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1.
Proc Natl Acad Sci U S A ; 118(22)2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34039711

RESUMO

Mammalian oviducts play an essential role in female fertility by picking up ovulated oocytes and transporting and nurturing gametes (sperm/oocytes) and early embryos. However, the relative contributions to these functions from various cell types within the oviduct remain controversial. The oviduct in mice deficient in two microRNA (miRNA) clusters (miR-34b/c and miR-449) lacks cilia, thus allowing us to define the physiological role of oviductal motile cilia. Here, we report that the infundibulum without functional motile cilia failed to pick up the ovulated oocytes. In the absence of functional motile cilia, sperm could still reach the ampulla region, and early embryos managed to migrate to the uterus, but the efficiency was reduced. Further transcriptomic analyses revealed that the five messenger ribonucleic acids (mRNAs) encoded by miR-34b/c and miR-449 function to stabilize a large number of mRNAs involved in cilium organization and assembly and that Tubb4b was one of their target genes. Our data demonstrate that motile cilia in the infundibulum are essential for oocyte pickup and thus, female fertility, whereas motile cilia in other parts of the oviduct facilitate gamete and embryo transport but are not absolutely required for female fertility.


Assuntos
Cílios/fisiologia , Fertilidade , Oócitos/fisiologia , Oviductos/fisiologia , Ovulação , Animais , Blastocisto/fisiologia , Implantação do Embrião , Feminino , Masculino , Camundongos Knockout , MicroRNAs/metabolismo , Movimento , Espermatozoides/fisiologia
2.
Int J Mol Sci ; 25(5)2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38474038

RESUMO

Biofilm-associated bacterial infections are the major reason for treatment failure in many diseases including burn trauma infections. Uncontrolled inflammation induced by bacteria leads to materiality, tissue damage, and chronic diseases. Specialized proresolving mediators (SPMs), including maresin-like lipid mediators (MarLs), are enzymatically biosynthesized from omega-3 essential long-chain polyunsaturated fatty acids, especially docosahexaenoic acid (DHA), by macrophages and other leukocytes. SPMs exhibit strong inflammation-resolving activities, especially inflammation provoked by bacterial infection. In this study, we explored the potential direct inhibitory activities of three MarLs on Gram-positive (Staphylococcus aureus) and Gram-negative (Pseudomonas aeruginosa and Escherichia coli) bacteria in their biofilms that are leading bacteria in burn trauma-related infections. We also examined the effects of MarLs on the bactericidal activities of a typical broad-spectrum antibiotic, carbenicillin (carb), on these bacteria in their preformed biofilms. The results revealed that MarLs combined with carbenicillin can inhibit the survival of Gram-positive and Gram-negative bacteria in their biofilms although MarLs alone did not exhibit bactericidal activity. Thus, our findings suggest that the combination of MarLs and carbenicillin can lower the antibiotic requirements to kill the bacteria in preformed biofilms.


Assuntos
Queimaduras , Doenças Transmissíveis , Infecções Estafilocócicas , Infecção dos Ferimentos , Humanos , Antibacterianos/farmacologia , Carbenicilina/farmacologia , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Biofilmes , Bactérias , Escherichia coli , Inflamação , Testes de Sensibilidade Microbiana
3.
Bioconjug Chem ; 33(9): 1602-1608, 2022 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-36018225

RESUMO

Selenium plays an important role in the biological system and can be used to treat various types of diseases. However, the current selenium delivery systems face the problems of low activity of released Se-containing compounds or nonspecific toxicity of reactive organic selenium donors in living systems. In response to these problems, we constructed a reactive organic selenium delivery platform by the activation of HOCl. Compared with prodrugs without activation capability, the hypochloroselenoite derivatives released from the present platform after activation displayed higher reactivity and could react with various nucleophiles to participate in specific life processes. Taking the selected compound (DHU-Se1) as an example, we found that it could alleviate the process of inflammation by blocking the polarization of macrophages from M0 to M1. Therefore, the development of this system is of great significance for expanding the application of selenium-containing compounds and treating related diseases.


Assuntos
Pró-Fármacos , Compostos de Selênio , Selênio , Humanos , Inflamação/tratamento farmacológico , Pró-Fármacos/farmacologia , Pró-Fármacos/uso terapêutico , Selênio/farmacologia , Compostos de Selênio/farmacologia
4.
Proc Natl Acad Sci U S A ; 116(9): 3584-3593, 2019 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-30659149

RESUMO

Cilia are cell-surface, microtubule-based organelles that project into extracellular space. Motile cilia are conserved throughout eukaryotes, and their beat induces the flow of fluid, relative to cell surfaces. In mammals, the coordinated beat of motile cilia provides highly specialized functions associated with the movement of luminal contents, as seen with metachronal waves transporting mucus in the respiratory tract. Motile cilia are also present in the male and female reproductive tracts. In the female, wave-like motions of oviductal cilia transport oocytes and embryos toward the uterus. A similar function has been assumed for motile cilia in efferent ductules of the male-i.e., to transport immotile sperm from rete testis into the epididymis. However, we report here that efferent ductal cilia in the male do not display a uniform wave-like beat to transport sperm solely in one direction, but rather exert a centripetal force on luminal fluids through whip-like beating with continual changes in direction, generating turbulence, which maintains immotile spermatozoa in suspension within the lumen. Genetic ablation of two miRNA clusters (miR-34b/c and -449a/b/c) led to failure in multiciliogenesis in murine efferent ductules due to dysregulation of numerous genes, and this mouse model allowed us to demonstrate that loss of efferent duct motile cilia causes sperm aggregation and agglutination, luminal obstruction, and sperm granulomas, which, in turn, induce back-pressure atrophy of the testis and ultimately male infertility.


Assuntos
Cílios/genética , Infertilidade Masculina/genética , MicroRNAs/genética , Animais , Epididimo/crescimento & desenvolvimento , Epididimo/patologia , Feminino , Genitália Masculina/crescimento & desenvolvimento , Humanos , Infertilidade Masculina/fisiopatologia , Masculino , Camundongos , Camundongos Knockout , Microtúbulos/genética , Microtúbulos/metabolismo , Espermatozoides/crescimento & desenvolvimento , Espermatozoides/patologia , Testículo/crescimento & desenvolvimento , Testículo/metabolismo
5.
Proc Natl Acad Sci U S A ; 115(2): E325-E333, 2018 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-29279410

RESUMO

N6-methyladenosine (m6A) represents one of the most common RNA modifications in eukaryotes. Specific m6A writer, eraser, and reader proteins have been identified. As an m6A eraser, ALKBH5 specifically removes m6A from target mRNAs and inactivation of Alkbh5 leads to male infertility in mice. However, the underlying molecular mechanism remains unknown. Here, we report that ALKBH5-mediated m6A erasure in the nuclei of spermatocytes and round spermatids is essential for correct splicing and the production of longer 3'-UTR mRNAs, and failure to do so leads to aberrant splicing and production of shorter transcripts with elevated levels of m6A that are rapidly degraded. Our study identified reversible m6A modification as a critical mechanism of posttranscriptional control of mRNA fate in late meiotic and haploid spermatogenic cells.


Assuntos
Homólogo AlkB 5 da RNA Desmetilase/metabolismo , Glicoproteínas de Membrana/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Splicing de RNA/fisiologia , Espermatócitos/fisiologia , Regiões 3' não Traduzidas , Homólogo AlkB 5 da RNA Desmetilase/genética , Animais , Desmetilação , Células Germinativas , Masculino , Glicoproteínas de Membrana/genética , Camundongos , Camundongos Knockout , Proteínas do Tecido Nervoso/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
6.
Zhongguo Zhong Yao Za Zhi ; 46(16): 4208-4213, 2021 Aug.
Artigo em Zh | MEDLINE | ID: mdl-34467734

RESUMO

In this study, emotional stress-induced herpes simplex virus type 1(HSV-1) susceptibility model was employed to simu-late the pathological state of " depression-induced liver fire", and the protection effect of Qingre Xiaoyanning(QX) in clearing liver fire was investigated. BALB/c mice were randomly divided into a normal group, a HSV-1 group, a restraint stress + HSV-1 group,low-(0. 658 g·kg~(-1)) and high-dose(1. 316 g·kg~(-1)) QX groups, and an acyclovir group. Except for the normal group and the HSV-1 group, the mice in other groups received daily restraint stress for 6 h from day 3 of medication. On day 9 of medication, mice were anesthetized by isoflurane and infected intranasally with HSV-1. Survival rate, weight change, encephalitis symptoms, and eye injury of mice were recorded for 14 d after virus infection. Hematoxylin-eosin(HE) staining and immunohistochemical staining were used to detect pathological changes and HSV-1 antigen distribution. Plaque assay was performed to detect the titer of HSV-1. The protein ex-pression of ICP27 in the mouse brain was detected by Western blot. The experimental results showed that QX could increase the survival rate of HSV-1-infected mice loaded with emotional stress(P<0. 001), reduce the titer of HSV-1 in the mouse brain(P<0. 01), relieve brain inflammation(P<0. 05) and eye injury(P<0. 05), down-regulate the expression of ICP27 related to HSV-1(P<0. 05), and decrease the distribution of HSV-1 antigen in the mouse brain. The results demonstrated that QX significantly reduced the susceptibility to HSV-1 induced by emotional stress, which is expected to provide a theoretical basis for the treatment and preven-tion of HSV-1 infection and promote the clinical development and application of Chinese medicine effective in clearing liver fire.


Assuntos
Herpes Simples , Herpesvirus Humano 1 , Angústia Psicológica , Animais , Cápsulas , Camundongos , Camundongos Endogâmicos BALB C
7.
BMC Nephrol ; 19(1): 206, 2018 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-30115010

RESUMO

BACKGROUND: Obesity is a well-established risk factor for atherosclerosis. However, it is unknown which measure of adiposity best relates to atherosclerosis in relatively lean maintenance hemodialysis (MHD) patients. We aimed to explore and compare the associations between different adiposity indices reflecting general, abdominal, visceral adiposity and arteriosclerosis risk with atherogenic index of plasma(AIP) in relatively lean MHD patients. METHODS: We conducted a multicenter, cross-sectional study in Guizhou Province, Southwest China. General/abdominal adiposity indices like body mass index (BMI), waist circumference(WC), waist-height ratio(WHtR), conicity index (Ci) and visceral obesity indices including visceral adiposity index (VAI), lipid accumulation product (LAP) and the hypertriglyceridemic waist phenotype (HW phenotype) were recorded. Univariate and multivariate linear regression models were used. RESULTS: All adiposity indices correlated positively with AIP in univariate analysis both in men and women except for Ci. After adjustment for age and traditional atherosclerosis risk factors, BMI, WC, WHtR, VAI and LAP still had associations with AIP both in men (ß = 0.265, 0.153, 0.16, 0.788 and 0.74, respectively, all P < 0.001) and women (ß = 0.34,0.199, 0.21, 0.83 and 0.74, respectively, all P < 0.001). After further adjustment for BMI, associations between AIP and VAI, LAP remained significant, but associations between WC, WHtR and AIP disappeared. CONCLUSIONS: The HW phenotype, VAI, and LAP, validated and convenient markers of visceral obesity, were superior to classical anthropometric general/ abdominal adiposity indices for atherosclerosis risk assessment, especially in relatively lean MHD patients aged 40 years or older.


Assuntos
Aterosclerose/epidemiologia , Índice de Massa Corporal , Obesidade/epidemiologia , Diálise Renal/tendências , Magreza/epidemiologia , Circunferência da Cintura/fisiologia , Adulto , Idoso , Aterosclerose/fisiopatologia , Aterosclerose/terapia , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Gordura Intra-Abdominal/fisiopatologia , Masculino , Pessoa de Meia-Idade , Obesidade/fisiopatologia , Obesidade/terapia , Obesidade Abdominal/epidemiologia , Obesidade Abdominal/fisiopatologia , Obesidade Abdominal/terapia , Magreza/fisiopatologia , Magreza/terapia
8.
J Occup Environ Hyg ; 12(8): 555-63, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26131762

RESUMO

The objectives of this study are to demonstrate for the first time the use of a field portable X-Ray Fluorescence Analyzer (XRF) in a multi-media environmental survey and to use the survey results to determine if residual lead from a once-active secondary lead smelter in Cairo, Egypt, still posed a health risk to the residents when comparing results with US EPA standards. Results were analyzed to determine if relationships among the variables indicated that there were residual impacts of the former smelter. Samples collected inside and near a total of 194 dwellings were analyzed. The mean floor dust lead loading was 7.48 µg lead/ft(2). Almost 10% of the dwellings had at least one floor dust wipe sample that exceeded the United States Environmental Protection Agency's (USEPA) interior settled dust lead level of 40 µg lead/ft(2). The median paint lead level was 0.04 mg lead/cm(2). 17% of the dwellings had at least one interior paint sample that exceeded the USEPA standard of 1.0 mg lead/cm(2). Mean soil lead concentration in the study area was 458 ppm and 91 ppm outside the study area. Four of nine composite soil samples exceeded the US EPA limit for bare soil in play areas. Lead concentrations in samples collected in locations outside the study area did not exceed the limit. The highest concentration was in the plot closest to the smelter and may represent residual impact from the former smelter. Statistically significant relationships were not detected between interior floor dust lead loading and either interior paint lead loading or exterior dust lead concentration. Thus, no significant exposure from the former smelter was indicated by these analyses. This may have resulted from the time elapsed since the closing of the smelter and/or the relatively low paint lead levels. Further study is needed in other areas of Egypt near former and active lead smelters. Elevated levels of mercury and arsenic detected in soil samples do not appear to be related to the smelter but warrant further study.


Assuntos
Poeira/análise , Exposição Ambiental/análise , Chumbo/análise , Pintura/análise , Poluentes do Solo/análise , Egito , Pisos e Cobertura de Pisos , Habitação , Chumbo/normas , Metalurgia , Espectrometria por Raios X/métodos
9.
Environ Res ; 132: 233-43, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24819125

RESUMO

Paints with high lead concentrations (ppm) continue to be sold around the world in many developing countries and those with economies in transition representing a major preventable environmental health hazard that is being increased as the economies expand and paint consumption is increasing. Prior lead paint testing had been performed in Brazil and India and these countries were selected to examine the impact of a new regulatory limit in Brazil and the impact of efforts of non-governmental organizations and others to stop the use of lead compounds in manufacturing paints. Armenia and Kazakhstan, in Central Asia, were selected because no information on lead concentration in those regions was available, no regulatory activities were evident and non-governmental organizations in the IPEN network were available to participate. Another objective of this research was to evaluate the lead loading (µg/cm(2)) limit determined by X-Ray Fluorescence (XRF) for areas on toys that are too small to obtain a sample of sufficient size for laboratory analysis. The lead concentrations in more than three-fourths of the paints from Armenia and Kazakhstan exceeded 90 ppm, the limit in the United States, and 600 ppm, the limit in Brazil. The percentages were about one-half as high in Brazil and India. The average concentration in paints purchased in Armenia, 25,000 ppm, is among the highest that has been previously reported, that in Kazakhstan, 15,700 ppm, and India, 16,600, about median. The average concentration in Brazil, 5600 ppm, is among the lowest observed. Paints in Brazil that contained an average of 36,000 ppm before the regulatory limit became effective were below detection (< 9 ppm) in samples collected in the current study. The lack of any apparent public monitoring of paint lead content as part of regulatory enforcement makes it difficult to determine whether the regulation was a major factor contributing to the decline in lead use in these paints. Using data from the current study and those available from other studies 24 of 28 paints from major brands in India decreased from high concentrations to 90 ppm or lower. Since lead concentrations in golden yellow paints from these brands were found to decrease to ≤ 90 ppm, it is possible that all 28 of these paints now contain ≤ 90 ppm since yellow paints usually have the highest lead concentrations. Other brands in Brazil and India that have been analyzed only one time had lead concentrations up to 59,000 ppm and 134,000 ppm, respectively. Less than one-third of the paints had notations on their labels with information about lead content and these were sometimes inaccurate. The label from one brand indicating "no added lead" contained paint with 134,000 ppm lead, the highest found in this study. Three percent (3 of 98) of the paints with surface lead loading that did not exceed 2 µg/cm(2), the limit established by the Consumer Product Safety Improvement Act for small areas on toys, contained greater than 90 ppm lead and thus were false negatives. Of the new paint samples that contained ≤ 600 ppm, 88% contained ≤ 90 ppm. Of the samples that contained ≤ 90 ppm, 97% contained ≤ 45 ppm and 92% contained ≤ 15 ppm. Based on these data it appears to be technically feasible to manufacture paints containing ≤ 90 ppm and in many cases to produce paints that have lead concentrations that do not exceed 15 ppm.


Assuntos
Chumbo/análise , Pintura/análise , Armênia , Ásia , Brasil , Regulamentação Governamental
10.
Theranostics ; 14(10): 3900-3908, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38994024

RESUMO

Background: Osteoarthritis (OA) standing as the most prevalent form of arthritis, closely associates with heightened levels of reactive oxygen species, particularly hypochlorous acid (HOCl). Although there are numerous probes available for detecting HOCl in the OA region, probes with dual functions of diagnostic and therapeutic capabilities are still significantly lacking. While this type of probe can reduce the time gap between diagnosis and treatment, which is clinically needed. Methods: We developed a fluorescent probe (DHU-CBA1) toward HOCl with theranostics functions through the release of methylene blue (MB) and ibuprofen (IBP) in this work. DHU-CBA1 can detect HOCl with high specificity and sensitivity, releasing MB and IBP with an impressive efficiency of ≥ 95% in vitro. Results: DHU-CBA1 exhibits good biosafety, enabling in vivo imaging of endogenous HOCl, along with reducing arthritis scores, improving synovitis and cartilage damage, and maintaining catabolic balance while alleviating senescence in cartilage. Conclusions: This study proposes a novel approach to enhance osteoarthritis therapy by releasing IBP via a smart HOCl-enabled fluorescent probe.


Assuntos
Corantes Fluorescentes , Ácido Hipocloroso , Ibuprofeno , Azul de Metileno , Osteoartrite , Osteoartrite/tratamento farmacológico , Corantes Fluorescentes/química , Ibuprofeno/administração & dosagem , Animais , Azul de Metileno/química , Camundongos , Humanos , Nanomedicina Teranóstica/métodos , Masculino , Imagem Óptica/métodos , Espécies Reativas de Oxigênio/metabolismo
11.
Front Cell Dev Biol ; 12: 1380059, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38533089

RESUMO

Introduction: Stem cells can be used to treat diabetic mellitus and complications. ω3-docosahexaenoic acid (DHA) derived lipid mediators are inflammation-resolving and protective. This study found novel DHA-derived 7S,14R-dihydroxy-4Z,8E,10Z,12E,16Z,19Z-docosahexaenoic acid (7S,14R-diHDHA), a maresin-1 stereoisomer biosynthesized by leukocytes and related enzymes. Moreover, 7S,14R-diHDHA can enhance mesenchymal stem cell (MSC) functions in the amelioration of diabetic mellitus and retinal pericyte loss in diabetic db/db mice. Methods: MSCs treated with 7S,14R-diHDHA were delivered into db/db mice i.v. every 5 days for 35 days. Results: Blood glucose levels in diabetic mice were lowered by 7S,14R-diHDHA-treated MSCs compared to control and untreated MSC groups, accompanied by improved glucose tolerance and higher blood insulin levels. 7S,14R-diHDHA-treated MSCs increased insulin+ ß-cell ratio and decreased glucogan+ α-cell ratio in islets, as well as reduced macrophages in pancreas. 7S,14R-diHDHA induced MSC functions in promoting MIN6 ß-cell viability and insulin secretion. 7S,14R-diHDHA induced MSC paracrine functions by increasing the generation of hepatocyte growth factor and vascular endothelial growth factor. Furthermore, 7S,14R-diHDHA enhanced MSC functions to ameliorate diabetes-caused pericyte loss in diabetic retinopathy by increasing their density in retina in db/db mice. Discussion: Our findings provide a novel strategy for improving therapy for diabetes and diabetic retinopathy using 7S,14R-diHDHA-primed MSCs.

12.
Mol Reprod Dev ; 80(1): 59-69, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23150429

RESUMO

Uterine decidualization, characterized by stromal cell proliferation and differentiation into polyploid decidual cells, is critical to the establishment of pregnancy in mice, although the mechanism underlying this process remains poorly understood. This study is the first to investigate the expression of gamma-amino butyric acid (GABA) and the GABA A-type receptor π subunit (GABPR) in the early-pregnancy mouse uterus and their roles in decidualization. The expression of GABRP was detected from Day 4 to 8 of pregnancy. The effects of GABA and GABA A-type receptor on cell proliferation and apoptosis were investigated using the Cell Titer 96® AQueous One Solution Cell Proliferation Assay and flow cytometry. The levels of cyclin D3 protein were measured in cultured stromal cells artificially induced to undergo decidualization, and treated with GABA and a GABA A-type receptor agonist or antagonist, respectively, at the same time. mRNA expression of gabrp in implantation sites was lower than that in inter-implanted sites. GABA and GABRP protein were localized in the luminal and glandular epithelium, stromal cells, and decidual cells. In vitro, GABPR protein level was decreased in cultured stromal cells during the decidualization process. The addition of GABA and the GABA A-type receptor agonist Muscimol inhibited stromal cell proliferation, promoted apoptosis, and arrested cells in S-phase, followed by decreased expression of cyclin D3. These results show that in mice, GABA was actively involved in inhibiting stromal cell proliferation and suppresses decidualization progress through GABA A-type receptors by down-regulating cyclin D3 level.


Assuntos
Ciclina D3/metabolismo , Decídua/fisiologia , Receptores de GABA-A/metabolismo , Células Estromais/fisiologia , Útero/fisiologia , Ácido gama-Aminobutírico/metabolismo , Animais , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/fisiologia , Processos de Crescimento Celular/efeitos dos fármacos , Processos de Crescimento Celular/fisiologia , Decídua/citologia , Decídua/efeitos dos fármacos , Decídua/metabolismo , Regulação para Baixo , Feminino , Citometria de Fluxo , Agonistas de Receptores de GABA-A/farmacologia , Antagonistas de Receptores de GABA-A/farmacologia , Camundongos , Células Estromais/citologia , Células Estromais/efeitos dos fármacos , Útero/citologia , Útero/efeitos dos fármacos , Útero/metabolismo , Ácido gama-Aminobutírico/farmacologia
13.
Ther Apher Dial ; 27(6): 1079-1087, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37424269

RESUMO

OBJECTIVE: To investigate the effect of sodium thiosulfate (STS) on serum calcification factors in patients undergoing maintenance hemodialysis. METHODS: Forty-four Patients were randomly divided into control group (n = 22) and observation group (n = 22) by envelope method (block 4 randomization). The control group received routine treatment while observation group was treated with STS on the basis of routine treatment. The biochemical indicators, including BUN, UA, SCr, Ca2+ , P3- , calcium-phosphorus product, PTH, hs-CRP, TG, TC, HDL, LDL, and serum calcification factor MGP, FA, FGF-23, and OPG levels were compared before and after treatment. RESULTS: Control group had no statistically significant difference in the levels of vascular calcification factors MGP, FA, FGF-23, and OPG before and after treatment (p > 0.05). Whereas observation group had higher levels of MGP and FA, and lower levels of FGF-23 and OPG after treatment than before treatment (p < 0.05). The levels of MGP and FA in observation group were higher than those in control group, and FGF-23 and OPG were lower than those in control group (p < 0.05). CONCLUSION: It is speculated that sodium thiosulfate can alleviate the progression of vascular calcification by changing the levels of calcification factors.


Assuntos
Diálise Renal , Calcificação Vascular , Humanos , Diálise Renal/métodos , Tiossulfatos/farmacologia , Tiossulfatos/uso terapêutico , Calcificação Vascular/etiologia , Proteína C-Reativa
14.
Chin J Nat Med ; 21(8): 589-598, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37611977

RESUMO

Total glucosides of Rhizoma Smilacis Glabrae (RSG) are selective immunosuppressants that exhibit primary efficacy in the treatment of rheumatoid arthritis through targeted inhibition of activated T cells. In this study, we aimed to investigate the potential application of RSG in the treatment of psoriasis and elucidate its mechanism of action and material basis. Our findings revealed significant improvements upon administration of RSG in an imiquimod (IMQ)-induced psoriasis model. These improvements were characterized by a remarkable increase in the number of tail scales in mice and a substantial amelioration of skin erythema, ulceration, and flaking. By transcriptome sequencing and T-cell flow sorting assay, we identified notable effects of RSG on the modulation of various cellular processes. Specifically, RSG prominently down-regulated the Th17/Treg ratio in damaged skin tissues and reduced the proportion of G2 phase cells. Furthermore, RSG exhibited a stimulatory effect on the proliferation and differentiation of epithelial cells. Of particular interest, we discovered that ß-sitosterol, sitostenone, stigmasterol, smiglanin, and cinchonain Ib displayed potent inhibitory effects on the IL-17-mediated inflammatory response in HaCaT cells. In summary, our study highlights the therapeutic potential of RSG in the treatment of psoriasis, attributed to its ability to regulate the Th17/Treg balance. These findings contribute to the development of new indications for RSG and provide a solid theoretical foundation for further exploration in this field.


Assuntos
Artrite Reumatoide , Psoríase , Animais , Camundongos , Linfócitos T Reguladores , Psoríase/tratamento farmacológico , Bioensaio , Glucosídeos/farmacologia
15.
J Biol Chem ; 286(6): 4349-56, 2011 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-21148315

RESUMO

Pregnancy loss is a serious social and medical issue, with one important cause associated with aberrant embryo implantation during early pregnancy. However, whether and how the process of embryo implantation is affected by environmental factors such as stress-induced sympathetic activation remained elusive. Here we report an unexpected, transient effect of ß(2)-adrenoreceptor (ß(2)-AR) activation (day 4 postcoitus) in disrupting embryo spacing at implantation, leading to substantially increased midterm pregnancy loss. The abnormal embryo spacing could be prevented by pretreatment of ß(2)-AR antagonist or genetic ablation of ß-AR. Similar ß(2)-AR activation at day 5 postcoitus, when implantation sites have been established, did not affect embryo spacing or pregnancy outcome, indicating that the adverse effect of ß(2)-AR activation is limited to the preimplantation period before embryo attachment. In vitro and in vivo studies demonstrated that the transient ß(2)-AR activation abolished normal preimplantation uterine contractility without adversely affecting blastocyst quality. The contractility inhibition is mediated by activation of the cAMP-PKA pathway and accompanied by specific down-regulation of lpa3, a gene previously found to be critical for uterine contraction and embryo spacing. These results indicated that normal uterine contraction-mediated correct intrauterine embryo distribution is crucial for successful ongoing pregnancy. Abnormal ß(2)-AR activation at early pregnancy provided a molecular clue in explaining how maternal stress at early stages could adversely affect the pregnancy outcome.


Assuntos
Blastocisto/metabolismo , Implantação do Embrião , Perda do Embrião/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Receptores Adrenérgicos beta 2/metabolismo , Estresse Fisiológico , Animais , Blastocisto/patologia , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Perda do Embrião/patologia , Feminino , Masculino , Camundongos , Gravidez , Resultado da Gravidez
16.
Front Psychol ; 13: 912970, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35874382

RESUMO

Self-efficacy is crucial for successful self-regulated learning, particularly in an online environment, yet research on self-efficacy for online self-regulated learning has received relatively little empirical attention in the language education domain. In this study, we investigated the dynamic features of English as a Foreign Language (EFL) university students' self-efficacy for self-regulated learning (SESRL) in the online environment, and explored the influencing factors on SESRL. Multiple sources of data (questionnaires, reflective journals, and semi-structured interviews) over a period of one semester were collected, analysed, and triangulated. Our results demonstrated that most students displayed a relatively constant and high self-efficacy for self-regulated online learning, and that a few students also experienced an increased or decreased SESRL. Thematic analysis further revealed a variety of task-, learner-, course-, and technology-level factors contributing to learners' self-efficacy beliefs for self-regulated online learning. Our findings thus offer pedagogical implications for self-regulated foreign language learning in an online context.

17.
Front Psychol ; 13: 899400, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35800938

RESUMO

The present study adopted a novel parallel-process growth mixture modeling (GMM) technique to research the adaptive interaction between foreign language learners' learning motivation and emotions, with a view to advancing our understanding of how language learning motivation and emotions (enjoyment and anxiety) adaptively interact with each other over time. The present study, situated in the Chinese English as a foreign language (EFL) learning context, collected learning motivation and emotion data from 176 Chinese EFL learners over a period of two semesters (12 months). The GMM technique adopted in the study identified three developmental profiles of motivation and two of emotions, respectively. The study further distilled salient patterns of motivation-emotion interaction over time, patterns significant for designing and implementing pedagogical interventions for motivation enhancement. The parallel-process GMM technique was also proven to be a useful approach to parsing learner variety and learning heterogeneity, efficiently summarizing the complex, dynamic processes of motivation and emotion development.

18.
Environ Res ; 111(6): 757-60, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21663901

RESUMO

Five brands of new enamel household paints from Taiwan were analyzed: two multi-nationals and three local. The median lead concentration of 2574 parts per million (ppm) dry weight was more than 30 times the current US standard of 90ppm for new paints and was more than 4 times the former standard of 600ppm. Lead levels ranged from below detection (4.5ppm) to 158,000ppm. Lead concentrations varied significantly by color of paint and paint brand but not by price per liter. Fifty-six percent of Taiwan paints had lead levels above the 90ppm US limit. One of the multi-national brands and two of the local brands had high levels of lead with the averages ranging from 12,890 to 53,640ppm. Concentrations were less than 90ppm in each of the samples from the other two brands. One of the two multi-national paint brands was imported as the house brand for its big box store in Taipei and had lead levels above 600ppm in four of five samples. Comparison of the lead concentrations of paints from Taiwan with those that we previously analyzed from mainland China revealed higher levels in Taiwan where the median level was 2574ppm compared to 46ppm in mainland China.


Assuntos
Chumbo/análise , Pintura/análise , China , Habitação , Taiwan
19.
Front Nutr ; 8: 714690, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34926540

RESUMO

Background and Aims: To investigate the relationship among maternal demographic and clinical characteristics, gestational and postpartum oral glucose tolerance test (ppOGTT) results in patients with gestational diabetes mellitus (GDM). Methods: Patients with gestational diabetes mellitus from January 1, 2016, to August 31, 2019, were enrolled. General characteristics, dietary energy intake, pre-gestational body mass index (BMI), gestational oral glucose tolerance test (gOGTT), and 42 days ppOGTT results of all participants were collected. The relationships among maternal clinical characteristics, fasting glucose of gOGTT (gOGTT-FPG), 1 h postprandial glucose of gOGTT (gOGTT-1h PG), 2 h postprandial glucose of gOGTT (gOGTT-2h PG), and maternal postpartum glucose outcomes were evaluated. Results: A total of 156 patients with GDM were included in this study. Among them, 73.7% had inadequate daily total energy intake, an insufficient ratio of carbohydrates and protein, and an excessive fat ratio. Most of the patients (81.4%) were normal in their ppOGTT examination. Less than 20% of the patients (16.7%) were in the pre-diabetic situation, and 3 patients (1.9%) had diabetes. Pre-pregnancy BMI of patients with GDM was a risk factor for increased gOGTT-FPG levels. Those who were overweight before pregnancy had a greater risk for a higher gOGTT-FPG compared to those who had normal pre-pregnancy BMI (P = 0.021, odds ratio [OR] = 4.583). Abnormal gOGTT-2hPG was a risk factor for abnormal ppOGTT (P = 0.04). Those who had an elevated gOGTT-2hPG (≧8.5 mmol/L) had a 2.426 times higher risk for abnormal ppOGTT than those who had normal gOGTT-2hPG (<8.5 mmol/L) results. Conclusion: For women who are overweight before pregnancy, it is better to control their BMI to normal before getting pregnant. Women who had abnormal gOGTT-2h PG should pay more attention to the ppOGTT results.

20.
Front Pharmacol ; 12: 778072, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35273491

RESUMO

Objective: The present study aimed to investigate the effects of irbesartan and amlodipine besylate tablets on the intestinal microflora of rats with hypertensive renal damage. Methods: Eighteen 12-week-old male spontaneous hypertensive rats were randomly divided into three groups. The Ai-HDG group was given irbesartan at 15 mg/kg per day by gavage, the Ci-HDG group was given amlodipine besylate tablets at 1 mg/kg per day by gavage, and the Wi-HDG group, i.e., the control, was given the same dose of distilled water per day by gavage. The treatment lasted for 6 weeks. Six 12-week-old male Wistar-Kyoto rats were used as the reference group. Bacterial DNA was extracted from the feces of all the rats for high-throughput sequencing before and after the experiment. Operational taxonomic units were used to analyze the species of the intestinal flora, and the alpha diversity index was used to analyze the diversity. The relative abundance of the intestinal microflora in each group of rats was therefore analyzed at the phylum and genus levels. Results: Compared with the Wi-HDG group, the alpha diversity of the Ai-HDG group increased (p < 0.05), while in the Ci-HDG group, only the Shannon index increased significantly. At the phylum level, compared with the control group, in the Ai-HDG and Ci-HDG groups, Firmicutes (F) decreased, Bacteroides (B) increased, and the F/B ratio decreased (p < 0.05). At the genus level, compared with the Wi-HDG group, the Ai-HDG and Ci-HDG groups did not show a significantly delayed decline in lactic acid bacteria. However, in the Ai-HDG group, the relative abundance of Bifidobacteria increased. Conclusion: After the administration of irbesartan and amlodipine besylate, the disorder of intestinal flora in the rats with hypertensive renal damage improved. However, irbesartan was better than amlodipine besylate at improving the diversity of the intestinal flora in these rats.

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