Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 61
Filtrar
1.
Front Mol Neurosci ; 17: 1366855, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38685914

RESUMEN

As wireless communication devices gain popularity, concerns about the potential risks of environmental exposure to complex frequency electromagnetic radiation (EMR) on mental health have become a public health issue. Historically, EMR research has predominantly focused on single- frequency electromagnetic waves, neglecting the study of multi-frequency electromagnetic waves, which more accurately represent everyday life. To address these concerns, our study compared the emotional effects of single-frequency and dual-frequency EMR while exploring potential molecular mechanisms and intervention targets. Our results revealed that single-frequency EMR at 2.65 or 0.8 GHz did not induce anxiety-like behavior in mice. However, exposure to dual-frequency EMR at 2.65/0.8 GHz significantly led to anxiety-like behavior in mice. Further analysis of mouse sera revealed substantial increases in corticosterone and corticotrophin releasing hormone levels following exposure to 2.65/0.8 GHz EMR. Transcriptome sequencing indicated a significant decrease in the expression of Cnr1, encoding cannabinoid receptor 1 Type (CB1R), in the cerebral. This finding was consistently verified through western blot analysis, revealing a substantial reduction in CB1R content. Additionally, a significant decrease in the endocannabinoid 2-arachidonoylglycerol was observed in the cerebral cortex. Remarkably, administering the cannabinoid receptor agonist Win55-212-2 significantly alleviated the anxiety-like behavior, and the cannabinoid receptor antagonist AM251 effectively counteracted the anti-anxiety effects of Win55-212-2. In summary, our research confirmed that dual-frequency EMR is more likely to induce anxiety-like behavior in mice than single-frequency EMR, with implications for the hypothalamic-pituitary-adrenal axis and the endocannabinoid system. Furthermore, our findings suggest that Win55-212-2 may represent a novel avenue for researching and developing anti-EMR drugs.

2.
Biochim Biophys Acta Mol Basis Dis ; 1870(4): 167059, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38336104

RESUMEN

Oviductal smooth muscle exhibits spontaneous rhythmic contraction (SRC) and controls the passage of the ova at the exact time, but its mechanistic regulation remains to be determined. In this study, female mice with Ano1SMKO (smooth muscle-specific deletion of Ano1) had reduced fertility. Deficiency of Ano1 in mice resulted in impaired oviductal SRC function and reduced calcium signaling in individual smooth muscle cells in the oviduct. The Ano1 antagonist T16Ainh-A01 dose-dependently inhibited SRCs and [Ca2+]i in the oviducts of humans and mice. A similar inhibitory effect of SRCs and [Ca2+]i was observed after treatment with nifedipine. In our study, ANO1 acted primarily as an activator or amplifier in [Ca2+]i and contraction of tubal smooth muscle cells. We found that tubal SRC was markedly attenuated in patients with ectopic pregnancy. Then, our study was designed to determine whether chloride channel Ano1-mediated smooth muscle motility is associated with tubal SRC. Our findings reveal a new mechanism for the regulation of tubal motility that may be associated with abnormal pregnancies such as ectopic pregnancies.


Asunto(s)
Calcio , Músculo Liso , Animales , Femenino , Humanos , Ratones , Embarazo , Calcio/metabolismo , Canales de Cloruro/genética , Canales de Cloruro/metabolismo , Músculo Liso/metabolismo , Miocitos del Músculo Liso/metabolismo , Oviductos/metabolismo
3.
Cell Death Dis ; 14(11): 779, 2023 11 27.
Artículo en Inglés | MEDLINE | ID: mdl-38012141

RESUMEN

Mitochondria have been identified to be involved in oxidative phosphorylation, lipid metabolism, cell death, and cell proliferation. Previous studies have demonstrated that mitoguardin (Miga), a mitochondrial protein that governs mitochondrial fusion, mitochondria-endoplasmic reticulum (ER) contacts, lipid formation, and autophagy, is crucial for ovarian endocrine and follicular development. Nevertheless, whether mammalian MIGA1 or MIGA2 (MIGA1,-2) regulates ovarian granulosa cell proliferation remains unclear. This study revealed that mammalian MIGA1,-2 promotes cell proliferation and regulates the phosphorylation and localization of Yes-associated protein 1 (YAP1) in ovarian granulosa cells. MIGA2 upregulation resulted in reduced YAP1 activity, while MIGA2 removal led to increased YAP1 activity. Further analysis indicated that MIGA1,-2 regulated YAP1 via the Hippo signaling pathway and regulated protein kinase B (AKT) activity in collaboration with YAP1. In addition, lysophosphatidic acid (LPA) regulated MIGA2 expression and AKT activity by activating YAP1. Briefly, we demonstrated that the mitochondrial MIGA1 and MIGA2, especially MIGA2, promoted cellular proliferation by activating AKT and regulating the Hippo/YAP1 signaling pathway in ovarian granulosa cells, which may contribute to the molecular pathogenesis of reproductive endocrine diseases, such as polycystic ovary syndrome (PCOS).


Asunto(s)
Proteínas de la Membrana , Proteínas Mitocondriales , Síndrome del Ovario Poliquístico , Proteínas Proto-Oncogénicas c-akt , Animales , Femenino , Humanos , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proliferación Celular , Células de la Granulosa/metabolismo , Vía de Señalización Hippo , Síndrome del Ovario Poliquístico/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Factores de Transcripción/metabolismo , Proteínas Mitocondriales/metabolismo , Proteínas de la Membrana/metabolismo
4.
Antimicrob Agents Chemother ; 67(5): e0172122, 2023 05 17.
Artículo en Inglés | MEDLINE | ID: mdl-37022169

RESUMEN

Data on the distribution of voriconazole (VRC) in the human peritoneal cavity are sparse. This prospective study aimed to describe the pharmacokinetics of intravenous VRC in the peritoneal fluid of critically ill patients. A total of 19 patients were included. Individual pharmacokinetic curves, drawn after single (first dose on day 1) and multiple (steady-state) doses, displayed a slower rise and lower fluctuation of VRC concentrations in peritoneal fluid than in plasma. Good but variable penetration of VRC into the peritoneal cavity was observed, and the median (range) peritoneal fluid/plasma ratios of the area under the concentration-time curve (AUC) were 0.54 (0.34 to 0.73) and 0.67 (0.63 to 0.94) for single and multiple doses, respectively. Approximately 81% (13/16) of the VRC steady-state trough concentrations (Cmin,ss) in plasma were within the therapeutic range (1 to 5.5 µg/mL), and the corresponding Cmin,ss (median [range]) in peritoneal fluid was 2.12 (1.39 to 3.72) µg/mL. Based on the recent 3-year (2019 to 2021) surveillance of the antifungal susceptibilities for Candida species isolated from peritoneal fluid in our center, the aforementioned 13 Cmin,ss in peritoneal fluid exceeded the MIC90 of C. albicans, C. glabrata, and C. parapsilosis (0.06, 1.00, and 0.25 µg/mL, respectively), which supported VRC as a reasonable choice for initial empirical therapies against intraabdominal candidiasis caused by these three Candida species, prior to the receipt of susceptibility testing results.


Asunto(s)
Líquido Ascítico , Enfermedad Crítica , Humanos , Voriconazol/farmacocinética , Estudios Prospectivos , Antifúngicos/farmacocinética , Candida glabrata , Pruebas de Sensibilidad Microbiana
5.
J Endocr Soc ; 7(5): bvad034, 2023 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-36936714

RESUMEN

Polycystic ovary syndrome (PCOS) is an endocrinopathy characterized by hyperandrogenism, anovulation, and polycystic ovaries, in which hyperandrogenism manifests by excess androgen and other steroid hormone abnormalities. Mitochondrial fusion is essential in steroidogenesis, while the role of mitochondrial fusion in granulosa cells of hyperandrogenic PCOS patients remains unclear. In this study, mRNA expression of mitochondrial fusion genes mitoguardin1, -2 (MIGA 1, -2) was significantly increased in granulosa cells of hyperandrogenic PCOS but not PCOS with normal androgen levels, their mRNA expression positively correlated with testosterone levels. Dihydrotestosterone (DHT) treatment in mice led to high expression of MIGA2 in granulosa cells of ovulating follicles. Testosterone or forskolin/ phorbol 12-myristate 13-acetate treatments increased expression of MIGA2 and the steroidogenic acute regulatory protein (StAR) in KGN cells. MIGA2 interacted with StAR and induced StAR localization on mitochondria. Furthermore, MIGA2 overexpression significantly increased cAMP-activated protein kinase A (PKA) and phosphorylation of AMP-activated protein kinase (pAMPK) at T172 but inhibited StAR protein expression. However, MIGA2 overexpression increased CYP11A1, HSD3B2, and CYP19A1 mRNA expression. As a result, MIGA2 overexpression decreased progesterone but increased estradiol synthesis. Besides the androgen receptor, testosterone or DHT might also regulate MIGA2 and pAMPK (T172) through LH/choriogonadotropin receptor-mediated PKA signaling. Taken together, these findings indicate that testosterone regulates MIGA2 via PKA/AMP-activated protein kinase signaling in ovarian granulosa cells. It is suggested mitochondrial fusion in ovarian granulosa cells is associated with hyperandrogenism and potentially leads to abnormal steroidogenesis in PCOS.

6.
Psychiatry Res ; 313: 114603, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35544986

RESUMEN

Adolescent depression is becoming a public health problem. In this study the association between depressive symptoms and internet usage time in adolescents was examined, with data collected from the China Education Tracking Survey (CEPS). The survey is publicly available and carried out nationwide. A logistic regression analysis was conducted with odds ratios (OR) and 95% confidence intervals (CI), the subgroup analysis examined the relationships between internet usage time and depressive symptoms. A total of 10,705 adolescents were involved, where 46.4% of them are caught by the internet for more than two hours per day. Adolescents keeping on the internet for 6-8 h per day were reported to have higher odds of depressive symptoms than adolescents who were free from it with the confounders of individual, family, and school adjusted, which were observed among groups with a medium family economic status without living with their father and with a sleep time less than nine hours. The results revealed that adolescents spending more time online had a higher risk of experiencing depression symptoms. This study suggested that it is helpful for mental health professionals to evaluate and develop prevention interventions for depressive symptoms in adolescents promptly through monitoring and managing online time.


Asunto(s)
Depresión , Uso de Internet , Adolescente , Estudios Transversales , Depresión/epidemiología , Humanos , Internet , Instituciones Académicas , Encuestas y Cuestionarios
7.
Int J Low Extrem Wounds ; 21(2): 161-173, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32527164

RESUMEN

Some patients with diabetic foot ulcers (DFUs) may suffer from depression, but the latest information regarding the incidence of depression in patients with DFUs is limited. This review aimed to provide up-to-date information concerning the incidence of depression in patients with DFUs. We searched the literature in PubMed and Web of Science databases, limited to English publications. 11 eligible studies with a total of 2117 participants were included in this review. A random-effects model was applied due to high heterogeneity. The incidence of depression in patients with DFUs ranged from 26% (95% confidence interval [CI] = 19% to 33%) to 85% (95% CI = 78% to 92%), and was 47% (95% CI = 36% to 58%) after systematically summarizing. Subgroup analyses suggested that the incidence of depression were 49% (95%CI = 35% to 63%) in Europe, 37% (95% CI = 23% to 51%) in Asia, 62% (95% CI = 48% to 76%) in North America. Additionally, the incidence of depression were 40% (95% CI = 29% to 50%) in prospective studies, 55% (95% CI = 28% to 82%) in retrospective studies, 40% (95% CI = 29% to 50%) in cross-sectional studies. Furthermore, the incidence of depression were 43% (95% CI = 25% to 60%), 49% (95% CI = 35% to 63%), 68% (95% CI = 35% to 102%), 32% (95% CI = 26% to 38%), and 28% (95% CI = 18% to 38%) in patients with DFUs assessed by the Hospital Anxiety and Depression Scale, EuroQol 5-Dimension Questionnaire, Geriatric Depression Scale, Diagnostic and Statistical Manual of Mental Disorders, 4th edition, and the Center for Epidemiologic Studies Depression Scale, respectively. The estimates were robust in the sensitivity analysis. According to the meta-regression analyses, diabetes mellitus duration (t = 0.93, P = .422), publication years (t = -0.72, P = .488), and age of subjects (t = 0.01, P = .989) were not the sources of high heterogeneity. Our meta-analysis showed nearly half of patients with DFUs had depression problems.


Asunto(s)
Diabetes Mellitus , Pie Diabético , Anciano , Estudios Transversales , Depresión/epidemiología , Depresión/etiología , Pie Diabético/diagnóstico , Pie Diabético/epidemiología , Humanos , Incidencia , Estudios Prospectivos , Estudios Retrospectivos
8.
Pharmacotherapy ; 42(1): 23-33, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34655497

RESUMEN

STUDY OBJECTIVES: This study aimed to establish a population pharmacokinetic (PPK) model of intravenous voriconazole (VRC) in critically ill patients with liver dysfunction and to explore the optimal dosing strategies in specific clinical scenarios for invasive fungal infections (IFIs) caused by common Aspergillus and Candida species. DESIGN: Prospective pharmacokinetics study. SETTING: The intensive care unit in a tertiary-care medical center. PATIENTS: A total of 297 plasma VRC concentrations from 26 critically ill patients with liver dysfunction were included in the PPK analysis. METHODS: Model-based simulations with therapeutic range of 2-6 mg/L as the plasma trough concentration (Cmin ) target and the free area under the concentration-time curve from 0 to 24 h (ƒAUC24 ) divided by the minimum inhibitory concentration (MIC) (ie, ƒAUC24 /MIC) ≥25 as the effective target were performed to optimize VRC dosing regimens for Child-Pugh class A and B (CP-A/B) and Child-Pugh class C (CP-C) patients. RESULTS: A two-compartment model with first-order elimination adequately described the data. Significant covariates in the final model were body weight on both central and peripheral distribution volume and Child-Pugh class on clearance. Intravenous VRC loading dose of 5 mg/kg every 12 h (q12h) for the first day was adequate for CP-A/B and CP-C patients to attain the Cmin target at 24 h. The maintenance dose regimens of 100 mg q12h or 200 mg q24h for CP-A/B patients and 50 mg q12h or 100 mg q24h for CP-C patients could obtain the probability of effective target attainment of >90% at an MIC ≤0.5 mg/L and achieve the cumulative fraction of response of >90% against C. albicans, C. parapsilosis, C. glabrata, C. krusei, A. fumigatus, and A. flavus. Additionally, the daily VRC doses could be increased by 50 mg for CP-A/B and CP-C patients at an MIC of 1 mg/L, with plasma Cmin monitored closely to avoid serious adverse events. It is recommended that an appropriate alternative antifungal agent or a combination therapy could be adopted when an MIC ≥2 mg/L is reported, or when the infection is caused by C. tropicalis but the MIC value is not available. CONCLUSIONS: For critically ill patients with liver dysfunction, the loading dose of intravenous VRC should be reduced to 5 mg/kg q12h. Additionally, based on the types of fungal pathogens and their susceptibility to VRC, the adjusted maintenance dose regimens with lower doses or longer dosing intervals should be considered for CP-A/B and CP-C patients.


Asunto(s)
Hepatopatías , Voriconazol , Administración Intravenosa , Antifúngicos/administración & dosificación , Antifúngicos/farmacocinética , Enfermedad Crítica , Relación Dosis-Respuesta a Droga , Humanos , Hepatopatías/tratamiento farmacológico , Pruebas de Sensibilidad Microbiana , Estudios Prospectivos , Voriconazol/administración & dosificación , Voriconazol/farmacocinética
9.
J Chemother ; 34(4): 272-276, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34904531

RESUMEN

The pharmacokinetics (PK) of several drugs including antimicrobials might be highly altered during extracorporeal membrane oxygenation (ECMO) therapy. We present the change of voriconazole (VRC) PK during ECMO in a critically ill patient who received intravenous VRC at a maintenance dose of 200 mg every 12 h for empirical antifungal therapy. Two PK profiles were drawn before and after the initiation of ECMO therapy. Though the trough levels (both C0 and C12) with ECMO were slightly lower than that without ECMO (12.58 and 12.84 vs. 14.02 µg/mL), the peak levels and the area under the concentration-time curve from 0 h to 6 h (AUC0-6) were comparable (16.36 vs. 16.06 µg/mL and 90.78 vs. 91.45 µg·h/mL, respectively), indicating that VRC plasma exposure during ECMO therapy did not greatly decrease in our patient. The circuit factors including the type of membrane should be taken into account to further identify the effects of ECMO on the PK of VRC.


Asunto(s)
Oxigenación por Membrana Extracorpórea , Administración Intravenosa , Antifúngicos/farmacocinética , Antifúngicos/uso terapéutico , Enfermedad Crítica/terapia , Humanos , Voriconazol/uso terapéutico
10.
Elife ; 102021 11 12.
Artículo en Inglés | MEDLINE | ID: mdl-34766549

RESUMEN

Exosomes may mediate cell-to-cell communication by transporting various proteins and nucleic acids to neighboring cells. Some protein and RNA cargoes are significantly enriched in exosomes. How cells efficiently and selectively sort them into exosomes remains incompletely explored. Previously, we reported that YBX1 is required in sorting of miR-223 into exosomes. Here, we show that YBX1 undergoes liquid-liquid phase separation (LLPS) in vitro and in cells. YBX1 condensates selectively recruit miR-223 in vitro and into exosomes secreted by cultured cells. Point mutations that inhibit YBX1 phase separation impair the incorporation of YBX1 protein into biomolecular condensates formed in cells, and perturb miR-233 sorting into exosomes. We propose that phase separation-mediated local enrichment of cytosolic RNA-binding proteins and their cognate RNAs enables their targeting and packaging by vesicles that bud into multivesicular bodies. This provides a possible mechanism for efficient and selective engulfment of cytosolic proteins and RNAs into intraluminal vesicles which are then secreted as exosomes from cells.


Asunto(s)
Condensados Biomoleculares/metabolismo , Exosomas/metabolismo , MicroARNs/genética , Proteína 1 de Unión a la Caja Y/genética , Humanos , MicroARNs/metabolismo , Transporte de Proteínas , Proteínas de Unión al ARN/metabolismo , Proteína 1 de Unión a la Caja Y/metabolismo
11.
Proc Natl Acad Sci U S A ; 118(42)2021 10 19.
Artículo en Inglés | MEDLINE | ID: mdl-34649994

RESUMEN

Selfish, non-long terminal repeat (non-LTR) retroelements and mobile group II introns encode reverse transcriptases (RTs) that can initiate DNA synthesis without substantial base pairing of primer and template. Biochemical characterization of these enzymes has been limited by recombinant expression challenges, hampering understanding of their properties and the possible exploitation of their properties for research and biotechnology. We investigated the activities of representative RTs using a modified non-LTR RT from Bombyx mori and a group II intron RT from Eubacterium rectale Only the non-LTR RT supported robust and serial template jumping, producing one complementary DNA (cDNA) from several templates each copied end to end. We also discovered an unexpected terminal deoxynucleotidyl transferase activity of the RTs that adds nucleotide(s) of choice to 3' ends of single- and/or double-stranded RNA or DNA. Combining these two types of activity with additional insights about nontemplated nucleotide additions to duplexed cDNA product, we developed a streamlined protocol for fusion of next-generation sequencing adaptors to both cDNA ends in a single RT reaction. When benchmarked using a reference pool of microRNAs (miRNAs), library production by Ordered Two-Template Relay (OTTR) using recombinant non-LTR retroelement RT outperformed all commercially available kits and rivaled the low bias of technically demanding home-brew protocols. We applied OTTR to inventory RNAs purified from extracellular vesicles, identifying miRNAs as well as myriad other noncoding RNAs (ncRNAs) and ncRNA fragments. Our results establish the utility of OTTR for automation-friendly, low-bias, end-to-end RNA sequence inventories of complex ncRNA samples.


Asunto(s)
ARN no Traducido/genética , ADN Polimerasa Dirigida por ARN/metabolismo , Retroelementos , Moldes Genéticos
12.
J Cell Sci ; 134(19)2021 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-34499173

RESUMEN

Protein-protein interactions are vital for executing nearly all cellular processes. To facilitate the detection of protein-protein interactions in living cells of the fission yeast Schizosaccharomyces pombe, here we present an efficient and convenient method termed the Pil1 co-tethering assay. In its basic form, we tether a bait protein to mCherry-tagged Pil1, which forms cortical filamentary structures, and examine whether a GFP-tagged prey protein colocalizes with the bait. We demonstrate that this assay is capable of detecting pairwise protein-protein interactions of cytosolic proteins and nuclear proteins. Furthermore, we show that this assay can be used for detecting not only binary protein-protein interactions, but also ternary and quaternary protein-protein interactions. Using this assay, we systematically characterized the protein-protein interactions in the Atg1 complex and in the phosphatidylinositol 3-kinase (PtdIns3K) complexes and found that Atg38 is incorporated into the PtdIns3K complex I via an Atg38-Vps34 interaction. Our data show that this assay is a useful and versatile tool and should be added to the routine toolbox of fission yeast researchers. This article has an associated First Person interview with the first author of the paper.


Asunto(s)
Proteínas de Schizosaccharomyces pombe , Schizosaccharomyces , Citoesqueleto , Humanos , Proteínas Nucleares , Schizosaccharomyces/genética , Proteínas de Schizosaccharomyces pombe/genética
13.
Sci Rep ; 11(1): 14393, 2021 07 13.
Artículo en Inglés | MEDLINE | ID: mdl-34257377

RESUMEN

Successful early embryo development requires the correct reprogramming and configuration of gene networks by the timely and faithful execution of zygotic genome activation (ZGA). However, the regulatory principle of molecular elements and circuits fundamental to embryo development remains largely obscure. Here, we profiled the transcriptomes of single zygotes and blastomeres, obtained from in vitro fertilized (IVF) or parthenogenetically activated (PA) porcine early embryos (1- to 8-cell), focusing on the gene expression dynamics and regulatory networks associated with maternal-to-zygote transition (MZT) (mainly maternal RNA clearance and ZGA). We found that minor and major ZGAs occur at 1-cell and 4-cell stages for both IVF and PA embryos, respectively. Maternal RNAs gradually decay from 1- to 8-cell embryos. Top abundantly expressed genes (CDV3, PCNA, CDR1, YWHAE, DNMT1, IGF2BP3, ARMC1, BTG4, UHRF2 and gametocyte-specific factor 1-like) in both IVF and PA early embryos identified are of vital roles for embryo development. Differentially expressed genes within IVF groups are different from that within PA groups, indicating bi-parental and maternal-only embryos have specific sets of mRNAs distinctly decayed and activated. Pathways enriched from DEGs showed that RNA associated pathways (RNA binding, processing, transport and degradation) could be important. Moreover, mitochondrial RNAs are found to be actively transcribed, showing dynamic expression patterns, and for DNA/H3K4 methylation and transcription factors as well. Taken together, our findings provide an important resource to investigate further the epigenetic and genome regulation of MZT events in early embryos of pigs.


Asunto(s)
RNA-Seq , Cigoto , Animales , Blastómeros , Fertilización In Vitro , Regulación del Desarrollo de la Expresión Génica , Oocitos , Porcinos
14.
EMBO J ; 40(15): e107497, 2021 08 02.
Artículo en Inglés | MEDLINE | ID: mdl-34169534

RESUMEN

In selective autophagy, cargo selectivity is determined by autophagy receptors. However, it remains scarcely understood how autophagy receptors recognize specific protein cargos. In the fission yeast Schizosaccharomyces pombe, a selective autophagy pathway termed Nbr1-mediated vacuolar targeting (NVT) employs Nbr1, an autophagy receptor conserved across eukaryotes including humans, to target cytosolic hydrolases into the vacuole. Here, we identify two new NVT cargos, the mannosidase Ams1 and the aminopeptidase Ape4, that bind competitively to the first ZZ domain of Nbr1 (Nbr1-ZZ1). High-resolution cryo-EM analyses reveal how a single ZZ domain recognizes two distinct protein cargos. Nbr1-ZZ1 not only recognizes the N-termini of cargos via a conserved acidic pocket, similar to other characterized ZZ domains, but also engages additional parts of cargos in a cargo-specific manner. Our findings unveil a single-domain bispecific mechanism of autophagy cargo recognition, elucidate its underlying structural basis, and expand the understanding of ZZ domain-mediated protein-protein interactions.


Asunto(s)
Péptidos y Proteínas de Señalización Intracelular/química , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Proteínas de Schizosaccharomyces pombe/química , Proteínas de Schizosaccharomyces pombe/metabolismo , Sitios de Unión , Microscopía por Crioelectrón , Péptidos y Proteínas de Señalización Intracelular/genética , Mutación , Dominios Proteicos , Schizosaccharomyces/metabolismo , Proteínas de Schizosaccharomyces pombe/genética
16.
Zhongguo Zhen Jiu ; 41(4): 371-5, 2021 Apr 12.
Artículo en Chino | MEDLINE | ID: mdl-33909355

RESUMEN

OBJECTIVE: To compare the therapeutic effect on type 2 diabetes mellitus (T2DM) complicated with angina pectoris of coronary heart disease between the combined therapy of acupuncture and western medication and the simple administration of western medication. METHODS: A total of 134 patients with T2DM and angina pectoris of coronary heart disease were randomly divided into two groups, i.e. an acupuncture plus medication group (67 cases, 3 cases dropped off) and a medication group (67 cases, 4 cases dropped off). The routine western medication was used according to symptoms in the patients of both groups. In the acupuncture plus medication group, on the base of medication, acupuncture was applied to Jianshi (PC 5), Quchi (LI 11), Neiguan (PC 6), etc. The needles were retained for 20 min in each treatment and 3 treatments of acupuncture were required weekly. The treatment was given consecutively for 8 weeks in the two groups. Separately, before and after treatment, the symptom scores of TCM were observed and the indexes were detected, including glycolipid metabolism [fasting plasma glucose (FPG), 2-h plasma glucose (2hPG), glucosylated hemoglobin (HbA1c), triacylglycerol (TG) and total cholesterol (TC)], islet ß cell function [homeostasis model assessment-ß (HOMA-ß), homeostasis model assessment-IR (HOMA-IR), fasting insulin (FINS) and insulin sensitivity index (ISI)], cardiac function indexes [cardiac output (CO), early diastolic peak velocity/late diastolic peak velocity (E/A), left ventricular end diastolic diameter (LVEDD) and left ventricular ejection fraction (LVEF)], as well as electrocardiogram QT dispersion (QTd). Besides, the clinical therapeutic effects were compared between the two groups. RESULTS: After treatment, the TCM symptom scores and the values of FPG, 2hPG, HbA1c, TG, TC, HOMA-IR, FINS, E/A and LVEDD as well as QTd were all lower than those before treatment in the two groups (P<0.05), and the levels of the above-mentioned indexes in the acupuncture plus medication group were all lower than those in the medication group (P<0.05). The values of HOMA-ß, ISI, CO and LVEF after treatment were higher than those before treatment in the two groups (P<0.05), and the levels of the above-mentioned indexes in the acupuncture plus medication group were all higher than those in the medication group (P<0.05). The total effective rate was 93.8% (60/64) in the acupuncture plus medication group, higher than 79.4% (50/63) in the medication group (P<0.05). CONCLUSION: The combined therapy of acupuncture and medication is effective in treatment of T2DM complicated with angina pectoris of coronary heart disease. Such therapy effectively improves glucolipid metabolism, islet ß cell function, cardiac function and myocardial blood supply. Its curative effect is better than the simple administration of western medicine.


Asunto(s)
Terapia por Acupuntura , Enfermedad Coronaria , Diabetes Mellitus Tipo 2 , Angina de Pecho/tratamiento farmacológico , Angina de Pecho/etiología , Glucemia , Enfermedad Coronaria/complicaciones , Enfermedad Coronaria/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Humanos , Volumen Sistólico , Función Ventricular Izquierda
17.
Reprod Domest Anim ; 56(4): 642-657, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33496347

RESUMEN

The faithful execution of molecular programme underlying oocyte maturation and meiosis is vital to generate competent haploid gametes for efficient mammalian reproduction. However, the organization and principle of molecular circuits and modules for oocyte meiosis remain obscure. Here, we employed the recently developed single-cell RNA-seq technique to profile the transcriptomes of germinal vesicle (GV) and metaphase II (MII) oocytes, aiming to discover the dynamic changes of mRNAs and long non-coding RNAs (lncRNAs) during oocyte in vitro meiotic maturation. During the transition from GV to MII, total number of detected RNAs (mRNAs and lncRNAs) in oocytes decreased. Moreover, 1,807 (602 up- and 1,205 down-regulated) mRNAs and 313 (177 up- and 136 down-regulated) lncRNAs were significantly differentially expressed (DE), i.e., more mRNAs down-regulated, but more lncRNAs up-regulated. During maturation of pig oocytes, mitochondrial mRNAs were actively transcribed, eight of which (ND6, ND5, CYTB, ND1, ND2, COX1, COX2 and COX3) were significantly up-regulated. Both DE mRNAs and targets of DE lncRNAs were enriched in multiple biological and signal pathways potentially associated with oocyte meiosis. Highly abundantly expressed mRNAs (including DNMT1, UHRF2, PCNA, ARMC1, BTG4, ASNS and SEP11) and lncRNAs were also discovered. Weighted gene co-expression network analysis (WGCNA) revealed 20 hub mRNAs in three modules to be important for oocyte meiosis and maturation. Taken together, our findings provide insights and resources for further functional investigation of mRNAs/lncRNAs in in vitro meiotic maturation of pig oocytes.


Asunto(s)
Técnicas de Maduración In Vitro de los Oocitos/veterinaria , Oocitos/fisiología , ARN Largo no Codificante/metabolismo , ARN Mensajero/metabolismo , Animales , Femenino , Regulación del Desarrollo de la Expresión Génica , Meiosis , ARN Largo no Codificante/genética , ARN Mensajero/genética , RNA-Seq/veterinaria , Transducción de Señal , Porcinos
18.
Eur J Cancer Care (Engl) ; 30(2): e13382, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33277772

RESUMEN

OBJECTIVE: To quantitatively examine the relationship between social support and suicidal ideation (SI) among patients with cancer and identify the moderators that influence the magnitude of this association. METHODS: Publications were searched in PubMed, PsycINFO, EMBASE, Cochrane Library and Chinese National Knowledge Infrastructure from database inception to May, 2020. Correlation coefficients (r) were chosen as the effect size with a random model to evaluate the overall effect size between social support and SI in patients with cancer. To assess statistical heterogeneity, we examined potential moderator variables on the social support and SI. RESULTS: A total of 881 studies were identified in initial search, and twelve studies were eligible. A negative, small but significant correlation (r = -0.22, 95% CIs: -0.30,-0.14, p < 0.001) was observed between social support and SI in patients with cancer, with a significant heterogeneity (I2  = 95.24%, Q = 231.27, p < 0.001). Moderator analyses indicated that race/ethnicity (Q(1) = 8.4, p < 0.05) and measurements of social support (Q(3) = 9.78, p < 0.05) and SI (Q(3) = 9.69, p < 0.05) significantly moderate the effect size between social support and SI. CONCLUSION: Taken together, we found a negative yet significant association between social support and SI in patients with cancer, which supported the importance of social support for the prevention of SI in patients with cancer.


Asunto(s)
Neoplasias , Ideación Suicida , Bases de Datos Factuales , Etnicidad , Humanos , Apoyo Social
19.
Theriogenology ; 159: 77-86, 2021 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-33113448

RESUMEN

Coenzyme Q10 (CoQ10) is essential to many fundamental biological processes. However, the effect of CoQ10 on meiotic maturation of pig oocytes still remains elusive. In the present study we aimed to understand the effects of CoQ10 on porcine oocyte maturation, by supplementing different concentrations of CoQ10 (25, 50 and 100 µM) into the maturation medium. We showed that CoQ10 at 50 µM had better capacity to promote the nuclear maturation of pig oocytes derived from both small and large antral follicles. Though the cleavage and blastocyst rates of parthenotes stayed stable, 50 µM CoQ10 treatment could accelerate the development of parthenotes to blastocyst stage, and increase the average cell number of blastocyst. For cumulus-oocyte complexes from large antral follicles categorized by the brilliant cresyl blue (BCB) test, 50 µM CoQ10 treatment could specifically promote the nuclear maturation of poor-quality oocytes in the BCB-negative group. Mitochondrial function of oocytes treated by 50 µM CoQ10 could be boosted, through increasing the levels of mitochondrial membrane potential, ATP production and CoQ6, and changing the pattern of mitochondrial distribution as well. Moreover, 50 µM CoQ10 treatment suppressed the level of reactive oxygen species and reduced the percentage of oocytes with early apoptosis signal. Taken together, CoQ10 could improve the meiotic maturation of pig oocytes, especially for poor-quality oocytes, mainly through enhancing mitochondrial function and suppressing oxidative stress to reduce apoptosis.


Asunto(s)
Fenómenos Biológicos , Oocitos , Animales , Blastocisto/metabolismo , Técnicas de Maduración In Vitro de los Oocitos/veterinaria , Mitocondrias/metabolismo , Oocitos/metabolismo , Estrés Oxidativo , Porcinos , Ubiquinona/análogos & derivados
20.
Nat Methods ; 17(11): 1167, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33067594

RESUMEN

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

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA