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1.
Int J Mol Sci ; 25(11)2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38892073

RESUMO

Xanthomonas oryzae pv. oryzicola (Xoc) is a notorious plant pathogen. Like most bacterial pathogens, Xoc has evolved a complex regulatory network to modulate the expression of various genes related to pathogenicity. Here, we have identified TfmR, a transcriptional regulator belonging to the TetR family, as a key player in the virulence mechanisms of this phytopathogenic bacterium. We have demonstrated genetically that tfmR is involved in the hypersensitive response (HR), pathogenicity, motility and extracellular polysaccharide production of this phytopathogenic bacterium. Our investigations extended to exploring TfmR's interaction with RpfG and HrpX, two prominent virulence regulators in Xanthomonas species. We found that TfmR directly binds to the promoter region of RpfG, thereby positively regulating its expression. Notably, constitutive expression of RpfG partly reinstates the pathogenicity compromised by TfmR-deletion mutants. Furthermore, our studies revealed that TfmR also exerts direct positive regulation on the expression of the T3SS regulator HrpX. Similar to RpfG, sustained expression of HrpX partially restores the pathogenicity of TfmR-deletion mutants. These findings underscore TfmR's multifaceted role as a central regulator governing key virulence pathways in Xoc. Importantly, our research sheds light on the intricate molecular mechanisms underlying the regulation of pathogenicity in this plant pathogen.


Assuntos
Proteínas de Bactérias , Regulação Bacteriana da Expressão Gênica , Doenças das Plantas , Regiões Promotoras Genéticas , Fatores de Transcrição , Xanthomonas , Xanthomonas/patogenicidade , Xanthomonas/genética , Xanthomonas/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Virulência/genética , Doenças das Plantas/microbiologia , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Oryza/microbiologia
2.
Physiol Plant ; 172(2): 733-747, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33215699

RESUMO

As a conserved microRNA (miRNA) family in plants, miR408 is known to be involved in different abiotic stress responses, including drought. Interestingly, some studies indicated a species- and/or cultivar-specific drought-responsive characteristic of miR408 in plant drought stress. Moreover, the functions of miR408 in perennial grass species are unknown. In this study, we investigated the role of miR408 in perennial ryegrass (Lolium perenne L.) by withholding water for 10 days for both wild type and transgenic plants with heterologous expression of rice (Oryza sativa L.) miR408 gene, Os-miR408. The results showed that transgenic perennial ryegrass plants displayed morphological changes under normal growth conditions, such as curl leaves and sunken stomata, which could be related to decreased leaf water loss. Moreover, transgenic perennial ryegrass exhibited improved drought tolerance, as demonstrated by maintaining higher leaf relative water content (RWC), lower electrolyte leakage (EL), and less lipid peroxidation compared to WT plants under drought stress. Furthermore, the transgenic plants showed higher antioxidative capacity under drought. These results showed that the improved drought tolerance in Os-miR408 transgenic plants could be due to leaf morphological changes favoring the maintenance of water status and to increased antioxidative capacity protecting against the reactive oxygen species damages under stress. These findings implied that miR408 could serve as a potential target for genetic manipulations to engineer perennial grass plants for improved water stress tolerance.


Assuntos
Secas , Lolium , MicroRNAs/genética , Estresse Fisiológico , Regulação da Expressão Gênica de Plantas , Lolium/genética , Lolium/metabolismo , Oryza/genética , Folhas de Planta/genética , Folhas de Planta/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/metabolismo
3.
Drug Dev Res ; 82(8): 1206-1216, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34056735

RESUMO

Bladder cancer is one of the most common types of urothelial carcinoma with a rising incidence rate worldwide. Circular RNAs (circRNAs) are involved in the development of numerous cancers, including bladder cancer. We aimed to uncover the role and associated mechanism of circMYLK in bladder cancer. The expression levels of circMYLK, miRNA-34a (miR-34a) and Cyclin D3 (CCND3) mRNA were investigated using real-time quantitative polymerase chain reaction. The protein level of CCND3 was investigated using western blot. In functional assays, flow cytometry assays were utilized for cell cycle analysis and cell apoptosis analysis. Transwell assays were used for cell migration and invasion analysis. Caspase-3 activity was examined to monitor cell apoptosis. The putative relationship between miR-34a and circMYLK or CCND3 was validated by dual-luciferase reporter assay and RNA immunoprecipitation assay. CircMYLK was highly expressed in bladder cancer tissues and cells. CircMYLK downregulation inhibited bladder cancer cell migration and invasion, and promoted cancer cell apoptosis and cell cycle arrest. MiR-34a, a target of circMYLK, was downregulated in bladder cancer tissues and cells. MiR-34a inhibition reversed the effects of circMYLK downregulation and then recovered bladder cell malignant behaviors. Further analysis showed that CCND3 was a downstream target of miR-34a, and CCND3 was upregulated in bladder cancer tissues and cells. MiR-34a overexpression blocked bladder cancer cell migration and invasion, and induced cell apoptosis and cycle arrest, while these effects were abolished by CCND3 overexpression. CircMYLK contributed to the malignant development of bladder cancer cells partly through the miR-34a/CCND3 regulatory network, showing the significance of circMYLK in bladder cancer pathogenesis.


Assuntos
Proteínas de Ligação ao Cálcio/genética , Ciclina D3/genética , MicroRNAs/fisiologia , Quinase de Cadeia Leve de Miosina/genética , RNA Circular/fisiologia , Neoplasias da Bexiga Urinária/patologia , Adulto , Idoso , Apoptose , Linhagem Celular Tumoral , Movimento Celular , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Regulação para Cima , Neoplasias da Bexiga Urinária/genética
4.
Yi Chuan ; 43(9): 910-920, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34702703

RESUMO

Xanthomonas campestris pv. campestris (Xcc) is a vascular pathogen that causes black rot in host. It is an important model strain for studying the interaction between the phytopathogen and plants. In Xcc, global transcription regulator HpaR1 that belongs to the GntR family regulates many cellular processes such as the movement and synthesis of extracellular polysaccharides and extracellular enzymes, and is associated with hypersensitive response (HR) and pathogenicity. On the other hand, the global transcriptional regulator Clp regulates the secretion and synthesis of extracellular enzymes and extracellular polysaccharides, and is associated with the pathogenicity of Xanthomonas. Previous studies have shown that both HpaR1 and Clp bind to the promoter region of the glycoside hydrolase encoding gene (named ghy gene). This study investigates the molecular mechanism of the co-regulation of HpaR1 and Clp on the expression of ghy gene. Through electrophoresis mobility shift assay (EMSA), we found that both HpaR1 and Clp bind to the promoter regions of gene ghy in vitro. Both HpaR1 and Clp also bind to the promoter regions of gene ghy in vivo by chromatin immunoprecipitation (ChIP) assays. DNase I footprinting and 5'-RACE assays showed that both HpaR1 and Clp bind to the -35 region upstream of the ghy promoter. The HpaR1 binding site was located upstream of the Clp binding site. RT-qPCR and in vitro transcription assays showed that HpaR1 negatively while Clp positively regulates the transcription of gene ghy. Furthermore, HpaR1 inhibits the activation of Clp on the transcription of gene ghy in vitro. Our findings indicate that HpaR1 and Clp exhibit opposite effect on the transcription of gene ghy. It is speculated that HpaR1 may regulate the expression of gene ghy by inhibiting the activity of RNA polymerase.


Assuntos
Xanthomonas campestris , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Regulação Bacteriana da Expressão Gênica , Glicosídeo Hidrolases/genética , Glicosídeos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Xanthomonas campestris/genética , Xanthomonas campestris/metabolismo
5.
Front Microbiol ; 15: 1352555, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38444807

RESUMO

Introduction: Numerous studies have demonstrated that C57BL/6 mice exhibit superior growth rates and overall growth performance compared to DBA mice. To investigate whether this discrepancy in growth performance is linked to the composition of gut microorganisms, we conducted fecal microbiome transplantation (FMT) experiments. Methods: Specifically, we transplanted fecal fluids from adult C57BL/6 mice, high-fat C57BL/6 mice, and Wistar rats into weaned DBA mice (0.2mL/d), and subsequently analyzed their gut contents and gene expression through 16S rRNA sequencing and transcriptome sequencing. During the test period, C57BL/6 mice and Wistar rats were provided with a normal diet, and high-fat C57BL/6 mice were provided with a high-fat diet. Results: The results of our study revealed that mice receiving FMT from all three donor groups exhibited significantly higher daily weight gain and serum triglyceride (TG) levels compared to mice of CK group. 16S rRNA sequensing unveiled substantial differences in the abundance and function of the gut microbiota between the FMT groups and the CK group. Transcriptome analysis revealed a total of 988 differential genes, consisting of 759 up-regulated genes and 187 down-regulated genes, between the three experimental groups and the CK group. Functional Gene Ontology (GO) annotation suggested that these genes were primarily linked to lipid metabolism, coagulation, and immunity. Pearson correlation analysis was performed on the differential genes and clusters, and it revealed significant correlations, mainly related to processes such as fatty acid metabolism, fat digestion and absorption, and cholesterol metabolism. Discussion: In summary, FMT from dominant strains improved the growth performance of DBA mice, including body weight gain, institutional growth, and immune performance. This change may be due to the increase of probiotic content in the intestinal tract by FMT and subsequent alteration of intestinal gene expression. However, the effects of cross-species fecal transplantation on the intestinal flora and gene expression of recipient mice were not significant.

6.
Antioxidants (Basel) ; 13(4)2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38671906

RESUMO

The aim of this experiment was to investigate the effects of dietary Phytosterol Ester (PSE) supplementation on egg characteristics, eggshell ultrastructure, antioxidant capacity, liver function, hepatic metabolites, and its mechanism of action in Hy-Line Brown laying hens during peak laying period. A total of 256 healthy Hy-Line Brown laying hens were randomly allocated into four groups. The hens in the control group were fed a basal diet, while those in the experimental groups were fed a basal diet further supplemented with 10, 20, and 40 mg/kg PSE, respectively. It was found that the addition of 20 mg/kg and 40 mg/kg PSE to the diets increased egg weight, but decreased egg breaking strength (p < 0.05). The addition of PSEs to the diets increased albumen height and Haugh unit in all experimental groups (p < 0.05). Electron microscopic observation revealed that the mammillary thickness increased significantly at doses of 20 and 40 mg/kg, but the total thickness decreased, and the effective thickness also thinned (p < 0.05). The mammillary width narrowed in all experimental groups (p < 0.001). Dietary supplementation with 40 mg/kg PSE significantly increased egg yolk Phenylalanine, Leucine, and Isoleucine levels (p < 0.05). In untargeted liver metabolomic analyses, L-Phenylalanine increased significantly in all experimental groups. Leucyl-Lysine, Glutamyl-Leucyl-Arginine, and L-Tryptophan increased significantly at doses of 10 and 20 mg/kg (p < 0.05), and L-Tyrosine increased significantly at doses of 10 and 40 mg/kg (p = 0.033). Aspartyl-Isoleucine also increased significantly at a dose of 10 mg/kg (p = 0.044). The concentration of total protein in the liver was significantly higher at doses of 20 and 40 mg/kg than that of the control group, and the concentrations of total cholesterol and low-density lipoprotein cholesterol were significantly reduced (p < 0.05). The concentration of triglyceride and alkaline phosphatase were significantly reduced in all experimental groups (p < 0.05). Steatosis and hemorrhage in the liver were also improved by observing the H&E-stained sections of the liver. Concerning the antioxidant capacity in the liver, malondialdehyde concentration was significantly reduced (p < 0.05) at a dose of 40 mg/kg. In the ovary, malondialdehyde and nitric oxide concentrations were significantly reduced (p < 0.001). In all the experimental groups, plasma nitric oxide concentration was significantly decreased while superoxide dismutase was significantly increased, and total antioxidant capacity concentration was significantly increased (p < 0.05) in the 10 mg/kg and 40 mg/kg doses. Metabolomics analyses revealed that PSEs play a role in promoting protein synthesis by promoting Aminoacyl-tRNA biosynthesis and amino acid metabolism, among other pathways. This study showed that the dietary addition of PSEs improved egg characteristics, antioxidant capacity, liver function, and symptoms of fatty liver hemorrhagic syndrome in Hy-Line Brown laying hens at peak laying stage. The changes in liver metabolism suggest that the mechanism of action may be related to pathways such as Aminoacyl-tRNA biosynthesis and amino acid metabolism. In conclusion, the present study demonstrated that PSEs are safe and effective dietary additives as an alternative to antibiotics.

7.
PLoS One ; 19(5): e0297788, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38743661

RESUMO

This study was conducted to evaluate the effects of phytosterols (PS) and phytosterol esters (PSE) on C57BL/6 mice. Three groups of 34 six-week-old C57BL/6 mice of specific pathogen free (SPF) grade, with an average initial body weight (IBW) of 17.7g, were fed for 24 days either natural-ingredient diets without supplements or diets supplemented with 89 mg/kg PS or diets supplemented with 400 mg/kg PSE. Growth performance, blood biochemistry, liver and colon morphology as well as intestinal flora status were evaluated. Both PS and PSE exhibited growth promotion and feed digestibility in mice. In blood biochemistry, the addition of both PS and PSE to the diet resulted in a significant decrease in Total Cholesterol (TC) and Triglyceride (TG) levels and an increase in Superoxide Dismutase (SOD) activity. No significant changes in liver and intestinal morphology were observed. Both increased the level of Akkermansia in the intestinal tract of mice. There was no significant difference between the effects of PS and PSE. It was concluded that dietary PS and PSE supplementation could improve growth performance, immune performance and gut microbiome structure in mice, providing insights into its application as a potential feed additive in animals production.


Assuntos
Suplementos Nutricionais , Microbioma Gastrointestinal , Fígado , Camundongos Endogâmicos C57BL , Fitosteróis , Animais , Fitosteróis/farmacologia , Fitosteróis/administração & dosagem , Microbioma Gastrointestinal/efeitos dos fármacos , Camundongos , Fígado/metabolismo , Fígado/efeitos dos fármacos , Ésteres/farmacologia , Masculino , Colesterol/sangue , Triglicerídeos/sangue , Ração Animal/análise , Superóxido Dismutase/metabolismo , Superóxido Dismutase/sangue
8.
Nutrients ; 15(5)2023 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-36904149

RESUMO

Acute liver failure (ALF) refers to the occurrence of massive hepatocyte necrosis in a short time, with multiple complications, including inflammatory response, hepatic encephalopathy, and multiple organ failure. Additionally, effective therapies for ALF are lacking. There exists a relationship between the human intestinal microbiota and liver, so intestinal microbiota modulation may be a strategy for therapy of hepatic diseases. In previous studies, fecal microbiota transplantation (FMT) from fit donors has been used to modulate intestinal microbiota widely. Here, we established a mouse model of lipopolysaccharide (LPS)/D-galactosamine (D-gal) induced ALF to explore the preventive and therapeutic effects of FMT, and its mechanism of action. We found that FMT decreased hepatic aminotransferase activity and serum total bilirubin levels, and decreased hepatic pro-inflammatory cytokines in LPS/D-gal challenged mice (p < 0.05). Moreover, FMT gavage ameliorated LPS/D-gal induced liver apoptosis and markedly reduced cleaved caspase-3 levels, and improved histopathological features of the liver. FMT gavage also restored LPS/D-gal-evoked gut microbiota dysbiosis by modifying the colonic microbial composition, improving the abundance of unclassified_o_Bacteroidales (p < 0.001), norank_f_Muribaculaceae (p < 0.001), and Prevotellaceae_UCG-001 (p < 0.001), while reducing that of Lactobacillus (p < 0.05) and unclassified_f_Lachnospiraceae (p < 0.05). Metabolomics analysis revealed that FMT significantly altered LPS/D-gal induced disordered liver metabolites. Pearson's correlation revealed strong correlations between microbiota composition and liver metabolites. Our findings suggest that FMT ameliorate ALF by modulating gut microbiota and liver metabolism, and can used as a potential preventive and therapeutic strategy for ALF.


Assuntos
Microbioma Gastrointestinal , Falência Hepática Aguda , Camundongos , Humanos , Animais , Transplante de Microbiota Fecal , Microbioma Gastrointestinal/fisiologia , Lipopolissacarídeos , Galactosamina , Falência Hepática Aguda/patologia , Metaboloma
9.
World J Clin Cases ; 10(4): 1326-1332, 2022 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-35211566

RESUMO

BACKGROUND: In the clinical treatment of diseases related to ureteral duplication, it is very important to make a clear diagnosis before surgery because different types of ureteral duplication correspond to different treatment options. Inverted Y ureteral duplication with ectopic ureters and multiple urinary calculi is clinically rare. This case can help clinicians increase their understanding of this disease and gain some experience in its diagnosis and treatment. CASE SUMMARY: A 36-year-old male who was previously healthy presented to the hospital with lumbar pain. Percussion of the right kidney area showed the patient had pain. Computed tomography scans revealed multiple urinary calculi in the right urinary system. Computed tomography urography revealed a duplicated ureteral malformation with an ectopic ureter. A transurethral ureteroscopic holmium laser lithotripsy was performed successfully. Intraoperative retrograde ureterography was performed, and the ectopic ureter was visible. We informed the family of the intraoperative findings and suggested laparoscopic ectopic ureterectomy for the ectopic ureteral stones. Unfortunately, the family temporarily refused laparoscopic surgery. The patient did not feel any discomfort after one year of follow-up. CONCLUSION: Inverted Y ureteral duplication with an ectopic ureter and multiple urinary calculi is rare. Clinicians must be highly vigilant, make a correct diagnosis before surgery, determine the type of ureteral duplication and the distribution of urinary calculi, and then draw up a reasonable treatment plan to avoid unnecessary complications.

10.
Front Bioeng Biotechnol ; 10: 833920, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35127664

RESUMO

Resveratrol, a bioactive natural product found in many plants, is a secondary metabolite and has attracted much attention in the medicine and health care products fields due to its remarkable biological activities including anti-cancer, anti-oxidation, anti-aging, anti-inflammation, neuroprotection and anti-glycation. However, traditional chemical synthesis and plant extraction methods are impractical for industrial resveratrol production because of low yield, toxic chemical solvents and environmental pollution during the production process. Recently, the biosynthesis of resveratrol by constructing microbial cell factories has attracted much attention, because it provides a safe and efficient route for the resveratrol production. This review discusses the physiological functions and market applications of resveratrol. In addition, recent significant biotechnology advances in resveratrol biosynthesis are systematically summarized. Furthermore, we discuss the current challenges and future prospects for strain development for large-scale resveratrol production at an industrial level.

11.
Animals (Basel) ; 12(3)2022 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-35158703

RESUMO

The present study evaluated the impact of dietary multienzyme complex (MEC) supplementation on growth performance, digestive enzyme activity, histomorphology, serum metabolism and hepatopancreas glycometabolism in snakeheads (Channa argus). A total of 600 fish (initial weight, 69.70 ± 0.30 g) were randomly divided into four groups. Four diets were formulated: (1) control (basic diet); (2) E1 (400 U kg-1 amylase, 150 U kg-1 acid protease, 1900 U kg-1 neutral protease and basic diet); (3) E2 (800 U kg-1 amylase, 300 U kg-1 acid protease, 3800 U kg-1 neutral protease and basic diet); and (4) E3 (1200 U kg-1 amylase, 450 U kg-1 acid protease, 5700 U kg-1 neutral protease and basic diet). The results show that the E2 group increased the specific growth rate, weight gain rate and the final body weight, as well as decreasing the blood urea nitrogen, alanine aminotransferase and triglyceride. The mRNA levels and activities of digestive enzymes and key glucose metabolism enzymes in the hepatopancreas were enhanced in snakeheads fed the MEC. Meanwhile, moderate MEC diet (E2 groups) supplementation improved digestive tract morphology, increased the glycogen in the hepatopancreas and the lipids in the dorsal muscle. Moreover, plasma metabolomics revealed differential metabolites mainly involved in amino acid metabolism. These findings suggest that dietary supplementation with the MEC improved growth performance, digestive tract morphology, gene expression and the activity of digestive enzymes, enhanced the glycolysis-gluconeogenesis and amino acid metabolism of snakeheads, and the optimal composition of the MEC was group E2.

12.
Front Oncol ; 12: 932889, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35992804

RESUMO

Purpose: This study aims to evaluate the value of the clinical application of ultrasound-guided percutaneous thermal ablation in focal nodular hyperplasia (FNH) by comparing its safety, effectiveness, and patient experience to surgery in the treatment of hepatic FNH ≤5 cm. Method: This retrospective study enrolled 82 patients with hepatic FNH having a maximum diameter of ≤5 cm, confirmed by postoperative pathologic diagnosis or needle biopsy, who underwent thermal ablation or surgery between January 2019 and September 2021. Postoperative efficacy, surgical trauma (operation time, intraoperative bleeding volume, liver function, and lost volume of normal liver tissue), postoperative complications (postoperative infection, pleural effusion, and liver dysfunction), patient experience (degree and time of postoperative pain, postoperative fasting time, indwelling thoracic chest drain, and scar size), and economic indices (postoperative hospitalization and total charges) were compared between both groups. Result: No significant difference existed in postoperative efficacy between both groups (p > 0.05). No recurrent or new lesions were observed during the 6-month follow-up in both groups. However, significant differences were observed in operation time, intraoperative bleeding volume, and lost volume of normal liver tissue (p < 0.05), with significantly less trauma in the thermal ablation group. No statistically significant differences in ALT, AST, and Hb existed between both groups (p > 0.05); however, albumin was higher in the ablation group compared to the surgery group (38.21 ± 3.32 vs. 34.84 ± 3.71 g/L, p < 0.05), and WBC were lower in the ablation group (11.91 ± 3.37 vs. 13.94 ± 3.65/L, p < 0.05). The incidence of postoperative complications in the ablation group was significantly lower than that in the surgery group (p < 0.05). Patient experiences were significantly better than in the surgical group (p < 0.05), with economic indicators being significantly less in the ablation group (p < 0.05). Conclusion: Ultrasound-guided percutaneous thermal ablation can treat hepatic FNH ≤5 cm with similar clinical efficacy as surgery and is an economical, safe, and minimally invasive treatment method worthy of recommendation.

13.
Front Immunol ; 13: 1061627, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36713373

RESUMO

Introduction: Campylobacter jejuni (C. jejuni) is a common food-borne bacterial pathogen that can use the host's innate immune response to induce the development of colitis. There has been some research on the role of normal intestinal flora in C. jejuni-induced colitis, but the mechanisms that play a central role in resistance to C. jejuni infection have not been explored. Methods: We treated Campylobacter jejuni-infected mice with fecal microbiota transplantation (FMT), oral butyric acid and deoxycholic acid in a controlled trial and analyzed the possible mechanisms of treatment by a combination of chromatography, immunohistochemistry, fluorescence in situ hybridization, 16s rRNA gene, proteomics and western blot techniques. Results: We first investigated the therapeutic effect of FMT on C. jejuni infection. The results showed that FMT significantly reduced the inflammatory response and blocked the invasion of C.jejuni into the colonic tissue. We observed a significant increase in the abundance of Akkermansia in the colon of mice after FMT, as well as a significant increase in the levels of butyric acid and deoxycholic acid. We next demonstrated that oral administration of sodium butyrate or deoxycholic acid had a similar therapeutic effect. Further proteomic analysis showed that C.jejuni induced colitis mainly through activation of the PI3K-AKT signaling pathway and MAPK signaling pathway, whereas Akkermansia, the core flora of FMT, and the gut microbial metabolites butyric acid and deoxycholic acid both inhibited these signaling pathways to counteract the infection of C. jejuni and alleviate colitis. Finally, we verified the above idea by in vitro cellular assays. In conclusion, FMT is highly effective in the treatment of colitis caused by C. jejuni, with which Akkermansia and butyric and deoxycholic acids are closely associated.The present study demonstrates that Akkermansia and butyric and deoxycholic acids are effective in the treatment of colitis caused by C. jejuni. Discussion: This is the first time that Akkermansia has been found to be effective in fighting pathogens, which provides new ideas and insights into the use of FMT to alleviate colitis caused by C. jejuni and Akkermansia as a treatment for intestinal sexually transmitted diseases caused by various pathogens.


Assuntos
Infecções por Campylobacter , Colite , Gastroenterite , Camundongos , Animais , Akkermansia , Infecções por Campylobacter/terapia , Hibridização in Situ Fluorescente , RNA Ribossômico 16S , Fosfatidilinositol 3-Quinases/genética , Proteômica , Camundongos Endogâmicos C57BL , Ácido Desoxicólico , Butiratos
14.
Front Bioeng Biotechnol ; 9: 696514, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34307323

RESUMO

In the recent few decades, the increase in multidrug-resistant (MDR) bacteria has reached an alarming rate and caused serious health problems. The incidence of infections due to MDR bacteria has been accompanied by morbidity and mortality; therefore, tackling bacterial resistance has become an urgent and unmet challenge to be properly addressed. The field of nanomedicine has the potential to design and develop efficient antimicrobials for MDR bacteria using its innovative and alternative approaches. The uniquely constructed nano-sized antimicrobials have a predominance over traditional antibiotics because their small size helps them in better interaction with bacterial cells. Moreover, surface engineering of nanocarriers offers significant advantages of targeting and modulating various resistance mechanisms, thus owe superior qualities for overcoming bacterial resistance. This review covers different mechanisms of antibiotic resistance, application of nanocarrier systems in drug delivery, functionalization of nanocarriers, application of functionalized nanocarriers for overcoming bacterial resistance, possible limitations of nanocarrier-based approach for antibacterial delivery, and future of surface-functionalized antimicrobial delivery systems.

15.
World J Gastroenterol ; 27(23): 3327-3341, 2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-34163115

RESUMO

BACKGROUND: Abnormal tuftelin 1 (TUFT1) has been reported in multiple cancers and exhibits oncogenic roles in tumor progression. However, limited data are available on the relationship between TUFT1 and hepatocellular carcinoma (HCC), and the exact biological mechanism of TUFT1 is still poorly understood in HCC. AIM: To investigate TUFT1 expression in HCC and how interfering TUFT1 transcription affects HCC growth. METHODS: TUFT1 in HCC and non-HCC tissues based on databases of the Cancer Genome Atlas and Oncomine were analyzed, and TUFT1 in human HCC tissues on microarray were detected by immunohistochemistry for clinicopathological features, overall survival, and disease-free survival. HCC cells were transfected with constructed vectors of TUFT1 that interfere or over-express TUFT1 for analyzing the biological behaviors of HCC cells. Proliferation, invasion, migration, and apoptosis of cells were detected by cell counting kit-8, scratch assay, transwell tests, and flow cytometry and confirmed by Western blotting, respectively. RESULTS: Abnormal TUFT1 levels in databases expressed in HCC at messenger RNA (mRNA) level and HCC tissues were mainly located in cytoplasm and membrane. The level of TUFT1 expression in the HCC group was significantly higher (χ 2 = 18.563, P < 0.001) than that in the non-cancerous group, closely related to clinical staging, size, vascular invasion of tumor, hepatitis B e-antigen positive, and ascites (P < 0.01) of HCC patients, and negatively to HCC patients' overall survival and disease-free survival (P < 0.001). After interfering with TUFT1 transcription at mRNA level in the MHCC-97H cells by the specific TUFT1-short hairpin RNA, cell proliferation, invasion, and metastasis were significantly inhibited with increasing apoptosis rate. In contrast, proliferation, invasion, and migration were significantly enhanced after over-expression of TUFT1 mRNA in Hep3B cells in vitro. CONCLUSION: Oncogenic TUFT1 was associated with the progression of HCC and could be a potential molecular-target for inhibiting HCC growth.


Assuntos
Carcinoma Hepatocelular , Proteínas do Esmalte Dentário/genética , Neoplasias Hepáticas , Proteínas Oncogênicas/genética , Apoptose , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/genética , Invasividade Neoplásica
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