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1.
Food Technol Biotechnol ; 62(1): 4-14, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38601963

RESUMEN

Research background: Peanut allergy poses a significant threat to human health due to the increased risk of long-term morbidity at low doses. Modifying protein structure to affect sensitization is a popular topic. Experimental approach: In this study, the purified peanut allergen Ara h 1 was enzymatically hydrolysed using Flavourzyme, alkaline protease or a combination of both. The binding ability of Ara h 1 to antibodies, gene expression and secretion levels of the proinflammatory factors interleukin-5 and interleukin-6 in Caco-2 cells was measured. Changes in the secondary and tertiary structures before and after treatment with Ara h 1 were analysed by circular dichroism and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Results and conclusions: The results indicated a decrease of the allergenicity and proinflammatory ability of Ara h 1. The evaluation showed that the Flavourzyme and alkaline protease treatments caused particle shortening and aggregation. The fluorescence emission peak increased by 3.4-fold after the combined treatment with both proteases. Additionally, the secondary structure underwent changes and the hydrophobicity also increased 8.95-fold after the combined treatment. Novelty and scientific contribution: These findings partially uncover the mechanism of peanut sensitization and provide an effective theoretical basis for the development of a new method of peanut desensitization.

2.
Int Immunopharmacol ; 131: 111898, 2024 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-38513573

RESUMEN

Vancomycin (VCM) is the first-line antibiotic for severe infections, but nephrotoxicity limits its use. Leonurine (Leo) has shown protective effects against kidney damage. However, the effect and mechanism of Leo on VCM nephrotoxicity remain unclear. In this study, mice and HK-2 cells exposed to VCM were treated with Leo. Biochemical and pathological analysis and fluorescence probe methods were performed to examine the role of Leo in VCM nephrotoxicity. Immunohistochemistry, q-PCR, western blot, FACS, and Autodock software were used to verify the mechanism. The present results indicate that Leo significantly alleviates VCM-induced renal injury, morphological damage, and oxidative stress. Increased intracellular and mitochondrial ROS in HK-2 cells and decreased mitochondrial numbers in mouse renal tubular epithelial cells were reversed in Leo-administrated groups. In addition, molecular docking analysis using Autodock software revealed that Leo binds to the PPARγ protein with high affinity. Mechanistic exploration indicated that Leo inhibited VCM nephrotoxicity via activating PPARγ and inhibiting the TLR4/NF-κB/TNF-α inflammation pathway. Taken together, our results indicate that the PPARγ inhibition and inflammation reactions were implicated in the VCM nephrotoxicity and provide a promising therapeutic strategy for renal injury.


Asunto(s)
Ácido Gálico/análogos & derivados , Insuficiencia Renal , Vancomicina , Ratones , Animales , Vancomicina/metabolismo , Vancomicina/farmacología , Vancomicina/uso terapéutico , FN-kappa B/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , PPAR gamma/metabolismo , Receptor Toll-Like 4/metabolismo , Simulación del Acoplamiento Molecular , Riñón/patología , Insuficiencia Renal/metabolismo , Inflamación/tratamiento farmacológico
3.
Small ; : e2311228, 2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-38225708

RESUMEN

Sonodynamic therapy (SDT) as a promising non-invasive anti-tumor means features the preferable penetration depth, which nevertheless, usually can't work without sonosensitizers. Sonosensitizers produce reactive oxygen species (ROS) in the presence of ultrasound to directly kill tumor cells, and concurrently activate anti-tumor immunity especially after integration with tumor microenvironment (TME)-engineered nanobiotechnologies and combined therapy. Current sonosensitizers are classified into organic and inorganic ones, and current most reviews only cover organic sonosensitizers and highlighted their anti-tumor applications. However, there have few specific reviews that focus on inorganic sonosensitizers including their design principles, microenvironment regulation, etc. In this review, inorganic sonosensitizers are first classified according to their design rationales rather than composition, and the action rationales and underlying chemistry features are highlighted. Afterward, what and how TME is regulated based on the inorganic sonosensitizers-based SDT nanoplatform with an emphasis on the TME targets-engineered nanobiotechnologies are elucidated. Additionally, the combined therapy and their applications in non-cancer diseases are also outlined. Finally, the setbacks and challenges, and proposed the potential solutions and future directions is pointed out. This review provides a comprehensive and detailed horizon on inorganic sonosensitizers, and will arouse more attentions on SDT.

4.
Hum Exp Toxicol ; 42: 9603271231215499, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37950702

RESUMEN

Cyclosporine (CsA) is an immunosuppressive agent that often causes acute kidney injury (AKI) in children. The specific mechanisms underlying CsA-induced AKI are currently unknown. This study used an integrated network analysis of microRNA (miRNA) and mRNA expression profiles, biochemical and pathological analyses to further investigate these potential mechanisms of CsA-induced AKI. Small RNA sequence analysis identified 25 differentially expressed miRNAs, RNA sequencing analysis identified 4,109 differentially expressed mRNAs. We obtained a total of 4,367 target genes from the 25 differentially expressed miRNAs based on three algorithms, including the Mirdb, Mirtarbase, and TargetScan. 971 target genes overlapped between the 4,367 target genes and 4,109 differentially expressed mRNAs were identified for further bioinformatics analysis. Finally, 30 hub genes and two main modules were recognized. Functional enrichment analysis of 30 hub genes indicated that inflammation and epithelial-mesenchymal transition (EMT) related genes were mainly concentrated together. Pathway analysis revealed that the PI3K-Akt signaling pathway plays an integral role in CsA-induced AKI. Network analysis identified 3 important miRNAs, mmu-miR-17b-5p, mmu-miR-19b-3p, and mmu-mir-423-5p that may further promote the development of inflammatory responses and EMT by mediating a complex network of factors. Our research provides a clearer understanding the molecular mechanism of this specific drug-induced AKI by CsA use, which is useful for discovering potential targets for gene therapies, and drug development in CsA-induced AKI.


Asunto(s)
Lesión Renal Aguda , MicroARNs , Niño , Humanos , Animales , Ratones , Ciclosporina/toxicidad , ARN Mensajero/genética , Fosfatidilinositol 3-Quinasas/genética , MicroARNs/genética , MicroARNs/metabolismo , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/genética
6.
Spectrochim Acta A Mol Biomol Spectrosc ; 303: 123143, 2023 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-37478706

RESUMEN

Melamine is one of the common limited contaminations in dairy products. The traditional detection method has a long period and complicated pretreatment process. The rapid detection method is the better method to solve the screening of limited contaminations. In this paper, taking melamine as the research object, the surface enhanced Raman spectrum of melamine in liquid milk were collected by portable Raman spectrometer, and melamine was qualitatively identified and semi-quantitatively analyzed by Raman characteristic peak and Raman intensity, and a simple and efficient rapid screening method for limited contaminations was developed. The limit of detection is 0.25 mg/kg. The probability of detection is 100% at 2.5 mg/kg, which is the same between the two laboratories, indicating that the semi-quantitative method has good repeatability. The method of melamine proposed in this study can meet the rapid screening requirements of limited contaminations at the maximum residue limit, and has a good application prospect.


Asunto(s)
Leche , Espectrometría Raman , Animales , Leche/química , Espectrometría Raman/métodos , Triazinas/análisis , Contaminación de Alimentos/análisis
7.
Hum Exp Toxicol ; 42: 9603271231183885, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37340591

RESUMEN

Vancomycin (VCM)-induced nephrotoxicity impedes its treatment applications. Thus, it is important to clarify the relevant mechanism. This study investigated phosphoprotein changes attributable to the VCM nephrotoxicity mechanisms. Biochemical, pathological and phosphoproteomic analyses based on C57BL/6 mice were performed to explore the mechanisms.VCM-treated mice showed increased levels of blood urea nitrogen and creatinine, and signs of acute tubular necrotic lesions. Phosphoproteomic profiling identified 3025 differentially phosphorylated phosphopeptides between the model and control group. Gene Ontology enrichment analysis demonstrated that Molecular Function "oxidoreductase activity" and Cellular Component "peroxisome" were markedly enriched. KEGG pathway analysis identified an enrichment in peroxisome pathway and PPAR (peroxisome proliferator-activated receptor) signaling pathways. Parallel reaction monitoring analysis revealed a significant downregulation of CAT, SOD-1, AGPS, DHRS4, and EHHADH at phosphorylation level by VCM. Notably, the phosphorylation of ACO, AMACR, and SCPX was downregulated by VCM, which are the fatty acid ß-oxidation-related proteins involved in PPAR signaling pathways. The phosphorylated PEX5 involved in peroxisome biogenesis was upregulated by VCM. Collectively, these findings indicated that VCM-induced nephrotoxicity is closely associated with peroxisome pathway and PPAR signaling pathways. The current study provides important insight into the mechanisms of VCM nephrotoxicity and will aid in the development of preventive and therapeutic strategies against this nephropathy.


Asunto(s)
Insuficiencia Renal , Vancomicina , Ratones , Animales , Vancomicina/toxicidad , Vancomicina/metabolismo , Proteoma/metabolismo , Antibacterianos/metabolismo , Receptores Activados del Proliferador del Peroxisoma/metabolismo , Ratones Endogámicos C57BL , Riñón
8.
Drug Des Devel Ther ; 17: 283-295, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36756189

RESUMEN

Background: Vancomycin (VCM) has long been used clinically to fight against Gram-positive bacterial infections. In recent decades, an increased number of kidney injury cases caused by VCM overdose have been reported. In this study, we further investigated the mechanism of VCM-overdose-induced kidney injury. Methods: Immunohistochemistry (IHC) staining, RT-qPCR and Western blot assays were used to determine ki67, DDX5, PTGS2, GPX4 and SLC7A11 expressions in the kidney tissues of mice. CCK-8 and flow cytometry assays were used to determine HK2 cell viability and apoptosis. In addition, RT-qPCR and Western blot assays was applied to evaluate the expressions of ACSL4, PTGS2, GPX4, SLC7A11, DDX5 and Ki67 in HK2 cells. Results: We found that VCM induced ferroptosis in vitro and in vivo. Ferrostatin-1 (Fer-1) is a potent inhibitor of ferroptosis, Fer-1 rescued cell viability and renal function renal morphology in VCM-treated cells and mice, respectively. Further, GPX4, which plays an essential role in reducing lipid hydroperoxides and preventing ferroptosis, was observed to be downregulated by VCM treatment. Interestingly, we found that GPX4-knockdown HK-2 cells exhibited a similar phenotype and gene expression level of ACSL4, PTGS2, DDX5 and Ki67 compared with VCM-treated cells, which suggested that VCM could induce ferroptosis in HK2 cells by down-regulating GPX4. Conclusion: In conclusion, VCM induced renal injury in the kidney tissues of mice. In addition, VCM induced ferroptosis cell death in HK-2 cells and in the kidney tissues of mice by down-regulating GPX4 and causing the accumulation of peroxides. These data suggested that VCM could induce renal injury in vitro and in vivo via triggering ferroptosis. This study further elucidates the mechanism of VCM-induced renal injury and provides additional references for clinical use of VCM.


Asunto(s)
Fármacos Dermatológicos , Ferroptosis , Animales , Ratones , Peróxidos , Fosfolípido Hidroperóxido Glutatión Peroxidasa , Vancomicina , Ciclooxigenasa 2 , Antígeno Ki-67
9.
BMC Infect Dis ; 22(1): 929, 2022 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-36503381

RESUMEN

BACKGROUNDS: Interleukin-6 (IL-6) blockers including tocilizumab and sarilumab were approved by the U.S. Food and Drug Administration (FDA) in June 2021 for the treatment of patients with moderate to severe COVID-19. The use of sarilumab or tocilizumab in COVID-19 patients has been related to a reduction in mortality compared to standard care. Recent evidence has emerged concerning drug-induced liver injury (DILI) after sarilumab or tocilizumab applications in COVID-19 patients. AIMS: The study aimed to estimate DILI associated with sarilumab or tocilizumab in treating moderate to severe patients infected with SARS-Cov-2. METHODS: We conducted a retrospective pharmacovigilance study by data mining of the FDA's adverse event reporting systems (FAERS) database from the first quarter of 2004 to the fourth quarter of 2021 in confirmed COVID-19 patients. We analyzed DILI cases associated with tocilizumab or sarilumab in treating COVID-19 patients from the FAERS during this period. Disproportionality analysis and Bayesian analysis of COVID-19 patients were utilized for case analysis, and we also next compared the onset time and fatality rates of DILI following tocilizumab or sarilumab. RESULTS: A total of 275 cases of TCZ or SAR-related DILI reports were extracted. A total of 192 AEs cases were related to tocilizumab (TCZ), and 83 were related to sarilumab (SAR). In patients treated with TCZ, most were < 75 years old (51.57%), with more male than female (46.35% vs. 13.02%). The correlation between IL-6 receptor antagonists and DILI was stronger in SAR (ROR = 12.94; 95%CI 9.6-17.44) than in TCZ (ROR = 1.33; 95%CI 1.14-1.55). The onset time of DILI was different between TCZ and SAR, and a significant difference was observed in TCZ than SAR (P < 0.0001). A significant difference was observed in the mortality rate of TCZ and SAR (P = 0.0009). DILI associated with COVID-19 patients treated with TCZ appeared to have earlier onset-time (1(0-46) day) VS. SAR (3.5(0-27) day). CONCLUSION: This study shows strict monitor ought to be paid for TCZ or SAR when used for COVID-19 patients with poor liver function.


Asunto(s)
COVID-19 , Enfermedad Hepática Inducida por Sustancias y Drogas , Humanos , Masculino , Femenino , Anciano , SARS-CoV-2 , Estudios Retrospectivos , Teorema de Bayes , Enfermedad Hepática Inducida por Sustancias y Drogas/epidemiología , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología
10.
BMC Vet Res ; 18(1): 419, 2022 Nov 29.
Artículo en Inglés | MEDLINE | ID: mdl-36447274

RESUMEN

BACKGROUND: Peste des petits ruminants (PPR) is a serious disease that affects goats, sheep and other small ruminants. As one of the earliest and most serious countries, PPR has seriously threatened India's animal husbandry economy. RESULTS: In this study, the spatiotemporal characteristics of the PPR in India outbreaks were analyzed. Between 2010 and 2018, the epidemic in India broke out all over the country in a cluster distribution. Epidemic clusters in northern and southern India are at higher risk, and the outbreak time of PPR has significant seasonality. The results of the analysis of the development and transmission of PPR under the natural infection conditions showed that the PPR outbreak in India reached a peak within 15 days. Finally, the quantitative risk analysis results based on scenario tree show showed that the average probability of infecting PPRV in live sheep exported from India was 1.45 × 10-4. CONCLUSIONS: This study analyzed the prevalence of PPR in India. The analysis of transmission dynamics on the development of the epidemic provides a reference for the prevention and control of the epidemic. At the same time, it provides risk analysis and suggestions on trade measures for the trading countries of India.


Asunto(s)
Epidemias , Enfermedades de las Cabras , Peste de los Pequeños Rumiantes , Enfermedades de las Ovejas , Animales , Ovinos , Peste de los Pequeños Rumiantes/epidemiología , Brotes de Enfermedades/veterinaria , Cabras , India/epidemiología , Medición de Riesgo , Enfermedades de las Cabras/epidemiología , Enfermedades de las Ovejas/epidemiología
11.
Front Vet Sci ; 9: 955366, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36406078

RESUMEN

Bluetongue disease (BT) is a viral disease that can be introduced through imported animals and animal products, affecting local animal husbandry. In this study, the spatial and temporal patterns of BT outbreaks (outbreak: a BT infection in cattle, sheep, or goats on a farm, involving at least one infected animal) in France were analyzed and the risk of introducing bluetongue virus (BTV) into countries through trade was assessed. A spatiotemporal analysis of BT reported during the study period (2015-2018) showed that there were clustered outbreaks of BT in France in 2016 and 2017, with outbreaks concentrated from August to December. The outbreak moved eastward from the center of mainland France to surrounding countries. A semi-quantitative risk analysis framework was established by combining the likelihood assessment and consequence analysis of introducing BTV into trading countries through trade. Exemplified by China, the research showed that in the analysis of the likelihood of BTV from France being introduced into trading countries through live cattle trade, China imports a large number of live cattle, bringing high risks. The likelihood of introducing bovine semen into trading countries was similar to that of live cattle, but the harm caused by the trade in live cattle was higher than that caused by the trade in bovine semen. This risk analysis framework can provide a reference for other countries to quickly assess the risk of bluetongue transmission in import and export trade.

12.
Contrast Media Mol Imaging ; 2022: 8212370, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36003998

RESUMEN

With the development of the economy, the food safety problems caused by aflatoxin have become increasingly prominent. With regard to the control of aflatoxin pollution, the Chinese government has promulgated a series of legal documents on food safety related to aflatoxin pollution, such as the formulation of industry standards for allowable limits of aflatoxin and various penalties for violators. Although these measures have achieved good results to some extent, there are still many legal problems. This study reviews the current situation of aflatoxin pollution control in food in China. The court judgment documents related to aflatoxin pollution from January 1st 2014 to January 1st 2020 are investigated to analyze the accountability status of aflatoxin pollution treatment in China. Furthermore, this study mainly cross verified the above problems by means of the literature survey and an organization interview and proposed solutions on the basis of in-depth analysis of their causes. Finally, some suggestions are put forward to solve the problem of aflatoxin pollution accountability in China.


Asunto(s)
Aflatoxinas , Criminales , China , Contaminación Ambiental/análisis , Humanos , Juicio
13.
Molecules ; 27(13)2022 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-35807472

RESUMEN

The current detection method of carbendazim suffers from the disadvantages of complicated preprocessing and long cycle time. In order to solve the problem of rapid quantitative screening of finite contaminants, this article proposed a qualitative method based on characteristic peaks and a semi-quantitative method based on threshold to detect carbendazim in apple, and finally the method is evaluated by a validation system based on binary output. The results showed that the detection limit for carbendazim was 0.5 mg/kg, and the detection probability was 100% when the concentration was no less than 1 mg/kg. The semi-quantitative analysis method had a false positive rate of 0% and 5% at 0.5 mg/kg and 2.5 mg/kg, respectively. The results of method evaluation showed that when the added concentration was greater than 2.5 mg/kg, the qualitative detection method was consistent with the reference method. When the concentration was no less than 5 mg/kg, the semi-quantitative method is consistent between different labs. The semi-quantitative method proposed in this study can achieve the screening of finite contaminants in blind samples and simplify the test validation process through the detection probability model, which can meet the needs of rapid on-site detection and has a good application prospect.


Asunto(s)
Frutas , Espectrometría Raman , Bencimidazoles/análisis , Carbamatos/análisis , Frutas/química , Espectrometría Raman/métodos
14.
J Med Case Rep ; 16(1): 163, 2022 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-35462530

RESUMEN

BACKGROUND: Capecitabine is widely used in chemotherapy for breast, colorectal, and gastric cancers. The frequent adverse reactions of capecitabine mainly include gastrointestinal side effects, anemia, and cardiovascular toxicity. Here, we report a rare case of severe hyperglycemia and hypokalemia during long-term treatment with capecitabine. CASE PRESENTATION: A 48-year-old Chinese female was hospitalized with the complaint of breathlessness and weakness after activity, for 1 month. Her past history is significant for a diagnosis of right-sided breast cancer 7 years ago. She underwent right mastectomy, following which capecitabine was started 1.5 years prior to the current admission as part of her primary treatment at the discovery of systemic osseous metastasis. Her fasting plasma glucose and hemoglobin A1c levels were quite normal 7 months ago but increased to 15.3 mmol/L and 11.2%, respectively, at the present admission. Her serum potassium level was as low as 2.5 mmol/L. Plasma autoantibodies related to islets and insulin were all negative. Capecitabine was discontinued, and an insulin pump and potassium supplement were given after admission. Her blood sugar and potassium levels returned to their normal ranges soon. Self-injection of insulin was withdrawn completely at 2 months after discharge, and no oral hypoglycemic agents were added. Her plasma glucose and electrolyte levels were at normal levels at her 1-year follow-up. CONCLUSION: Glucose intolerance and hypokalemia may be rare but serious adverse effects during long-term chemotherapy with capecitabine.


Asunto(s)
Neoplasias de la Mama , Diabetes Mellitus , Hipopotasemia , Glucemia , Neoplasias de la Mama/tratamiento farmacológico , Capecitabina/efectos adversos , Diabetes Mellitus/inducido químicamente , Femenino , Fluorouracilo/efectos adversos , Humanos , Hipopotasemia/inducido químicamente , Insulina , Mastectomía , Persona de Mediana Edad , Potasio
15.
ACS Omega ; 7(2): 2064-2073, 2022 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-35071894

RESUMEN

To develop a rapid detection method for nonprotein nitrogen adulterants, this experiment sets up a set of point-scan Raman hyperspectral imaging systems to qualitatively distinguish and quantitatively and positionally analyze samples spiked with a single nonprotein nitrogen adulterant and samples spiked with a mixture of nine nonprotein nitrogen adulterants at different concentrations (5 × 10-3 to 2.000%, w/w). The results showed that for samples spiked with single nonprotein nitrogen adulterants, the number of pixels corresponding to the adulterant in the region of interest increased linearly with an increase in the analyte concentration, the average coefficient of determination (R 2) was above 0.99, the minimum detection concentration of nonprotein nitrogen adulterants reached 0.010%, and the relative standard deviation (RSD) of the predicted concentration was less than 6%. For the sample spiked with a mixture of nine nonprotein nitrogen adulterants, the standard curve could be used to accurately predict the additive concentration when the additive concentration was greater than 1.200%. The detection method established in this study has good accuracy, high sensitivity, and strong stability. It provides a method for technical implementation of real-time and rapid detection of adulterants in milk powder at the port site and has good application and promotion prospects.

16.
Toxicol Res (Camb) ; 10(4): 687-695, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34484661

RESUMEN

Renal transporters involved in tubular excretion pathway are considered to be the key concern in drug evaluations in nephrotoxicity. However, the relationship between the alternation of renal transporters and the kinetic process of vancomycin (VCM)-induced nephrotoxicity has not been fully elucidated. The present study investigated the alteration of renal transporters expression in the kinetic process of VCM-induced nephrotoxicity in mice. C57BL/6 mice were administrated with normal saline or VCM for 7 days. Biochemical and pathological analyses were conducted to investigate the nephrotoxicity induced by VCM administration. Renal oxidative status, plasma, and kidney content of VCM were monitored. Quantitative real-time polymerase chain reaction and immunohistochemistry analyses were performed to analyze the expression of renal transporters. Finally, our data showed that the exposure of VCM (400 mg/kg) caused a slight nephrotoxicity in mice, whereas exposure of VCM (600 mg/kg) resulted in the severe nephrotoxicity in mice as evidenced by biochemical parameters and renal morphological changes. In addition, the accumulation of VCM in kidney is higher than plasma. Interestingly, VCM (600 mg/kg, body weight) resulted in the induction of Oct2-Mate1 and Oat1/3-Mrp2/Mrp4/Bcrp pathways. However, VCM (400 mg/kg, body weight) caused the induction of Oct2-Mate1/Mate2 and Oat1/3-Mrp4/Bcrp pathways. The changes of renal transporters in association with the kinetic process of VCM-induced nephrotoxicity may exert important practical implications for its optimal use in clinic.

17.
Acta Pharm Sin B ; 11(6): 1541-1554, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34221867

RESUMEN

Obesity and its associated complications are highly related to a current public health crisis around the world. A growing body of evidence has indicated that G-protein coupled bile acid (BA) receptor TGR5 (also known as Gpbar-1) is a potential drug target to treat obesity and associated metabolic disorders. We have identified notoginsenoside Ft1 (Ft1) from Panax notoginseng as an agonist of TGR5 in vitro. However, the pharmacological effects of Ft1 on diet-induced obese (DIO) mice and the underlying mechanisms are still elusive. Here we show that Ft1 (100 mg/100 diet) increased adipose lipolysis, promoted fat browning in inguinal adipose tissue and induced glucagon-like peptide-1 (GLP-1) secretion in the ileum of wild type but not Tgr5 -/- obese mice. In addition, Ft1 elevated serum free and taurine-conjugated bile acids (BAs) by antagonizing Fxr transcriptional activities in the ileum to activate Tgr5 in the adipose tissues. The metabolic benefits of Ft1 were abolished in Cyp27a1 -/- mice which have much lower BA levels. These results identify Ft1 as a single compound with opposite activities on two key BA receptors to alleviate high fat diet-induced obesity and insulin resistance in mice.

18.
Vet Res ; 52(1): 75, 2021 Jun 02.
Artículo en Inglés | MEDLINE | ID: mdl-34078437

RESUMEN

Brucella spp. are Gram-negative, facultative intracellular bacteria that cause brucellosis in humans and various animals. The threat of brucellosis has increased, yet currently available live attenuated vaccines still have drawbacks. Therefore, subunit vaccines, produced using protein antigens and having the advantage of being safe, cost-effective and efficacious, are urgently needed. In this study, we used core proteome analysis and a compositive RV methodology to screen potential broad-spectrum antigens against 213 pathogenic strains of Brucella spp. with worldwide geographic distribution. Candidate proteins were scored according to six biological features: subcellular localization, antigen similarity, antigenicity, mature epitope density, virulence, and adhesion probability. In the RV analysis, a total 32 candidate antigens were picked out. Of these, three proteins were selected for assessment of immunogenicity and preliminary protection in a mouse model: outer membrane protein Omp19 (used as a positive control), type IV secretion system (T4SS) protein VirB8, and type I secretion system (T1SS) protein HlyD. These three antigens with a high degree of conservation could induce specific humoral and cellular immune responses. Omp19, VirB8 and HlyD could substantially reduce the organ bacterial load of B. abortus S19 in mice and provide varying degrees of protection. In this study, we demonstrated the effectiveness of this unique strategy for the screening of potential broad-spectrum antigens against Brucella. Further evaluation is needed to identify the levels of protection conferred by the vaccine antigens against wild-type pathogenic Brucella species challenge.


Asunto(s)
Vacuna contra la Brucelosis/farmacología , Brucella abortus/inmunología , Brucella melitensis/inmunología , Brucella suis/inmunología , Brucelosis/veterinaria , Animales , Brucelosis/prevención & control , Femenino , Ratones , Ratones Endogámicos C57BL , Distribución Aleatoria , Vacunología/métodos
19.
Proc Natl Acad Sci U S A ; 118(6)2021 02 09.
Artículo en Inglés | MEDLINE | ID: mdl-33526687

RESUMEN

Vertical sleeve gastrectomy (VSG) is one of the most effective and durable therapies for morbid obesity and its related complications. Although bile acids (BAs) have been implicated as downstream mediators of VSG, the specific mechanisms through which BA changes contribute to the metabolic effects of VSG remain poorly understood. Here, we confirm that high fat diet-fed global farnesoid X receptor (Fxr) knockout mice are resistant to the beneficial metabolic effects of VSG. However, the beneficial effects of VSG were retained in high fat diet-fed intestine- or liver-specific Fxr knockouts, and VSG did not result in Fxr activation in the liver or intestine of control mice. Instead, VSG decreased expression of positive hepatic Fxr target genes, including the bile salt export pump (Bsep) that delivers BAs to the biliary pathway. This reduced small intestine BA levels in mice, leading to lower intestinal fat absorption. These findings were verified in sterol 27-hydroxylase (Cyp27a1) knockout mice, which exhibited low intestinal BAs and fat absorption and did not show metabolic improvements following VSG. In addition, restoring small intestinal BA levels by dietary supplementation with taurocholic acid (TCA) partially blocked the beneficial effects of VSG. Altogether, these findings suggest that reductions in intestinal BAs and lipid absorption contribute to the metabolic benefits of VSG.


Asunto(s)
Colestanotriol 26-Monooxigenasa/genética , Gastrectomía/métodos , Obesidad Mórbida/cirugía , Receptores Citoplasmáticos y Nucleares/genética , Animales , Ácidos y Sales Biliares/biosíntesis , Ácidos y Sales Biliares/metabolismo , Dieta Alta en Grasa/efectos adversos , Humanos , Metabolismo de los Lípidos/genética , Lípidos/genética , Ratones , Ratones Noqueados , Obesidad Mórbida/metabolismo , Obesidad Mórbida/fisiopatología , Pérdida de Peso/genética
20.
Transplant Proc ; 53(1): 3-15, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-32631582

RESUMEN

BACKGROUND: Pediatric living donor liver transplantation (LDLT) is the only way to save children with end-stage liver disease. The donor for liver transplantation (LT) may have a complicated psychosocial condition. PURPOSE: This review aims to identify the domains of the donor psychosocial questions that should be addressed and summarize the aspects and tools future psychosocial assessments should include. METHODS: We searched the PubMed, Medline, Cochrane Library, Embase, Web of Science, and Google Scholar databases for the terms pediatric, liver transplantation, donor, and psychosocial. We used the Joanna Briggs Institute Critical Appraisal Tool to appraise reporting quality. Two researchers independently selected the papers and performed data extraction and quality appraisal. RESULTS: The articles included in this review contain 26 quantitative studies and 2 qualitative studies. The study quality was moderate to high. Donors have ambivalence, anxiety, the need for family and social support, the need for adequate information, distress, and low self-esteem during the preoperative period. In the postoperative period they have poor psychological condition, panic disorder, conversion disorder and substance use/abuse disorder, abnormal family functioning, better psychosocial outcome, or among others. The assessment methods consisted of the questionnaire survey and semi-structured interview. Among the 28 studies, 17 different psychosocial domains were mentioned. The most frequently referred to was family and social support. CONCLUSION: The contents of the psychosocial assessment must include anxiety or depression, family and social support, ambivalence, information, and positive psychosocial characteristics. Assessment methods should use the questionnaire survey and semi-structured interview. According to this review, future research can develop a specific psychosocial assessment tool for pediatric LT donors.


Asunto(s)
Trasplante de Hígado/psicología , Donadores Vivos/psicología , Pediatría , Afecto , Ansiedad , Niño , Femenino , Humanos , Masculino , Encuestas y Cuestionarios
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