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1.
Am J Pathol ; 193(11): 1833-1844, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37423550

RESUMO

Retinal detachment (RD) refers to the separation between the neuroepithelium and the pigment epithelium layer. It is an important disease leading to irreversible vision damage worldwide, in which photoreceptor cell death plays a major role. α-Synuclein (α-syn) is reportedly involved in numerous mechanisms of neurodegenerative diseases, but the association with photoreceptor damage in RD has not been studied. In this study, elevated transcription levels of α-syn and parthanatos proteins were observed in the vitreous of patients with RD. The expression of α-syn- and parthanatos-related proteins was increased in experimental rat RD, and was involved in the mechanism of photoreceptor damage, which was related to the decreased expression of miR-7a-5p (miR-7). Interestingly, subretinal injection of miR-7 mimic in rats with RD inhibited the expression of retinal α-syn and down-regulated the parthanatos pathway, thereby protecting retinal structure and function. In addition, interference with α-syn in 661W cells decreased the expression of parthanatos death pathway in oxygen and glucose deprivation model. In conclusion, this study demonstrates the presence of parthanatos-related proteins in patients with RD and the role of the miR-7/α-syn/parthanatos pathway in photoreceptor damage in RD.


Assuntos
MicroRNAs , Parthanatos , Descolamento Retiniano , Ratos , Humanos , Animais , Descolamento Retiniano/genética , Descolamento Retiniano/metabolismo , Apoptose , Células Fotorreceptoras de Vertebrados/metabolismo , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismo , Células Fotorreceptoras/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Modelos Animais de Doenças
2.
Immunology ; 170(3): 301-318, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37317655

RESUMO

According to reports, gut microbiota and metabolites regulate the intestinal immune microenvironment. In recent years, an increasing number of studies reported that bile acids (BAs) of intestinal flora origin affect T helper cells and regulatory T cells (Treg cells). Th17 cells play a pro-inflammatory role and Treg cells usually act in an immunosuppressive role. In this review, we emphatically summarised the influence and corresponding mechanism of different configurations of lithocholic acid (LCA) and deoxycholic acid (DCA) on intestinal Th17 cells, Treg cells and intestinal immune microenvironment. The regulation of BAs receptors G protein-coupled bile acid receptor 1 (GPBAR1/TGR5) and farnesoid X receptor (FXR) on immune cells and intestinal environment are elaborated. Furthermore, the potential clinical applications above were also concluded in three aspects. The above will help researchers better understand the effects of gut flora on the intestinal immune microenvironment via BAs and contribute to the development of new targeted drugs.


Assuntos
Microbioma Gastrointestinal , Receptores Acoplados a Proteínas G/metabolismo , Intestinos , Ácidos e Sais Biliares
3.
Mol Cancer ; 22(1): 29, 2023 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-36759842

RESUMO

In recent years, breakthroughs have been made in tumor immunotherapy. However, tumor immunotherapy, particularly anti-PD-1/PD-L1 immune checkpoint inhibitors, is effective in only a small percentage of patients in solid cancer. How to improve the efficiency of cancer immunotherapy is an urgent problem to be solved. As we all know, the state of the tumor microenvironment (TME) is an essential factor affecting the effectiveness of tumor immunotherapy, and the cancer-associated fibroblasts (CAFs) in TME have attracted much attention in recent years. As one of the main components of TME, CAFs interact with cancer cells and immune cells by secreting cytokines and vesicles, participating in ECM remodeling, and finally affecting the immune response process. With the in-depth study of CAFs heterogeneity, new strategies are provided for finding targets of combination immunotherapy and predicting immune efficacy. In this review, we focus on the role of CAFs in the solid cancer immune microenvironment, and then further elaborate on the potential mechanisms and pathways of CAFs influencing anti-PD-1/PD-L1 immunotherapy. In addition, we summarize the potential clinical application value of CAFs-related targets and markers in solid cancers.


Assuntos
Fibroblastos Associados a Câncer , Neoplasias , Humanos , Antígeno B7-H1/metabolismo , Fibroblastos Associados a Câncer/metabolismo , Citocinas/metabolismo , Neoplasias/metabolismo , Imunoterapia , Microambiente Tumoral
4.
Endocr Pract ; 28(2): 148-158, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33610808

RESUMO

OBJECTIVE: Nondipping heart rate (HR), defined as a night/day HR ratio >0.90, has been associated with increased mortality in epidemiologic studies. However, its prognostic value in stage 5 chronic kidney disease (CKD5) patients and the effects of parathyroidectomy (PTX) on nondipping HR remain unknown. METHODS: This case-control study of 162 healthy controls and 502 CKD5 patients was performed between 2011 and 2018, in which CKD5 patients were further divided into non-PTX (n = 186) and severe secondary hyperparathyroidism (SHPT) with PTX (n = 316) subgroups. Each participant underwent 24-hour Holter monitoring for HR ratio. Mortality was followed up in CKD5 patients (median time: 46.0 months). RESULTS: The HR ratio in CKD5 patients was higher than in controls (0.92 ± 0.08 vs 0.81 ± 0.08, P <.001), associated with a 44% increase in mortality risk per 0.1 increment (hazard ratio, 1.44; 95% CI: 1.02-2.03; P =.04), and was positively related to serum intact parathyroid hormone levels (P <.001). PTX reversed nondipping HR in SHPT patients (n = 50, median time: 6.3 months, P <.001). Survival probabilities for PTX (n = 294) were better than non-PTX (n = 47) (hazard ratio, 0.31; 95% CI: 0.14-0.67; P <.01) in SHPT patients (serum intact parathyroid hormone >500.0 pg/mL). CONCLUSION: CKD5 patients displayed a nondipping HR pattern, which is a prognostic marker of all-cause mortality. PTX for SHPT patients was associated with a reversal in nondipping HR ratio, which may mediate a better outcome.


Assuntos
Hiperparatireoidismo Secundário , Falência Renal Crônica , Insuficiência Renal Crônica , Estudos de Casos e Controles , Frequência Cardíaca , Humanos , Hiperparatireoidismo Secundário/cirurgia , Hormônio Paratireóideo , Paratireoidectomia
5.
Environ Microbiol ; 23(2): 757-773, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32656931

RESUMO

A LuxI/R-like quorum sensing (QS) system (AfeI/R) has been reported in the acidophilic and chemoautotrophic Acidithiobacillus spp. However, the function of AfeI/R remains unclear because of the difficulties in the genetic manipulation of these bacteria. Here, we constructed different afeI mutants of the sulfur- and iron-oxidizer A. ferrooxidans, identified the N-acyl homoserine lactones (acyl-HSLs) synthesized by AfeI, and determined the regulatory effects of AfeI/R on genes expression, extracellular polymeric substance synthesis, energy metabolism, cell growth and population density of A. ferrooxidans in different energy substrates. Acyl-HSLs-mediated distinct regulation strategies were employed to influence bacterial metabolism and cell growth of A. ferrooxidans cultivated in either sulfur or ferrous iron. Based on these findings, an energy-substrate-dependent regulation mode of AfeI/R in A. ferrooxidans was illuminated that AfeI/R could produce different types of acyl-HSLs and employ specific acyl-HSLs to regulate specific genes in response to different energy substrates. The discovery of the AfeI/R-mediated substrate-dependent regulatory mode expands our knowledge on the function of QS system in the chemoautotrophic sulfur- and ferrous iron-oxidizing bacteria, and provides new insights in understanding energy metabolism modulation, population control, bacteria-driven bioleaching process, and the coevolution between the acidophiles and their acidic habitats.


Assuntos
Acidithiobacillus/metabolismo , Acil-Butirolactonas/metabolismo , Metabolismo Energético/fisiologia , Percepção de Quorum/fisiologia , Acidithiobacillus/genética , Acidithiobacillus/crescimento & desenvolvimento , Proteínas de Bactérias/metabolismo , Matriz Extracelular de Substâncias Poliméricas/metabolismo , Regulação Bacteriana da Expressão Gênica/genética , Ferro/metabolismo , Percepção de Quorum/efeitos dos fármacos , Enxofre/metabolismo , Fatores de Transcrição/metabolismo
6.
Endocr Pract ; 27(11): 1065-1071, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33895317

RESUMO

OBJECTIVE: Persistent secondary hyperparathyroidism (SHPT) may occur because of residual cervicothoracic parathyroids in parathyroidectomy (PTX) patients with chronic kidney disease. We prospectively compared the predictive values of intraoperative plasma (1-84) parathyroid hormone (PTH) and intact PTH (iPTH) levels to improve the safety and efficacy of PTX. METHODS: We included 100 healthy controls, 162 stage 5 chronic kidney disease patients without SHPT, and 214 patients who underwent PTX because of SHPT. Plasma iPTH and (1-84) PTH levels were measured before incision (io-iPTH0 and io-[1-84]PTH0, respectively) and 10 minutes (io-iPTH10 and io-[1-84]PTH10, respectively) and 20 minutes (io-iPTH20 and io-[1-84]PTH20, respectively) after removing all parathyroids. The percentage reduction of iPTH and (1-84) PTH at 10 minutes (io-iPTH10% and io-[1-84]PTH10%, respectively) and 20 minutes (io-iPTH20%, and io-[1-84]PTH20%, respectively) was calculated. iPTH and (1-84) PTH were measured using second- and third-generation PTH assays, respectively. RESULTS: Compared with the controls and non-PTX patients, the PTX group had more obvious mineral metabolism disorders. There were 187 successful PTXs, 19 patients with persistent SHPT, and 8 patients lost to follow-up. The receiver operating characteristic curves revealed that io-(1-84)PTH10% >86.6% and io-(1-84)PTH20% >87.5% suggested successful PTX. The sensitivity of io-iPTH20% and io-(1-84)PTH20% were higher than those at the timepoint of 10 minutes. Moreover, the specificity and sensitivity of the (1-84) PTH reduction percentage were superior to that of iPTH. CONCLUSION: Intraoperative reduction percentages of plasma (1-84) PTH levels are superior to iPTH for accurately predicting successful PTX, especially at 20 minutes after all cervicothoracic parathyroids had been resected.


Assuntos
Hiperparatireoidismo Secundário , Falência Renal Crônica , Humanos , Hiperparatireoidismo Secundário/diagnóstico , Hiperparatireoidismo Secundário/cirurgia , Glândulas Paratireoides , Hormônio Paratireóideo , Paratireoidectomia
7.
Ren Fail ; 43(1): 890-899, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34044733

RESUMO

INTRODUCTION: Circulating intact parathyroid hormone (iPTH) levels include full-length (1-84) PTH and long C-PTH fragments, but primarily (7-84) PTH, which have been reported to have antagonistic effects on the bones and kidneys. However, their effects on the cardiovascular system remain unclear. In this study, the relationships between the plasma PTH fragments levels and heart rate variability (HRV) in stage 5 chronic kidney disease (CKD5) patients are explored. Furthermore, the effects of parathyroidectomy (PTX) on the above indices are investigated. METHODS: In this cross-sectional study, 164 healthy controls and 354 CKD5 patients, including 208 secondary hyperparathyroidism (SHPT) subgroup with PTX, were enrolled. Circulating (7-84) PTH levels were calculated by subtracting plasma (1-84) PTH levels from iPTH levels. The HRV parameters were measured using a 24-hour Holter. RESULTS: The baseline levels of plasma iPTH, (1-84) PTH, and (7-84) PTH in the CKD5 patients were 930.40 (160.65, 1792.50) pg/mL, 448.60 (99.62, 850.45) pg/mL, and 468.20 (54.22, 922.55) pg/mL, respectively. In the CKD5 patients, plasma (1-84) PTH levels were independently correlated with the standard deviation of the normal-to-normal R-R intervals (SDNN) and the standard deviation of the five-minute average of the normal R-R intervals (SDANN). With a median follow up time of 6.50 months after PTX in the SHPT patients (n = 30), improved SDNN and SDANN markers were related with decreased (1-84) PTH levels. Furthermore, an improved SDNN was related with decreased (7-84) PTH levels. CONCLUSIONS: The CKD5 patients' baseline (1-84) PTH levels were correlated with the SDNN and SDANN. After PTX, an improved SDNN was related with decreased (1-84) PTH and (7-84) PTH levels, while improved SDANN was related with decreased (1-84) PTH levels. No antagonistic effects of (1-84) PTH and (7-84) PTH on HRV were found in the CKD5 patients.


Assuntos
Frequência Cardíaca/fisiologia , Hormônio Paratireóideo/sangue , Paratireoidectomia , Insuficiência Renal Crônica/sangue , Adulto , Estudos de Casos e Controles , China , Estudos Transversais , Feminino , Humanos , Hiperparatireoidismo Secundário/sangue , Hiperparatireoidismo Secundário/cirurgia , Masculino , Pessoa de Meia-Idade , Análise de Regressão
8.
Front Microbiol ; 15: 1412776, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38903802

RESUMO

Prodigiosin (PG) is a red tripyrrole pigment from the prodiginine family that has attracted widespread attention due to its excellent biological activities, including anticancer, antibacterial and anti-algal activities. The synthesis and production of PG is of particular significance, as it has the potential to be utilized in a number of applications, including those pertaining to clinical drug development, food safety, and environmental management. This paper provides a systematic review of recent research on PG, covering aspects like chemical structure, bioactivity, biosynthesis, gene composition and regulation, and optimization of production conditions, with a particular focus on the biosynthesis and regulation of PG in Serratia marcescens. This provides a solid theoretical basis for the drug development and production of PG, and is expected to promote the further development of PG in medicine and other applications.

9.
Virology ; 598: 110166, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-39024722

RESUMO

Porcine epidemic diarrhea virus (PEDV) results in severe economic losses to the swine industry due to its widespread prevalence and high mortality. Currently, there is no effective treatment against PEDV. New antiviral therapies are urgently needed to control this highly contagious pathogen. In this research, the anti-PEDV activity and mechanism of Dehydroevodiamine (DHED) were investigated in vitro. Our results showed that DHED exerted satisfactory anti-PEDV activity by ameliorating cytopathic effects (CPEs), reducing virus titer, and inhibiting PEDV N protein expression and gene transcription dose-dependently. The antiviral mechanism of DHED is related to its inhibition of the entry, replication, and assembly stages of PEDV life cycle. In addition, DHED can regulate the MAPK signaling pathway, and suppress phosphorylated ERK1/2 activation, thus exerting antiviral effects. In conclusion, our research confirmed the anti-PEDV activity and mechanism of DHED, preliminarily providing a new strategy for anti-PEDV drug development.

10.
Ultrason Sonochem ; 107: 106936, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38834000

RESUMO

This study focuses on developing a water-in-oil-in-water (W1/O/W2) double emulsion system using high-intensity ultrasound (HIU)-treated pea protein isolate (HIU-PPI) and pectin to encapsulate Lactobacillus plantarum (L. plantarum). The effects of ultrasound treatment on pea protein isolate (PPI) characteristics such as solubility, particle size, emulsification, surface hydrophobicity, and surface free sulfhydryl group were examined, determining optimal HIU processing conditions was 400 W for 10 min. The developed W1/O/W2 double emulsion system based on HIU-PPI demonstrated effective encapsulation and protection of L. plantarum, especially at the HIU-PPI concentration of 4 %, achieving an encapsulation efficiency of 52.65 %. Incorporating both HIU-PPI and pectin as emulsifiers increased the particle size and significantly enhanced the emulsion's viscosity. The highest bacterial encapsulation efficiency of the emulsion, 59.94 %, was attained at a HIU to pectin concentration ratio of 3:1. These emulsions effectively encapsulate and protect L. plantarum, with the concentration of HIU-PPI being a critical factor in enhancing probiotic survival under simulated gastrointestinal digestion. However, the concurrent utilization of pectin and HIU-PPI as emulsifiers did not provide a notable advantage compared to the exclusive use of HIU-PPI in enhancing probiotic viability during in vitro simulated digestion. This research offers valuable perspectives for the food industry on harnessing environmentally friendly, plant-based proteins as emulsifiers in probiotic delivery systems. It underscores the potential of HIU-modified pea protein and pectin in developing functional food products that promote the health benefits of probiotics.


Assuntos
Emulsões , Lactobacillus plantarum , Proteínas de Ervilha , Pectinas , Proteínas de Ervilha/química , Pectinas/química , Tamanho da Partícula , Água/química , Ondas Ultrassônicas , Sonicação , Solubilidade , Probióticos/química , Óleos/química , Interações Hidrofóbicas e Hidrofílicas
11.
Front Microbiol ; 15: 1354447, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38384263

RESUMO

Akkermansia muciniphila is a gram-negative bacterium that colonizes the human gut, making up 3-5% of the human microbiome. A. muciniphila is a promising next-generation probiotic with clinical application prospects. Emerging studies have reported various beneficial effects of A. muciniphila including anti-cancer, delaying aging, reducing inflammation, improving immune function, regulating nervous system function, whereas knowledge on its roles and mechanism in infectious disease is currently unclear. In this review, we summarized the basic characteristics, genome and phenotype diversity, the influence of A. muciniphila and its derived components on infectious diseases, such as sepsis, virus infection, enteric infection, periodontitis and foodborne pathogen induced infections. We also provided updates on mechanisms how A. muciniphila protects intestinal barrier integrity and modulate host immune response. In summary, we believe that A. muciniphila is a promising therapeutic probiotic that may be applied for the treatment of a variety of infectious diseases.

12.
Front Cell Infect Microbiol ; 14: 1324895, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38465230

RESUMO

Klebsiella pneumoniae is a Gram-negative bacterium within the Enterobacteriaceae family that can cause multiple systemic infections, such as respiratory, blood, liver abscesses and urinary systems. Antibiotic resistance is a global health threat and K. pneumoniae warrants special attention due to its resistance to most modern day antibiotics. Biofilm formation is a critical obstruction that enhances the antibiotic resistance of K. pneumoniae. However, knowledge on the molecular mechanisms of biofilm formation and its relation with antibiotic resistance in K. pneumoniae is limited. Understanding the molecular mechanisms of biofilm formation and its correlation with antibiotic resistance is crucial for providing insight for the design of new drugs to control and treat biofilm-related infections. In this review, we summarize recent advances in genes contributing to the biofilm formation of K. pneumoniae, new progress on the relationship between biofilm formation and antibiotic resistance, and new therapeutic strategies targeting biofilms. Finally, we discuss future research directions that target biofilm formation and antibiotic resistance of this priority pathogen.


Assuntos
Infecções por Klebsiella , Klebsiella pneumoniae , Humanos , Klebsiella pneumoniae/genética , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/microbiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Resistência Microbiana a Medicamentos , Biofilmes , Testes de Sensibilidade Microbiana
13.
Poult Sci ; 103(4): 103501, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38350386

RESUMO

Previous studies have shown that avian hepatitis E virus (HEV) decreases egg production by 10-40% in laying hens, but have not fully elucidated the mechanism of there. In this study, we evaluated the replication of avian HEV in the ovaries of laying hens and the mechanism underlying the decrease in egg production. Forty 150-days-old commercial laying hens were randomly divided into 2 groups of 20 hens each. A total of 1 mL (104GE) of avian HEV stock was inoculated intravenously into each chicken in the experimental group, with 20 chickens in the other group serving as negative controls. Five chickens from each group were necropsied weekly for histopathological examination. The pathogenicity of avian HEV has been characterized by seroconversion, viremia, fecal virus shedding, ovarian lesions, and decreased egg production. Both positive and negative-strand avian HEV RNA, and ORF2 antigens can be detected in the ovaries, suggesting that avian HEV can replicate in the ovaries and serve as an important extrahepatic replication site. The ovaries of laying hens underwent apoptosis after avian HEV infection. These results indicate that avian HEV infection and replication in ovarian tissues cause structural damage to the cells, leading to decreased egg production.


Assuntos
Vírus da Hepatite E , Hepevirus , Cistos Ovarianos , Neoplasias Ovarianas , Doenças das Aves Domésticas , Animais , Feminino , Galinhas , Cistos Ovarianos/veterinária , Neoplasias Ovarianas/veterinária , Hepevirus/genética , Apoptose
14.
Biomed Pharmacother ; 174: 116576, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38593707

RESUMO

PURPOSE: We aim to establish an LPS-induced human aortic endothelial cells (HAECs) inflammatory injury model and explore the optimal conditions for inducing its injury. We expect to provide modeling references for the related experiments of vascular inflammatory diseases. METHODS: HAECs were cultured in vitro and treated with different concentrations of lipopolysaccharide (LPS) (0.1, 1, 10, 50, 100 µg/mL) for 6, 12, and 24 h to establish the HAECs inflammatory injury model. The cell viability was determined by CCK-8 assay; the expression levels of inflammatory cytokines in the cells were detected by RT-PCR;the apoptosis rate of the cells was detected by flow cytometry. RESULTS: ① Within 24 h of LPS treatment, the cell viability of the 0.1 and 1 µg/mL groups showed an overall increasing trend with time, while the cell viability of the 10, 50, and 100 µg/mL groups increased first and then decreased with time, and the cell viability of 50 and 100 µg/mL groups was significantly lower than the normal control group at 24 h (P<0.01). ② RT-PCR results showed that after 50 and 100 µg/mL LPS for 24 h, the inflammatory cytokines all showed an apparent upward trend compared with the normal control group (P<0.05), which was more significant in the 100 µg/mL group. ③ After 100 µg/mL LPS for 24 h, the apoptotic necrosis rate of HAECs was higher than the normal control group (P<0.01). CONCLUSIONS: This experiment successfully established a HAECs injury model, indicating that the optimal conditions for inducing injury are an LPS concentration of 100 µg/mL and a treatment time of 24 h.


Assuntos
Aorta , Apoptose , Sobrevivência Celular , Citocinas , Células Endoteliais , Inflamação , Lipopolissacarídeos , Humanos , Aorta/patologia , Aorta/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Sobrevivência Celular/efeitos dos fármacos , Inflamação/patologia , Inflamação/induzido quimicamente , Apoptose/efeitos dos fármacos , Citocinas/metabolismo , Células Cultivadas , Mediadores da Inflamação/metabolismo , Relação Dose-Resposta a Droga , Modelos Biológicos
15.
J Pharm Anal ; 14(5): 100909, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38799235

RESUMO

Atherosclerosis (AS) is a chronic inflammatory disease of large and medium-sized arteries that leads to ischemic heart disease, stroke, and peripheral vascular disease. Despite the current treatments, mortality and disability still remain high. Sonodynamic therapy (SDT), a non-invasive and localized methodology, has been developed as a promising new treatment for inhibiting atherosclerotic progression and stabilizing plaques. Promising progress has been made through cell and animal assays, as well as clinical trials. For example, the effect of SDT on apoptosis and autophagy of cells in AS, especially macrophages, and the concept of non-lethal SDT has also been proposed. In this review, we summarize the ultrasonic parameters and known sonosensitizers utilized in SDT for AS; we elaborate on SDT's therapeutic effects and mechanisms in terms of macrophages, T lymphocytes, neovascularization, smooth muscle cells, lipid, extracellular matrix and efferocytosis within plaques; additionally, we discuss the safety of SDT. A comprehensive summary of the confirmed effects of SDT on AS is conducted to establish a framework for future researchers.

16.
Virulence ; 15(1): 2331265, 2024 12.
Artigo em Inglês | MEDLINE | ID: mdl-38532247

RESUMO

Flagella play a crucial role in the invasion process of Salmonella and function as a significant antigen that triggers host pyroptosis. Regulation of flagellar biogenesis is essential for both pathogenicity and immune escape of Salmonella. We identified the conserved and unknown function protein STM0435 as a new flagellar regulator. The ∆stm0435 strain exhibited higher pathogenicity in both cellular and animal infection experiments than the wild-type Salmonella. Proteomic and transcriptomic analyses demonstrated dramatic increases in almost all flagellar genes in the ∆stm0435 strain compared to wild-type Salmonella. In a surface plasmon resonance assay, purified STM0435 protein-bound c-di-GMP had an affinity of ~8.383 µM. The crystal structures of apo-STM0435 and STM0435&c-di-GMP complex were determined. Structural analysis revealed that R33, R137, and D138 of STM0435 were essential for c-di-GMP binding. A Salmonella with STM1987 (GGDEF protein) or STM4264 (EAL protein) overexpression exhibits completely different motility behaviours, indicating that the binding of c-di-GMP to STM0435 promotes its inhibitory effect on Salmonella flagellar biogenesis.


Assuntos
Proteínas de Bactérias , GMP Cíclico/análogos & derivados , Proteômica , Animais , Virulência , Proteínas de Bactérias/genética , Biofilmes , Salmonella/metabolismo , GMP Cíclico/análise , GMP Cíclico/metabolismo , Regulação Bacteriana da Expressão Gênica
17.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 33(8): 1129-34, 2013 Aug.
Artigo em Zh | MEDLINE | ID: mdl-24325068

RESUMO

OBJECTIVE: To study effects of Yishen Kangxian Compound (YKC) and benazepril containing serums on HK-2 cells (human renal proximal tubule epithelial cells) in the process of renal tubular epithelial cells to mesenchymal myofibroblasts transdifferentiation (TEMT) by gene chip. METHODS: YKC and benazepril containing serums were prepared. Their inhibitory effects on HK-2 cells in the transforming growth factor-beta1 (TGF-beta1)-induced TEMT process were observed. HK-2 cells were randomly divided into four groups, i.e., the blank control group, the model group, the benazepril group, and the YKC group. The gross RNAs were extracted and purified by taking advantage of the HumanHT-12 v4 of IlluminaBeadChip. Differentially expressed genes were obtained after they were reversely transcribed to cDNA, incorporating biotin labeling probe, hybridized with GeneChip, picture signals of fluorescence in gene array scanned and compared with differential genes by computer analysis. RESULTS: Differentially expressed genes were successfully identified by gene chip. Compared with the model group, there were 227 differentially expressed genes in the benazepril group, including 118 up-regulated genes and 109 downregulated genes. Compared with the model group, there were 97 differentially expressed genes in the YKC group, including 69 up-regulated genes and 28 down-regulated genes. The Gene Ontology (GO) analysis indicated that YKC was more actively involved in the regulatory process than benazepril in terms of cell damage, apoptosis, growth, NF-KB, protein kinase, neuron, and blood vessel growth. CONCLUSIONS: YKC and benazepril could inhibit the TEMT process of HK-2 cells. But YKC also had taken part in cell damage, apoptosis, growth,and more pathways of early stage TEMT.


Assuntos
Transdiferenciação Celular/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Células Epiteliais/efeitos dos fármacos , Linhagem Celular , Células Epiteliais/citologia , Genômica , Humanos , Túbulos Renais Proximais/citologia , Túbulos Renais Proximais/patologia
18.
Metabolites ; 13(8)2023 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-37623832

RESUMO

Atractylodes chinensis (DC.) Koidez. (AC) is a type of Atractylodis Rhizoma that is widely used in China to treat diarrhea and arthritis, as well as a nutritional supplement. The objective of this study was to investigate and identify the phytochemicals in the aqueous extract of AC using an ultra-high-performance liquid chromatography (UHPLC)-Orbitrap-HRMS platform based on a non-targeted metabolomic approach. There were 76 compounds in the AC, the majority of which were phenylpropanoids (16) and terpenoids (15). The hierarchical clustering analysis (HCA) and principal component analysis (PCA) results revealed variations across eight AC samples and classified them into four groups. Using Pareto modeling, the orthogonal partial least squares-discriminant analysis (OPLS-DA) identified 11 distinct AC compounds. Furthermore, the antioxidant activity of eight AC samples was assessed using ABTS, DPPH, and OH· methods. The AC samples with concentrations ranging from 0 to 25 mg/mL had no toxic effects on A549 cells. They have a strong therapeutic potential against oxidation-related diseases, and further research on AC is warranted.

19.
Int J Ophthalmol ; 16(3): 348-353, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36935782

RESUMO

AIM: To detect the concentrations of reactive oxygen species (ROS), transient receptor potential mucin-1 (TRPML1), and autophagy-related (Atg) proteins (LC3-I, LC3-II, and Beclin1) in vitreous humor of patients with simple rhegmatogenous retinal detachment (RRD). METHODS: RRD patients enrolled as the RRD group, and patients with idiopathic macular hole (IMH) and idiopathic macular epiretinal membrane (IMEM) were enrolled as control group. The levels of ROS, TRPML1, LC3-I, LC3-II, and Beclin1 in vitreous humor of patients in the RRD and control groups were detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: The RRD group included 28 eyes 28 patients and had a higher concentration of ROS in vitreous humor (631.86±18.05 vs 436.34±108.22 IU/mL, P<0.05). The ROS level in patients with a wide retinal detachment (RD) extent (RD range ≥1/2) was higher than that with a narrow RD extent (RD range<1/2, P<0.05). ROS concentration was negatively correlated with RD time (r=-0.46, P=0.01). The expression levels of LC3-I and Beclin1 significantly decreased in RRD (P<0.05), but there were no correlations with the RD time, RD extent, or macular involvement. CONCLUSION: In eyes with RRD, the concentration of ROS in vitreous humor increases and the expression levels of Atg proteins decrease, reflecting possibly that autophagy is inhibited.

20.
Nutrients ; 14(9)2022 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-35565730

RESUMO

Body dissatisfaction and eating disorders have become major global concerns, including in Asian populations. Few studies have examined intervention effects on body dissatisfaction and disordered eating in China, especially for interventions with positive psychological perspectives (e.g., intuitive eating). In this pilot study, 66 women participated in an eight-module intuitive eating intervention delivered online (n = 42; mean age, 30.74 years) and face-to-face (n = 24; mean age, 19.46 years) for 8 weeks. Measures of body image and eating behaviors were used to assess the intervention's feasibility, acceptability, and initial efficacy. Linear mixed models were used to analyze the data. The intervention had significant effects on both groups, promoting positive body image and intuitive eating and reducing negative body image and disordered eating behaviors. The effects of the online and face-to-face interventions did not differ significantly. Thus, whether delivered online or face-to-face, an intuitive eating intervention may effectively improve Chinese women's body image and eating behaviors. However, the efficacy of the intuitive intervention in the Chinese context should be confirmed in future studies with designs in randomized control trials.


Assuntos
Imagem Corporal , Transtornos da Alimentação e da Ingestão de Alimentos , Adulto , Imagem Corporal/psicologia , China , Estudos de Viabilidade , Comportamento Alimentar/psicologia , Feminino , Humanos , Projetos Piloto , Adulto Jovem
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