Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.934
Filtrar
1.
JAMA ; 329(4): 318-324, 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36692560

RESUMO

Importance: VEXAS (vacuoles, E1-ubiquitin-activating enzyme, X-linked, autoinflammatory, somatic) syndrome is a disease with rheumatologic and hematologic features caused by somatic variants in UBA1. Pathogenic variants are associated with a broad spectrum of clinical manifestations. Knowledge of prevalence, penetrance, and clinical characteristics of this disease have been limited by ascertainment biases based on known phenotypes. Objective: To determine the prevalence of pathogenic variants in UBA1 and associated clinical manifestations in an unselected population using a genomic ascertainment approach. Design, Setting, and Participants: This retrospective observational study evaluated UBA1 variants in exome data from 163 096 participants within the Geisinger MyCode Community Health Initiative. Clinical phenotypes were determined from Geisinger electronic health record data from January 1, 1996, to January 1, 2022. Exposures: Exome sequencing was performed. Main Outcomes and Measures: Outcome measures included prevalence of somatic UBA1 variation; presence of rheumatologic, hematologic, pulmonary, dermatologic, and other findings in individuals with somatic UBA1 variation on review of the electronic health record; review of laboratory data; bone marrow biopsy pathology analysis; and in vitro enzymatic assays. Results: In 163 096 participants (mean age, 52.8 years; 94% White; 61% women), 11 individuals harbored likely somatic variants at known pathogenic UBA1 positions, with 11 of 11 (100%) having clinical manifestations consistent with VEXAS syndrome (9 male, 2 female). A total of 5 of 11 individuals (45%) did not meet criteria for rheumatologic and/or hematologic diagnoses previously associated with VEXAS syndrome; however, all individuals had anemia (hemoglobin: mean, 7.8 g/dL; median, 7.5 g/dL), which was mostly macrocytic (10/11 [91%]) with concomitant thrombocytopenia (10/11 [91%]). Among the 11 patients identified, there was a pathogenic variant in 1 male participant prior to onset of VEXAS-related signs or symptoms and 2 female participants had disease with heterozygous variants. A previously unreported UBA1 variant (c.1861A>T; p.Ser621Cys) was found in a symptomatic patient, with in vitro data supporting a catalytic defect and pathogenicity. Together, disease-causing UBA1 variants were found in 1 in 13 591 unrelated individuals (95% CI, 1:7775-1:23 758), 1 in 4269 men older than 50 years (95% CI, 1:2319-1:7859), and 1 in 26 238 women older than 50 years (95% CI, 1:7196-1:147 669). Conclusions and Relevance: This study provides an estimate of the prevalence and a description of the clinical manifestations of UBA1 variants associated with VEXAS syndrome within a single regional health system in the US. Additional studies are needed in unselected and genetically diverse populations to better define general population prevalence and phenotypic spectrum.


Assuntos
Síndromes Mielodisplásicas , Dermatopatias Genéticas , Enzimas Ativadoras de Ubiquitina , Feminino , Humanos , Masculino , Biópsia , Registros Eletrônicos de Saúde , Prevalência , Síndromes Mielodisplásicas/complicações , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/epidemiologia , Síndromes Mielodisplásicas/genética , Enzimas Ativadoras de Ubiquitina/genética , Mutação , Estudos Retrospectivos , Exoma , Pessoa de Meia-Idade , Dermatopatias Genéticas/complicações , Dermatopatias Genéticas/diagnóstico , Dermatopatias Genéticas/epidemiologia , Dermatopatias Genéticas/genética , Estados Unidos/epidemiologia
2.
ACS Appl Mater Interfaces ; 15(3): 4652-4667, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36698266

RESUMO

Tendon injuries are some of the most commonly diagnosed musculoskeletal diseases. Tendon regeneration is sensitive to the topology of the substitute as it affects the cellular microenvironment and homeostasis. To bionic in vivo three-dimensional (3D) aligned microenvironment, an ordered 3D sandwich model was used to investigate the cell response in the tendon. First, high-resolution 3D printing provided parallel-grooved topographical cues on the hydrogel surface. Then the cells were seeded on its surface to acquire a 2D model. Afterward, an additional hydrogel coating layer was applied to the cells to create the 3D model. The interaction between cells and order structures in three-dimensions is yet to be explored. The study found that the tendon stem/progenitor cells (TSPCs) still maintain their ordering growth in the 3D model as in the 2D model. The study also found that the 3D-aligned TSPCs exhibited enhanced tenogenic differentiation through the PI3K-AKT signaling pathway and presented a less inflammatory phenotype than those in the 2D model. The in vivo implantation of such a 3D-aligned TSPC composite promoted tendon regeneration and mitigated heterotopic ossification in an Achilles defect model. These findings demonstrated that 3D-aligned TSPCs within a biomimetic topology environment are promising for functional tendon regeneration.


Assuntos
Tendão do Calcâneo , Tecidos Suporte , Tecidos Suporte/química , Engenharia Tecidual/métodos , Biomimética , Fosfatidilinositol 3-Quinases , Células-Tronco , Diferenciação Celular , Hidrogéis/química , Regeneração
3.
Behav Sci (Basel) ; 13(1)2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36661617

RESUMO

The current study aimed to understand parents' perceptions of the effects of early intensive behavioral intervention (EIBI) based on the principles of applied behavioral analysis (ABA) and the lasting outcomes for their children with Autism spectrum disorder (ASD). In particular, this study sought to examine parent perceptions of the relationship between the intensity of ABA interventions and current autism symptom severity, adaptive functioning, and school placement. The current study employed a convergent parallel mixed-methods design, which consisted of collecting, analyzing, interpreting, and combining both quantitative and qualitative data. Overall, results suggested that the intensity of previous ABA interventions was a unique predictor of current school placement. Additionally, results suggested that the intensity of previous ABA interventions was a unique predictor of adaptive skills, which was supported by parent interviews. However, the intensity of previous ABA interventions was not a unique predictor of current autism severity. Parent responses to interview questions revealed the imperative nature of the interventions and their effect on service delivery for their children with ASD. Overall, this study provided an increased understanding of parents' perceptions of the effectiveness of EIBI, which in turn may be central to understanding service utilization.

4.
Integr Cancer Ther ; 22: 15347354221144310, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36624619

RESUMO

Holothurian glycosaminoglycan (hGAG) is extracted from the body wall of the sea cucumber, and previous studies have shown many unique bioactivities of hGAG, including antitumor, anti-angiogenesis, anti coagulation, anti thrombosis, anti-inflammation, antidiabetic effect, antivirus, and immune regulation. The effects of 3W and 5W molecular weights hGAG with hematoporphyrin derivative-photodynamic therapy (HPD-PDT) on lung cancer were investigated. Human lung adenocarcinoma A549 cells were divided into 6 groups: control group, 3W molecular weight hGAG group, 5W molecular weight hGAG group, HPD-PDT group, 3W molecular weight hGAG + HPD-PDT group, and 5W molecular weight hGAG + HPD-PDT group. Cell morphology was observed under inverted phase contrast microscope. Cell proliferative activity was detected by CCK8 and cell apoptosis was assayed by Hoechst33258 staining and flow cytometry. The results showed that two different molecular weights hGAG could inhibit proliferation, promote apoptosis rates of A549 cells, and enhance the sensitivity of A549 cells to HPD-PDT. The combined use of hGAG and HPD-PDT has synergistic inhibitory effects on A549 cells, and the effects of 3W molecular weight hGAG are better than that of 5W molecular weight hGAG.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Fotoquimioterapia , Humanos , Peso Molecular , Adenocarcinoma de Pulmão/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Apoptose , Glicosaminoglicanos , Derivado da Hematoporfirina , Proliferação de Células
5.
J Agric Food Chem ; 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36655791

RESUMO

Camptothecin (CPT) is a prominent molecule in natural product research because of its application prospects in medicine and agriculture. In this study, CPT and its derivatives were discovered to be competitive inhibitors of group II and group h insect chitinases, both of which are key components of insect chitinolytic systems. CPT and 7-ethyl-10-hydroxycamptothecin (SN-38) inhibited group II chitinase from Ostrinia furnacalis (OfChtII) with Ki values of 5.1 and 2.0 µM, respectively. Results from tryptophan fluorescence spectroscopy, molecular docking analysis, and molecular dynamics simulations revealed that both CPT and SN-38 inhibit OfChtII-C1 by interacting with solvent-exposed tryptophan residues in a substrate-binding cleft. CPT exhibited high insecticidal activity toward the orthopteran pest Locusta migratoria, possibly because of the midgut metabolism of CPT, with only moderate activities toward lepidopteran pests. Even though SN-38 exhibited much lower insecticidal activities than CPT, it still showed higher inhibitory activity toward chitinase. This study reports a new molecular target of CPT and provides insights into molecular design of CPT-based insecticides against different kinds of pests.

6.
Transl Vis Sci Technol ; 12(1): 2, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36595279

RESUMO

Purpose: To establish a Beagle dog model of dry eye disease (DED). Methods: DED models were induced by surgical removal of orbital lacrimal glands and entire resection of third eyelids in the left eyes of six Beagle dogs. Intact right eyes served as self-controls. Non-anaesthetized Schirmer test (STT), tear break-up time (TBUT), and fluorescein staining grading were performed monthly after operation. Interleukin (IL)-1ß, IL-8, IL-10, and tumor necrosis factor-α (TNF-α) levels were detected in tears and conjunctiva tissues. Six months after surgery, conjunctiva and cornea were collected and histopathologically analyzed. Results: Signs of DED appeared within one month after surgery and then remained stable. STT values were significantly reduced by 88% within 3 weeks after operation and remained stable over months with 1.6 ± 0.4 mm. Mean TBUT decreased significantly within two months after operation and maintained 5.2 ± 1.1 seconds. The mean fluorescein staining score was highest at the first month and then was reduced, eventually reaching a balance with 11.0 ± 1.3 points. Elevated levels of IL-1ß, IL-8, IL-10, and TNF-α were detected in tears and conjunctivas of operated eyes. Hematoxylin and eosin staining showed cornea neovascularization in the corneal stroma with thickened stroma layer and disorganized collagen bundles. Periodic acid-Schiff staining revealed a reduced function of conjunctival goblet cells. Conclusions: A combined type of DED model on the Beagle dog was established by removal of the orbital lacrimal gland and resection of the third eyelid. This DED model is easily accessible and is stable at six-month observation. Translational Relevance: The surgery-induced Beagle dog DED model is easily accessible and stable over a relatively long time.


Assuntos
Síndromes do Olho Seco , Interleucina-10 , Cães , Animais , Fator de Necrose Tumoral alfa , Interleucina-8 , Fluoresceína
7.
Clin Res Hepatol Gastroenterol ; 47(2): 102076, 2023 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-36623769

RESUMO

BACKGROUND: Crohn's disease (CD) is characterized by non-caseating intestinal granulomas. However, the reported detection rate of granulomas on endoscopy is low. This study aimed to analyze the differences in the detection rate of granulomas in different intestinal segments and lesions in Chinese patients with CD to improve the detection rate of granulomas in clinical practice. PATIENTS AND METHODS: 113 patients with CD were analyzed retrospectively. Patients were divided into two groups: those with (n = 51) and without granulomas (n = 62) on endoscopic biopsies. Clinical information was collected from the medical records, including age; erythrocyte sedimentation rate (ESR); C-reactive protein (CRP), albumin, and hemoglobin (Hb) levels; platelet count; disease course; sex; smoking history; related operation history; Montreal classification; and lesion location, size, and shape. RESULTS: The detection rates of granulomas in different lesion shapes were significantly different (P < 0.001), with those of longitudinal ulcers and circular ulcers being higher than those of erosion and irregular ulcers. We also found that the detection rates of granulomas in ascending colon and sigmoid colon were relatively higher than other segments of the intestine, however, the difference was not statistically significant (P = 0.716). Additionally, age, sex, smoking history, Montreal classification, related surgical history, disease course, and serum biochemical indicators (ESR; platelet count; and CRP, albumin, and Hb levels) were not significantly different between the two groups. CONCLUSIONS: The detection rate of granulomas in patients with CD is related to the morphology of the intestinal lesions. Meanwhile, lesion location may be correlated with the detection rate of granulomas.

8.
Phytomedicine ; 110: 154645, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36634382

RESUMO

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic and recurrent inflammatory disorder in gastrointestinal tract. Shen Ling Bai Zhu San (SLBZS), which has a long history of use in Traditional Chinese Medicine (TCM), has been widely used to treat gastrointestinal diseases. The isolated fractions of TCM have also been proved to possess an important potential for treating diseases, which are due to their effective components. PURPOSE: In this study, we examined the possibility that SLBZS and its isolated active fractions may prevent DSS-induced colitis, and investigated the potential mechanisms by regulating genetic profile of colon. METHODS: Colitis mice were induced by 2.5% DSS for 7 days, and then SLBZS and different SLBZS extracts were administrated to protect the mice for 7 days. Body weight, diarrhea, bleeding in stool, colon length, spleen weight, cytokines of serum and colon and pathology of colon were assessed. The level of Ginsenoside Rg1, Re and Rb1 in different SLBZS extracts and qualitative analysis of n-butanol extract of SLBZS (S-Nb) was performed by HPLC and LC-MS, respectively. And the effects of S-Nb on the transcriptome in colitis were investigated. RESULTS: Our results showed that SLBZS and S-Nb significantly regained body weight, reduced DAI, splenomegaly and the length of colon and attenuated histological damage of the colon. Meanwhile, SLBZS and S-Nb markedly reduced the levels of TNF-α, IL-1ß and IL-6 and increased the level of IL-10 in serum and colon. These effects may be associated with the high levels of Ginsenoside Rg1, Re and Rb1 and rich variety of compounds in S-Nb including 6 ginsenosides, glycyrrhizin, L-tryptophan, and so on. Transcriptome analysis revealed that S-Nb selectively regulated 103 differentially expressed genes (DEGs), 36 of which were changed in DSS-induced mice. And the genes of Per2, Per3, Npy and Serpina3m were closely related to colitis and also restored by S-Nb with different extent. Remarkably, these DEGs modulated the biological functions of colitis mice, including extracellular region, response to external stimulus, MAPK signaling pathway and arginine and proline metabolism. CONCLUSIONS: These data indicated that SLBZS and S-Nb blunted DSS-induced colitis by modulating differentially expression gene profile and biological functions based on their ginsenosides and rich compounds.


Assuntos
Colite , Ginsenosídeos , Camundongos , Animais , Ginsenosídeos/farmacologia , 1-Butanol/farmacologia , Butanóis/farmacologia , Cromatografia Líquida , Espectrometria de Massas em Tandem , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/patologia , Colo/patologia , Doença Crônica , Perfilação da Expressão Gênica , Peso Corporal , Sulfato de Dextrana , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Citocinas
9.
Med Oncol ; 40(2): 73, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36607478

RESUMO

Colorectal cancer (CRC) is the third leading malignancy worldwide in both new cases and deaths. Neoadjuvant radiotherapy is the standard preoperative regimens for locally advanced patients. However, approximately 50% of patients develop recurrence and metastasis after radiotherapy, which is largely due to the radiation resistance properties of the tumor, and the internal mechanism has not been elucidated. Here we found that CEMIP expression is up-regulated in a variety of tumor types, particularly in CRC. Public databases and clinical samples revealed that CEMIP expression is significantly higher in tumor tissues than in adjacent normal tissues in patients with locally advanced CRC who received neoadjuvant chemoradiotherapy, and it is closely related to the poor prognosis. Functional characterization uncovered that downregulation of CEMIP expression can enhance the radiosensitivity of CRC cells, which is confirmed to be achieved by promoting DNA damage and apoptosis. In vivo studies further verified that CEMIP knockdown can significantly improve the radiosensitivity of subcutaneously implanted colorectal tumors in mice, suggesting that CEMIP may be a radiation-resistant gene in CRC. Mechanistically, EGFR/PI3K/Akt signaling pathway is hypothesized to play a key role in CEMIP mediating radiation resistance. These results provide a potential new strategy targeting CEMIP gene for the comprehensive treatment of locally advanced CRC patients.


Assuntos
Neoplasias Colorretais , Animais , Camundongos , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/radioterapia , Neoplasias Colorretais/metabolismo , Regulação para Baixo , Fosfatidilinositol 3-Quinases/metabolismo , Tolerância a Radiação/genética , Hialuronoglucosaminidase/genética
10.
Int Immunopharmacol ; 114: 109523, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36508916

RESUMO

AIMS: Preeclampsia (PE) is characterised by systemic vascular endothelium dysfunction. Circulating trophoblastic secretions contribute to endothelial dysfunction, resulting in PE; however, the underlying mechanisms remain unclear. Herein, we aimed to determine the potential correlation between the release of trophoblastic mitochondrial deoxyribonucleic acid (DNA) (mtDNA) and endothelium damage in PE. MATERIALS AND METHODS: Umbilical cord sera and tissues from patients with PE were investigated for inflammasome activation. Following this, trophoblastic mitochondria were isolated from HTR-8/SVneo trophoblasts under 21 % oxygen (O2) or hypoxic conditions (1 % O2 for 48 h) for subsequent treatments. Primary human umbilical veinendothelial cells (HUVECs) were isolated from the human umbilical cord and then exposed to a vehicle (phosphate-buffered saline [PBS]), mtDNA, hypo-mtDNA, or hypo-mtDNA with INF39 (nucleotide oligomerisation domain-like receptor family pyrin domain containing 3 [NLRP3]-specific inhibitor) for 12 h before flow cytometry and immunoblotting. The effects of trophoblastic mtDNA on the endothelium were further analysed in vivo using enzyme-linked immunosorbent assay (ELISA) and vascular reactivity assay. The effects of mtDNA on vascular phenotypes were also tested on NLRP3 knockout mice. RESULTS: Elevated interleukin (IL)-1ß in PE sera was accompanied by NLRP3 inflammasome activation in cord tissues. In vitro and in vivo experiments revealed that the release of trophoblastic mtDNA could damage the endothelium via NLRP3 activation, resulting in the overexpression of NLRP3, caspase-1 p20, IL-1ß p17, and gasdermin D (GSDMD); reduced endothelial nitric oxide synthase (eNOS) levels; and impaired vascular relaxation. Flow cytometric analysis confirmed that extensive cell death was induced by mtDNA, and simultaneously, a more pronounced pro-apoptotic effect was caused by hypoxia-treated trophoblastic mtDNA. The NLRP3 knockout or pharmacologic NLRP3 inhibition partially reversed tumour necrosis factor-α (TNF-α) and IL-1ß levels and endothelium-dependent vasodilation in mice. CONCLUSION: These findings demonstrate that trophoblastic mtDNA induced NLRP3/caspase-1/IL-1ß signalling activation, eNOS-related endothelial injury, and vasodilation dysfunction in PE.


Assuntos
Pré-Eclâmpsia , Doenças Vasculares , Feminino , Humanos , Camundongos , Animais , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Células Endoteliais da Veia Umbilical Humana , Trofoblastos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Caspase 1/metabolismo , DNA Mitocondrial , Interleucina-1beta/metabolismo
11.
Rev. bras. med. esporte ; 29: e2022_0334, 2023. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1407599

RESUMO

ABSTRACT Introduction: For over 100 years, elastic band training has been used in fitness training, including mainly male physical strength training, female body sculpting training, and stimulation of stages in child development. Objective: Verify the impacts of elastic band training on lower limb strength in aerobic gymnastics athletes. Methods: The method of literary data, expert interview, and logical analysis were adopted. Mainly through the logical analysis method, 20 aerobics athletes in a rhythmic gymnastics club were selected as volunteers for the experiment. They were randomly divided into the experimental and control groups and then performed a jump test for 14 weeks, involving three steps. Results: It was found that before the experiment, the athletes in the experimental group performed slightly better in the three-step approach and level 1 straight step jump than the control group. Elastic band training significantly improved trunk strength and lower limb strength. Conclusions: Factors affecting the selection of lower body strength training content for aerobic gymnastics athletes are: physical factors, training cycle factors, multi-age factors, and coaches' factors. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.


RESUMO Introdução: Há mais de 100 anos, o treinamento de banda elástica tem sido utilizado no treino de aptidão física, incluído principalmente no treinamento de força física masculina, treinamento de escultura corporal feminina e estimulação de estágios no desenvolvimento infantil. Objetivo: Verificar os impactos do treinamento com banda elástica na força dos membros inferiores em atletas de ginástica aeróbica. Métodos: Adotou-se o método de dados literários, entrevista especializada e análise lógica. Principalmente através do método de análise lógica, 20 atletas de ginástica aeróbica em um clube de ginástica rítmica foram selecionados como voluntários para o experimento. Eles foram divididos aleatoriamente no grupo experimental e no grupo de controle, e então realizaram um teste de salto por 14 semanas, envolvendo três etapas. Resultados: Verificou-se que antes do experimento, os atletas do grupo experimental tiveram um desempenho ligeiramente maior na abordagem de três etapas e salto de passo direito nível 1 do que o grupo de controle. O treinamento de banda elástica melhorou significativamente a força do tronco e a força dos membros inferiores. Conclusões: Os fatores que afetam a seleção de conteúdos de treinamento de menor força corporal para atletas de ginástica aeróbica são: fatores físicos, fatores de ciclo de treinamento, fatores de várias idades e fatores próprios dos treinadores. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.


RESUMEN Introducción: Desde hace más de 100 años, el entrenamiento con bandas elásticas se utiliza en el entrenamiento de la condición física, incluyendo principalmente el entrenamiento de la fuerza física masculina, el entrenamiento de la escultura corporal femenina y la estimulación de las etapas del desarrollo infantil. Objetivo: Verificar los impactos del entrenamiento con bandas elásticas en la fuerza de los miembros inferiores en atletas de gimnasia aeróbica. Métodos: Se adoptó el método de los datos literarios, la entrevista especializada y el análisis lógico. Principalmente mediante el método de análisis lógico, se seleccionaron 20 atletas de aeróbic de un club de gimnasia rítmica como voluntarios para el experimento. Se dividieron aleatoriamente en el grupo experimental y en el grupo de control, y luego realizaron una prueba de salto durante 14 semanas, con tres etapas. Resultados: Se comprobó que, antes del experimento, los atletas del grupo experimental rendían ligeramente mejor en la aproximación de tres pasos y en el salto de paso recto de nivel 1 que el grupo de control. El entrenamiento con bandas elásticas mejoró significativamente la fuerza del tronco y de las extremidades inferiores. Conclusiones: Los factores que afectan a la selección del contenido del entrenamiento de la fuerza de la parte inferior del cuerpo para los atletas de gimnasia aeróbica son: factores físicos, factores del ciclo de entrenamiento, factores de la edad múltiple y factores propios de los entrenadores. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

12.
Zhongguo Zhong Yao Za Zhi ; 47(22): 6175-6182, 2022 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-36471942

RESUMO

This study aims to explore the molecular mechanism of Lycium barbarum polysaccharides(LBP) in alleviating premature ovarian failure(POF) in mice via the 5'-adenosine monophosphate activated protein kinase(AMPK)/silent information regulator 1(Sirt1) signaling pathway. The POF mouse model was established by D-galactose(D-gal) injection at the back. Six groups were set up, including a normal control group, a model group, a LBP group, a 3-MA(autophagy inhibitor 3-methyladenine) group, an AMPK inhibitor group, and a LBPAMPK inhibitor group, with 15 mice in each group. After 28 continuous days of administration, enzyme-linked immunosorbent assay(ELISA) was employed to determine the levels of sex hormones [estradiol(E_2), luteinizing hormone(LH), and follicle-stimulating hormone(FSH)] in serum. The ovarian mass coefficient was measured. Senescence-associated ß-Galactosidase(SA-ß-Gal) staining and hematoxylin-eosin(HE) staining were performed for observing the state of ovarian senescence and the morphological changes of the ovary. Immunohistochemical method was used to measure the expression of the autophagy marker LC3-Ⅱ in ovarian tissue. Western blot was employed to measure the expression levels of the senescence marker p16~(INK4 a), autophagy markers(LC3-Ⅱ and Beclin-1), the autophagy substrate p62, lysosome-associated membrane protein 2(LAMP2), and the proteins in the AMPK/Sirt1 pathway and mammalian target of rapamycin complex 1(mTORC1)/UNC-51-like kinase 1 Ser757 site(Ulk1 Ser757) pathway. Compared with the normal control group, the modeling of POF decreased the ovarian granulosa cells and follicles, led to the ovarian aging and severe sex hormone secretion disorders, weakened ovarian autophagy activity, and down-regulated the expression of proteins in the AMPK/Sirt1 pathway(P<0.05). Compared with the model group, the treatment with LBP increased ovarian granulosa cells and follicles, alleviated aging and sex hormone disorders, increased autophagy activity, and activated the AMPK/Sirt1 pathway(P<0.05). Both 3-MA and AMPK inhibitor can inhibit autophagy and aggravate ovarian damage and aging in mice. AMPK inhibitor can partially attenuate the role of LBP in promoting autophagy activation and alleviating aging and ovarian tissue damage(P<0.05). LBP can alleviate the symptoms of POF induced by D-gal by promoting the activation of AMPK/Sirt1 pathway.


Assuntos
Lycium , Insuficiência Ovariana Primária , Sirtuínas , Humanos , Feminino , Camundongos , Animais , Insuficiência Ovariana Primária/induzido quimicamente , Insuficiência Ovariana Primária/tratamento farmacológico , Proteínas Quinases Ativadas por AMP/genética , Sirtuína 1/genética , Autofagia , Hormônio Foliculoestimulante/efeitos adversos , Polissacarídeos/farmacologia , Mamíferos
13.
Rev Sci Instrum ; 93(11): 113103, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36461454

RESUMO

In this study, we propose a hybrid coded-aperture and Compton camera based on cerium-doped Gd3Al2Ga3O12 (GAGG:Ce) scintillator arrays coupled with Multi-Pixel Photon Counter (MPPC) arrays. The sensitive detector of the gamma camera consists of a single GAGG:Ce crystal coupled with a single-chip MPPC unit module. An impedance bridge circuit and a 64-channel data acquisition system were employed to record the code-aperture events and Compton coincidence events. After the calibration of position and energy, the total energy resolution for 662 keV gamma-rays from 137Cs was 6.6%. The hybrid camera had the characteristics of mechanical collimation and electronic collimation at the same time. In the code aperture mode, the reconstructed images were obtained by direct deconvolution and maximum likelihood expectation maximization (MLEM) methods. In the Compton imaging mode, the energy-dependent method was applied to order the sequence of Compton scatter events. The simple back-projection algorithm and list-mode MLEM algorithm were adopted for image reconstruction. Practical performances demonstrated that the angular resolutions in two modes were measured as 5.2° and 11.4°, respectively. In addition, the hybrid camera had a desirable imaging capability in a wide energy range (32 keV-2.6 MeV) and a wide field of view (∼210° in the horizontal direction). As for the sensitivity, the camera had a commercially available sensitivity level of localizing a 137Cs point source, producing ∼0.026 µSv/h in 5 min. Furthermore, the function of distinction for different radiation sources was preliminarily realized.

14.
J Mater Chem B ; 2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36468674

RESUMO

Periodontitis is defined as a chronic inflammatory disease in which the continuous activation of oxidative stress surpasses the reactive oxygen species (ROS) scavenging capacity of the endogenous antioxidative defense system. Studies have demonstrated that ROS-scavenging biomaterials should be promising candidates for periodontitis therapy. To benefit the understanding and design of scavenging biomaterials for periodontitis, this review details the relationship between ROS and periodontitis, including direct and indirect damage, the application of ROS-scavenging biomaterials in periodontitis, including organic and inorganic ROS-scavenging biomaterials, and the various dosage forms of fabricated materials currently used for periodontal therapy. Finally, the current situation and further prospects of ROS-scavenging biomaterials in periodontal applications are summarized. Expecting that improved ROS-scavenging biomaterials could be better designed and developed for periodontal and even clinical application.

15.
Int J Biol Macromol ; 2022 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-36455823

RESUMO

Open poly(3-hydroxybutyrate) (PHB) fermentation is of great potential, and batch PHB synthesis with piperazine as the nitrogen switch has been realized. However, it is vital to explore the feasibility of continuous PHB fermentation with piperazine-contained wastewater remediation collaboratively. Here, an aerobic membrane bioreactor was constructed for consecutive PHB synthesis. The removal efficiency of piperazine decreased from 100 % to 82.6 % after three cycles, meanwhile, the PHB concentration was 0.39 g·L-1, 0.18 g·L-1, and undetected for each cycle. Microbial community analysis showed that Proteobacteria, Actinobacteriota, and Bacteroidota were the main contaminating microbes. Furthermore, three metagenome-assembled genomes related to Flavobacterium collumnare, Herbaspirillum aquaticum, and Microbacterium enclense were identified as the dominant contaminating strains. These microbes obtained nitrogenous substrates transformed by Paracoccus sp. TOH, such as amino acids and dissolved organic matter, as nutrient for accumulation. This study verified the practicability of coupling continuous PHB synthesis with industrial wastewater treatment and revealed the derivation mechanism of contaminating species, which could provide a reference for the targeted nitrogen release gene knockout of functional PHB fermentation chassis.

16.
Front Public Health ; 10: 1038391, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36568751

RESUMO

Objectives: To investigate the prevalence of adverse pregnancy outcomes (APOs) in women and the impact of pre-pregnancy couples' genital Chlamydia Trachomatis (GCT) infection and other infections on APOs. Study design: Data on genital infections were collected from the Free Pre-pregnancy Health Check (FPHC) in Shenzhen, China. Data on APOs were collected from a 1-year telephone follow-up of pregnancy status and subsequent pregnancy outcomes. Methods: APO data were used to count adverse outcomes, and logistic regression was conducted to determine the association between APOs and GCT infection. Results: From December 2018 to December 2019, among 4,429 couples who underwent FPHC; 1,925 were pregnant, and 1,816 couples were tracked for pregnancy outcomes, including 1,471 normal pregnancies and 345 (19.00%) APOs. The rest of 109 pregnant couples did not answer the phone or refused to answer the pregnancy outcome during the follow-up. Among APOs, the number of spontaneous abortions was 122 (35.36%), the number of macrosomia was 85 (24.64%), the number of low birth weight (LBW) & preterm births (PTB) was 39 (11.30%), the number of LBW was 34 (9.86%), and the number of PTB was 31 (8.99%). The prevalence of GCT infection in females and males was 4.24% [95% Confidence Interval, (CI): 3.41-5.27%] and 3.58% (95% CI: 2.79-4.57%), respectively. More than half (52.69%, 49/93) of the couples were GCT-concordant. The prevalence of APOs in couples without GCT infection was 18.74% (332/1,772). The prevalence of APOs in female GCT-discordant was 32.14% (9/28), and the prevalence of APOs in male GCT-discordant was 25% (4/16). The prevalence of APOs in GCT-concordant was 12.24% (6/49). Multivariable analysis indicated that females 30-35 years old [adjusted Odds Ratio (aOR) = 1.08, 95% CI: 1.01-1.17] and over 35 years old (aOR = 1.16, 95% CI: 1.03-1.32) were more likely to experiencing APOs. Conclusion: Although only women's age was found to be associated with APOs, the prevalence of APOs with GCT-discordant in couples, especially female GCT-discordant, was higher than in those without infection or who were GCT-concordant, suggesting that these groups, especially in older women, should be paid more attention to in follow-ups to improve reproductive health.


Assuntos
Infecções por Chlamydia , Nascimento Prematuro , Recém-Nascido , Gravidez , Feminino , Masculino , Humanos , Idoso , Adulto , Resultado da Gravidez/epidemiologia , Estudos Transversais , Chlamydia trachomatis , Infecções por Chlamydia/epidemiologia , Nascimento Prematuro/epidemiologia , Genitália
17.
Nanomaterials (Basel) ; 12(23)2022 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-36500911

RESUMO

N, S co-doped bio-carbons with a hierarchical porous structure and high surface area were prepared using a molten salt method and by adopting Entermorpha prolifera (EP) as a precursor. The structure and composition of the bio-carbons could be manipulated by the salt types adopted in the molten salt assisted pyrolysis. When the carbons were used as an activating agent for peroxydisulfate (PDS) in SMX degradation in the advanced oxidation process (AOP), the removal performance in the case of KCl derived bio-carbon (EPB-K) was significantly enhanced compared with that derived from NaCl (EPB-Na). In addition, the optimized EPB-K also demonstrated a high removal rate of 99.6% in the system that used local running water in the background, which proved its excellent application potential in real water treatment. The degradation mechanism study indicated that the N, S doping sites could enhance the surface affinity with the PDS, which could then facilitate 1O2 generation and the oxidation of the SMX. Moreover, a detailed techno-economic assessment suggested that the price of the salt reaction medium was of great significance as it influenced the cost of the bio-carbons. In addition, although the cost of EPB-K was higher (USD 2.34 kg-1) compared with that of EPB-Na (USD 1.72 kg-1), it was still economically competitive with the commercial active carbons for AOP water treatment.

18.
Opt Express ; 30(26): 46460-46470, 2022 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-36558599

RESUMO

We report a new approach to the correlation between intensity fluctuations (CIF) of light waves on weak scattering from a collection of particles with L types. Two L×L matrices called a pair-potential matrix (PPM) and a pair-structure matrix (PSM) are introduced to jointly formulate the CIF of the scattered field for the first time. We show that the CIF equals the squared modulus of the trace of the product of the PSM and the transpose of the PPM, and thus these two matrices provide sufficient amount of information to determine the CIF of the scattered field. Based on this, we further analyze the normalized version of the CIF of the scattered field. It is found that the expression of the normalized CIF can have pretty compact and profound forms in three special cases: (I) the spatial distributions of the scattering potentials of particles of different types are similar (II) the spatial distributions of the densities of particles of different types are similar (III) both the scattering potentials and the densities of particles of different types are similarly distributed in space. Finally, the effects of the off-diagonal elements of the PPM and the PSM on the normalized CIF of the scattered field are illustrated by two examples. The results show that the non-zero cross correlation between particles of different types can induce intense changes in the normalized CIF of the scattered field.

19.
Nanotechnology ; 34(10)2022 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-36562513

RESUMO

Owning to limited supply of lithium for Li-ion batteries, the development of non-Li-ion batteries (such as Na+, K+Mg2+, Ca2+, and Al3+ion batteries) has attracted significant research interest. In this work, by means of the first-principles calculations, we systematically investigated the performance of chalcogenide-terminated MXenes Ti2CT2(T = O, S, Se, and Te) as electrodes for Li-ion and non-Li-ion batteries, as well as the layer-stacking and electronic properties of Ti2CT2. We find that the stacking type of O and Te terminated Ti2C multilayers with AA stacking differs from that of S and Se terminated Ti2C multilayers with AB stacking. More importantly, Ti2CO2monolayer can be potential anode material for Na- and K-ion batteries with high capacities and very low diffusion barriers (0.03-0.11 eV), while Ti2CS2and Ti2CSe2are promising anode materials with relatively low average open circuit voltages (OCVs) for Na-, K-, and Ca-ion batteries (0.4-0.87 V). Among these materials, Ti2CS2exhibits the largest ion capacity of 616 mAh g-1. These results of our work may inspire further studies of Ti2C-MXenes multilayers as electrodes for metal-ion batteries either experimentally or theoretically.

20.
Front Pediatr ; 10: 996946, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36518778

RESUMO

Familial renal glucosuria (FRG) is a rare genetic condition featured by isolated glucosuria without hyperglycemia or other kidney diseases. It is caused by pathogenic mutations of the SGLT2 (Sodium-Glucose Cotransporter 2) gene, whose protein product is responsible for reabsorbing the majority of glucose in the early proximal convoluted tubule. Hitherto, quite an array of variants of SGLT2 have been identified in patients of FRG. In this study, we performed whole exome sequencing on three Chinese pediatric patients with FRG and uncovered three compound heterozygous variants of SGLT2: c.1333C > T (p.Q445X) and c.1130-5 C > G; c.1438G > T (p.V480F) and c.346G > A (p.V116M); c.1175C > G (p.S392C) and c.1333C > T (p.Q445X). Among the total of five variants, c.1333C > T (p.Q445X), c.1438G > T (p.V480F) and c.1175C > G (p.S392C) represented novel variants that had not been reported in any genetic databases. All five variants had extremely low allele frequencies and the amino acids loci affected by missense variants were highly conserved in vertebrate species. Bioinformatic tools predicted that all five variants might disrupt the function of SGLT2, which were likely to be causal for FRG in these patients. Our findings expand the variant spectrum of SGLT2 associated with FRG and provide novel insights into mechanism of action of this transporter, which will aid in the development of novel SGLT2 inhibitors for treatment of type 2 diabetes and cardiovascular diseases.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...