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1.
Toxicol Appl Pharmacol ; 486: 116952, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38705399

RESUMO

The incidence of contrast-induced acute kidney injury (CI-AKI) has escalated to become the third most prevalent cause of hospital-acquired AKI, with a lack of efficacious interventions. Berberine (BBR) possesses diverse pharmacological effects and exhibits renoprotective properties; however, limited knowledge exists regarding its impact on CI-AKI. Therefore, our study aimed to investigate the protective effects and underlying mechanisms of BBR on CI-AKI in a mice model, focusing on the nucleotide-binding oligomerization domain-like pyrin domain-containing protein 3 (NLRP3) inflammasome and mitophagy. The CI-AKI mice model was established by administering NG-nitro-L-arginine methyl ester (L-NAME) (10 mg/kg), indomethacin (10 mg/kg), and iohexol (11 g/kg) following water deprivation. A pretreatment of 100 mg/kg of BBR was orally administered to the mice for two weeks. Renal injury markers, damage-associated molecular patterns (DAMPs), renal histopathology, mitochondrial morphology, autophagosomes, and potential mechanisms were investigated. BBR effectively reduced levels of renal injury biomarkers such as serum cystatin C, urea nitrogen, and creatinine, downregulated the protein level of kidney injury molecule 1 (KIM1), and mitigated renal histomorphological damage. Moreover, BBR reduced DAMPs, including high mobility group box-1 (HMGB1), heat shock protein 70 (HSP70), and uric acid (UA). It also alleviated oxidative stress and inflammatory factors such as monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1ß). Furthermore, the activation of NLRP3 inflammasome was attenuated in the BBR pretreatment group, as evidenced by both mRNA and protein levels. Electron microscopy and western blotting examination revealed that BBR mitigated mitochondrial damage and enhanced mitophagy. Additionally, BBR increased the P-AMPK/AMPK ratio. These findings indicated that BBR exerted a protective effect against CI-AKI by suppressing NLRP3 inflammasome activation and modulating mitophagy, providing a potential therapeutic strategy for its prevention.


Assuntos
Injúria Renal Aguda , Berberina , Meios de Contraste , Modelos Animais de Doenças , Inflamassomos , Camundongos Endogâmicos C57BL , Mitofagia , Proteína 3 que Contém Domínio de Pirina da Família NLR , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Mitofagia/efeitos dos fármacos , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/patologia , Injúria Renal Aguda/prevenção & controle , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/tratamento farmacológico , Inflamassomos/metabolismo , Inflamassomos/efeitos dos fármacos , Camundongos , Berberina/farmacologia , Masculino , Rim/efeitos dos fármacos , Rim/patologia , Rim/metabolismo
2.
Pest Manag Sci ; 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38587094

RESUMO

BACKGROUND: The fall armyworm (FAW, Spodoptera frugiperda (J.E. Smith)) is a polyphagous agricultural pest with rapidly evolving adaptations to host plants. We found the oral secretion (OS) of FAW from different plants influences plant defense response differentially, suggesting its role in adapting to host plants. However, the protein expression profile of FAW OS respond to different plants is largely unknown. RESULTS: Here, from the mass spectrometry assay, we identified a total of 256 proteins in the OS of FAW fed on cotton (Gossypium hirsutum L.), tobacco (Nicotiana benthamiana Domin), maize (Zea mays L.) and artificial diet. The FAW OS primarily comprise of 60 proteases, 32 esterases and 92 non-enzymatic proteins. It displays high plasticity across different diets. We found that more than half of the esterases are lipases which have been reported as insect elicitors to enhance plant defense response. The lipase accumulation in cotton-fed larvae was the highest, followed by maize-fed larvae. In the presence of lipase inhibitors, the enhanced induction on defense genes in wounded leaves by OS was attenuated. However, the putative effectors were most highly accumulated in the OS from FAW larvae fed on maize compared to those fed on other diets. We identified that one of them (VRLP4) reduces the OS-mediated induction on defense genes in wounded leaves. CONCLUSION: Together, our investigation presents the proteomic landscape of the OS of FAW influenced by different diets and reveals diet-mediated plasticity of OS is involved in FAW adaptation to host plants. © 2024 Society of Chemical Industry.

3.
Front Immunol ; 15: 1356075, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38529274

RESUMO

Background: During aging, chronic inflammation can promote tumor development and metastasis. Patients with chronic inflammatory bowel diseases (IBD) are at an increased risk of developing colorectal cancer (CRC). However, the molecular mechanism underlying is still unclear. Methods: We conducted a large-scale single-cell sequencing analysis comprising 432,314 single cells from 92 CRC and 24 IBD patients. The analysis focused on the heterogeneity and commonality of CRC and IBD with respect to immune cell landscape, cellular communication, aging and inflammatory response, and Meta programs. Results: The CRC and IBD had significantly different propensities in terms of cell proportions, differential genes and their functions, and cellular communication. The progression of CRC was mainly associated with epithelial cells, fibroblasts, and monocyte-macrophages, which displayed pronounced metabolic functions. In particular, monocyte-macrophages were enriched for the aging and inflammation-associated NF-κB pathway. And IBD was enriched in immune-related functions with B cells and T cells. Cellular communication analysis in CRC samples displayed an increase in MIF signaling from epithelial cells to T cells, and an increase in the efferent signal of senescence-associated SPP1 signaling from monocyte-macrophages. Notably, we also found some commonalities between CRC and IBD. The efferent and afferent signals showed that the pro-inflammatory cytokine played an important role. And the activity of aging and inflammatory response with AUCell analysis also showed a high degree of commonality. Furthermore, using the Meta programs (MPs) with the NMF algorithm, we found that the CRC non-malignant cells shared a substantial proportion of the MP genes with CRC malignant cells (68% overlap) and IBD epithelial cells (52% overlap), respectively. And it was extensively involved in functions of cell cycle and immune response, revealing its dual properties of inflammation and cancer. In addition, CRC malignant and non-malignant cells were enriched for the senescence-related cell cycle G2M phase transition and the p53 signaling pathway. Conclusion: Our study highlights the characteristics of aging, inflammation and tumor in CRC and IBD at the single-cell level, and the dual property of inflammation-cancer in CRC non-malignant cells may provide a more up-to-date understanding of disease transformation.


Assuntos
Neoplasias Colorretais , Doenças Inflamatórias Intestinais , Humanos , Transcriptoma , Inflamação/genética , Inflamação/complicações , Citocinas , Microambiente Tumoral/genética
4.
Biochem Biophys Res Commun ; 700: 149535, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38308909

RESUMO

To compare the merits and drawbacks of three approaches for establishing a rabbit model of nonobstructive coronary microcirculatory disease, namely, open thoracic subtotal ligation of coronary arteries, ultrasound-guided cardiac microsphere injection, and sodium laurate injection. New Zealand rabbits were allocated to four groups: a normal group (Blank group), an Open-chest group (Open-chest), a microsphere group (Echo-M), and a sodium laurate group (Echo-SL), each comprising 10 rabbits. The rabbits were sacrificed 24 h after the procedures, and their echocardiography, stress myocardial contrast echocardiography, pathology, and surgical times were compared. The results demonstrated varying degrees of reduced cardiac function in all three experimental groups, the Open-chest group exhibiting the most significant decline. The myocardial filling in the affected areas was visually analyzed by myocardial contrast echocardiography, revealing sparse filling at rest but more after stress. Quantitative analysis of perfusion parameters (ß, A, MBF) in the affected myocardium showed reduced values, the Open-chest group having the most severe reductions. No differences were observed in stress myocardial acoustic imaging parameters between the Echo-M and Echo-SL groups. Among the pathological presentations, the Open-chest model predominantly exhibited localized ischemia, while the Echo-M model was characterized by mechanical physical embolism, and the Echo-SL model displayed in situ thrombosis as the primary pathological feature. Inflammatory responses and collagen deposition were observed in all groups, with the severity ranking of Open-chest > Echo-SL > Echo-M. The ultrasound-guided intracardiac injection method used in this experiment outperformed open-chest surgery in terms of procedural efficiency, invasiveness, and maneuverability. This study not only optimizes established cardiac injection techniques but also offers valuable evidence to support clinical investigations through a comparison of various modeling methods.


Assuntos
Doença da Artéria Coronariana , Circulação Coronária , Coelhos , Animais , Microcirculação , Circulação Coronária/fisiologia , Miocárdio/patologia
5.
Nat Biotechnol ; 42(3): 518-528, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37231262

RESUMO

The development of cancer neoantigen vaccines that prime the anti-tumor immune responses has been hindered in part by challenges in delivery of neoantigens to the tumor. Here, using the model antigen ovalbumin (OVA) in a melanoma model, we demonstrate a chimeric antigenic peptide influenza virus (CAP-Flu) system for delivery of antigenic peptides bound to influenza A virus (IAV) to the lung. We conjugated attenuated IAVs with the innate immunostimulatory agent CpG and, after intranasal administration to the mouse lung, observed increased immune cell infiltration to the tumor. OVA was then covalently displayed on IAV-CPG using click chemistry. Vaccination with this construct yielded robust antigen uptake by dendritic cells, a specific immune cell response and a significant increase in tumor-infiltrating lymphocytes compared to peptides alone. Lastly, we engineered the IAV to express anti-PD1-L1 nanobodies that further enhanced regression of lung metastases and prolonged mouse survival after rechallenge. Engineered IAVs can be equipped with any tumor neoantigen of interest to generate lung cancer vaccines.


Assuntos
Vacinas Anticâncer , Vírus da Influenza A , Neoplasias Pulmonares , Animais , Camundongos , Neoplasias Pulmonares/prevenção & controle , Vacinas Anticâncer/genética , Antígenos , Pulmão , Peptídeos , Vacinação , Antígenos de Neoplasias/genética
7.
J Agric Food Chem ; 72(1): 4-26, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38156955

RESUMO

Food safety has become an attractive topic among consumers. Raw material production for food is also a focus of social attention. As hormones are widely used in agriculture and human disease control, consumers' concerns about the safety of hormone agents have never disappeared. The present review focuses on the interkingdom regulations of exogenous animal hormones in plants and phytohormones in animals, including physiology and stress resistance. We summarize these interactions to give the public, researchers, and policymakers some guidance and suggestions. Accumulated evidence demonstrates comprehensive hormonal regulation across plants and animals. Animal hormones, interacting with phytohormones, help regulate plant development and enhance environmental resistance. Correspondingly, phytohormones may also cause damage to the reproductive and urinary systems of animals. Notably, the disease-resistant role of phytohormones is revealed against neurodegenerative diseases, cardiovascular disease, cancer, and diabetes. These resistances derive from the control for abnormal cell cycle, energy balance, and activity of enzymes. Further exploration of these cross-kingdom mechanisms would surely be of greater benefit to human health and agriculture development.


Assuntos
Reguladores de Crescimento de Plantas , Plantas , Animais , Humanos , Reguladores de Crescimento de Plantas/farmacologia , Reguladores de Crescimento de Plantas/metabolismo , Plantas/metabolismo , Desenvolvimento Vegetal , Hormônios/metabolismo , Inocuidade dos Alimentos
8.
Cell Death Dis ; 14(11): 757, 2023 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-37985768

RESUMO

Aggressiveness and drug resistance are major challenges in the clinical treatment of glioblastoma (GBM). Our previously research reported a novel candidate oncogene ribosomal protein L22 like 1 (RPL22L1). The aim of this study was to elucidate the potential role and mechanism of RPL22L1 in progression and temozolomide (TMZ) resistance of GBM. Online database, tissue microarrays and clinical tissue specimens were used to evaluate the expression and clinical implication of RPL22L1 in GBM. We performed cell function assays, orthotopic and subcutaneous xenograft tumor models to evaluate the effects and molecular mechanisms of RPL22L1 on GBM. RPL22L1 expression was significantly upregulated in GBM and associated with poorer prognosis. RPL22L1 overexpression enhanced GBM cell proliferation, migration, invasion, TMZ resistance and tumorigenicity, which could be reduced by RPL22L1 knockdown. Further, we found RPL22L1 promoted mesenchymal phenotype of GBM and the impact of these effects was closely related to EGFR/STAT3 pathway. Importantly, we observed that STAT3 specific inhibitor (Stattic) significantly inhibited the malignant functions of RPL22L1, especially on TMZ resistance. RPL22L1 overexpressed increased combination drug sensitive of Stattic and TMZ both in vitro and in vivo. Moreover, Stattic effectively restored the sensitive of RPL22L1 induced TMZ resistance in vitro and in vivo. Our study identified a novel candidate oncogene RPL22L1 which promoted the GBM malignancy through STAT3 pathway. And we highlighted that Stattic combined with TMZ therapy might be an effective treatment strategy in RPL22L1 high-expressed GBM patients.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Humanos , Temozolomida/uso terapêutico , Glioblastoma/tratamento farmacológico , Glioblastoma/genética , Glioblastoma/patologia , Linhagem Celular Tumoral , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Oncogenes , Resistencia a Medicamentos Antineoplásicos/genética , Antineoplásicos Alquilantes/farmacologia , Antineoplásicos Alquilantes/uso terapêutico , Ensaios Antitumorais Modelo de Xenoenxerto , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Proteínas Ribossômicas/genética , Proteínas Ribossômicas/metabolismo
9.
J Matern Fetal Neonatal Med ; 36(1): 2210731, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37158067

RESUMO

Perinatal tuberculosis is a rare disease with high mortality and a challenging diagnosis. We reported a 56-day-old female infant with cough and wheezing. Her mother had miliary tuberculosis. Gastric aspirate smear, tuberculin skin test, blood and sputum culture of the infant were negative. Thoracic computed tomography demonstrated several consolidated patches with diffuse high-density nodular opacities in bilateral lungs. Fiberoptic bronchoscopy was performed to obtain bronchoalveolar lavage fluid, reduce secretion and restore airway patency on 2 days after admission. Mycobacterium tuberculosis was detected by bronchoalveolar lavage fluid Xpert MTB/RIF and rifampicin resistance was negative on 3 days after admission. Appropriate anti-tuberculosis drug was chosen. The infant made a good recovery. Fiberoptic bronchoscopy plays a vital role in diagnosing rapidly and treating perinatal tuberculosis. And it could be promoted as an important approach to the management of perinatal tuberculosis.


Assuntos
Mycobacterium tuberculosis , Tuberculose Pulmonar , Humanos , Lactente , Feminino , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/microbiologia , Broncoscopia , Escarro/microbiologia , Rifampina/uso terapêutico , Sensibilidade e Especificidade
10.
J Ethnopharmacol ; 315: 116703, 2023 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-37257704

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Dingkun Pill (DKP) is a traditional Chinese medicine that has been shown to have beneficial effects on reproductive function. However, the specific mechanism underlying its effect on POI is not well understood. AIM OF THE STUDY: To investigate the effect of different doses of Dingkun Pill on ovarian function in cyclophosphamide (CTX)-induced premature ovarian insufficiency (POI) mice and to explore its molecular mechanism through PTEN/PI3K/AKT/FOXO3a signaling pathway. This study will provide valuable insights into the potential clinical application of Dingkun Pill for the treatment of POI. MATERIALS AND METHODS: Fifty female ICR mice were randomly divided into normal control (NC) group, model control (MC) group, and Dingkun Pill low, medium, high dose (DKP-L, M, H) groups. Mice were injected with CTX to construct the POI model. Mice in the DKP-L, M, and H groups were given 0.9 g/kg, 1.8 g/kg, and 3.6 g/kg of Dingkun Pill suspension for 21 days, respectively. Mice in the NC and MC groups were given the same amount of normal saline by gavage. Changes in body weight, estrous cycle and gonadal index were observed in each group of mice. Serum levels of FSH, LH, E2 and AMH were detected by ELISA. Hematoxylin-eosin (HE) staining observed the changes of ovarian pathological morphology and follicle counts at all levels. qRT-PCR was used to measure the levels of the PTEN and FOXO3a genes in ovarian tissue. The expression of PTEN/PI3K/AKT/FOXO3a signaling pathway related proteins were detected by Western-blot and immunohistochemistry (IHC). RESULTS: In POI mice, Dingkun Pill increased body weight, promoted the recovery of estrous cycle, increased ovarian index, and improved pathological morphology of the ovaries. The FSH level decreased in the medium dose group (P < 0.05), the LH level reduced significantly in the medium and high dose groups (P < 0.01), and the E2 level in the high dose group increased (P < 0.05). There was no significant difference in AMH levels across all dose groups. The number of growing follicles improved at all levels in the low and medium dose groups, but declined significantly in the high dose group. However, the number of corpus luteum increased significantly in the high dose group (P < 0.001), and the atretic follicles in the three dose groups decreased. Results from qRT-PCR, Western-blot and IHC showed that the moderate dose of Dingkun Pill suppressed the levels of the p-PI3K and p-AKT proteins by upregulating the expression of PTEN in the ovarian tissues of POI mice, thereby inhibiting the expression of the key protein p-FOXO3a. However, the inhibitory effect of the higher dose may be less than that of the lower and intermediate dose groups. CONCLUSIONS: The Dingkun Pill modulated hormonal levels, promoted follicle growth and induced ovulation in mice with CTX-induced POI, with better results in the low and moderate dose groups. Its mechanism may be related to the regulation of the PTEN/PI3K/AKT/FOXO3a signaling pathway.


Assuntos
Antineoplásicos , Menopausa Precoce , Insuficiência Ovariana Primária , Humanos , Camundongos , Feminino , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Camundongos Endogâmicos ICR , Insuficiência Ovariana Primária/induzido quimicamente , Insuficiência Ovariana Primária/tratamento farmacológico , Insuficiência Ovariana Primária/genética , Transdução de Sinais , Hormônio Foliculoestimulante , Antineoplásicos/uso terapêutico , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo
11.
World J Clin Cases ; 11(11): 2510-2520, 2023 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-37123315

RESUMO

BACKGROUND: Primary schwannoma is a rare submucosal tumor of the esophagus, which is most often benign, and surgery is the only effective treatment. So far, only a few cases have been reported. Herein, we reported a single case diagnosed with primary esophageal schwannoma that was totally removed by submucosal tunneling endoscopic resection (STER). CASE SUMMARY: A 62-year-old man presented to the hospital with a history of resection of a malignant gastric tumor and mild dysphagia. Endoscopic examination revealed a large submucosal elevated lesion in the esophagus 25-30 cm from the incisors. Endoscopic ultrasonography detected a 45 mm × 35 mm × 31 mm hypoechoic lesion; chest computed tomography showed a mass of approximately 55 mm × 35 mm × 29 mm. A preliminary examination showed features suggestive of a stromal tumor. Pathological findings indicated esophageal schwannoma. Next, STER alone was performed to completely resect the mass, and the patient recovered well post-surgery. Afterward, the patient was discharged and showed no tumor recurrence at 33 mo of follow-up. CONCLUSION: Endoscopic resection is still an effective treatment for large esophageal schwannomas (> 30 mm) under meticulous morphological evaluation.

12.
Front Endocrinol (Lausanne) ; 14: 1153719, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37124724

RESUMO

Background: As a common cancer with high incidence rate and mortality, colorectal cancer (CRC) is seriously threatening human health. S-nitrosylation (SNO) proteins mediated by nitric oxide (NO) has important implications in the genesis, progression, and apoptosis of CRC. It's worth noting that the SNO proteins also play an important role in the tumor endocrine and metabolic pathways of CRC. Materials and methods: In this study, the protein extracts of human tissues and cell lines were treated by biotin switch technology and magnetic beads enrichment. The proteomic results of endogenous and potential SNO proteins were analyzed by mass spectrometry (MS). Through the comparison and analysis of MS results, Gene Ontology (GO) analysis, and literatures, some endogenous and potential SNO proteins were identified in CRC, which were closely related to the tumor endocrine and metabolic pathways, the apoptotic signaling pathways, protein maturation, and other biological processes of the proliferation and apoptosis of CRC cells. Results: A total of 19 proteins containing potential or endogenous SNO sites were detected in both human cancer tissue and SW 480 cells. Through the cross validation of MS results, GO analysis, and literatures, several SNO proteins were identified frequently in CRC, such as the actin, cytoplasmic 1 (ACTB), peroxiredoxin-4 (PRDX4), protein S100A8 (S100A8), pyruvate kinase PKM (PKM), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), which were closely related to the tumor endocrine and metabolic pathways and the apoptotic signaling pathways of CRC. Conclusion: Different CRC cells and tissues contained potential and endogenous SNO modified proteins. In addition, some SNO proteins could participate in the proliferation, metastasis and apoptosis of CRC by regulating the tumor endocrine and metabolic pathways.


Assuntos
Neoplasias Colorretais , Proteoma , Humanos , Proteômica/métodos , Espectrometria de Massas , Linhagem Celular
13.
Front Mol Neurosci ; 16: 1064579, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37181652

RESUMO

Cisplatin is widely used in clinical tumor chemotherapy but has severe ototoxic side effects, including tinnitus and hearing damage. This study aimed to determine the molecular mechanism underlying cisplatin-induced ototoxicity. In this study, we used CBA/CaJ mice to establish an ototoxicity model of cisplatin-induced hair cell loss, and our results showed that cisplatin treatment could reduce FOXG1 expression and autophagy levels. Additionally, H3K9me2 levels increased in cochlear hair cells after cisplatin administration. Reduced FOXG1 expression caused decreased microRNA (miRNA) expression and autophagy levels, leading to reactive oxygen species (ROS) accumulation and cochlear hair cell death. Inhibiting miRNA expression decreased the autophagy levels of OC-1 cells and significantly increased cellular ROS levels and the apoptosis ratio in vitro. In vitro, overexpression of FOXG1 and its target miRNAs could rescue the cisplatin-induced decrease in autophagy, thereby reducing apoptosis. BIX01294 is an inhibitor of G9a, the enzyme in charge of H3K9me2, and can reduce hair cell damage and rescue the hearing loss caused by cisplatin in vivo. This study demonstrates that FOXG1-related epigenetics plays a role in cisplatin-induced ototoxicity through the autophagy pathway, providing new ideas and intervention targets for treating ototoxicity.

14.
Microbiol Spectr ; 11(1): e0190622, 2023 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-36625575

RESUMO

The gut microbiota is known to play a role in regulating host metabolism, yet the mechanisms underlying this regulation are not well elucidated. Our study aimed to characterize the differences in gut microbiota compositions and their roles in iron absorption between wild-type (WT) and CD163/pAPN double-gene-knockout (DKO) weaned piglets. A total of 58 samples along the entire digestive tract were analyzed for microbial community using 16S rRNA gene sequencing. The colonic microbiota and their metabolites were determined by metagenomic sequencing and untargeted liquid chromatography-mass spectrometry (LC-MS), respectively. Our results showed that no alterations in microbial community structure and composition were observed between DKO and WT weaned piglets, with the exception of colonic microbiota. Interestingly, the DKO piglets had selectively increased the relative abundance of the Leeia genus belonging to the Neisseriaceae family and decreased the Ruminococcaceae_UCG_014 genus abundance. Functional capacity analysis showed that organic acid metabolism was enriched in the colon in DKO piglets. In addition, the DKO piglets showed increased iron levels in important tissues compared with WT piglets without any pathological changes. Pearson's correlation coefficient indicated that the specific bacteria such as Leeia and Ruminococcaceae_UCG_014 genus played a key role in host iron absorption. Moreover, the iron levels had significantly (P < 0.05) positive correlation with microbial metabolites, particularly carboxylic acids and their derivatives, which might increase iron absorption by preventing iron precipitation. Overall, this study reveals an interaction between colonic microbiota and host metabolism and has potential significance for alleviating piglet iron deficiency. IMPORTANCE Iron deficiency is a major risk factor for iron deficiency anemia, which is among the most common nutritional disorders in piglets. However, it remains unclear how the gut microbiota interacts with host iron absorption. The current report provides the first insight into iron absorption-microbiome connection in CD163/pAPN double knockout piglets. The present results showed that carboxylic acids and their derivatives contributed to the absorption of nonheme iron by preventing ferric iron precipitation.


Assuntos
Microbioma Gastrointestinal , Animais , Suínos , Microbioma Gastrointestinal/fisiologia , RNA Ribossômico 16S/genética , Antígenos CD , Colo/microbiologia
15.
J Transl Med ; 21(1): 47, 2023 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-36698149

RESUMO

BACKGROUND: Genetic knowledge of gestational diabetes mellitus (GDM) in Chinese women is quite limited. This study aimed to identify the risk factors and mechanism of GDM at the genetic level in a Chinese population. METHODS: We conducted a genome-wide association study (GWAS) based on single nucleotide polymorphism (SNP) array genotyping (ASA-CHIA Bead chip, Illumina) and a case-cohort study design. Variants including SNPs, copy number variants (CNVs), and insertions-deletions (InDels) were called from genotyping data. A total of 2232 pregnant women were enrolled in their first/second trimester between February 2018 and December 2020 from Anqing Municipal Hospital in Anhui Province, China. The GWAS included 193 GDM patients and 819 subjects without a diabetes diagnosis, and risk ratios (RRs) and their 95% confidence intervals (CIs) were estimated by a regression-based method conditional on the population structure. The calling and quality control of genotyping data were performed following published guidelines. CNVs were merged into CNV regions (CNVR) to simplify analyses. To interpret the GWAS results, gene mapping and overexpression analyses (ORAs) were further performed to prioritize the candidate genes and related biological mechanisms. RESULTS: We identified 14 CNVRs (false discovery rate corrected P values < 0.05) and two suggestively significant SNPs (P value < 0.00001) associated with GDM, and a total of 19 candidate genes were mapped. Ten genes were significantly enriched in gene sets related to lipase (triglyceride lipase and lipoprotein lipase) activity (LIPF, LIPK, LIPN, and LIPJ genes), oxidoreductase activity (TPH1 and TPH2 genes), and cellular components beta-catenin destruction complex (APC and GSK3B genes), Wnt signalosome (APC and GSK3B genes), and lateral element in the Gene Ontology resource (BRCA1 and SYCP2 genes) by two ORA methods (adjusted P values < 0.05). CONCLUSIONS: Genes related to lipolysis, redox reaction, and proliferation of islet ß-cells are associated with GDM in Chinese women. Energy metabolism, particularly lipolysis, may play an important role in GDM aetiology and pathology, which needs further molecular studies to verify.


Assuntos
Diabetes Gestacional , Humanos , Feminino , Gravidez , Diabetes Gestacional/genética , Estudo de Associação Genômica Ampla , Estudos de Coortes , População do Leste Asiático , Lipólise , Polimorfismo de Nucleotídeo Único/genética
16.
Pharmacol Res ; 187: 106569, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36427798

RESUMO

Phenolipids are characteristic phytochemicals of Syzygium genus. However, the antidiabetic potential and underlying molecular mechanism of these components are not fully elucidated. Herein, we studied the anti-diabetic effects of jambone E (JE), a phenolipid from S. cumini, with in vitro and in vivo models. Data from current study showed that JE enhanced glucose consumption and uptake, promoted glycogen synthesis, and suppressed gluconeogenesis in insulin resistant (IR)-HepG2 cells and primary mouse hepatocytes. JE also attenuated streptozotocin-induced hyperglycemia and hyperlipidemia in type 1 diabetic (T1D) mice. Eleven metabolites (e.g. trimethylamine n-oxide, 4-pyridoxic acid, phosphatidylinositol 39:4, phenaceturic acid, and hippuric acid) were identified as potential serum biomarkers for JE's antidiabetic effects by an untargeted metabolomics approach. The further molecular mechanistic study revealed that JE up-regulated phosphorylation levels of protein kinase B (AKT), glycogen synthase kinase 3 beta, and forkhead box O1 (FoxO1), promoted nuclear exclusion of FoxO1 whilst decreased gene expression levels of peroxisome proliferator-activated receptor gamma coactivator-1 alpha, phosphoenolpyruvate carboxykinase and glucose 6-phosphatase in IR-HepG2 cells and T1D mice. Our data suggested that JE might be a potent activator for AKT-mediated insulin signaling pathway, which was confirmed by the usage of AKT inhibitor and AKT-target siRNA interference, as well as the cellular thermal shift assay. Findings from the current study shed light on the anti-diabetic effects of phenolipids in the Syzygium species, which supports the use of medicinal plants in the Syzygium genus for potential pharmaceutical applications.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , Hipoglicemiantes , Resistência à Insulina , Compostos Fitoquímicos , Syzygium , Animais , Camundongos , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Gluconeogênese , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/química , Insulina/metabolismo , Fígado , Metaboloma , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Estreptozocina , Syzygium/química , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico
17.
Front Plant Sci ; 13: 918155, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36507421

RESUMO

Phylogenomic studies based on plastid genome have resolved recalcitrant relationships among various plants, yet the phylogeny of Dennstaedtiaceae at the level of family and genera remains unresolved due to conflicting plastid genes, limited molecular data and incomplete taxon sampling of previous studies. The present study generated 30 new plastid genomes of Dennstaedtiaceae (9 genera, 29 species), which were combined with 42 publicly available plastid genomes (including 24 families, 27 genera, 42 species) to explore the evolution of Dennstaedtiaceae. In order to minimize the impact of systematic errors on the resolution of phylogenetic inference, we applied six strategies to generate 30 datasets based on CDS, intergenic spacers, and whole plastome, and two tree inference methods (maximum-likelihood, ML; and multispecies coalescent, MSC) to comprehensively analyze the plastome-scale data. Besides, the phylogenetic signal among all loci was quantified for controversial nodes using ML framework, and different topologies hypotheses among all datasets were tested. The species trees based on different datasets and methods revealed obvious conflicts at the base of the polypody ferns. The topology of the "CDS-codon-align-rm3" (CDS with the removal of the third codon) matrix was selected as the primary reference or summary tree. The final phylogenetic tree supported Dennstaedtiaceae as the sister group to eupolypods, and Dennstaedtioideae was divided into four clades with full support. This robust reconstructed phylogenetic backbone establishes a framework for future studies on Dennstaedtiaceae classification, evolution and diversification. The present study suggests considering plastid phylogenomic conflict when using plastid genomes. From our results, reducing saturated genes or sites can effectively mitigate tree conflicts for distantly related taxa. Moreover, phylogenetic trees based on amino acid sequences can be used as a comparison to verify the confidence of nucleotide-based trees.

18.
Front Surg ; 9: 899195, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36338644

RESUMO

Background: Pierre Robin sequence (PRS) is a congenital craniofacial deformity characterized by micrognathia, glossoptosis and airway obstruction. Some affected neonates are born with severe life-threatening upper airway obstruction that requires surgery. If without timely treatment, it is possible to cause not only organ damage and developmental abnormalities but also early newborn mortality. Case presentation: In this report, a 51-hours-old neonate was diagnosed with PRS, who had severe upper airway obstruction and required surgery. We performed the modified mandible traction with wires at four days old and achieved a satisfactory result in improving airway obstruction. No other complications were observed except for mild local infection. No overlap of other more complex syndromes was found, such as ocular abnormalities, hearing loss, other skeletal abnormalities, cardiac abnormalities or other atypical abnormalities. At the present follow-up until 2 years old, there were no significant differences in the maxillofacial appearance, teeth growth, breathing, feeding, growth and development between the patient and normal children. Conclusion: The modified mandible traction with wires can safely and effectively resolve micrognathia, the key to treating PRS, which is minimally invasive, simple and provides immediate relief of airway obstruction with no long term complications compared with other surgical methods. This report aims to provide more evidence of the successful treatment of neonatal PRS micrognathia by modified mandible traction with wires.

19.
Foods ; 11(18)2022 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-36141055

RESUMO

Daqu provides functional microbiota and various nutrients for artificial pit mud (APM) cultivation. However, little is known about whether its attributes affect the microbiome and metabolome of APM. Here, two types of APM were manufactured by adding fortified Daqu (FD) and conventional Daqu (CD); they were comprehensively compared by polyphasic detection methods after being used for two years. The results showed that FD altered the prokaryotic communities rather than the fungal ones, resulting in increased archaea and Clostridium_sensu_stricto_12 and decreased eubacteria and Lactobacillus. Correlation analysis suggested that these variations in community structure promoted the formation of hexanoic acid, butyric acid, and the corresponding ethyl esters, whereas they inhibited that of lactic acid and ethyl lactate and thus improved the flavor quality of the APM. Notably, pH was the main driving factor for the bacterial community variation, and the total acid mediated the balance between the stochastic and the deterministic processes. Furthermore, the results of the network analysis and PICRUSt2 indicated that FD also enhanced the modularity and robustness of the co-occurrence network and the abundance of enzymes related to hexanoic acid and butyric acid production. Our study highlights the importance of Daqu attributes in APM cultivation, which are of great significance for the production of high-quality strong-flavor Baijiu.

20.
World J Clin Cases ; 10(26): 9323-9331, 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36159406

RESUMO

BACKGROUND: Gardnerella vaginalis (G. vaginalis) is a facultative anaerobic bacteria known to cause bloodstream infections. However, cases are very rare in clinics. There is very limited clinical experience in the treatment of bloodstream infections caused by G. vaginalis. Therefore, there is an urgent need for effective antibacterial drugs to treat patients with bloodstream infections caused by G. vaginalis. CASE SUMMARY: A woman who underwent a cesarean section presented with a sudden onset of high fever 1-d post-surgery. The blood cultures suggested an infection due to G. vaginalis, and treatment with cefoperazone-sulbactam was started. After 5 d of treatment, there was a decrease in the hemogram; however, the temperature and C-reactive protein levels remained high. Based on clinical experience and a review of literature, the treatment was modified to include ornidazole in combination with cefoperazone-sulbactam. Following a week of treatment, the temperature, hemogram and C-reactive protein levels returned to normal, and blood cultures turned negative, suggesting a therapeutic effect of the combination treatment. CONCLUSION: This case highlighted the effective use of cefoperazone-sulbactam combined with ornidazole for bloodstream infection caused by G. vaginalis following a cesarean section.

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