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1.
Reprod Toxicol ; 110: 172-179, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35504548

RESUMO

Zearalenone is a mycotoxin produced by fungi of the genus Fusarium, which has severe toxicity on animal and human health including reproduction. Previous study showed that zearalenone exposure inhibited oocyte polar body extrusion, while in present study we found that high dose zearalenone disturbed oocyte meiosis resumption. Our results showed that a high concentration of 100 µM zearalenone reduced the rate of germinal vesicle (GV) breakdown in mouse oocytes. Further analysis indicated that zearalenone caused the decrease of Cyclin B1 and CDK1 expression, indicating MPF activity was affected, which further induced G2/M arrest, and this could be rescued by the inhibition of Wee1 activity. We found that the oocytes under high concentration of zearalenone showed lower γ-H2A.X expression, suggesting that DNA damage repair was disturbed, which further activated of DNA damage checkpoints. This could be confirmed by the altered expression of CHK1 and CHK2 after zearalenone treatment. Moreover, the organelles such as mitochondria, ribosome, endoplasmic reticulum and Golgi apparatus were diffused from germinal vesicle periphery after zearalenone exposure, indicating that zearalenone affected protein synthesis, modification and transport, which further induced the arrest of G2/M transition. Taken together, our results showed that high dose of zearalenone exposure induced G2/M transition defect by affecting organelle function-related CHK1/2-Wee1-MPF pathway.

2.
Eur J Immunol ; 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35476255

RESUMO

The pancreas contains exocrine glands, which release enzymes (e.g., amylase, trypsin, and lipase) that are important for digestion and islets, which produce hormones. Digestive enzymes and hormones are secreted from the pancreas into the duodenum and bloodstream, respectively. Growing evidence suggests that the roles of the pancreas extend to not only the secretion of digestive enzymes and hormones but also to the regulation of intestinal homeostasis and inflammation (e.g., mucosal defense to pathogens and pathobionts). Organ crosstalk between the pancreas and intestine is linked to a range of physiological, immunological, and pathological activities, such as the regulation of the gut microbiota by the pancreatic proteins and lipids, the retroaction of the gut microbiota on the pancreas, the relationship between inflammatory bowel disease, and pancreatic diseases. We herein discuss the current understanding of the pancreas-intestinal barrier axis and the control of commensal bacteria in intestinal inflammation.

3.
Oncogenesis ; 11(1): 16, 2022 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-35418575

RESUMO

Alginate oligosaccharide (AOS) has the function to inhibit tumor progression and the sulfated modification can enhance the antitumor activity. To date, the function and mechanism of sulfated AOS (AOS-SO4) in tumors remain largely elusive. We prepared AOS by the enzymatic degradation of alginate, collected AOS-SO4 by sulfating following the canonical procedure. Using these materials, in vitro assays showed that both AOS and AOS-SO4 elicited antitumor effects in osteosarcoma cells. Sulfated modification significantly enhanced the antitumor activity. In addition, AOS-SO4 had obvious effects on cell cycle arrest, apoptosis, and autophagy induction in vitro and in vivo. Mechanistically, we observed that AOS-SO4 treatment triggered proapoptotic autophagy by inhibiting MEK1/ERK/mTOR signaling. The ERK activator reversed AOS-SO4-induced autophagy. More importantly, we found that KSR1 interacted with MEK1 and functioned as a positive regulator of MEK1 protein in osteosarcoma cells. High KSR1 expression was significantly associated with poor survival in osteosarcoma patients. Together, these results suggest that AOS-SO4 has a better antitumor effect in osteosarcoma by inhibiting MEK1/ERK/mTOR signaling, which is KSR1-dependent; thus, AOS-SO4 can be a new potential therapeutic candidate for the treatment of osteosarcoma.

4.
Development ; 149(5)2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35142352

RESUMO

Mammalian oocyte maturation is a unique asymmetric division, which is mainly because of actin-based spindle migration to the cortex. In the present study, we report that a kinesin motor KIFC1, which is associated with microtubules for the maintenance of spindle poles in mitosis, is also involved in actin dynamics in murine oocyte meiosis, co-localizing with microtubules during mouse oocyte maturation. Depletion of KIFC1 caused the failure of polar body extrusion, and we found that meiotic spindle formation and chromosome alignment were disrupted. This might be because of the effects of KIFC1 on HDAC6 and NAT10-based tubulin acetylation, which further affected microtubule stability. Mass spectroscopy analysis revealed that KIFC1 also associated with several actin nucleation factors and we found that KIFC1 was essential for the distribution of actin filaments, which further affected spindle migration. Depletion of KIFC1 leaded to aberrant expression of formin 2 and the ARP2/3 complex, and endoplasmic reticulum distribution was also disturbed. Exogenous KIFC1 mRNA supplement could rescue these defects. Taken together, as well as its roles in tubulin acetylation, our study reported a previously undescribed role of kinesin KIFC1 on the regulation of actin dynamics for spindle migration in mouse oocytes.


Assuntos
Tubulina (Proteína) , beta Carioferinas/metabolismo , Acetilação , Actinas/metabolismo , Animais , Mamíferos/metabolismo , Meiose , Camundongos , Oócitos/metabolismo , Fuso Acromático/metabolismo , Tubulina (Proteína)/metabolismo
5.
J Anal Methods Chem ; 2022: 7359197, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35083094

RESUMO

Phosphate concentration in natural water has been used as a water quality indicator, as it is one of the major nutrients for aquatic plants. However, the traditional phosphomolybdenum blue (PMB) method has limited sensitivity for visual or camera-based detection, leading to underestimation of the phosphate concentration. We present an ultralow-cost, rapid field preconcentration and digital image colorimetric sensing of low-concentration phosphate method for water analysis. A novel hand-powered paper centrifuge (paperfuge) is used for sample preparation and preconcentration. This paperfuge is made of two circular paper discs and a string. Six centrifuge tubes (CTs) originally used as glue dispensing tips with a sample capacity of ∼230 µL, are loaded on the paperfuge. After sampling, phosphate in the water sample is reacted to form PMB. Then, the reacted sample is drawn into a CT using an autopipette before the CT bottom is sealed by glue. After Oasis® HLB sorbents are added through the top of the CT, the CT top is also sealed with glue. The HLB sorbents adsorb PMB and are accumulated in the CT tip through centrifugation. The CT tips are cut and analyzed with the ImageJ software. It was found that the blue color intensity of sorbents is in a linear relationship to the phosphate concentration, with a linear range of 0-5 µM (r 2 = 0.9921) and limit of detection of 0.19 µM. In addition, this method has been applied to in-field water analysis. The results are in agreement with the standard PMB method.

6.
Toxicol Appl Pharmacol ; 436: 115882, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-35016910

RESUMO

Oocyte maturation is essential for fertilization and early embryo development, and proper organelle functions guarantee this process to maintain high-quality oocytes. The type B trichothecene nivalenol (NIV) is a mycotoxin produced by Fusarium oxysporum and is commonly found in contaminated food. NIV intake affect growth, the immune system, and the female reproductive system. Here, we investigated NIV toxicity on mouse oocyte quality. Transcriptome analysis results showed that NIV exposure altered the expression of multiple genes involved in spindle formation and organelle function in mouse oocytes, indicating its toxicity on mouse oocyte maturation. Further analysis indicated that NIV exposure disrupted spindle structure and chromosome alignment, possibly through tubulin acetylation. NIV exposure induced aberrant mitochondria distribution and reduced mitochondria number, mitochondria membrane potential (MMP), and ATP levels. In addition, NIV caused the abnormal distribution of the Golgi apparatus and altered the expression of the vesicle trafficking protein Rab11. ER distribution was also disturbed under NIV exposure, indicating the effects of NIV on protein modification and transport in oocytes. Thus, our results demonstrated that NIV exposure affected spindle structure and organelles function in mouse oocytes.


Assuntos
Desenvolvimento Embrionário/efeitos dos fármacos , Oócitos/efeitos dos fármacos , Organelas/efeitos dos fármacos , Fuso Acromático/efeitos dos fármacos , Tricotecenos/efeitos adversos , Acetilação/efeitos dos fármacos , Trifosfato de Adenosina/metabolismo , Animais , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Cromossomos/efeitos dos fármacos , Feminino , Meiose/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos ICR , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Micotoxinas/efeitos adversos , Oócitos/metabolismo , Oogênese/efeitos dos fármacos , Organelas/metabolismo , Fuso Acromático/metabolismo , Transcriptoma/efeitos dos fármacos , Tubulina (Proteína)/metabolismo
7.
Environ Res ; 207: 112219, 2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-34656638

RESUMO

Carbon capture and storage (CCS) is the key technology to reduce CO2 emissions from the conventional power systems. CCS has the flexibility, compatibility, and great potential to reduce emissions when combined with the current energy infrastructure. Through quantifying the environmental benefits of the combustion-based electricity generation system with CCS by life cycle assessment (LCA), decision-makers can grasp the contribution of upstream and downstream processes to various environmental impacts, a better trade-off between climate change and non-climate impact categories. This work reviews the LCA research on the combustion-based electricity generation system integrated with CCS in the past 10 years. These studies show that CCS can reduce the direct CO2 emissions from power plants by nearly 90%. While CCS effectively mitigates climate change, it also increases other environmental impacts to varying degrees and results in energy penalty of 15-44%. The actual greenhouse gas of the power plant is reduced by 40-80%. We further analyze a series of key issues involved in the LCA of the combustion-based electricity generation system integrated with CCS, including the functional unit, basic assumptions, system boundaries and assessment methods. Time span and the leakage need to be considered by researchers in LCA. The perspective of research needs to shift from the specific application of a single CCS to the impact assessment of large-scale deployment, and a single environment or economic discipline to interdisciplinary assessment. It is more cost-effective to realize the coordinated emission reduction between the power plant and the upstream and downstream supply chain.


Assuntos
Dióxido de Carbono , Carbono , Animais , Eletricidade , Estágios do Ciclo de Vida , Tecnologia
8.
Acta Pharmacol Sin ; 43(2): 307-315, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33911193

RESUMO

Interleukin-17A (IL-17), a potent proinflammatory cytokine, has been shown to participate in cardiac electrical disorders. Diabetes mellitus is an independent risk factor for ventricular arrhythmia. In this study, we investigated the role of IL-17 in ventricular arrhythmia of diabetic mice. Diabetes was induced in both wild-type and IL-17 knockout mice by intraperitoneal injection of streptozotocin (STZ). High-frequency electrical stimuli were delivered into the right ventricle to induce ventricular arrhythmias. We showed that the occurrence rate of ventricular tachycardia was significantly increased in diabetic mice, which was attenuated by IL-17 knockout. We conducted optical mapping on perfused mouse hearts and found that cardiac conduction velocity (CV) was significantly decreased, and action potential duration (APD) was prolonged in diabetic mice, which were mitigated by IL-17 knockout. We performed whole-cell patch clamp recordings from isolated ventricular myocytes, and found that the densities of Ito, INa and ICa,L were reduced, the APDs at 50% and 90% repolarization were increased, and early afterdepolarization (EAD) was markedly increased in diabetic mice. These alterations were alleviated by the knockout of IL-17. Moreover, knockout of IL-17 alleviated the downregulation of Nav1.5 (the pore forming subunit of INa), Cav1.2 (the main component subunit of ICa,L) and KChIP2 (potassium voltage-gated channel interacting protein 2, the regulatory subunit of Ito) in the hearts of diabetic mice. The expression of NF-κB was significantly upregulated in the hearts of diabetic mice, which was suppressed by IL-17 knockout. In neonatal mouse ventricular myocytes, knockdown of NF-κB significantly increased the expression of Nav1.5, Cav1.2 and KChIP2. These results imply that IL-17 may represent a potential target for the development of agents against diabetes-related ventricular arrhythmias.


Assuntos
Diabetes Mellitus Experimental/metabolismo , Cardiomiopatias Diabéticas/metabolismo , Interleucina-17/metabolismo , NF-kappa B/metabolismo , Remodelação Ventricular , Animais , Western Blotting , Técnicas de Inativação de Genes , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Técnicas de Patch-Clamp , Reação em Cadeia da Polimerase em Tempo Real
9.
J Gastroenterol Hepatol ; 37(1): 169-178, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34532890

RESUMO

BACKGROUND AND AIM: Diagnosis of esophageal squamous cell carcinoma (ESCC) is complicated and requires substantial expertise and experience. This study aimed to develop an artificial intelligence (AI) system for detecting superficial ESCC under multiple endoscopic imaging modalities. METHODS: Endoscopic images were retrospectively collected from West China Hospital, Sichuan University as a training dataset and an independent internal validation dataset. Images from other four hospitals were used as an external validation dataset. The AI system was compared with 11 experienced endoscopists. Furthermore, videos were collected to assess the performance of the AI system. RESULTS: A total of 53 933 images from 2621 patients and 142 videos from 19 patients were used to develop and validate the AI system. In the internal and external validation datasets, the performance of the AI system under all or different endoscopic imaging modalities was satisfactory, with sensitivity of 92.5-99.7%, specificity of 78.5-89.0%, and area under the receiver operating characteristic curves of 0.906-0.989. The AI system achieved comparable performance with experienced endoscopists. Regarding superficial ESCC confined to the epithelium, the AI system was more sensitive than experienced endoscopists on white-light imaging (90.8% vs 82.5%, P = 0.022). Moreover, the AI system exhibited good performance in videos, with sensitivity of 89.5-100% and specificity of 73.7-89.5%. CONCLUSIONS: We developed an AI system that showed comparable performance with experienced endoscopists in detecting superficial ESCC under multiple endoscopic imaging modalities and might provide valuable support for inexperienced endoscopists, despite requiring further evaluation.


Assuntos
Inteligência Artificial , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Neoplasias Esofágicas/diagnóstico por imagem , Carcinoma de Células Escamosas do Esôfago/diagnóstico por imagem , Humanos , Estudos Retrospectivos , Sensibilidade e Especificidade
10.
J Mol Cell Biol ; 14(1)2022 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-34918122

RESUMO

Leucine-rich-repeat kinase 2 (LRRK2) belongs to the Roco GTPase family and is a large multidomain protein harboring both GTPase and kinase activities. LRRK2 plays indispensable roles in many processes, such as autophagy and vesicle trafficking in mitosis. In this study, we showed the critical roles of LRRK2 in mammalian oocyte meiosis. LRRK2 is mainly accumulated at the meiotic spindle periphery during oocyte maturation. Depleting LRRK2 led to the polar body extrusion defects and also induced large polar bodies in mouse oocytes. Mass spectrometry analysis and co-immunoprecipitation results showed that LRRK2 was associated with several actin-regulating factors, such as Fascin and Rho-kinase (ROCK), and depletion of LRRK2 affected the expression of ROCK, phosphorylated cofilin, and Fascin. Further analysis showed that LRRK2 depletion did not affect spindle organization but caused the failure of spindle migration, which was largely due to the decrease of cytoplasmic actin filaments. Moreover, LRRK2 showed a similar localization pattern to mitochondria, and LRRK2 was associated with several mitochondria-related proteins. Indeed, mitochondrial distribution and function were both disrupted in LRRK2-depleted oocytes. In summary, our results indicated the critical roles of LRRK2 in actin assembly for spindle migration and mitochondrial function in mouse oocyte meiosis.


Assuntos
Actinas , Meiose , Actinas/metabolismo , Animais , GTP Fosfo-Hidrolases/metabolismo , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina , Mamíferos , Camundongos , Mitocôndrias/metabolismo , Oócitos/metabolismo
11.
Small ; 18(12): e2106712, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35098640

RESUMO

Here, a universal template-activation strategy is proposed to prepare two different types of porous carbonaceous materials for potassium ion hybrid capacitor (PIHC) anode and cathode, which is realized by only changing the type of cation (Na+ and K+ ) in the polysilicic acid-organic mixed hydrogel precursor originating from adding organic acid into Na2 SiO3 and K2 SiO3 solution, respectively. TG-IR data demonstrate that K+ exhibits a stronger etching ability for activating carbonaceous materials during the annealing process. Accordingly, a 3D carbon anode obtained with the assistance of NaOH (NPC-500) exhibits abundant edge-N doping (8.14 at%), displaying a high K-storage capacity of 314.1 mA h g-1 at 0.2 A g-1 and a capacity of 219.3 mA h g-1 at 10 A g-1 after 10000 cycles. A porous carbon particles cathode prepared in the presence of KOH (KCP-800) shows a high specific surface area (1326.8 m2 g-1 ), contributing to high PF6 - (de)adsorb capacity of 103.0 mA h g-1 at 1 A g-1 . Remarkably, the assembled NPC//KCP PIHC delivers a high energy density of 137.7 W h kg-1 at a power density of 275.4 W kg-1 even over 20 000 cycles.


Assuntos
Carbono , Potássio , Cátions , Eletrodos , Hidrogéis
12.
J Cell Signal ; 2(3): 195-205, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34604860

RESUMO

Cullin-RING E3 ubiquitin ligase 4 (CRL4) plays an essential role in cell cycle progression. Recent efforts using high throughput screening and follow up hit-to-lead studies have led to identification of small molecules 33-11 and KH-4-43 that inhibit E3 CRL4's core ligase complex and exhibit anticancer potential. This review provides: 1) an updated perspective of E3 CRL4, including structural organization, major substrate targets and role in cancer; 2) a discussion of the challenges and strategies for finding the CRL inhibitor; and 3) a summary of the properties of the identified CRL4 inhibitors as well as a perspective on their potential utility to probe CRL4 biology and act as therapeutic agents.

13.
Biol Reprod ; 105(6): 1474-1483, 2021 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-34505141

RESUMO

Mammalian oocyte quality is critical for fertilization and early embryo development. The type B trichothecene nivalenol (NIV) is a mycotoxin produced by Fusarium oxysporum, and it is commonly found with deoxynivalenol in contaminated food or feed. NIV has been shown to affect the immune system and female reproductive system, cause emesis and growth retardation. Here, we investigated the toxicity of NIV on mouse oocyte quality, as well as the protective effects of melatonin on the NIV-exposed oocytes. We found NIV exposure caused meiotic arrest and further induced the failure of polar body extrusion in mouse oocytes. Transcriptome analysis data showed that NIV exposure altered the expression of multiple pathway-related genes in oocytes, indicating its wide toxicity on oocyte maturation. Based on the RNA-seq data, we showed that NIV exposure induced oxidative stress and caused DNA damage in oocytes. Besides, autophagy, and early apoptosis were also found in NIV-exposed oocytes. Treatment with melatonin significantly ameliorated these defects through its effects on ROS level. Thus, our results demonstrated that exposure to NIV affected oocyte quality and melatonin treatment could reduce the defects caused by NIV in mouse oocytes.


Assuntos
Apoptose , Dano ao DNA , Melatonina/farmacologia , Micotoxinas/toxicidade , Oócitos/efeitos dos fármacos , Estresse Oxidativo , Substâncias Protetoras/farmacologia , Tricotecenos/toxicidade , Animais , Camundongos , Oócitos/fisiologia
14.
Cell Death Dis ; 12(10): 868, 2021 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-34556636

RESUMO

Giant cell tumor of bone (GCTB) is an aggressive osteolytic bone tumor characterized by the within-tumor presence of osteoclast-like multinucleated giant cells (MGCs), which are induced by the neoplastic stromal cells and lead to extensive bone destruction. However, the underlying mechanism of the pathological process of osteoclastogenesis in GCTB is poorly understood. Here we show that the proteoglycan Serglycin (SRGN) secreted by neoplastic stromal cells plays a crucial role in the formation of MGCs and tumorigenesis in GCTB. Upregulated SRGN expression and secretion are observed in GCTB tumor cells and patients. Stromal-derived SRGN promotes osteoclast differentiation from monocytes. SRGN knockdown in stromal cells inhibits tumor growth and bone destruction in a patient-derived orthotopic xenograft model of mice. Mechanistically SRGN interacts with CD44 on the cell surface of monocytes and thus activates focal adhesion kinase (FAK), leading to osteoclast differentiation. Importantly, blocking CD44 with a neutralizing antibody reduces the number of MGCs and suppresses tumorigenesis in vivo. Overall, our data reveal a mechanism of MGC induction in GCTB and support CD44-targeting approaches for GCTB treatment.


Assuntos
Tumor de Células Gigantes do Osso/metabolismo , Tumor de Células Gigantes do Osso/patologia , Osteogênese , Proteoglicanas/metabolismo , Proteínas de Transporte Vesicular/metabolismo , Animais , Anticorpos Neutralizantes/farmacologia , Carcinogênese/efeitos dos fármacos , Carcinogênese/genética , Carcinogênese/patologia , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Ativação Enzimática/efeitos dos fármacos , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Tumor de Células Gigantes do Osso/genética , Células Gigantes/efeitos dos fármacos , Células Gigantes/metabolismo , Células Gigantes/patologia , Humanos , Receptores de Hialuronatos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Osteogênese/efeitos dos fármacos , Osteogênese/genética , Osteossarcoma/genética , Osteossarcoma/patologia , Proteoglicanas/genética , Células RAW 264.7 , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genética , Proteínas de Transporte Vesicular/genética
15.
Ecotoxicol Environ Saf ; 225: 112783, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34544023

RESUMO

Sudan I is one of the industry dyes and widely used in cosmetics, wax agent, solvent and textile. Sudan I has multiple toxicity such as carcinogenicity, mutagenicity, genotoxicity and oxidative damage. However, Sudan I has been illegally used as colorant in food products, triggering worldwide attention about food safety. Nevertheless, the toxicity of Sudan I on reproduction, particularly on oocyte maturation is still unclear. In the present study, using mouse in vivo models, we report the toxicity effects of Sudan I on mouse oocyte. The results reflect that Sudan I exposure disrupts spindle organization and chromosomes alignment as well as cortical actin distribution, thus leading to the failure of polar body extrusion. Based on the transcriptome results, it is found that the exposure of Sudan I leads to the change in expression of 764 genes. Moreover, it's further reflected that the damaging effects of Sudan I are mediated by the destruction of mitochondrial functions, which induces the accumulated ROS to stimulate oxidative stress-induced apoptosis. As an endogenous hormone, melatonin within the ovarian follicle plays function on improving oocyte quality and female reproduction by efficiently suppressing oxidative stress. Moreover, melatonin supplementation also improves oocyte quality and increases fertilization rate during in vitro culture. Consistent with these, we find that in vivo supplementation of melatonin efficaciously suppresses mitochondrial dysfunction and the accompanying apoptosis, thus reverses oocyte meiotic deteriorations. Collectively, our results prove the reproduction toxicity of Sudan I for the exposure of Sudan I reduces the oocyte quality, and demonstrate the protective effects of melatonin against Sudan I-induced meiotic deteriorations.


Assuntos
Melatonina , Animais , Apoptose , Feminino , Meiose , Melatonina/metabolismo , Melatonina/farmacologia , Camundongos , Mitocôndrias , Naftóis , Oócitos/metabolismo , Estresse Oxidativo
16.
J Hazard Mater ; 416: 125862, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34492810

RESUMO

Di (2-ethylhexyl) phthalate (DEHP) is widely used as a plastic additive and it could induce reproduction defects and fertility in mammals as environmental endocrine disruptor. However, the effects and potential mechanism of DEHP exposure during lactation stage on follicular development of offspring are still unclear. In this study, we found that the total primordial follicle number and antral follicles in the suckling of mice exposed to DEHP during lactation was significantly reduced. RNA-seq analysis results showed that the transcription levels of genes related to steroid production, ovarian hormone secretion and oxidative stress were significantly changed, which led to a decrease in 17ß-estradiol and an increase in oxidative stress. The proportion of DNA damage marker γH2AX in the ovary of female suckling exposed to DEHP was significantly increased. We also found an increase in the level of ovarian apoptosis, and the proliferation of ovarian granulosa cells was inhibited. These alterations also lead to abnormal spindle and chromosome misalignment during oocyte maturation. Overall, our data indicate that lactation exposure to DEHP can affect the secretion of hormones and the development of antral follicles in suckling mice by affecting the secretion pathways of ovarian hormone enzymes and oxidative stress pathway.


Assuntos
Dietilexilftalato , Ovário , Animais , Dietilexilftalato/toxicidade , Estradiol , Feminino , Lactação , Camundongos , Folículo Ovariano
17.
Acta Pharmacol Sin ; 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34493812

RESUMO

Myocardial ischemia-reperfusion (I/R) injury is a pathological process characterized by cardiomyocyte apoptosis, which leads to cardiac dysfunction. Increasing evidence shows that abnormal expression of long noncoding RNAs (lncRNAs) plays a crucial role in cardiovascular diseases. In this study we investigated the role of lncRNAs in myocardial I/R injury. Myocardial I/R injury was induced in mice by ligating left anterior descending coronary artery for 45 min followed by reperfusion for 24 h. We showed that lncRNA KnowTID_00006395, termed lncRNA-6395 was significantly upregulated in the infarct area of mouse hearts following I/R injury as well as in H2O2-treated neonatal mouse ventricular cardiomyocytes (NMVCs). Overexpression of lncRNA-6395 led to cell apoptosis and the expression change of apoptosis-related proteins in NMVCs, whereas knockdown of lncRNA-6395 attenuated H2O2-induced cell apoptosis. LncRNA-6395 knockout mice (lncRNA-6395+/-) displayed improved cardiac function, decreased plasma LDH activity and infarct size following I/R injury. We demonstrated that lncRNA-6395 directly bound to p53, and increased the abundance of p53 protein through inhibiting ubiquitination-mediated p53 degradation and thereby facilitated p53 translocation to the nucleus. More importantly, overexpression of p53 canceled the inhibitory effects of lncRNA-6395 knockdown on cardiomyocyte apoptosis, whereas knockdown of p53 counteracted the apoptotic effects of lncRNA-6395 in cardiomyocytes. Taken together, lncRNA-6395 as an endogenous pro-apoptotic factor, regulates cardiomyocyte apoptosis and myocardial I/R injury by inhibiting degradation and promoting sub-cellular translocation of p53.

18.
Cell Prolif ; 54(9): e13104, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34323331

RESUMO

OBJECTIVES: RAB14 is a member of small GTPase RAB family which localizes at the endoplasmic reticulum (ER), Golgi apparatus and endosomal compartments. RAB14 acts as molecular switches that shift between a GDP-bound inactive state and a GTP-bound active state and regulates circulation of vesicles between the Golgi and endosomal compartments. In present study, we investigated the roles of RAB14 during oocyte meiotic maturation. MATERIALS AND METHODS: Microinjection with siRNA and exogenous mRNA for knock down and rescue, and immunofluorescence staining, Western blot and real-time RT-PCR were utilized for the study. RESULTS: Our results showed that RAB14 localized in the cytoplasm and accumulated at the cortex during mouse oocyte maturation, and it was also enriched at the spindle periphery. Depletion of RAB14 did not affect polar body extrusion but caused large polar bodies, indicating the failure of asymmetric division. We found that absence of RAB14 did not affect spindle organization but caused the spindle migration defects, and this might be due to the regulation on cytoplasmic actin assembly via the ROCK-cofilin signalling pathway. We also found that RAB14 depletion led to aberrant Golgi apparatus distribution. Exogenous Myc-Rab14 mRNA supplement could significantly rescue these defects caused by Rab14 siRNA injection. CONCLUSIONS: Taken together, our results suggest that RAB14 affects ROCK-cofilin pathway for actin-based spindle migration and Golgi apparatus distribution during mouse oocyte meiotic maturation.


Assuntos
Meiose/fisiologia , Oócitos/metabolismo , Oócitos/fisiologia , Oogênese/fisiologia , Proteínas rab de Ligação ao GTP/metabolismo , Actinas , Animais , Citoplasma/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Fosforilação/fisiologia , Transdução de Sinais/fisiologia , Quinases Associadas a rho/metabolismo
19.
J Cell Physiol ; 236(11): 7725-7733, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34018605

RESUMO

During mouse oocyte meiotic maturation, actin filaments play multiple roles in meiosis such as spindle migration and cytokinesis. FASCIN is shown to be an actin-binding and bundling protein, making actin filaments tightly packed and parallel-aligned, and FASCIN is involved in several cellular processes like adhesion and migration. FASCIN is also a potential prognostic biomarker and therapeutic target for the treatment of metastatic disease. However, little is known about the functions of FASCIN in oocyte meiosis. In the present study, we knocked down the expression of FASCIN, and our results showed that FASCIN was essential for oocyte maturation. FASCIN was all expressed in the different stages of oocyte meiosis, and it mainly localized at the cortex of oocytes from the GV stage to the MII stage and showed a similar localization pattern with actin and DAAM1. Depletion of FASCIN affected the extrusion of the first polar body, and we also observed that some oocytes extruded from the large polar bodies. This might have resulted from the defects of actin assembly, which further affected the meiotic spindle positioning. In addition, we showed that inhibition of PKC activity decreased FASCIN expression, indicating that FASCIN might be regulated by PKC. Taken together, our results provided evidence for the important role of FASCIN on actin filaments for spindle migration and polar body extrusion in mouse oocyte meiosis.


Assuntos
Citoesqueleto de Actina/metabolismo , Proteínas de Transporte/metabolismo , Meiose , Proteínas dos Microfilamentos/metabolismo , Oócitos/metabolismo , Corpos Polares/metabolismo , Fuso Acromático/metabolismo , Citoesqueleto de Actina/genética , Animais , Proteínas de Transporte/genética , Células Cultivadas , Feminino , Camundongos Endogâmicos ICR , Proteínas dos Microfilamentos/genética , Proteína Quinase C/metabolismo , Fuso Acromático/genética , Proteínas rho de Ligação ao GTP/metabolismo
20.
Transl Androl Urol ; 10(2): 724-733, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33718074

RESUMO

BACKGROUND: Erectile dysfunction (ED) shares common risk factors with cardiovascular disease (CVD), such as diabetes mellitus (DM) and dyslipidemia, but the relationship between the risk factors of CVD in biochemical markers and young men with ED age 20-40 years is not fully clarified. METHODS: A total of 289 ED outpatients (20-40 years old) were allocated under ED group, based on patients' complaints and physical examinations. According to the frequency matching ratio of 1:4, 1,155 male individuals (20-40 years old) without ED were set as control group. All participants were tested for lipid profiles including total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL), low density lipoprotein (LDL), blood glucose (BG), homocysteine (HCY), liver function including alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and renal function including uric acid (UA) and creatinine (CR). The study was designed to compare the two groups using an established binary logistic regression analysis model. The ED group was then subdivided into a younger ED group (20-30 years old) and an older ED group (31-40 years old) for further comparisons. RESULTS: After comparison, no obvious differences were found in medians of age, TC, TG, HDL, HCY, UA, and ALT in the two groups. Median LDL, BG, and CR were significantly higher and AST was much lower in the ED group (P<0.01). In binary logistic regression analysis, odds ratios (OR) for LDL, BG, CR, and AST were 1.279, 1.237, 1.026, and 0.978, respectively. The sensitivity value and specificity value were 43.25% and 72.56%, respectively. The medians of LDL, TG, and TC were higher and HDL was much lower in the older ED group, as compared with the younger group (P<0.05). No significant differences were displayed in medians of other biochemical markers in the above comparisons. CONCLUSIONS: Elevated LDL, BG, and CR were related factors of ED in young men. Lipid profile was significantly different between young men with ED aged 20-30 and 31-40 years.

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