF1s and absolute mid-parent heterosis in two locations. Furthermore, overdominance and underdominance were detected to play predominant effects on most traits in this study, suggesting overdominance and underdominance as well as epistasis are the main genetic bases of heterosis in rice. Some M-QTLs exhibiting positive overdominance effects such as qPN1.2, qPN1.5 and qPN4.3 for increased panicle number per plant, qGYP9 and qGYP12.1 for increased grain yield per plant, and qTGW3.4 and qTGW8.2 for enhanced 1000-grain weight would be highly valuable for breeding to enhance grain yield of hybrid rice by marker-assisted selection.


Assuntos
Vigor Híbrido/genética , Oryza/genética , Agricultura/métodos , China , Mapeamento Cromossômico/métodos , Cromossomos/genética , Cruzamentos Genéticos , Grão Comestível/genética , Epistasia Genética/genética , Genes Dominantes/genética , Genes de Plantas/genética , Genótipo , Fenótipo , Melhoramento Vegetal/métodos , Polimorfismo de Nucleotídeo Único/genética , Locos de Características Quantitativas/genética
9.
Sci China Life Sci ; 64(9): 1423-1436, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33881742

RESUMO

Chemical modifications expand the composition of RNA molecules from four standard nucleosides to over 160 modified nucleosides, which greatly increase the complexity and utility of RNAs. Transfer RNAs (tRNAs) are the most heavily modified cellular RNA molecules and contain the largest variety of modifications. Modification of tRNAs is pivotal for protein synthesis and also precisely regulates the noncanonical functions of tRNAs. Defects in tRNA modifications lead to numerous human diseases. Up to now, more than 100 types of modifications have been found in tRNAs. Intriguingly, some modifications occur widely on all tRNAs, while others only occur on a subgroup of tRNAs or even only a specific tRNA. The modification frequency of each tRNA is approximately 7% to 25%, with 5-20 modification sites present on each tRNA. The occurrence and modulation of tRNA modifications are specifically noticeable as plenty of interplays among different sites and modifications have been discovered. In particular, tRNA modifications are responsive to environmental changes, indicating their dynamic and highly organized nature. In this review, we summarized the known occurrence order, cross-talk, and cooperativity of tRNA modifications.

10.
Artigo em Inglês | MEDLINE | ID: mdl-33759181

RESUMO

OBJECTIVE: To explore treatment strategies for patients with positive margins after cervical cold knife conization (CKC) by estimating the risk of residual or recurrent CIN2 or worse (CIN2+). METHODS: A retrospective study included 569 patients receiving CKC for CIN3 in Xiangya Hospital from January 2013 to December 2017. Demographic characteristics and test results were obtained before CKC, after CKC, at 6, 12, and 24 months, then annually thereafter. The primary end point was residual/recurrent CIN2+ post-CKC. RESULTS: Fourteen (2.46%) patients had residual/recurrent CIN2+ with a median time of occurrence at 12 months post-CKC. Taking the average age and hrHPV viral load tested by Hybrid Capture 2 (HC2) as thresholds, the risk of residual/recurrent CIN2+ was higher in women aged over 40 years or with a baseline HC2 of 300 or more for the ratio of relative light units to positive cut-off values. Patients with positive margins were at higher risk of residual/recurrent CIN2+ (hazard ratio 3.66, 95% confidence interval 1.25-10.71), especially when endocervix was involved. A total of 536 (94.20%) patients received HPV testing within 6 months after CKC. Patients with both positive HPV testing results and positive margins were at the highest risk of residual/recurrent CIN2+. CONCLUSION: Patients with positive endocervical margins are at high risk for residual/recurrent CIN2+, independent of the severity of margins. HPV testing within 6 months after CKC may be a feasible triage strategy for these patients.

11.
Front Cell Neurosci ; 15: 653487, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33776653

RESUMO

Objective: Brain-computer interface (BCI) training is becoming increasingly popular in neurorehabilitation. However, around one third subjects have difficulties in controlling BCI devices effectively, which limits the application of BCI training. Furthermore, the effectiveness of BCI training is not satisfactory in stroke rehabilitation. Intermittent theta burst stimulation (iTBS) is a powerful neural modulatory approach with strong facilitatory effects. Here, we investigated whether iTBS would improve BCI accuracy and boost the neuroplastic changes induced by BCI training. Methods: Eight right-handed healthy subjects (four males, age: 20-24) participated in this two-session study (BCI-only session and iTBS+BCI session in random order). Neuroplastic changes were measured by functional near-infrared spectroscopy (fNIRS) and single-pulse transcranial magnetic stimulation (TMS). In BCI-only session, fNIRS was measured at baseline and immediately after BCI training. In iTBS+BCI session, BCI training was followed by iTBS delivered on the right primary motor cortex (M1). Single-pulse TMS was measured at baseline and immediately after iTBS. fNIRS was measured at baseline, immediately after iTBS, and immediately after BCI training. Paired-sample t-tests were used to compare amplitudes of motor-evoked potentials, cortical silent period duration, oxygenated hemoglobin (HbO2) concentration and functional connectivity across time points, and BCI accuracy between sessions. Results: No significant difference in BCI accuracy was detected between sessions (p > 0.05). In BCI-only session, functional connectivity matrices between motor cortex and prefrontal cortex were significantly increased after BCI training (p's < 0.05). In iTBS+BCI session, amplitudes of motor-evoked potentials were significantly increased after iTBS (p's < 0.05), but no change in HbO2 concentration or functional connectivity was observed throughout the whole session (p's > 0.05). Conclusions: To our knowledge, this is the first study that investigated how iTBS targeted on M1 influences BCI accuracy and the acute neuroplastic changes after BCI training. Our results revealed that iTBS targeted on M1 did not influence BCI accuracy or facilitate the neuroplastic changes after BCI training. Therefore, M1 might not be an effective stimulation target of iTBS for the purpose of improving BCI accuracy or facilitate its effectiveness; other brain regions (i.e., prefrontal cortex) are needed to be further investigated as potentially effective stimulation targets.

12.
Pestic Biochem Physiol ; 173: 104771, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33771249

RESUMO

A series of novel 1-phenyl-5-amine-4-pyrazole thioether derivatives containing a 1,3,4-oxadiazole moiety was designed and synthesised. In vivo antiviral bioassay results showed that most of the target compounds exhibited excellent inactivation activity against Tobacco mosaic virus (TMV). The EC50 values of the inactivation activities for T2, T7, T9, T24, T25 and T27 were 15.7, 15.7, 15.5, 11.9, 12.5 and 16.5 µg/mL, respectively, which were remarkably superior over that of the commercialised antiviral agent ningnanmycin (40.3 µg/mL). Morphological study using AFM and TEM of TMV treated with T24 showed that T24 could significantly shorten the polymerization length of TMV particles and formed a distinct break on the rod-shaped TMV. Investigations for virus infection efficiency on tobacco leaves demonstrated that infectivity of virion had been reduced obviously upon T24 treatment. Subsequently, a strong interaction between T24 and TMV-CP (Kd = 3.8 µM, score 6.11) was observed through MST experiments. Molecular docking study further revealed that target compounds interact with amino acid residue Glu50 in TMV CP, causing disassembly of virion, shorting the length of the virion and reducing the infectivity of virion, and resulting in high inactivating activity of target compounds. This study provides a new insight for discovery of antiviral compounds through a new action mechanism with a new binding site.


Assuntos
Vírus do Mosaico do Tabaco , Aminas , Antivirais/farmacologia , Simulação de Acoplamento Molecular , Pirazóis/farmacologia , Relação Estrutura-Atividade , Sulfetos
13.
Am J Perinatol ; 38(11): 1181-1191, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-32446263

RESUMO

OBJECTIVE: The delivery mode is considered to be a significant influencing factor in the early gut microbiota composition, which is associated with the long-term health of the host. In this study, we tried to explore the effects of probiotics on the intestinal microbiota of C-section neonates. STUDY DESIGN: Twenty-six Chinese neonates were enrolled in this study. The neonates were divided into four groups: VD (natural delivery neonates, n = 3), CD (cesarean-born neonates, n = 9), CDL (cesarean-born neonates supplemented with probiotic at a lower dosage, n = 7), and CDH (cesarean-born neonates supplemented with probiotic at a higher dosage, n = 7). Fecal samples were collected on the 3rd, 7th, and 28th day since birth. The V3-V4 region of the 16S ribosomal ribonucleic acid gene was sequenced by next-generation sequencing technology. RESULTS: The α-diversity of the intestinal microbiota of cesarean delivery neonates was significantly lower than that of the naturally delivered neonates on the 28th day (p = 0.005). After supplementation with probiotics for 28 days, the α-diversity and the ß-diversity of the gut flora in the cesarean-born infants (CDL28 and CDH28) was similar to that in the vaginally delivery infants. Meanwhile, the abundances of Lactobacillus and Bifidobacterium were significantly increased since the 3rd day of probiotic supplementation. Besides, the sustained supplementation of probiotics to neonates would help improve the abundance of the operational taxonomic units in several different Clusters of Orthologous Groups of proteins. CONCLUSION: This study showed that probiotics supplementation to cesarean-born neonates since birth might impact the diversity and function of gut microbiota. KEY POINTS: · Cesarean-born neonates. · Probiotic supplementation impact gut flora. · Bifidobacterium and Lactobacillus.

14.
PLoS One ; 15(12): e0243326, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33270804

RESUMO

Bradykinin-related peptides (BRPs) family is one of the most significant myotropic peptide families derived from frog skin secretions. Here, a novel BRP callitide was isolated and identified from the red-eyed leaf frog, Agalychnis callidryas, with atypical primary structure FRPAILVRPK-NH2. The mature peptide was cleaved N-terminally at a classic propeptide convertase cleavage site (-KR-) and at the C-terminus an unusual -GKGKGK sequence was removed using the first G residue as an amide donor for the C-terminally-located K residue. Thereafter, the synthetic replicates of callitide were assessed the myotropic activity and showed a significant contraction of balder, with the 0.63 nM EC50 value, more potent than most discovered myotropic peptides. The binding mode was further speculated by molecular docking and stimulation. The result indicated that the C-terminal of callitide might selectively bind to bradykinin receptor B2 (BKRB2). Further investigation of the callitide needs to be done in the future to be exploited as potential future drug leads.


Assuntos
Proteínas de Anfíbios/química , Anuros/genética , Simulação de Acoplamento Molecular , Contração Muscular/efeitos dos fármacos , Receptor B2 da Bradicinina , Pele/química , Bexiga Urinária/metabolismo , Proteínas de Anfíbios/genética , Proteínas de Anfíbios/metabolismo , Proteínas de Anfíbios/farmacologia , Animais , Anuros/metabolismo , Feminino , Ratos , Ratos Wistar , Receptor B2 da Bradicinina/agonistas , Receptor B2 da Bradicinina/química , Receptor B2 da Bradicinina/metabolismo , Pele/metabolismo
15.
Commun Biol ; 3(1): 659, 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33159129

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

16.
Front Pharmacol ; 11: 1247, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32982723

RESUMO

Cardiometabolic diseases are characterized as a combination of multiple risk factors for cardiovascular disease (CVD) and metabolic diseases including diabetes mellitus and dyslipidemia. Cardiometabolic diseases are closely associated with cell glucose and lipid metabolism, inflammatory response and mitochondrial function. Farnesoid X Receptor (FXR), a metabolic nuclear receptor, are found to be activated by primary BAs such as chenodeoxycholic acid (CDCA), cholic acid (CA) and synthetic agonists such as obeticholic acid (OCA). FXR plays crucial roles in regulating cholesterol homeostasis, lipid metabolism, glucose metabolism, and intestinal microorganism. Recently, emerging evidence suggests that FXR agonists are functional for metabolic syndrome and cardiovascular diseases and are considered as a potential therapeutic agent. This review will discuss the pathological mechanism of cardiometabolic disease and reviews the potential mechanisms of FXR agonists in the treatment of cardiometabolic disease.

17.
Biochim Biophys Acta Mol Cell Biol Lipids ; 1865(10): 158779, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32739616

RESUMO

Atherosclerosis (AS) is a chronic disease of the arterial wall where both innate and adaptive immunoinflammatory mechanisms are involved. Inflammation plays an important role in the pathological process of atherosclerosis at various stages. Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ, also known as WWTR1) behave as a novel drug target against atherosclerosis. Therefore, the mechanism relationship of YAP/TAZ, inflammation and AS was explored in this study. Experiments demonstrated that serine dephosphorylation and nuclear translocation of YAP was increased in ECs and pericytes induced by oxidative low-density lipoprotein (ox-LDL), while the inhibition of YAP degraded the expression of downstream inflammatory factors. The expression of YAP/TAZ and inflammation proteins (JNK, NF-κB and TNF-α) in ECs and pericytes was suppressed through the application of Sal-B. Besides, Sal-B protects ECs and pericytes from oxidative stress and apoptosis. In vivo, Sal-B reduced en face and aortic root sinus lesions size, and decreased the expression of inflammation related factors (IL-6, IL-1ß, TNF-α) and ox-LDL in serum sample of ApoE-/- mice fed a high fat diet. Therefore, our work provides a potential therapeutic strategy of using Sal-B to attenuate the development of atherosclerosis, the anti-atherosclerosis effects of Sal-B is related to regulate YAP/TAZ/JNK signaling pathway.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Aterosclerose/tratamento farmacológico , Benzofuranos/farmacologia , Células Endoteliais/efeitos dos fármacos , Fatores de Transcrição/genética , Proteínas Adaptadoras de Transdução de Sinal/antagonistas & inibidores , Animais , Apolipoproteínas E/genética , Aterosclerose/genética , Aterosclerose/metabolismo , Aterosclerose/patologia , Sobrevivência Celular/efeitos dos fármacos , Células Endoteliais/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , MAP Quinase Quinase 4/genética , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , Pericitos/efeitos dos fármacos , Pericitos/metabolismo , Fatores de Transcrição/antagonistas & inibidores
18.
Gynecol Endocrinol ; 36(10): 934-937, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32516003

RESUMO

Introduction: Malignant germ cell tumors (MGCT) can occur in both genders. In this study, we present eight cases of mixed ovarian MGCT in patients. Most patients reported in the current study are young women, among whom clinical characteristics of gonadal dysgenesis associated MGCT were rarely reported.Methods: Comprehensive information of eight patients with mixed ovarian MGCTs, including patients' age, clinical features, tumor markers, imaging findings, surgical records, pathology, karyotyping tests, chemotherapy and follow-up were collected. Surgical specimens were evaluated by two specialized gynecologic pathologists.Results: All patients received surgery, while seven received chemotherapy. Among them, two received a second surgery and three patients received hormone replacement therapy (HRT) after gonadectomy. Four of five patients with amenorrhea were found to have 46, XY karyotype. All patients showed no sign of recurrence at the latest follow-up.Discussion: Karyotyping or genetics testing in patients with amenorrhea is necessary, especially for patients with pelvic mass, which can help surgeons to evaluate the necessity of gonadectomy before surgery. The patients with gonadal dysgenesis associated mixed ovarian MGCT seem to have better prognosis and long survival time. Thus, HRT, an option that can improve life quality, is worth considering for these patients after gonadectomy.


Assuntos
Disgenesia Gonadal/complicações , Neoplasias Embrionárias de Células Germinativas/etiologia , Neoplasias Ovarianas/etiologia , Adolescente , Adulto , Antineoplásicos/uso terapêutico , Feminino , Procedimentos Cirúrgicos em Ginecologia , Terapia de Reposição Hormonal , Humanos , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias Embrionárias de Células Germinativas/cirurgia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Ovário/patologia , Estudos Retrospectivos , Adulto Jovem
19.
Thyroid ; 30(11): 1656-1665, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32586221

RESUMO

Background: Iodine intake is associated with thyroid autoimmunity. In this study, we evaluated the changes in thyroid autoimmunity after 20 years of universal salt iodization (USI) in China. Methods: A total of 78,470 subjects (18 years or older) from 31 provincial regions of mainland China participated in the study. Serum thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb), TSH receptor antibody, thyrotropin (TSH), and urinary iodine concentration (UIC) were measured. Results: Positive TPOAb and TgAb were detected in 10.19% [CI 9.80-10.59] and 9.70% [CI 9.28-10.13] of the subjects, respectively. The prevalence of positive isolated TPOAb (i-TPOAb), positive isolated TgAb (i-TgAb), and double positive TPOAb and TgAb (d-Ab) was 4.52%, 4.16%, and 5.94%, respectively. The prevalence of thyroid antibody positivity was the highest in the iodine-deficient (UIC <100 µg/L) groups. The prevalence of i-TPOAb was inversely associated with more than adequate iodine intake (MAI) and excessive iodine intake (EI); the odds ratio (OR) was 0.89 [CI 0.81-0.98] for MAI and 0.90 [CI 0.81-0.99] for EI. We observed that i-TgAb, like i-TPOAb, was a high-risk factor for subnormal TSH levels (OR = 3.64 [CI 2.62-5.05]) and elevated TSH levels (OR = 1.62 [CI 1.49-1.77]). The prevalence of thyroid antibody positivity varied among five ethnic groups. Conclusions: After two decades of USI, the prevalence of thyroid antibody positivity has remained low. MAI and EI had an inverse relationship with TPOAb positivity, which reveals that UIC between 100 and 299 µg/L is optimal and safe for thyroid autoimmunity. These conclusions need to be confirmed in a follow-up study because this study was a cross-sectional study.

20.
Commun Biol ; 3(1): 327, 2020 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-32581266

RESUMO

Chronic inflammation plays a crucial role in vascular calcification. However, only a few studies have revealed the mechanisms underlying the development of inflammation under high-phosphate conditions in chronic kidney disease (CKD) patients. Here, we show that inflammation resulting from the activation of the TGFBR1/TAK1 pathway is involved in calcification in CKD rats or osteogenic medium-cultured human aortic smooth muscle cells (HASMCs). Moreover, miR-135a-5p is demonstrated to be a key regulator of the TGFBR1/TAK1 pathway, which has been reported to be decreased in CKD rats. We further reveal that farnesoid X receptor (FXR) activation increases miR-135a-5p expression, thereby inhibiting the activation of the TGFBR1/TAK1 pathway, ultimately resulting in the attenuation of vascular inflammation and calcification in CKD rats. Our findings provide advanced insights into the mechanisms underlying the development of inflammation in vascular calcification, and evidence that FXR activation could serve as a therapeutic strategy for retarding vascular calcification in CKD patients.


Assuntos
Calcinose/metabolismo , MicroRNAs/genética , Receptores Citoplasmáticos e Nucleares/metabolismo , Vasculite/metabolismo , Animais , Aorta/citologia , Calcinose/genética , Células Cultivadas , Feminino , Humanos , MAP Quinase Quinase Quinases/genética , MAP Quinase Quinase Quinases/metabolismo , Masculino , Músculo Liso Vascular/citologia , Osteogênese , Ratos Wistar , Receptor do Fator de Crescimento Transformador beta Tipo I/genética , Receptor do Fator de Crescimento Transformador beta Tipo I/metabolismo , Receptores Citoplasmáticos e Nucleares/genética , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/patologia , Vasculite/genética , Vasculite/patologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...