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1.
Chem Biol Drug Des ; 103(5): e14536, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38725079

RESUMO

This research was designed to prospect the mechanism and impact of glycyrrhizic acid (GA) on DNA damage repair and cisplatin (CP)-induced apoptosis of melanoma cells. First, human melanoma cell SK-MEL-28 was stimulated using GA for 24, 48, and 72 h. Then, the optimal treatment time and dosage were selected. After that, cell counting kit-8 (CCK-8) was employed for testing the cell viability, flow cytometry for the apoptosis, comet assay for the DNA damage of cells, and western blot for the cleaved-Caspase3, Caspase3, Bcl-2, and γH2AX protein expression levels. The experimental outcomes exhibited that as the GA concentration climbed up, the SK-MEL-28 cell viability dropped largely, while the apoptosis level raised significantly, especially at the concentration of 100 µm. In addition, compared with GA or CPtreatment only, CP combined with GA notably suppressed the viability of melanoma cells and promoted cell apoptosis at the cytological level. At the protein level, the combined treatment notably downregulated the Bcl-2 and Caspase3 expression levels, while significantly upregulated the cleaved-Caspase3 and γH2AX expression levels. Besides, CP + GA treatment promoted DNA damage at the DNA molecular level. Collectively, both GA and CP can inhibit DNA damage repair and enhance the apoptosis of SK-MEL-28 cells, and the synergistic treatment of both exhibits better efficacy.


Assuntos
Apoptose , Cisplatino , Dano ao DNA , Reparo do DNA , Ácido Glicirrízico , Melanoma , Cisplatino/farmacologia , Humanos , Ácido Glicirrízico/farmacologia , Ácido Glicirrízico/química , Apoptose/efeitos dos fármacos , Melanoma/tratamento farmacológico , Melanoma/metabolismo , Melanoma/patologia , Linhagem Celular Tumoral , Dano ao DNA/efeitos dos fármacos , Reparo do DNA/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/química , Caspase 3/metabolismo , Sinergismo Farmacológico , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
2.
J Ovarian Res ; 17(1): 115, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38807213

RESUMO

Zinc (Zn) is a crucial trace element essential for human growth and development, particularly for reproductive health. Previous research has shown a decrease in serum zinc concentration with age and individuals with conditions such as polycystic ovary syndrome (PCOS) and diabetes mellitus. However, the specific effects of zinc deficiency on the female reproductive system, especially ovarian function, are not fully understood. In our study, we observed a significant reduction in the total number of follicles and mature follicles in the zinc deficiency group. This reduction correlated with decreased level of anti-Mullerian hormone (AMH) and abnormal gene expression affecting hormone secretion regulation. Furthermore, we found that zinc deficiency disrupted mitochondrial dynamics, leading to oxidative stress in the ovaries, which further inhibited autophagy and increased ovarian apoptosis. These changes ultimately resulted in the failure of germinal vesicle breakdown (GVBD) and reduced oocyte quality. Meanwhile, administration of zinc glycine effectively alleviated the oocyte meiotic arrest caused by dietary zinc deficiency. In conclusion, our findings demonstrated that dietary zinc deficiency can affect hormone secretion and follicle maturation by impairing mitochondrial function and autophagy.


Assuntos
Mitocôndrias , Folículo Ovariano , Zinco , Feminino , Zinco/deficiência , Zinco/metabolismo , Folículo Ovariano/metabolismo , Folículo Ovariano/crescimento & desenvolvimento , Folículo Ovariano/efeitos dos fármacos , Mitocôndrias/metabolismo , Animais , Autofagia , Oócitos/metabolismo , Oócitos/efeitos dos fármacos , Oócitos/crescimento & desenvolvimento , Hormônio Antimülleriano/metabolismo , Estresse Oxidativo , Camundongos , Apoptose , Humanos
3.
Pulm Circ ; 14(1): e12351, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38468630

RESUMO

This study aimed to evaluate the effectiveness and safety of an oral sequential triple combination therapy with selexipag after dual combination therapy with endothelin receptor antagonist (ERA) and phosphodiesterase-5 inhibitor (PDE5I)/riociguat in pulmonary arterial hypertension (PAH) patients. A total of 192 PAH patients from 10 centers had received oral sequential selexipag therapy after being on dual-combination therapy with ERA and PDE5i/riociguat for a minimum of 3 months. Clinical data were collected at baseline and after 6 months of treatment. The study analyzed the event-free survival at 6 months and all-cause death over 2 years. At baseline, the distribution of patients among the risk groups was as follows: 22 in the low-risk group, 35 in the intermediate-low-risk group, 91 in the intermediate-high-risk group, and 44 in the high-risk group. After 6 months of treatment, the oral sequential triple combination therapy resulted in reduced NT-proBNP levels (media from 1604 to 678 pg/mL), a decline in the percentage of WHO-FC III/IV (from 79.2% to 60.4%), an increased in the 6MWD (from 325 ± 147 to 378 ± 143 m) and a rise in the percentage of patients with three low-risk criteria (from 5.7% to 13.5%). Among the low-risk group, there was an improvement in the right heart remodeling, marked by a decrease in right atrium area and eccentricity index. The intermediate-low-risk group exhibited significant enhancements in WHO-FC and tricuspid annular plane systolic excursion. For those in the intermediate-high and high-risk groups, there were marked improvements in activity tolerance, as reflected by WHO-FC and 6MWD. The event-free survival rate at 6 months stood at 88%. Over the long-term follow-up, the survival rates at 1 and 2 years were 86.5% and 86.0%, respectively. In conclusion, the oral sequential triple combination therapy enhanced both exercise capacity and cardiac remodeling across PAH patients of different risk stratifications.

4.
Pharmacol Res ; 200: 107079, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38272334

RESUMO

The AIM2 inflammasome represents a multifaceted oligomeric protein complex within the innate immune system, with the capacity to perceive double-stranded DNA (dsDNA) and engage in diverse physiological reactions and disease contexts, including cancer. While originally conceived as a discerning DNA sensor, AIM2 has demonstrated its capability to discern various nucleic acid variations, encompassing RNA and DNA-RNA hybrids. Through its interaction with nucleic acids, AIM2 orchestrates the assembly of a complex involving multiple proteins, aptly named the AIM2 inflammasome, which facilitates the enzymatic cleavage of proinflammatory cytokines, namely pro-IL-1ß and pro-IL-18. This process, in turn, underpins its pivotal biological role. In this review, we provide a systematic summary and discussion of the latest advancements in AIM2 sensing various types of nucleic acids. Additionally, we discuss the modulation of AIM2 activation, which can cause cell death, including pyroptosis, apoptosis, and autophagic cell death. Finally, we fully illustrate the evidence for the dual role of AIM2 in different cancer types, including both anti-tumorigenic and pro-tumorigenic functions. Considering the above information, we uncover the therapeutic promise of modulating the AIM2 inflammasome in cancer treatment.


Assuntos
Neoplasias , Ácidos Nucleicos , Humanos , Inflamassomos/metabolismo , Ácidos Nucleicos/uso terapêutico , Neoplasias/tratamento farmacológico , DNA , RNA , Proteínas de Ligação a DNA/metabolismo
5.
J Endocr Soc ; 7(9): bvad093, 2023 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-37873498

RESUMO

Context: Paragangliomas located within the pericardium represent a rare yet challenging clinical situation. Objective: The current analysis aimed to describe the clinical characteristics of cardiac paragangliomas, with emphasis on the diagnostic approach, genetic background, and multidisciplinary management. Methods: Twenty-four patients diagnosed with cardiac paraganglioma (PGL) in Peking Union Medical College Hospital, Beijing, China, between 2003 and 2021 were identified. Clinical data was collected from medical record. Genetic screening and succinate dehydrogenase subunit B immunohistochemistry were performed in 22 patients. Results: The median age at diagnosis was 38 years (range 11-51 years), 8 patients (33%) were females, and 4 (17%) had familial history. Hypertension and/or symptoms related to catecholamine secretion were present in 22 (92%) patients. Excess levels of catecholamines and/or metanephrines were detected in 22 (96%) of the 23 patients who have completed biochemical testing. Cardiac PGLs were localized with 131I-metaiodobenzylguanidine scintigraphy in 11/22 (50%), and 99mTc-hydrazinonicotinyl-tyr3-octreotide scintigraphy in 24/24 (100%) patients. Genetic testing identified germline SDHx mutations in 13/22 (59%) patients, while immunohistochemistry revealed succinate dehydrogenase (SDH) deficiency in tumors from 17/22 (77%) patients. All patients were managed by a multidisciplinary team through medical preparation, surgery, and follow-up. Twenty-three patients received surgical treatment and perioperative death occurred in 2 cases. Overall, 21 patients were alive at follow-up (median 7.0 years, range 0.6-18 years). Local recurrence or metastasis developed in 3 patients, all of whom had SDH-deficient tumors. Conclusion: Cardiac PGLs can be diagnosed based on clinical manifestations, biochemical tests, and appropriate imaging studies. Genetic screening, multidisciplinary approach, and long-term follow-up are crucial in the management of this disease.

6.
Proc Natl Acad Sci U S A ; 120(44): e2306177120, 2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37871210

RESUMO

Lepidopterans affect crop production worldwide. The use of transgenes encoding insecticidal proteins from Bacillus thuringiensis (Bt) in crop plants is a well-established technology that enhances protection against lepidopteran larvae. Concern about widespread field-evolved resistance to Bt proteins has highlighted an urgent need for new insecticidal proteins with different modes or sites of action. We discovered a new family of insecticidal proteins from ferns. The prototype protein from Pteris species (Order Polypodiales) and variants from two other orders of ferns, Schizaeales and Ophioglossales, were effective against important lepidopteran pests of maize and soybean in diet-based assays. Transgenic maize and soybean plants producing these proteins were more resistant to insect damage than controls. We report here the crystal structure of a variant of the prototype protein to 1.98 Å resolution. Remarkably, despite being derived from plants, the structure resembles the 3-domain Cry proteins from Bt but has only two out of three of their characteristic domains, lacking the C-terminal domain which is typically required for their activities. Two of the fern proteins were effective against strains of fall armyworm that were resistant to Bt 3-domain Cry proteins Cry1Fa or Cry2A.127. This therefore represents a novel family of insecticidal proteins that have the potential to provide future tools for pest control.


Assuntos
Bacillus thuringiensis , Gleiquênias , Inseticidas , Traqueófitas , Animais , Inseticidas/metabolismo , Bacillus thuringiensis/genética , Bacillus thuringiensis/metabolismo , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Controle Biológico de Vetores , Endotoxinas/genética , Endotoxinas/metabolismo , Proteínas Hemolisinas/genética , Proteínas Hemolisinas/metabolismo , Traqueófitas/metabolismo , Zea mays/metabolismo
7.
Nat Commun ; 14(1): 4171, 2023 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-37443175

RESUMO

The broad adoption of transgenic crops has revolutionized agriculture. However, resistance to insecticidal proteins by agricultural pests poses a continuous challenge to maintaining crop productivity and new proteins are urgently needed to replace those utilized for existing transgenic traits. We identified an insecticidal membrane attack complex/perforin (MACPF) protein, Mpf2Ba1, with strong activity against the devastating coleopteran pest western corn rootworm (WCR) and a novel site of action. Using an integrative structural biology approach, we determined monomeric, pre-pore and pore structures, revealing changes between structural states at high resolution. We discovered an assembly inhibition mechanism, a molecular switch that activates pre-pore oligomerization upon gut fluid incubation and solved the highest resolution MACPF pore structure to-date. Our findings demonstrate not only the utility of Mpf2Ba1 in the development of biotechnology solutions for protecting maize from WCR to promote food security, but also uncover previously unknown mechanistic principles of bacterial MACPF assembly.


Assuntos
Besouros , Inseticidas , Animais , Inseticidas/farmacologia , Inseticidas/metabolismo , Zea mays/metabolismo , Besouros/fisiologia , Controle Biológico de Vetores , Plantas Geneticamente Modificadas/metabolismo , Animais Geneticamente Modificados , Perforina/metabolismo , Endotoxinas/metabolismo , Larva/metabolismo , Resistência a Inseticidas
8.
Kaohsiung J Med Sci ; 39(8): 811-823, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37132584

RESUMO

Skin is the first line of the body to resist pathogen invasion. A potentially fatal infection may result from problems with wound healing. Small molecule drugs like astragaloside IV (AS-IV) show pro-healing activities, but the mechanisms are not fully understood. Using real-time quantitative PCR and a western blot assay, the amount of gene expression was evaluated. The proliferation and migration of keratinocytes were determined by MTS and wound healing assay, respectively. The binding of lncRNA H19 to RBP protein ILF3 and the binding of ILF3 protein to CDK4 mRNA were confirmed by RNA immunoprecipitation. Treatment with AS-IV enhanced the expression of lncRNA H19, ILF3, and CDK4 and improved the proliferation and migration of keratinocytes HaCaT. Additionally, apoptosis of keratinocytes was attenuated by AS-IV. Further studies showed that both lncRNA H19 and ILF3 were important for AS-IV-mediated keratinocyte growth and migration. In addition, lncRNA H19 recruited ILF3 to increase CDK4 mRNA level and enhanced cell proliferation. We discovered a lncRNA H19/ILF3/CDK4 axis that is activated by AS-IV to promote keratinocyte migration and proliferation. These results elucidate the mechanism of action of AS-IV and justify its application in further application in wound healing treatment.


Assuntos
Quinase 4 Dependente de Ciclina , Queratinócitos , Proteínas do Fator Nuclear 90 , RNA Longo não Codificante , Proliferação de Células/genética , Queratinócitos/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro/genética , Células HaCaT , Humanos , Proteínas do Fator Nuclear 90/genética , Proteínas do Fator Nuclear 90/metabolismo , Quinase 4 Dependente de Ciclina/genética
9.
Front Oncol ; 12: 1020793, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36578927

RESUMO

This article described a patient with metastatic bladder cancer (mBC) who was successfully treated with nab-paclitaxel plus sintilimab. Localized muscle-invasive bladder cancer (MIBC) was discovered in a 56-year-old man who received radical cystectomy and platinum-based adjuvant chemotherapy. Eleven months after cystectomy, this patient developed numerous hepatic and pelvic metastases and progressed to mBC. The patient was given an anti-PD-1 antibody (sintilimab 200mg, q3w) in combination with Nab-paclitaxel (100mg, qw) for mBC. Complete remission (CR) was achieved after nine cycles of therapy, and the patient had no severe side effects during the treatment. The disease remained in CR after 41 months of follow-up. This case suggests that nab-paclitaxel combined with sintilimab is a safe and effective option in treatment of mBC.

10.
World J Psychiatry ; 12(11): 1323-1334, 2022 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-36438680

RESUMO

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has caused significant challenges for adolescent mental health. AIM: To survey adolescent students in China to determine the effects of the COVID-19 pandemic on their mental health. METHODS: A multicenter cross-sectional comparative investigation was conducted in March 2022. We collected demographic information and survey data related to the COVID-19 pandemic. The Patient Health Questionnaire-9 and Generalized Anxiety Disorder Screener scales were used for objective assessment of depression and anxiety. RESULTS: We collected mental health questionnaires from 3184 students. The investigation demonstrated that adolescents most strongly agreed with the following items: Increased time spent with parents, interference with academic performance, and less travel. Conversely, adolescents most strongly disagreed with the following items: Not having to go to school, feeling an increase in homework, and not socializing with people; 34.6% of adolescents were depressed before COVID-19, of which 1.9% were severely depressed. After COVID-19, 26.3% of adolescents were prone to depression, of which 1.4% were severely depressed. 24.4% of adolescents had anxiety before COVID-19, with severe anxiety accounting for 1.6%. After COVID-19, 23.5% of adolescents were prone to anxiety, of which 1.7% had severe anxiety. CONCLUSION: Chinese adolescents in different grades exhibited different psychological characteristics, and their levels of anxiety and depression were improved after the COVID-19 pandemic. Changes in educational management practices since the COVID-19 pandemic may be worth learning from and optimizing in long-term educational planning.

11.
JACC Asia ; 2(3): 247-255, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36338413

RESUMO

Background: The role of congenital thrombophilia in chronic thromboembolic pulmonary hypertension (CTEPH) remains unresolved. Objectives: The purpose of this study was to investigate the prevalence, genetic background, and clinical phenotype of congenital thrombophilia in CTEPH. Methods: In total, 367 patients with CTEPH from May 2013 to December 2020 were consecutively enrolled in this cross-sectional study in FuWai Hospital and Peking Union Medical College Hospital in China. The primary outcome was the occurrence of congenital thrombophilia diagnosed through tests for congenital anticoagulants activity (including protein C, protein S, and antithrombin III), factor V Leiden and prothrombin G20210A sequence variants. Next-generation sequencing was conducted for patients with congenital thrombophilia. Clinical phenotype was compared between patients with and without thrombophilia. Results: A total of 36 (9.8%; 95% CI: 6.8%-12.9%) patients were diagnosed as congenital thrombophilia, including 13 protein C deficiency (3.5%; 95% CI: 1.6%-5.4%), 19 protein S deficiency (5.2%; 95% CI: 2.9%-7.5%), and 4 antithrombin III deficiency (1.1%; 95% CI: 0%-2.2%). No factor V Leiden or prothrombin G20210A sequence variants were identified. Genotype for patients with thrombophilia revealed that 10 (76.9%) protein C deficiency patients were PROC sequence variant carriers, 4 (21.1%) protein S deficiency were PROS1 sequence variant carriers, and 2 (50.0%) antithrombin III deficiency were SERPINC1 sequence variant carriers. In the logistic regression model, male sex (OR: 3.24; 95% CI: 1.43-7.31) and proximal lesion in pulmonary arteries (OR: 4.10; 95% CI: 1.91-8.85) had significant differences between the congenital thrombophilia and nonthrombophilia group in CTEPH patients. Conclusions: Congenital thrombophilia was not rare. Male sex and proximal lesion in pulmonary arteries might be the specific clinical phenotype for CTEPH patients with congenital thrombophilia.

12.
Huan Jing Ke Xue ; 43(10): 4590-4600, 2022 Oct 08.
Artigo em Chinês | MEDLINE | ID: mdl-36224144

RESUMO

To understand the enrichment factors and pollution levels of heavy metals in agricultural soils in the semi-arid region of Hainan island, 1818 surface soil samples were collected in Gancheng Town and analyzed for their heavy metal contents and physicochemical composition. Correlation analysis was used to determine the heavy metal enrichment factors. The geo-accumulation index (Igeo), comprehensive ecological risk index (RI), and hazard index (HI), as well as carcinogenic risk (CR), were used to assess the degree of pollution and health risk. Positive matrix factorization (PMF) was used to determine the primary sources of pollution and priority sources. The average values of heavy metal contents in the topsoil were 22.7, 0.128, 33.4, 14.5, 0.032, 9.32, 32.5, and 43.3 mg·kg-1 for As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn, respectively. With the exception of Zn, the concentrations of other heavy metals in the topsoil were higher than the soil background values of Hainan, showing different degrees of heavy metal accumulation effect. The Igeo revealed that the major pollutant element in soils was As, followed by Cd and Cu. The RI showed that the proportion of soil samples that were high-risk level or worse was 29.4% of the total number of samples, among which As was the major source of risk. The health risk assessment results indicated that As, Cr, and Ni exposure presented carcinogenic risk for children with high CR values. Based on PMF, four major sources of heavy metals were identified in the study area. Hg was derived mainly from industrial sources, and As was closely associated with agricultural activities. Ni, Cu, Cr, and Zn were related to soil parent materials. Pb and Cd were associated with agricultural activities and traffic emissions. The PMF models combined with correlation analysis were useful for estimating the source apportionment of heavy metals in soils.


Assuntos
Mercúrio , Metais Pesados , Poluentes do Solo , Cádmio/análise , Carcinógenos/análise , Criança , China , Monitoramento Ambiental/métodos , Humanos , Chumbo/análise , Mercúrio/análise , Metais Pesados/análise , Medição de Risco , Solo/química , Poluentes do Solo/análise
14.
Pak J Med Sci ; 38(5): 1292-1297, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35799762

RESUMO

Objective: To observe the clinical efficacy of external ventricular drain combined with intraventricular urokinase injection and intravenous piracetam in the treatment of intraventricular hemorrhage. Methods: A randomized controlled trial was used in this study conducted at Baoding First Central Hospital, China from January 2017 to December 2019. Sixty patients with intraventricular hemorrhage were randomly divided into two groups. Patients in the control group were treated with external ventricular drain, while patients in the experimental group were given intraventricular urokinase injection and intravenous piracetam on the basis of the control group. The incidence of adverse drug reactions, hospitalization time, hematoma elimination time, and drainage tube removal time in two groups were compared and analyzed including the cerebrospinal fluid protein content, changes in GCS score, neurological function recovery (ADL score), and Glasgow outcome scale (GOS) of the two groups after treatment. Results: The hematoma elimination time, drainage tube removal time and hospitalization time of the experimental group were shorter than those of the control group, with a statistically significant difference (P<0.05). After treatment, compared with the control group, the protein content of cerebrospinal fluid in the experimental group decreased more significantly (P=0.00), the GCS score was higher (P=0.00), the overall good rate of neurological function was higher (P=0.04), while the rate of good prognosis was higher (P=0.03). Within one month of treatment, the incidence of surgical complications in experimental group was significantly lower than that in control group (P=0.04). Conclusions: External ventricular drain combined with intraventricular urokinase injection and intravenous piracetam is an effective method for the treatment of intraventricular hemorrhage, which is worthy of clinical promotion.

15.
Sci Rep ; 12(1): 10398, 2022 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-35729160

RESUMO

Extensive evidence has explored the involvement of microRNAs (miRNAs) in osteosarcoma (OS). Limitedly, the concrete function of microRNA-18b-5p (miR-18b-5p) in OS remains unexplored and largely elusive. Here, we validated that miR-18b-5p significantly elevated in OS via analyzing the data from GEO database. The results showed that miR-18b-5p was overexpressed in human OS tissues and cell lines. The clinical evidence suggested that high level of miR-18b-5p was negatively correlated with the poor prognosis of OS. Meanwhile, miR-18b-5p upregulation facilitated the proliferation and metastasis of OS cells in vitro and in vivo. The mechanism exploration demonstrated that miR-18b-5p acted as a potential inhibitor of PHF2, a tumor suppressor gene, at post-transcriptional level. Moreover, hypoxia induced gene expression of miR-18b-5p was clarified to be transcriptionally mediated by HIF-1α. The clinicopathological analysis in samples of OS patients further supported that miR-18b-5p had a positive correlation with HIF-1α expression, and negative correlation with PHF2. Collectively, the present study uncovered a new molecular mechanism of OS tumorigenesis and development and miR-18b-5p might be a prognostic biomarker and potential therapeutic target for OS treatment.


Assuntos
Neoplasias Ósseas , Proteínas de Homeodomínio , MicroRNAs , Osteossarcoma , Neoplasias Ósseas/genética , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Osteossarcoma/genética , Osteossarcoma/metabolismo , Osteossarcoma/patologia
16.
J Cell Mol Med ; 26(10): 2895-2907, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35373434

RESUMO

Pyroptosis is associated with various cardiovascular diseases. Increasing evidence suggests that long noncoding RNAs (lncRNAs) have been implicated in gene regulation, but how lncRNAs participate in the regulation of pyroptosis in the heart remains largely unknown. In this study, we aimed to explore the antipyroptotic effects of lncRNA FGF9-associated factor (FAF) in acute myocardial infarction (AMI). The expression patterns of lncRNA FAF, miR-185-5p and P21 activated kinase 2 (PAK2) were detected in hypoxia/ischaemia-induced cardiomyocytes. Hoechst 33342/PI staining, lactate dehydrogenase (LDH) release assay, immunofluorescence and Western blotting were conducted to assay cell pyroptosis. The interaction between lncRNA FAF, miR-185-5p and PAK2 was verified by bioinformatics analysis, small RNA sequencing luciferase reporter assay and qRT-PCR. The expression of LncRNA FAF was downregulated in hypoxic cardiomyocytes and myocardial tissues. Overexpression of lncRNA FAF could attenuate cardiomyocyte pyroptosis, improve cell viability and reduce infarct size during the procession of AMI. Moreover, lncRNA FAF was confirmed as a sponge of miR-185-5p and promoted PAK2 expression in cardiomyocytes. Collectively, our findings reveal a novel lncRNA FAF/miR-185-5p/PAK2 axis as a crucial regulator in cardiomyocyte pyroptosis, which might be a potential therapeutic target of AMI.


Assuntos
MicroRNAs , Infarto do Miocárdio , Miócitos Cardíacos , RNA Longo não Codificante , Quinases Ativadas por p21 , Apoptose , Humanos , Hipóxia/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Infarto do Miocárdio/genética , Infarto do Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Piroptose/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Quinases Ativadas por p21/genética , Quinases Ativadas por p21/metabolismo
17.
J Mol Cell Cardiol ; 166: 91-106, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35235835

RESUMO

Adult mammals have limited potential for cardiac regeneration after injury. In contrast, neonatal mouse heart, up to 7 days post birth, can completely regenerate after injury. Therefore, identifying the key factors promoting the proliferation of endogenous cardiomyocytes (CMs) is a critical step in the development of cardiac regeneration therapies. In our previous study, we predicted that mitogen-activated protein kinase (MAPK) interacting serine/threonine-protein kinase 2 (MNK2) has the potential of promoting regeneration by using phosphoproteomics and iGPS algorithm. Here, we aimed to clarify the role of MNK2 in cardiac regeneration and explore the underlying mechanism. In vitro, MNK2 overexpression promoted, and MNK2 knockdown suppressed cardiomyocyte proliferation. In vivo, inhibition of MNK2 in CMs impaired myocardial regeneration in neonatal mice. In adult myocardial infarcted mice, MNK2 overexpression in CMs in the infarct border zone activated cardiomyocyte proliferation and improved cardiac repair. In CMs, MNK2 binded to eIF4E and regulated its phosphorylation level. Knockdown of eukaryotic translation initiation factor (eIF4E) impaired the proliferation-promoting effect of MNK2 in CMs. MNK2-eIF4E axis stimulated CMs proliferation by activating cyclin D1. Our study demonstrated that MNK2 kinase played a critical role in cardiac regeneration. Over-expression of MNK2 promoted cardiomyocyte proliferation in vitro and in vivo, at least partly, by activating the eIF4E-cyclin D1 axis. This investigation identified a novel target for heart regenerative therapy.


Assuntos
Fator de Iniciação 4E em Eucariotos , Infarto do Miocárdio , Proteínas Serina-Treonina Quinases/metabolismo , Animais , Ciclina D1/metabolismo , Fator de Iniciação 4E em Eucariotos/metabolismo , Mamíferos/metabolismo , Camundongos , Infarto do Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Fosforilação
18.
Ying Yong Sheng Tai Xue Bao ; 33(1): 248-254, 2022 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-35224947

RESUMO

To explore the differences between growth and population dynamics of natural Lycorma delicatula in the plantations and semi-natural forests, the susceptible stages and major suppression factors were determined to provide basis for the prediction and controlling the pest. The development duration and life table of L. delicatula in different habitats were established by using tracking method. The index of exclusion effect for lethal factors and the K-value in each development stage were calculated. The population trends were analyzed through the survival curve and key drivers of population change. The results showed that the development duration of L. delicatula in the plantation habitat and semi-natural habitat was significantly different, with thelatter being 25.7 d longer than the former. There were significant differences in the development duration of 1st-3rd-instars nymphs and pre-oviposition period of adults between these two habitats, but no significant difference in the 4th-instar nymphs. The total mortality rate in the plantation habitat and semi-natural habitat was 83.6% and 98.6%, respectively. The index of population trend in the plantation habitat was significantly higher than that in the semi-natural habitat. The population of L. delicatula increased sharply in the plantation habitat, but showed a decline trend in the semi-natural habitat. All of the survival curves of L. delicatula were Deevey-Ⅲ type, and the EIPCs of the "parasitic natural enemies" in egg stage were the highest in both habitats as 1.3 and 1.6, and the total K values were 0.2 and 0.3, respectively. The regression slopes of K-value of natural enemies were the highest (both 0.6). These findings revealed that the semi-natural habitat played an important role in the natural regulation of L. delicatula.


Assuntos
Hemípteros , Animais , Ecossistema , Feminino , Florestas , Tábuas de Vida , Ninfa , Oviposição
19.
Ecotoxicol Environ Saf ; 230: 113105, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34954678

RESUMO

Simazine is a triazine pesticides that typically detected in ground water and soil, and can reportedly affect reproductive health in humans and animals. However, the effect of simazine on female germ cell development remains unclear. In the present study, we observed that simazine exposure decreased oocyte maturation competence and embryonic developmental capacity. Importantly, simazine exposure disrupted microtubule stability and actin polymerization, resulting in failure of spindle assembly and migration. In addition, simazine exposure impaired mitochondrial function and cytosolic Ca2+ homeostasis in both oocyte and 2-cell embryos, thus increasing the levels of reactive oxygen species (ROS). Moreover, simazine exposure induced DNA damage and early apoptosis during oocyte maturation. Collectively, our results demonstrate that simazine exposure-induced mitochondrial dysfunction and apoptosis are major causes of poor oocytes quality.

20.
Int J Ophthalmol ; 14(12): 1935-1940, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34926211

RESUMO

AIM: To evaluate the long-term effect of foldable capsular vitreous body (FCVB) in the treatment of severe ocular rupture to provide a practical basis for clinical selection. METHODS: A total of 26 patients (26 eyes), 23 men and 3 women, with severe ocular rupture who underwent FCVB implantation between March 2018 and September 2018 were retrospectively analysed. All open ocular wounds located in zone III, with preoperative visual acuity grade IV and above (Snellen less than 4/200). The best corrected visual acuity (BCVA), intraocular pressure (IOP), cornea, anterior chamber, iris, lens, choroid, and retina were evaluated before and after the surgery. The subjective feeling and the location of FCVB were also assessed. RESULTS: The average age of the 26 patients was 36y (20-60y). Postoperative follow-up was from 10 to 14mo. At the end of follow up, BCVA was light perception (LP) in 10 cases, no light perception (NLP) in 13 cases, hand motions (HM) in 3 cases. IOP was 11±5 mm Hg. Corneal degeneration was in 3 cases and corneal endothelial dystrophy was in 7 cases. Shallow anterior chamber was in 8 cases and hyphema was in 8 cases. Organized membrane in the pupil was in 14 cases. Epiphora occurred in 3 cases. FCVB drainage tube exposed in 3 cases. All FCVBs were in their normal location and no rejection occurred. CONCLUSION: FCVB implantation is a long-term effective treatment and may provide a practical selection for severe ocular rupture.

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