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1.
Oncology ; 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38262380

RESUMO

INTRODUCTION: The study explored the effects of SHOX2 and RASSF1A DNA methylation in lung cancer (LC). METHOD: Bronchoalveolar lavage fluid (BALF) samples as well as LC and normal adjacent tissues were collected from 72 LC patients and 35 patients with benign pulmonary nodules. Quantitative analysis of SHOX2 and RASSF1A DNA methylation was performed in benign pulmonary nodules and different stages of LC. The diagnostic value of SHOX2 and RASSF1A DNA methylation in LC and benign pulmonary nodules was determined by receiver operating characteristics analysis. Gain/loss-of-function experiments were constructed in LC cells and mouse models of xenograft and pulmonary nodule metastasis. The levels of SHOX2 and transfer-associated genes were tested through qRT-PCR and Western blot. Malignant phenotype of LC cells were assessed by functional experiment. The tumor volume and weight of mice in xenograft models were measured. Pulmonary nodule metastasis was determined through HE staining assay. 5-Azacytidine appeared as a positive control drug. RESULT: SHOX2 DNA methylation or RASSF1A DNA methylation had a diagnostic efficiency in pulmonary nodules and early LC, with the two combined had better diagnostic value. SHOX2 expression was upregulated in LC. Similar to 5-Azacytidine, SHOX2 knockdown inhibited LC cell viability, migration and invasion in vitro as well as restrained LC tumorigenesis and pulmonary nodule metastasis in vivo, whereas overexpressed SHOX2 had the opposite effects. CONCLUSION: The combination of SHOX2 and RASSF1A DNA methylation had a diagnostic value in pulmonary nodules and early LC. SHOX2 positively modulated the tumorigenesis and metastasis of LC by regulating DNA methylation processes.

2.
Int J Mol Sci ; 25(3)2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38338959

RESUMO

Hydropericardium hepatitis syndrome (HHS) is primarily caused by fowl adenovirus serotype 4 (FAdV-4), causing high mortality in chickens. Although vaccination strategies against FAdV-4 have been adopted, HHS still occurs sporadically. Furthermore, no effective drugs are available for controlling FAdV-4 infection. However, type I and III interferon (IFN) are crucial therapeutic agents against viral infection. The following experiments were conducted to investigate the inhibitory effect of chicken IFN against FadV-4. We expressed recombinant chicken type I IFN-α (ChIFN-α) and type III IFN-λ (ChIFN-λ) in Escherichia coli and systemically investigated their antiviral activity against FAdV-4 infection in Leghorn male hepatocellular (LMH) cells. ChIFN-α and ChIFN-λ dose dependently inhibited FAdV-4 replication in LMH cells. Compared with ChIFN-λ, ChIFN-α more significantly inhibited viral genome transcription but less significantly suppressed FAdV-4 release. ChIFN-α- and ChIFN-λ-induced IFN-stimulated gene (ISG) expression, such as PKR, ZAP, IRF7, MX1, Viperin, IFIT5, OASL, and IFI6, in LMH cells; however, ChIFN-α induced a stronger expression level than ChIFN-λ. Thus, our data revealed that ChIFN-α and ChIFN-λ might trigger different ISG expression levels, inhibiting FAdV-4 replication via different steps of the FAdV-4 lifecycle, which furthers the potential applications of IFN antiviral drugs in chickens.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Doenças das Aves Domésticas , Animais , Masculino , Galinhas , Interferon-alfa/farmacologia , Interferon-alfa/genética , Sorogrupo , Adenoviridae/genética , Antivirais/farmacologia , Doenças das Aves Domésticas/tratamento farmacológico
3.
Cell Biol Int ; 46(11): 1900-1914, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35989484

RESUMO

Ras-association domain family 1A (RASSF1A) is one of the most methylated genes in lung cancer (LC). We investigate whether the high DNA methylation level of RASSF1A can relieve the resistance of RASSF1A to LC by inhibiting RASSF1A's transcription factor binding to RASSF1A. RASSF1A expression in tissues and cells was tested utilizing quantitative real-time polymerase chain reaction (qRT-PCR), and Western blot. RASSF1A expression and RASSF1A methylation level in LC cells exposed to 5-Aza-dc were assessed by qRT-PCR and quantitative methylation-specific PCR. The association between CTCF and RASSF1A was assessed using hTFtarget, ChIP, and luciferase reporter gene analysis. The effects of 5-Aza-dc, CTCF, and RASSF1A on cell biological behaviors and epithelial-mesenchymal transition (EMT)-related markers were assessed by cell function experiments and Western blot. Moreover, we constructed the xenograft tumor and pulmonary nodule metastasis models, and assessed tumor volume and weight. RASSF1A expression and pulmonary nodule metastasis were tested utilizing qRT-PCR, Western blot, and H&E staining. RASSF1A was under-expressed in LC tissues and cells. 5-Aza-dc enhanced RASSF1A level and weakened RASSF1A methylation level in LC cells. RASSF1A silencing neutralized 5-Aza-dc-mediated repressing effects on LC cell biological function and EMT. The loss of CTCF binding to RASSF1A in LC cells was associated with DNA methylation. The effect of 5-Aza-dc on RASSF1A level, LC cell malignant behaviors, and EMT-related factors were strengthened by CTCF upregulation. RASSF1A overexpression suppressed LC tumor growth and pulmonary nodule metastasis in vivo. DNA methylation blocked the modulation of RASSF1A expression by CTCF and relieved the resistance of RASSF1A to LC.


Assuntos
Fator de Ligação a CCCTC/metabolismo , Metilação de DNA , Neoplasias Pulmonares , Azacitidina/farmacologia , Linhagem Celular Tumoral , Humanos , Neoplasias Pulmonares/genética , Regiões Promotoras Genéticas , Fatores de Transcrição/metabolismo , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo
4.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 39(11): 1211-1215, 2022 Nov 10.
Artigo em Chinês | MEDLINE | ID: mdl-36317205

RESUMO

OBJECTIVE: To investigate the clinical significance of miRNA-146, OX-LDL and ROS in patients with primary ovarian insufficiency (POI). METHODS: 100 patients with POI were prospectively collected and 100 women with normal ovarian function were randomly selected as control group. Serum miRNA-146 expression level was detected by qRT-PCR and serum OX-LDL and ROS expression levels were detected by ELISA. Ovarian granulosa cells of mouse were transfected with miRNA-146 mimics or inhibitors, and then treated with OX-LDL. Cell viability, colony forming ability, apoptosis rate and toll like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) of pathway proteins were evaluated respectively. RESULTS: Compared with control group, the expression level of miRNA-146 in POI group was significantly lower, the expression level of OX-LDL and ROS were significantly higher, and the ovarian volume and peak systolic blood flow velocity of ovarian artery were significantly decreased in POI group. Upregulation of miRNA-146 expression had a protective effect on OX-LDL injured ovarian granulosa cells, as evidenced by increased ovarian granulosa cell viability and colony number, reduced apoptosis, and downregulation of TLR4/NF-κB expression. CONCLUSION: miRNA-146 can target downstream TLR4/NF-κB signaling pathway affects oxidative stress and inflammatory response of POI induced by OX-LDL and ROS, and is expected to become a biomarker for early prediction of POI and a new target for treatment.


Assuntos
MicroRNAs , Insuficiência Ovariana Primária , Humanos , Feminino , Camundongos , Animais , Receptor 4 Toll-Like/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Espécies Reativas de Oxigênio/farmacologia , Insuficiência Ovariana Primária/genética , Apoptose/genética
5.
BMC Vet Res ; 16(1): 363, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32993639

RESUMO

BACKGROUND: Gut microbes significantly contribute to nutrient digestion and absorption, intestinal health and immunity, and are essential for the survival and environmental adaptation of wild animals. However, there are few studies on the gut microbiota of captive and wild North China leopard (Panthera pardus japonensis). RESULTS: A total of 10 mainly bacterial phyla were identified in the fecal microbiota of North China leopard, Lachnoclostridium (p = 0.003), Peptoclostridium (p = 0.005), Bacteroides (p = 0.008), Fusobacterium (p = 0.017) and Collinsella (p = 0.019) were significantly higher than those of wild North China leopard. Distinct differences in the fecal metabolic phenotypes of captive and wild North China leopard were found, such as content of l-methionine, n-acetyl-l-tyrosine, pentadecanoic acid and oleic acid. Differentially abundant gut microbes were associated with fecal metabolites, especially the bacteria in Firmicutes and Bacteroidetes, involved in the metabolism of N-acetyl-L-alanine and D-quinovose. CONCLUSION: This study reports for the first time the differences in gut microbiota abundance between captive and wild North China leopard, as well as significant differences in fecal metabolic phenotypes between two groups.


Assuntos
Fezes/microbiologia , Microbioma Gastrointestinal , Panthera/microbiologia , Animais , Animais Selvagens/metabolismo , Animais Selvagens/microbiologia , Animais de Zoológico/metabolismo , Animais de Zoológico/microbiologia , Bactérias/classificação , Bactérias/genética , China , Fezes/química , Feminino , Masculino , Metaboloma , Panthera/metabolismo , RNA Ribossômico 16S/genética
6.
Biochem Biophys Res Commun ; 503(4): 2590-2596, 2018 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-30017197

RESUMO

BACKGROUND: Ingredients in breast milk can help establish a healthy community of microorganisms in the infant gut, but no research exists regarding the effects of goat milk feeding and breast feeding on the gut microbiome of the Amur tiger, which is one of the most endangered species in the world. METHODS: In this study, we used whole-metagenome shotgun sequencing to analyze the effects of two different feeding patterns, goat milk feeding and breast feeding, on the composition and functional structures of gut microbiota in Amur tiger cubs. RESULTS: Goat milk-fed cubs have fewer beneficial bacteria and more pathogenic bacteria and a higher microbial diversity in their gut than breastfed cubs. A total of 15 genera showed statistically significant differences; the relative abundances of Streptomyces scabiei, Streptomyces avermitilis and Streptomyces davawensis were significantly decreased, whereas those of Niabella soli, Aeromonas media and Brochothrix thermosphacta were significantly increased in the goat milk-fed group compared with those in the breastfed group. At the functional level, carbohydrate metabolism, translation and replication and repair decreased, and amino acid metabolism, membrane transport and metabolism of cofactors and vitamins increased in the gut microbiota of goat milk-fed cubs compared with breastfed cubs. CONCLUSION: Our results indicate for the first time that the different milk feeding patterns of goat milk feeding and breast feeding can change the composition and functional structures of gut microbiota in Amur tiger cubs and that breastfed tiger cubs and goat milk-fed tiger cubs have distinct microbiotas in their guts.


Assuntos
Microbioma Gastrointestinal , Cabras , Metagenômica/métodos , Leite , Tigres , Animais , Animais Recém-Nascidos , Bactérias/isolamento & purificação , Comportamento Alimentar , Cabras/microbiologia , Tigres/microbiologia
7.
Biochem Biophys Res Commun ; 499(3): 447-453, 2018 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-29596832

RESUMO

BACKGROUND: The Amur tiger is one of the most endangered species in the world, and the healthy population of captive Amur tigers assists the recovery of the wild population. Gut microbes have been shown to be important for human disease and health, but little research exists regarding the microbiome of Amur tigers in captivity. METHODS: In this study, we used an integrated approach of 16S rRNA gene sequencing combined with ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS)-based metabolomics to analyze the effects of Fenbendazole and Ivermectin Tablets on the gut microbiota and fecal metabolic phenotype of the Amur tiger. RESULTS: The relative abundances of the bacterial genera Collinsella, Clostridium XI and Megamonas were decreased, whereas those of Escherichia and Clostridium sensu stricto were increased in experimental Amur tigers compared with those in normal controls. Meanwhile, distinct changes in the fecal metabolic phenotype of the experimental Amur tigers were also found, including lower levels of acrylic acid, acetoacetate and catechol and higher amounts of 5,6-dihydrouracil, adenine hydrochloride hydrate and galactitol. Moreover, the differentially abundant gut microbes were substantially associated with the altered fecal metabolites, especially the bacteria in the Firmicutes and Actinomycetes, which were involved in the metabolism of 5,6-dihydrouracil, 6-phospho-d-gluconate and 1-methylnicotinamide. CONCLUSION: Our results indicate for the first time that Fenbendazole and Ivermectin Tablets not only disturb the gut microbiota at the abundance level but also alter the metabolic homeostasis of the Amur tiger.


Assuntos
Fenbendazol/farmacologia , Microbioma Gastrointestinal/genética , Ivermectina/farmacologia , Espectrometria de Massas/métodos , Metabolômica , RNA Ribossômico 16S/genética , Análise de Sequência de RNA , Tigres/genética , Animais , Cromatografia Líquida , Análise Discriminante , Fezes , Análise dos Mínimos Quadrados , Fenótipo , Filogenia , Comprimidos , Tigres/microbiologia
8.
BMC Vet Res ; 14(1): 379, 2018 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-30509257

RESUMO

BACKGROUND: The gastrointestinal tracts of animals are home to large, complex communities of microbes. The compositions of these communities ultimately reflect the coevolution of microorganisms with their animal host and are influenced by the living environment, diet and immune status of the host. Gut microbes have been shown to be important for human disease and health, but little research exists in the gut microbiome of the Amur tiger, which is one of the most endangered species in the world. RESULTS: In this study, we present the use of whole-metagenome shotgun sequencing to analyze the composition and functional structures of the gut microbiota in captive Amur tigers. Our results showed a high abundance of four major phyla in captive Amur tigers, including Proteobacteria, Firmicutes, Actinobacteria and Fusobacteria. Moreover, at the genus level, Escherichia, Collinsella and Fusobacterium were most abundant in the captive Amur tiger fecal metagenome. At the species level, Escherichia coli, Fusobacterium ulcerans and Fusobacterium varium were the species with highest abundances in the captive Amur tiger gut microbiota. The primary functional categories of the Amur tiger faecal metagenome were associated mainly with Carbohydrate metabolism, Membrane transport and Amino acid metabolism based on the KEGG pathway database. The comparative metagenomic analyses showed that the captive Amur tiger fecal metagenome had a lower abundance of Spirochaetes, Cyanobacteria and Ascomycota than other animals, and the primary functional categories were primarily associated with carbohydrate metabolism subsystems, clustering-based subsystems and protein metabolism. CONCLUSIONS: We presented here for the first time the use of the shotgun metagenomic sequencing approach to study the composition and functional structures of the gut microbiota in captive Amur tiger.


Assuntos
Animais de Zoológico/microbiologia , Bactérias/classificação , Fezes/microbiologia , Microbioma Gastrointestinal , Metagenoma , Tigres/microbiologia , Animais , Bactérias/genética , Bactérias/metabolismo , Espécies em Perigo de Extinção
9.
Molecules ; 21(12)2016 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-27916965

RESUMO

Fresh-cut Chinese water chestnuts (CWC) turn yellow after being peeled, reducing their shelf life and commercial value. Metabolomics, the systematic study of the full complement of small molecular metabolites, was useful for clarifying the mechanism of fresh-cut CWC etiolation and developing methods to inhibit yellowing. In this study, metabolic alterations associated with etiolation at different growth stages (0 day, 2 days, 3 days, 4 days, 5 days) from fresh-cut CWC were investigated using LC-MS and analyzed by pattern recognition methods (principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA), and orthogonal projection to latent structures-discriminant analysis (OPLS-DA)). The metabolic pathways of the etiolation molecules were elucidated. The main metabolic pathway appears to be the conversion of phenylalanine to p-coumaroyl-CoA, followed by conversion to naringenin chalcone, to naringenin, and naringenin then following different pathways. Firstly, it can transform into apigenin and its derivatives; secondly, it can produce eriodictyol and its derivatives; and thirdly it can produce dihydrokaempferol, quercetin, and myricetin. The eriodictyol can be further transformed to luteolin, cyanidin, dihydroquercetin, dihydrotricetin, and others. This is the first reported use of metabolomics to study the metabolic pathways of the etiolation of fresh-cut CWC.


Assuntos
Eleocharis/metabolismo , Estiolamento/fisiologia , Metaboloma/fisiologia , Metabolômica
10.
Front Pharmacol ; 15: 1412231, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38933681

RESUMO

Introduction: Bacillus licheniformis (B.licheniformis) was widely used in poultry feeds. However, it is still unclear about how B.licheniformis regulates the growth and development of Pekin ducks. Methods: The experiment was designed to clarify the effect and molecular mechanism of B. licheniformis on the lipid metabolism and developmental growth of Pekin ducks through multiomics analysis, including transcriptomic and metabolomic analyses. Results: The results showed that compared with the control group, the addition of 400 mg/kg B. licheniformis could significantly increase the body weight of Pekin ducks and the content of triglyceride (p < 0.05), at the same time, the addition of B. licheniformis could affect the lipid metabolism of liver in Pekin ducks, and the addition of 400 mg/kg B. licheniformis could significantly increase the content of lipoprotein lipase in liver of Pekin ducks. Transcriptomic analysis revealed that the addition of B. licheniformis primarily impacted fatty acid and glutathione, amino acid metabolism, fatty acid degradation, as well as biosynthesis and elongation of unsaturated fatty acids. Metabolomic analysis indicated that B. licheniformis primarily affected the regulation of glycerol phospholipids, fatty acids, and glycerol metabolites. Multiomics analysis demonstrated that the addition of B. licheniformis to the diet of Pekin ducks enhanced the regulation of enzymes involved in fat synthesis via the PPAR signaling pathway, actively participating in fat synthesis and fatty acid transport. Discussion: We found that B. licheniformis effectively influences fat content and lipid metabolism by modulating lipid metabolism-associated enzymes in the liver. Ultimately, this study contributes to our understanding of how B. licheniformis can improve the growth performance of Pekin ducks, particularly in terms of fat deposition, thereby providing a theoretical foundation for its practical application. Conclusion: B. licheniformis can increase the regulation of enzymes related to fat synthesis through PPAR signal pathway, and actively participate in liver fat synthesis and fatty acid transport, thus changing the lipid metabolism of Pekin ducks, mainly in the regulation of glycerol phospholipids, fatty acids and glycerol lipid metabolites.

11.
GigaByte ; 2023: gigabyte79, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36999120

RESUMO

Cosmocercoid nematodes are common parasites of the digestive tract of amphibians. Genomic resources are important for understanding the evolution of a species and the molecular mechanisms of parasite adaptation. So far, no genome resource of Cosmocercoid has been reported. In 2020, a massive Cosmocercoid infection was found in the small intestine of a toad, causing severe intestinal blockage. We morphologically identified this parasite as A. chamaeleonis. Here, we report the first A. chamaeleonis genome with a genome size of 1.04 Gb. The repeat content of this A. chamaeleonis genome is 72.45%, and the total length is 751 Mb. This resource is fundamental for understanding the evolution of Cosmocercoid and provides the molecular basis for Cosmocercoid infection and control.

12.
GigaByte ; 2023: gigabyte99, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38033372

RESUMO

In China, 65 types of venomous snakes exist, with the Chinese Cobra Naja atra being prominent and a major cause of snakebites in humans. Furthermore, N. atra is a protected animal in some areas, as it has been listed as vulnerable by the International Union for Conservation of Nature. Recently, due to the medical value of snake venoms, venomics has experienced growing research interest. In particular, genomic resources are crucial for understanding the molecular mechanisms of venom production. Here, we report a highly continuous genome assembly of N. atra, based on a snake sample from Huangshan, Anhui, China. The size of this genome is 1.67 Gb, while its repeat content constitutes 37.8% of the genome. A total of 26,432 functional genes were annotated. This data provides an essential resource for studying venom production in N. atra. It may also provide guidance for the protection of this species.

13.
Medicine (Baltimore) ; 101(3): e28495, 2022 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-35060501

RESUMO

BACKGROUND: The trisomy of human chromosome 21 causes Down syndrome (DS), sometimes known as congenital folly's syndrome. The survivors show apparent mental impairment, unusual facial traits, growth and development abnormalities, and various deformities, with 60 percent of the infants having miscarriages in the early stages of the fetus. Plasma micRNA (miRNA) is a new diagnostic biomarker for DS; however, its significance in first-trimester maternal plasma is unknown. As a result, the purpose of this study is to assess the diagnostic significance of the biomarker miRNA in first-trimester maternal plasma for DS. MATERIALS AND METHODS: From January 2014 until the present, blood samples were obtained from pregnant women who visited our hospital. This study included 20 eligible DS pregnancies and 20 normal pregnant women. We looked at the differential miRNA expression profile in DS maternal plasma from the first and second trimesters using miRNA microarrays. Bioinformatics technology was used to compare the particular miRNA in DS maternal plasma from the first and second trimesters and screen the miRNA co-expressed in DS maternal plasma. Meanwhile, the expression level of chosen miRNAs was verified using quantitative real-time PCR (qRT-PCR). DISCUSSION: This study aims to see how useful the diagnostic biomarker miRNA in first-trimester maternal plasma is for diagnosing DS. The findings of this investigation will provide clinical evidence for the discovery of a new diagnostic biomarker miRNA in first-trimester maternal plasma for DS diagnosis. OSF REGRESSION NUMBER: DOI 10.17605/OSF.IO/R49FT.


Assuntos
Síndrome de Down , MicroRNAs , Primeiro Trimestre da Gravidez/sangue , Biomarcadores/sangue , Síndrome de Down/diagnóstico , Síndrome de Down/genética , Feminino , Humanos , Gravidez , Diagnóstico Pré-Natal , Trissomia
14.
Front Vet Sci ; 9: 879805, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35692296

RESUMO

Pullorum is one of the most serious diseases that endanger the chicken industry. With the advent of the era of anti-antibiotics in feed, the replacement of antibiotics by probiotics has become the focus and hotspot of related research. In this study, hematoxylin-eosin (H&E) staining, immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA) were used to observe the structural changes of intestinal mucosa in chicks infected with Salmonella pullorum, and to analyze TNF-α, IL-10, IFN-γ, proliferating cell nuclear antigen (PCNA), and secreted immunoglobulin A (sIgA) levels. The results showed that the intestinal villus height, villus height to crypt depth ratio (V/C), and muscle layer thickness of duodenum, jejunum and cecum in the JYBR-190 group were significantly higher than those of the infection group and antibiotic group. Furthermore, the levels of PCNA, sIgA and IL-10 in JYBR-190 group were significantly increased, whereas the expression of TNF-α and IFN-γ was significantly decreased. Taken together, Bifidobacterium lactis JYBR-190 has a protective effect on intestinal mucosal damage in chicks infected with Salmonella pullorum.

15.
Bioengineered ; 13(5): 11611-11623, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35531876

RESUMO

Premature ovarian insufficiency (POI) is a disease that seriously affects women's reproductive function and even leads to lifelong infertility. Little is known about the mechanism of lipopolysaccharide (LPS)-induced ovarian dysfunction. Thus, we aimed to identify the role of the up-regulation of microRNA (miRNA)-146 expression offered protection against ovarian dysfunction by inhibiting the toll-like receptor (TLR) 4, TLR4/phosphorylated (p)-nuclear factor (NF)-κB signaling pathway and inflammatory cytokine tumor necrosis factor (TNF)-a and Interleukin (IL)-6. In an in vivo study, we established an LPS-induced ovarian dysfunction mouse model. The mouse ovarian granulosa cells were transfected with miR-146 mimic or negative controls or inhibitor and then treated with LPS. Therefore, cell viability, cells apoptosis, IL-6 and TNF-a, TLR4, NF- κB were assessed, respectively. These results demonstrated that the up-regulation of miRNA-146 expression may protect against LPS-induced ovarian dysfunction and markedly increased the cell viability, and significantly reduced the ovarian granulosa cells apoptotic rate, and down-regulated IL-6 and TNF-a expression. In addition, miRNA-146 exerted protective ovarian functions might be via inhibiting TLR4/NF-κB signaling pathway. In summary, we reveal the up-regulation of miRNA-146 expression mitigated ovarian dysfunction by negatively regulating expression of the IL-6 and TNF-a, which may shed light on the potential molecular mechanisms of overexpression of miRNA-146 may reversed the ovarian dysfunction by inhibiting the TLR4/ NF-κB signaling pathway.


Assuntos
MicroRNAs , NF-kappa B , Doenças Ovarianas , Receptor 4 Toll-Like , Animais , Feminino , Humanos , Interleucina-6/genética , Interleucina-6/metabolismo , Lipopolissacarídeos/metabolismo , Camundongos , MicroRNAs/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Doenças Ovarianas/genética , Doenças Ovarianas/metabolismo , Ovário/fisiopatologia , Transdução de Sinais , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/genética
16.
Int J Biol Sci ; 17(5): 1289-1301, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33867846

RESUMO

Endometritis is a reproductive disorder characterized by an inflammatory response in the endometrium, which causes significant economic losses to the dairy farming industry. MicroRNAs (miRNAs) are implicated in the inflammatory response and immune regulation following infection by pathogenic bacteria. Recent miRNA microarray analysis showed an altered expression of miR-92b in cows with endometritis. In the present study, we set out to investigate the regulatory mechanism of miR-92b in endometritis. Here, qPCR results first validated that miR-92b was down-regulated during endometritis. And then, bovine endometrial epithelial cells (BEND cells) stimulated by high concentration of lipopolysaccharide (LPS) were employed as an in vitro inflammatory injury model. Our data showed that overexpression of miR-92b significantly suppressed the activation of Toll-like receptor 4 (TLR4) and nuclear factor-κB (NF-κB) in LPS-stimulated BEND cells, thereby reducing pro-inflammatory cytokines release and inhibiting cell apoptosis. Looking into the molecular mechanisms of regulation of inflammatory injury by miR-92b, we observed that overexpression of miR-92b restrained TLR4/NF-κB by activating the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT)/ß-catenin pathway. Furthermore, the luciferase reporter assay suggested that miR-92b targeted inhibition of phosphatase and tensin homolog (PTEN), an inhibitor of the PI3K/AKT/ß-catenin pathway. Importantly, in vivo experiments confirmed that up-regulation of miR-92b attenuated the pathological injury in an experimental murine model of LPS-induced endometritis. Collectively, these findings show that enforced expression of miR-92b alleviates LPS-induced inflammatory injury by activating the PI3K/AKT/ß-catenin pathway via targeting PTEN, suggesting a potential application for miR-92b-based therapy to treat endometritis or other inflammatory diseases.


Assuntos
Endometrite , MicroRNAs/genética , PTEN Fosfo-Hidrolase/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , beta Catenina/metabolismo , Animais , Apoptose , Bovinos , Modelos Animais de Doenças , Descoberta de Drogas , Endometrite/imunologia , Endometrite/metabolismo , Endometrite/patologia , Células Epiteliais/imunologia , Células Epiteliais/metabolismo , Feminino , Regulação da Expressão Gênica , Camundongos , NF-kappa B/metabolismo , Transdução de Sinais/imunologia , Receptor 4 Toll-Like/metabolismo , Regulação para Cima
17.
Front Genet ; 12: 819493, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35126472

RESUMO

The masked palm civet (Paguma larvata) is a small carnivore with distinct biological characteristics, that likes an omnivorous diet and also serves as a vector of pathogens. Although this species is not an endangered animal, its population is reportedly declining. Since the severe acute respiratory syndrome (SARS) epidemic in 2003, the public has been particularly concerned about this species. Here, we present the first genome of the P. larvata, comprising 22 chromosomes assembled using single-tube long fragment read (stLFR) and Hi-C technologies. The genome length is 2.41 Gb with a scaffold N50 of 105.6 Mb. We identified the 107.13 Mb X chromosome and one 1.34 Mb Y-linked scaffold and validated them by resequencing 45 P. larvata individuals. We predicted 18,340 protein-coding genes, among which 18,333 genes were functionally annotated. Interestingly, several biological pathways related to immune defenses were found to be significantly expanded. Also, more than 40% of the enriched pathways on the positively selected genes (PSGs) were identified to be closely related to immunity and survival. These enriched gene families were inferred to be essential for the P. larvata for defense against the pathogens. However, we did not find a direct genomic basis for its adaptation to omnivorous diet despite multiple attempts of comparative genomic analysis. In addition, we evaluated the susceptibility of the P. larvata to the SARS-CoV-2 by screening the RNA expression of the ACE2 and TMPRSS2/TMPRSS4 genes in 16 organs. Finally, we explored the genome-wide heterozygosity and compared it with other animals to evaluate the population status of this species. Taken together, this chromosome-scale genome of the P. larvata provides a necessary resource and insights for understanding the genetic basis of its biological characteristics, evolution, and disease transmission control.

20.
Arch Med Res ; 37(6): 787-93, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16824940

RESUMO

BACKGROUND: Hyperlipidemia is a risk factor for atherosclerotic events. Differences in lipid levels may exist in different races. Han is the largest group and Zhuang is the largest minority among the 56 nationalities in China. Geographically and linguistically, Zhuang can be classified into 43 ethnic subgroups, among which Hei Yi (means black worship and black dress) Zhuang, living in Napo County bordering northeast Vietnam and with a population of about 50,000, is a special ethnic group, and the most conservative with a unique culture. Little is known about the lipid levels in this population. The aim of this study was to compare the lipid levels, prevalence of hyperlipidemia, and risk factors in Hei Yi Zhuang and Han populations. METHODS: A total of 1068 people of Hei Yi Zhuang nationality were surveyed by a cluster sampling. Blood pressure, height, weight, serum lipid and apolipoprotein (Apo) levels were measured, and body mass index (BMI) was calculated. The results were compared with those in 933 people of Han nationality who also live in that district. RESULTS: The levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol, and Apo B in Hei Yi Zhuang nationality were significantly lower than those in Han nationality (p <0.05-0.001), but the levels of high-density lipoprotein cholesterol and the ratio of Apo A1 to Apo B in Hei Yi Zhuang nationality were significantly higher than those in Han nationality (p <0.001 and 0.05, respectively). The prevalence rates of hypercholesterolemia, hypertriglyceridemia, and hyperlipidemia in Hei Yi Zhuang and Han nationalities were 25.00 vs. 28.72% (p >0.05), 12.45 vs. 14.36% (p >0.05), and 31.37 vs. 35.91% (p <0.05); respectively. The prevalence of hyperlipidemia in Hei Yi Zhuang or Han population was positively correlated with age, BMI, blood pressure, and alcohol consumption (p <0.05-0.001), respectively, but was not associated with gender or cigarette smoking in both nationalities (p >0.05). CONCLUSIONS: The current study reveals that there were significant differences in lipid levels and prevalence of hyperlipidemia between Hei Yi Zhuang and Han ethnic groups, but no significant differences in the detected risk factors for hyperlipidemia between the two ethnic groups, which might result from the comprehensive role of different dietary habits, life style, and level of physical activity, as well as genetic background.


Assuntos
Hiperlipidemias , Lipídeos/sangue , Grupos Minoritários , Adulto , Idoso , Idoso de 80 Anos ou mais , Apolipoproteínas/sangue , China/epidemiologia , Feminino , Humanos , Hiperlipidemias/sangue , Hiperlipidemias/diagnóstico , Hiperlipidemias/epidemiologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco
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