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1.
Bioorg Chem ; 145: 107232, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38437762

RESUMEN

This study investigated the stability of milk fat globule membrane (MFGM) protein under simulated gastrointestinal conditions using an in vitro enzymatic digestion method. The optimal hydrolysis conditions were determined by monitoring the changes in particle size and zeta-potential of MFGM protein hydrolysates over time. Furthermore, the distribution of small molecular weight peptides with antioxidant activity was explored through DEAE-52 combined with in vitro cell experiments. Two novel antioxidant peptides (TGIIT and IITQ) were identified based on molecular docking technology and evaluated their potential scavenging activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-Azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS+) radicals. TGIIT and IITQ also demonstrated remarkable abilities in promoting mitochondrial biogenesis and activating Keap1/Nrf2 signaling pathway, which can effectively counteract skeletal muscle dysfunction induced by oxidative stress. Thus, MFGM-derived antioxidant peptides have the potential to be employed in food to regulate muscle protein metabolism and alleviate sarcopenia.


Asunto(s)
Antioxidantes , Glucolípidos , Glicoproteínas , Gotas Lipídicas , Factor 2 Relacionado con NF-E2 , Proteína 1 Asociada A ECH Tipo Kelch , Antioxidantes/farmacología , Simulación del Acoplamiento Molecular , Péptidos/farmacología , Digestión
2.
J Dairy Sci ; 107(1): 9-23, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37678791

RESUMEN

Milk fat globule epidermal growth factor 8 (MFG-E8) and whey protein have emerged as promising bionutrient supplements for enhancing skeletal muscle mass and function. In the present study, aging-related sarcopenia rat model was employed to elucidate the effects of the combined administration of MFG-E8 and whey protein on the catabolism and anabolism of gastrocnemius protein. Combined intervention led to notable enhancements in the antioxidative stress status and mitochondrial biogenesis capacity of gastrocnemius muscle fibers in the aging rats, concomitant with a significant inhibition of lipid accumulation. Moreover, the synergistic effect of MFG-E8 and whey protein was found to exert modulatory effects on key signaling pathways, including PI3K/Akt/PGC-1α pathway and MAPK/ERK signaling pathways in the gastrocnemius muscle of the aging rats. Specifically, this combined intervention was observed to promote mitochondrial biogenesis and regulate the expression of protein anabolism and catabolism-related regulators, thereby facilitating the alleviation of mitochondrial oxidative stress and enhancing biogenesis in gastrocnemius tissues. The findings of our study provide compelling evidence for the potential of MFG-E8 as a promising dietary supplement with antisarcopenic properties to ameliorate muscle protein metabolism disorders and mitigate mitochondrial-mediated myoblast apoptosis induced by oxidative stress.


Asunto(s)
Glucolípidos , Glicoproteínas , Gotas Lipídicas , Sarcopenia , Animales , Ratas , Factor VIII/farmacología , Galactosa/farmacología , Proteínas de la Leche/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Sarcopenia/prevención & control , Sarcopenia/veterinaria , Transducción de Señal , Proteína de Suero de Leche/farmacología
3.
Cardiol Young ; : 1-9, 2024 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-38682563

RESUMEN

OBJECTIVE: Challenges to communication between families and care providers of paediatric patients in intensive care units (ICU) include variability of communication preferences, mismatched goals of care, and difficulties carrying forward family preferences from provider to provider. Our objectives were to develop and test an assessment tool that queries parents of children requiring cardiac intensive care about their communication preferences and to determine if this tool facilitates patient-centred care and improves families' ICU experience. DESIGN: In this quality improvement initiative, a novel tool was developed, the Parental Communication Assessment (PCA), which asked parents with children hospitalised in the cardiac ICU about their communication preferences. Participants were prospectively randomised to the intervention group, which received the PCA, or to standard care. All participants completed a follow-up survey evaluating satisfaction with communication. MAIN RESULTS: One hundred thirteen participants enrolled and 56 were randomised to the intervention group. Participants who received the PCA preferred detail-oriented communication over big picture. Most parents understood the daily discussions on rounds (64%) and felt comfortable expressing concerns (68%). Eighty-six percent reported the PCA was worthwhile. Parents were generally satisfied with communication. However, an important proportion felt unprepared for difficult decisions or setbacks, inadequately included or supported in decision-making, and that they lacked control over their child's care. There were no significant differences between the intervention and control groups in their communication satisfaction results. CONCLUSIONS: Parents with children hospitalised in the paediatric ICU demonstrated diverse communication preferences. Most participants felt overall satisfied with communication, but individualising communication with patients' families according to their preferences may improve their experience.

4.
Health Promot Pract ; : 15248399231173702, 2023 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-37177790

RESUMEN

This report describes an Equity Lens Protocol and its use to guide partners' systematic reflection on harms and mitigation strategies of the COVID-19 response in a local public health system. This process evaluation tool is based on the Guidance document for assuring an equitable response to COVID-19 prepared by the Pan American Health Organization. We used a participatory approach to engage public health partners in systematically reflecting on harms, mitigation strategies, and lessons learned and implications for practice. Outputs from using this tool included identified: (a) specific harms (e.g., loss of income and challenges to learning) related to particular COVID-19 response measures (e.g., home confinement and school closure) and (b) mitigation strategies implemented to reduce harms. In response to the protocol's guiding questions, partners also identified lessons learned and practice recommendations for strengthening equity work in public health responses (e.g., an equitable response requires an investment in people, structures, and relationships before a crisis). This report-and accompanying protocol-illustrates use of a practical method for systematic reflection on public health responses through an equity lens.

5.
Clin Chem Lab Med ; 57(12): 1915-1922, 2019 Nov 26.
Artículo en Inglés | MEDLINE | ID: mdl-31377732

RESUMEN

Background α-Dicarbonyl compounds (α-DCs) have been detected in body fluids including plasma and urine and elevation of this sort of compounds in vivo has been associated with the development of many kinds of chronic diseases. However whether α-DCs are present in human saliva, and if their presence/absence can be related with various chronic diseases is yet to be determined. Methods In this study, a pre-column derivatization HPLC-UV method was developed to measure 3-deoxyglucosone (3-DG), glyoxal (GO), methylglyoxal (MGO), diacetyl (DA), and pentane-2,3-dione (PD) in human saliva employing 4-(2,3-dimethyl-6-quinoxalinyl)-1,2-benzenediamine (DQB) as a derivatizing reagent. The derivatization of the α-DCs is fast and the conditions are facile. The method was evaluated and the results show that it is suitable for the quantification of α-DCs in human saliva. Results In the measurements of these α-DCs in the saliva of 15 healthy subjects and 23 type 2 diabetes mellitus (T2DM) patients, we found that the concentrations of GO and MGO in the saliva of the diabetic patients were significantly higher than those in healthy subjects. As far as we know, this is the first time that salivary α-DC concentrations have been determined and associated with T2DM. Conclusions The developed method would be useful for the measurement of the salivary α-DC levels and the data acquired could be informative in the early screening for diabetes.


Asunto(s)
Desoxiglucosa/análogos & derivados , Glioxal/análisis , Piruvaldehído/análisis , Adulto , Cromatografía Líquida de Alta Presión/métodos , Desoxiglucosa/análisis , Diabetes Mellitus Tipo 2/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Saliva/química
6.
Sensors (Basel) ; 19(9)2019 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-31064125

RESUMEN

Bearing fault diagnosis of a rotating machine plays an important role in reliable operation. A novel intelligent fault diagnosis method for roller bearings has been developed based on a proposed hybrid classifier ensemble approach and the improved Dempster-Shafer theory. The improved Dempster-Shafer theory well considered the combination of unreliable evidence sources, the uncertainty information of basic probability assignment, and the relative credibility of the evidence on the weights in the process of decision making under the framework of fuzzy preference relations, which can effectively deal with conflicts of the evidences and then well improve the diagnostic accuracy for the hybrid classifier ensemble. The effectiveness of the improved Dempster-Shafer theory has been verified via a numerical example. In addition, deep neural networks, a support vector machine, and extreme learning machine techniques have been utilized in the single-stage classification based on singular spectrum entropy, power spectrum entropy, time-frequency entropy, and wavelet packet energy spectrum entropy in this work. Performances of the proposed hybrid ensemble classifier has been demonstrated on a bearing test-rig, compared with the original Dempster-Shafer theory. It can be found that the overall error rate can be greatly reduced with the hybrid ensemble classifier and the improved Dempster-Shafer theory.

7.
Ecotoxicol Environ Saf ; 145: 8-15, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28689070

RESUMEN

Dye dispersion and the interaction efficiency between azoreductases and dye molecules are rate-limiting steps for the decolorization of azo dyes. In this study, a biosurfactant-producing strain, Pseudomonas taiwanensis L1011, was isolated from crude oil. To increase the yield of the biosurfactant BS-L1011 from P. taiwanensis L1011, culture conditions were optimized including temperature, initial pH, carbon source, nitrogen source and C/N ratio. A maximum yield of 1.12g/L of BS-L1011 was obtained using D-mannitol as carbon source and yeast extract/urea as compound nitrogen source with C/N ratio of 10/4, pH 7.0 and 28°C. BS-L1011 exhibited a low critical micelle concentration (CMC) of 10.5mg/L and was able to reduce the surface tension of water to 25.8±0.1 mN/m. BS-L1011 was stable over a wide range of temperatures, pH values and salt concentrations. The biosurfactant is reported for the first time to accelerate chemical decolorization of Congo red by sodium hypochlorite, and biological decolorization of Amaranth by Bacillus circulans BWL1061, thus showing a potential in the treatment of dyeing wastewater.


Asunto(s)
Compuestos Azo/análisis , Colorantes/análisis , Pseudomonas/metabolismo , Tensoactivos/química , Contaminantes Químicos del Agua/análisis , Colorante de Amaranto/análisis , Biodegradación Ambiental , Rojo Congo/análisis , NADH NADPH Oxidorreductasas/química , Nitrorreductasas , Petróleo/microbiología , Pseudomonas/crecimiento & desarrollo , Pseudomonas/aislamiento & purificación , Tensoactivos/aislamiento & purificación , Aguas Residuales/química
8.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 39(5): 629-636, 2017 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-29125104

RESUMEN

Objective To investigate the polymorphisms of 23 Y-STR loci in a Han population in Jiangsu province. Methods Blood samples were collected from 4821 unrelated healthy Han males in Jiangsu province. DNA templates were amplified by PowerPlex Y23 kit,and the amplification products were detected by 3500xL genetic analyzer. Then,we calculated the allele frequencies and gene diversities respectively,as well as the haplotype frequencies and haplotype diversities. Results The gene diversity of these 23 Y-STR loci ranged 0.4099-0.9696. A total of 4781 haplotypes were detected,of which 4743 were found once. The haplotype diversity was 0.99999812. Conclusion The 23 Y-STR loci used in this study are highly polymorphic in Han individuals in Jiangsu province and therefore suitable for population genetic study and forensic individual identification.


Asunto(s)
Pueblo Asiatico/genética , Cromosomas Humanos Y/genética , Genética de Población , Polimorfismo Genético , China , Frecuencia de los Genes , Haplotipos , Humanos , Masculino , Repeticiones de Microsatélite
9.
Toxicol Appl Pharmacol ; 306: 134-43, 2016 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-27292126

RESUMEN

Emerging evidence has shown that microRNA-mediated gene expression modulation plays a crucial role in the pathogenesis of type 2 diabetes mellitus, but the novel miRNAs involved in type 2 diabetes and its functional regulatory mechanisms still need to be determined. In this study, we assessed the role of miR-10a in extracellular matrix accumulation in the kidney of diabetic mellitus induced by combining administration of chronic high fat diet (HFD) and low dosage of streptozotocin (STZ, 35mg/kg). Here, we found that HFD/STZ administration decreased the level of microRNA (miR-10a) expression in ICR strain mice. Overexpression of miR-10a alleviated the increased ratio of urine albumin-to-creatinine (ACR) ratio of HFD/STZ mice. In contrast, knockdown of miR-10a increased the ratio of kidney ACR in naïve mice. Furthermore, cAMP response element binding protein 1 (CREB1) was validated as a target of miR-10a in vitro and in vivo. CREB1 and its downstream fibronectin (FN, extracellular matrix) were increased in HFD/STZ-treated mice, which was reversed by kidney miR-10a overexpression. The content of CREB1 and FN was increased by miR-10a knockdown in kidney of naïve mice. Furthermore, histone deacetylase 3 (HDAC3) was revealed to be increased in kidney of HFD/STZ mice, accompanied with the augmentation of ACR ratio and FN level. Knockdown of HDAC3 with siRNA significantly caused the increase of miR-10a, resulting in the decrease in CREB1 and FN expression in kidney of HFD/STZ mice. Contrarily, HDAC3 overexpression mediated by lentivirus decreased miR-10a content, and enhanced ACR value, CREB1 and FN formation in naïve mice. Collectively, these results elucidate that HDAC3/miR-10a/CREB1 serves as a new mechanism underlying kidney injury, providing potential therapeutic targets in type 2 diabetes.


Asunto(s)
Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Histona Desacetilasas/metabolismo , Enfermedades Renales/metabolismo , MicroARNs/metabolismo , Animales , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/genética , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/patología , Dieta Alta en Grasa , Epigénesis Genética , Fibronectinas/metabolismo , Histona Desacetilasas/genética , Riñón/metabolismo , Riñón/patología , Enfermedades Renales/genética , Enfermedades Renales/patología , Masculino , Ratones Endogámicos ICR
10.
Fish Shellfish Immunol ; 36(1): 229-39, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24269520

RESUMEN

The gills are large mucosal surfaces and very important portals for pathogen entry in fish. The aim of this study was to determine the gill immune response at the protein levels, the differential proteomes of the zebrafish gill response to Aeromonas hydrophila infection were identified with isobaric tags for relative and absolute quantitation (iTRAQ) labeling followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). A total of 1338 proteins were identified and classified into the categories primarily related to cellular process (15.36%), metabolic process (11.95%) and biological regulation (8.29%). Of these, 82 differentially expressed proteins were reliably quantified by iTRAQ analysis, 57 proteins were upregulated and 25 proteins were downregulated upon bacterial infection. Gene ontology (GO) enrichment analysis showed that approximately 33 (8.8%) of the differential proteins in gills were involved in the stress and immune responses. Several upregulated proteins were observed such as complement component 5, serpin peptidase inhibitor clade A member 7, annexin A3a, histone H4, glyceraldehyde 3-phosphate dehydrogenase, creatine kinase, and peroxiredoxin. These protein expression changes were further validated at the transcript level using microarray analysis. Moreover, complement and coagulation cascades, pathogenic Escherichia coli infection and phagosome were the significant pathways identified by KEGG enrichment analysis. This is first report on proteome of fish gills against A. hydrophila infection, which contribute to understanding the defense mechanisms of the gills in fish.


Asunto(s)
Aeromonas hydrophila/inmunología , Enfermedades de los Peces/microbiología , Proteínas de Peces/inmunología , Branquias/microbiología , Infecciones por Bacterias Gramnegativas/veterinaria , Pez Cebra , Animales , Cromatografía Liquida , Enfermedades de los Peces/inmunología , Ontología de Genes , Branquias/inmunología , Infecciones por Bacterias Gramnegativas/inmunología , Infecciones por Bacterias Gramnegativas/microbiología , Proteómica/métodos , Distribución Aleatoria , Espectrometría de Masas en Tándem
11.
Pediatr Crit Care Med ; 15(1): 21-7, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24212284

RESUMEN

OBJECTIVE: To determine if aminophylline administration is associated with improved creatinine clearance and greater urine output in children with acute kidney injury in the cardiovascular ICU. DESIGN: Single-center retrospective cohort study. SETTING: Pediatric cardiovascular ICU, university-affiliated children's hospital. PATIENTS: Children with congenital or acquired heart disease in the cardiovascular ICU who received aminophylline to treat oliguric acute kidney injury and fluid overload. INTERVENTIONS: Patients received aminophylline after consultation with a pediatric nephrologist. Data were collected retrospectively over 7 days to assess if aminophylline was associated with improvement in creatinine clearance, urine output, and fluid overload. MEASUREMENTS AND MAIN RESULTS: Thirty-one patients received 52 aminophylline courses. Over the 7-day study period, serum creatinine decreased from a mean of 1.13 ± 0.91 to 0.87 ± 0.83 mg/dL (-0.05 mg/dL/d, p < 0.001). A concomitant increase was seen in estimated glomerular filtration rate from a mean of 50.0 ± 30.0 to 70.6 ± 58.1 mL/min/1.73 m (+3.66 mL/min/1.73 m/d, p < 0.001). Average daily urine output increased by 0.22 mL/kg/hr (p < 0.001), and fluid overload decreased on average by 0.42% per day in the 7-day study period (p = 0.005). Although mean furosemide dose increased slightly (0.12 mg/kg/d, p = 0.01), hydrochlorothiazide dosing did not significantly change over the study period. There were no complications related to aminophylline administration. CONCLUSIONS: Our study suggests that aminophylline therapy may be associated with significantly improved renal excretory function and may augment urine output in children who experience oliguric acute kidney injury in the cardiovascular ICU. Additionally, we did not identify any aminophylline-related side effects in this high-risk cardiac population. Future prospective studies are necessary to confirm the safety profile and to ensure that the beneficial effects are independent of other clinical interventions.


Asunto(s)
Lesión Renal Aguda/tratamiento farmacológico , Lesión Renal Aguda/fisiopatología , Aminofilina/administración & dosificación , Inhibidores de Fosfodiesterasa/administración & dosificación , Lesión Renal Aguda/orina , Aminofilina/efectos adversos , Niño , Preescolar , Creatinina/sangre , Creatinina/orina , Diuréticos/uso terapéutico , Femenino , Furosemida/uso terapéutico , Tasa de Filtración Glomerular , Cardiopatías/complicaciones , Cardiopatías/terapia , Humanos , Hidroclorotiazida/uso terapéutico , Lactante , Recién Nacido , Unidades de Cuidado Intensivo Pediátrico , Masculino , Oliguria/tratamiento farmacológico , Oliguria/etiología , Inhibidores de Fosfodiesterasa/efectos adversos , Estudios Retrospectivos
12.
Zhonghua Jie He He Hu Xi Za Zhi ; 37(2): 95-8, 2014 Feb.
Artículo en Zh | MEDLINE | ID: mdl-24796588

RESUMEN

OBJECTIVE: To explore the correlation between obstructive sleep apnea hypopnea syndrome (OSAHS) and multiple organ diseases. METHODS: Home-visit questionnaires were performed in 1 868 subjects (956 male, 912 female) with an average age of (79 ± 5) years, and a prospective follow-up was performed for a period of 20 years with annual medical examinations. Multiple organ diseases included hypertension, coronary heart disease, stroke, diabetes, pulmonary heart disease, renal insufficiency and erythrocytosis. The subjects were grouped by the diagnosis of OSAHS. RESULTS: Among the 1 868 subjects, 598 (32.0%) were diagnosed with OSAHS, and 1 270 (68.0%) of non-OSAHS as the control group. By the end of follow-up, in the OSAHS group there were 477 (79.8%) cases with hypertension, 337 (56.4%) cases with coronary heart disease, 167 (27.9%) cases with stroke, 76 (12.7%) cases with diabetes, 37 (6.2%) cases with pulmonary heart disease, 73 (12.2%) cases with renal insufficiency and 211(35.3%) cases with erythrocytosis, all of which were significantly higher than those of the control group [323(25.4%), 315 (24.8%), 95 (7.5%), 69 (5.4%), 40 (3.2%), 58 (4.6%), 30 (2.4%), P < 0.01]. The number of diseases in the OSAHS group was also higher than that in the control group (P < 0.05) . CONCLUSION: The incidence of multiple organ diseases was remarkably higher in the OSAHS group than that in the control group, which indicated that OSAHS was a risk factor for multiple organ diseases. These diseases in OSAHS patients may be related to hypoxia caused by OSAHS, endocrine and metabolic disorders, unhealthy lifestyles and arteriosclerosis.


Asunto(s)
Enfermedad Coronaria/epidemiología , Hipertensión/epidemiología , Apnea Obstructiva del Sueño/complicaciones , Apnea Obstructiva del Sueño/fisiopatología , Anciano , Anciano de 80 o más Años , Enfermedad Coronaria/etiología , Enfermedad Coronaria/fisiopatología , Femenino , Estudios de Seguimiento , Humanos , Hipertensión/etiología , Hipertensión/fisiopatología , Hipoxia/etiología , Hipoxia/fisiopatología , Masculino , Persona de Mediana Edad , Polisomnografía , Estudios Prospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Ronquido/complicaciones , Ronquido/fisiopatología
13.
Clin Neurol Neurosurg ; 236: 108111, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-38199117

RESUMEN

OBJECTIVES: The purpose of this study was to evaluate the effectiveness of endoscopic endonasal surgery (EES) for Rathke's cleft cysts (RCCs) and the advantages of detailed preoperative imaging evaluation, intraoperative personalized removal and multilevel sellar floor reconstruction. METHODS: The clinical data of 43 patients with RCCs who were treated by EES in the neurosurgery department of affiliated hospital of Jiangnan University and Wuxi No.2 People's Hospital from January 2018 to January 2023 were retrospectively analyzed. The effectiveness of EES for RCCs was analyzed by imaging information, surgical procedures, symptom improvement and complications. RESULTS: All 43 RCCs were completely removed by EES, and all clinical symptoms improved to varying degrees. Postoperative relief of headache was achieved in 23 out of 26 patients (88.5 %); there was improvement in 10 out of 13 patients with visual field disorders (76.9 %) and in 8 out of 10 patients with endocrine abnormalities (80 %). New hormonal deficiency was discovered in 7 of all the patients postoperatively. There were 8 patients with postoperative diabetes insipidus and 1 patient with cerebrospinal fluid leakage. The incidence of new hormonal dysfunction and postoperative DI in expanded EES (33.3 %, 33.3 %) was higher than it in conventional EES (4 %, 8 %) (P < 0.05). The average follow-up time was 29.1 ± 14.8 months, and there were no deaths or infections. Three patients presented with cyst recurrence on MRI. CONCLUSIONS: The clinical manifestations and imaging characteristics of RCCs are variable, and a detailed preoperative review of the imaging is helpful for the development of surgical plans. RCCs can be treated more safely and thoroughly with less trauma and complications by intraoperative personalized removal and multilevel sellar floor reconstruction. The high incidence of new hormonal dysfunction and postoperative DI may be related to the disturbance of the pituitary stalk. EES has unique advantages and high clinical application value for the treatment of RCCs.


Asunto(s)
Quistes del Sistema Nervioso Central , Quistes , Neoplasias Hipofisarias , Humanos , Estudios Retrospectivos , Quistes del Sistema Nervioso Central/diagnóstico por imagen , Quistes del Sistema Nervioso Central/cirugía , Quistes del Sistema Nervioso Central/complicaciones , Endoscopía , Quistes/complicaciones , Hipófisis/diagnóstico por imagen , Hipófisis/cirugía , Neoplasias Hipofisarias/cirugía
14.
Nat Med ; 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38969879

RESUMEN

It remains unclear whether metronomic chemotherapy is superior to conventional chemotherapy when combined with immune checkpoint blockade. Here we performed a phase 2 clinical trial of metronomic chemotherapy combined with PD-1 blockade to compare the efficacy of combined conventional chemotherapy and PD-1 blockade using Bayesian adaptive randomization and efficacy monitoring. Eligible patients had metastatic HER2-negative breast cancer and had not received more than one prior line of standard chemotherapy. Patients (total n = 97) were randomized to receive (1) metronomic vinorelbine (NVB) monotherapy (n = 11), (2) NVB plus anti-PD-1 toripalimab (n = 7), (3) anti-angiogenic bevacizumab, NVB and toripalimab (n = 27), (4) conventional cisplatin, NVB and toripalimab (n = 26), or (5) metronomic cyclophosphamide, capecitabine, NVB and toripalimab (the VEX cohort) (n = 26). The primary endpoint was disease control rate (DCR). Secondary objectives included progression-free survival (PFS) and safety. The study met the primary endpoint. The VEX (69.7%) and cisplatin (73.7%) cohorts had the highest DCR. The median PFS of patients in the VEX cohort was the longest, reaching 6.6 months, followed by the bevacizumab (4.0 months) and cisplatin (3.5 months) cohorts. In general, the five regimens were well tolerated, with nausea and neutropenia being the most common adverse events. An exploratory mass cytometry analysis indicated that metronomic VEX chemotherapy reprograms the systemic immune response. Together, the clinical and translational data of this study indicate that metronomic VEX chemotherapy combined with PD-1 blockade can be a treatment option in patients with breast cancer. ClinicalTrials.gov Identifier: NCT04389073 .

15.
Food Chem ; 403: 134473, 2023 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-36358083

RESUMEN

Milk fat globule membrane (MFGM) protein is a complex milk protein system with antioxidant property, which can alleviate skeletal muscle dysfunction caused by oxidative stress. In this study, peptide products of MFGM protein obtained through in vitro digestion were isolated and purified, and the composition and antioxidant activities of MFGM peptides (MFGMP) were identified and assessed using LC-MS/MS combined with molecular docking and in vitro approach. Three novel antioxidant peptides TGIIT, YAR and YYK were identified from MFGMPF1, among which TGIIT and YAR exhibited excellent antioxidant effects and protected dexamethasone (Dex)-induced L6 cells by enhancing mitochondrial function and biogenesis involving modulating Sirt-1/PGC-1α signaling pathway. Furthermore, YAR and TGIIT also significantly decreased expression of pro-apoptotic factors such as cyt-c, cleaved caspase-3 and caspase-9. Therefore, YAR and TGIIT, two novel antioxidant peptides, are expected to be utilized in functional food or medicine, providing an emerging role of MFGMP in maintaining anti-oxidant/oxidant status.


Asunto(s)
Antioxidantes , Hidrolisados de Proteína , Antioxidantes/farmacología , Antioxidantes/metabolismo , Hidrolisados de Proteína/farmacología , Hidrolisados de Proteína/metabolismo , Cromatografía Liquida , Simulación del Acoplamiento Molecular , Espectrometría de Masas en Tándem , Glucolípidos/química , Proteínas de la Leche/metabolismo , Gotas Lipídicas/metabolismo , Mitocondrias/metabolismo , Dexametasona/farmacología
16.
J Food Prot ; 85(12): 1790-1796, 2022 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-36150093

RESUMEN

ABSTRACT: Virulence genes expressed in Salmonella are a primary contributing factor leading to the high morbidity and mortality of salmonellosis in humans. The pathogenicity of Salmonella is mainly determined by the specific virulence factors that it carries. These factors also confer greater virulence and play a role in infection of a host and transmission of disease, and most Salmonella enterica can cause cross-infections between humans and animals. In this study, 265 samples in total were collected from a farmer's market and two supermarkets in Xuzhou, Jiangsu province, China, including 205 pork samples and 60 chicken samples. The suspected Salmonella isolates were isolated and identified using microbiological and molecular methods, and the confirmed isolates were used for serovar analysis and antimicrobial susceptibility testing. The virulence genes of Salmonella pathogenic islands (SPIs) and Salmonella virulence plasmids (Spv) in Salmonella-positive isolates were subsequently detected. Salmonella was isolated from 29.0% of samples, and all isolates were confirmed by PCR targeting the stn gene. Among the Salmonella isolates, resistance was most frequently observed against ciprofloxacin (84.4%), followed by tetracycline (71.4%) and streptomycin (68.8%). Resistance to amoxicillin-clavulanic acid (6.3%) and aztreonam (5%) was less commonly detected. The presence of the following virulence genes was determined by specific PCRs: hilA (SPI-1), sifA (SPI-2), misL (SPI-3), siiE (SPI-4), sopB (SPI-5), and spvC. The detection rate for SPI-1 to SPI-5 was 93.5, 87.0, 97.4, 97.4, and 97.4%, respectively. In addition, the detection rate of the spvC gene was 96.1%. Except for sopB (94.7%), all isolates of the dominant serovar S. enterica subsp.. enterica serovar Enteritidis contained all virulence genes from SPI-1 to SPI-5. This study demonstrated the epidemiological status of Salmonella in raw meat products in Xuzhou, and the complex antibiotic resistance and high isolation rate of virulence genes observed reveal many potential risks of which the findings presented herein will provide orientation to improve public health safeguards.


Asunto(s)
Productos de la Carne , Intoxicación Alimentaria por Salmonella , Salmonella enterica , Animales , Humanos , Antibacterianos/farmacología , Productos de la Carne/microbiología , Plásmidos , Salmonella/genética , Virulencia
17.
Diagnostics (Basel) ; 12(12)2022 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-36553002

RESUMEN

The IDH somatic mutation status is an important basis for the diagnosis and classification of gliomas. We proposed a "6-Step" general radiomics model to noninvasively predict the IDH mutation status by simultaneously tuning combined multi-sequence MRI and optimizing the full radiomics processing pipeline. Radiomic features (n = 3776) were extracted from multi-sequence MRI (T1, T2, FLAIR, and T1Gd) in low-grade gliomas (LGGs), and a total of 45,360 radiomics pipeline were investigated according to different settings. The predictive ability of the general radiomics model was evaluated with regards to accuracy, stability, and efficiency. Based on numerous experiments, we finally reached an optimal pipeline for classifying IDH mutation status, namely the T2+FLAIR combined multi-sequence with the wavelet image filter, mean data normalization, PCC dimension reduction, RFE feature selection, and SVM classifier. The mean and standard deviation of AUC, accuracy, sensitivity, and specificity were 0.873 ± 0.05, 0.876 ± 0.09, 0.875 ± 0.11, and 0.877 ± 0.15, respectively. Furthermore, 14 radiomic features that best distinguished the IDH mutation status of the T2+FLAIR multi-sequence were analyzed, and the gray level co-occurrence matrix (GLCM) features were shown to be of high importance. Apart from the promising prediction of the molecular subtypes, this study also provided a general tool for radiomics investigation.

18.
Zhongguo Yi Liao Qi Xie Za Zhi ; 35(2): 110-2, 2011 Mar.
Artículo en Zh | MEDLINE | ID: mdl-21706794

RESUMEN

A sort of absorbable Bondi of dura, whose main body is glue capsule, to compensate the deficiency of previous craniotomy, which easily causes delayed epidural hematoma. This device will help conglutinate dura to skull plate tightly, to stop bleeding and other purposes.


Asunto(s)
Implantes Absorbibles , Adhesivos , Duramadre , Craneotomía , Hemorragia/prevención & control , Diseño de Prótesis
19.
Methods Mol Biol ; 2182: 197-203, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-32894498

RESUMEN

Salmonella is considered as one of the most important foodborne zoonotic pathogens that can cause several foodborne diseases and is commonly associated with consumption of meats. Contaminated pork and pork products are major sources of human Salmonella infections in many countries. It is important to investigate and monitor the epidemiology of Salmonella in pork for public health and pork productivity. Here, we describe the method for isolation and identification of Salmonella from pork.


Asunto(s)
Carne de Cerdo/microbiología , Salmonella/aislamiento & purificación , Contaminación de Alimentos/análisis , Manipulación de Alimentos/métodos , Microbiología de Alimentos/métodos
20.
AMB Express ; 11(1): 60, 2021 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-33893895

RESUMEN

Salmonella, as a zoonotic pathogen, has attracted widespread attention worldwide, especially in the transmission between household pets and humans. Therefore, we investigated the epidemic distribution of dog Salmonella from pet hospitals and breeding base in Xuzhou, Jiangsu Province, China, and used multilocus sequence typing (MLST) and clustered regularly interspaced short palindromic repeats (CRISPRs) to subtype Salmonella isolates. From April 2018 to November 2019, a total of 469 samples were collected from pet hospitals and breeding base, including 339 dog samples and 60 cat samples. S. Kentucky (40.74%) was the most prevalent serotype, but other, such as S. Typhimurium (18.52%) and S. Indiana (18.52%), were also widespread. Eight different sequence type (ST) patterns were identified by MLST and ST198 was the highest proportion of these isolates. CRISPRs analysis showed that 9 different Kentucky CRISPR types (KCTs) was identified from ST198. 48 spacers including 29 (6 News) for CRISPR1 and 19 (4 News) for CRISPR2 that proved the polymorphic of Salmonella genes in samples from different sources. The analysis demonstrated that the common serotypes were widely present in pet hosts in the same area. This analysis shows that CRISPR genes have better recognition ability in the same serotype, which has a positive effect on the traceability of Salmonella and the prevention and treatment of salmonellosis.

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