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Objective: To study the curative effect of rehmannia glutinosa leaves total glycoside capsules and the role of mitochondrial autophagy on nucleos(t)ide drug-induced renal injury. Methods: Adefovir dipivoxil (ADV) was used to construct a hepatitis B virus (HBV) transgenic mouse model for renal injury. Renal function was measured in each group at one and two weeks of modeling. Mitochondrial autophagy indicators were measured at two weeks of modeling in renal tissue. Transmission electron microscopy was used to detect mitochondrial autophagy phenomena in renal tissue. The model was established for two weeks. Mouse with renal injury were treated with rehmannia glutinosa leaves total glycoside capsules or isotonic saline for eight weeks by intragastric administration. Renal function was measured. Renal tissue morphology was observed. Mitochondrial autophagy indicators were detected in renal tissue. The protective effect of different concentrations of verbascoside (the main active ingredient of rehmannia glutinosa capsule) was observed on HK-2 cell damage induced by ADV. HK-2 cells were divided into control, ADV, and ADV plus verbascoside groups. The effects of verbascoside at different times and concentrations were observed on the HK-2 mitochondrial autophagy indicators. Fifty patients with chronic hepatitis B were collected who presented with renal injury after treatment with nucleos(t)ide analogs. The random number method was used to divide 29 cases into a control group that received conventional treatment. The treatment group of 21 cases was treated with rehmannia glutinosa leaves total glycoside capsules on the basis of the control group. Serum creatinine (Scr) and urinary protein were detected at eight weeks.The χ(2) test or t-test was used for statistical analysis. Results: Compared with the control group, two weeks of modeling in the ADV group induced renal function injury in HBV mice. The expression of autophagy indicators was higher in the renal tissue of the ADV group than that of the control group. Transmission electron microscopy had revealed mitochondrial autophagy in the renal tissue of the ADV group. Compared with the control group, the renal function of HBV mice treated with rehmannia glutinosa leaves total glycoside capsules improved for two months, and the expressions of autophagy indicators were down-regulated.Verbascoside promoted proliferation in ADV-damaged HK-2 cells, and the expression of autophagy indicators was down-regulated compared with the ADV alone group. In 50 patients with renal function injury, the urinary protein improvement was significantly superior in the treatment group than that in the control group, with eighteen and three cases being effective and ineffective in the treatment group and 12 and 17 cases being effective and ineffective in the control group, with a statistically significant difference (χ(2)â =â 9.975 0, Pâ =â 0.001 6). Serum creatinine was decreased in the treatment group compared with the control group, with 11 and 10 cases being effective and ineffective in the treatment group and 12 and 17 cases being effective and ineffective in the control group, with no statistically significant difference (χ(2)â = 0.593 5, Pâ =â 0.441 1). Conclusion: Rehmannia glutinosa leaves total glycoside capsule can improve the nucleos(t)ide drug-induced renal function injury in chronic hepatitis B, possibly playing a role via inhibiting PINK1/Parkin-mediated mitochondrial autophagy.
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Glucósidos , Hepatitis B Crónica , Polifenoles , Rehmannia , Humanos , Ratones , Animales , Hepatitis B Crónica/tratamiento farmacológico , Glicósidos/farmacología , Glicósidos/uso terapéutico , Antivirales/uso terapéutico , Creatinina , Virus de la Hepatitis B , Riñón , AutofagiaRESUMEN
OBJECTIVE: To investigate the inhibitory effect of AZD2014, a dual mTORC1/2 inhibitor, against acute graft rejection in a rat model of allogeneic liver transplantation. METHODS: Liver transplantation from Lewis rat to recipient BN rat (a donor-recipient combination that was prone to induce acute graft rejection) was performed using Kamada's two-cuff technique. The recipient BN rats were randomized into 2 groups for treatment with daily intraperitoneal injection of AZD2014 (5 mg/kg, n=4) or vehicle (2.5 mL/kg, n=4) for 14 consecutive days, starting from the first day after the transplantation. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBIL) levels of the rats were measured 3 days before and at 1, 3, 5, 7, 10, and 14 days after the transplantation, and the survival time of the rats within 14 days were recorded. Immunohistochemical staining was used to examine the expressions of CD3 and Foxp3 in the liver graft, and acute graft rejection was assessed using HE staining based on the Banff schema. RESULTS: Three rats in the control group died within 14 days after the surgery, while no death occurred in the AZD2014 group, demonstrating a significantly longer survival time of the rats in AZD2014 group (χ2=4.213, P=0.04). Serum ALT, AST and TBIL levels in the control group increased progressively after the surgery and were all significantly higher than those in AZD2014 group at the same time point (P < 0.05). Pathological examination revealed significantly worse liver graft rejection in the control group than in AZD2014 group based on assessment of the rejection index (P < 0.01); the rats in the control group showed more serious T lymphocyte infiltration and significantly fewer Treg cells in the liver graft than those in AZD2014 group (P < 0.01). CONCLUSIONS: AZD2014 can effectively inhibit acute graft rejection in rats with allogeneic liver transplantation.
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Rechazo de Injerto , Trasplante de Hígado , Animales , Benzamidas , Rechazo de Injerto/prevención & control , Supervivencia de Injerto , Hígado/patología , Diana Mecanicista del Complejo 1 de la Rapamicina , Morfolinas , Pirimidinas , Ratas , Ratas Endogámicas LewRESUMEN
OBJECTIVE: To investigate the antitumor effects of AZD2014 (a dual mTORC1/2 inhibitor) against human hepatocellular carcinoma (HCC) xenograft in mice. METHODS: HCCLM3 cells were injected subcutaneously in the right flank of nude mice, and when the tumors were macroscopic, the mice were randomized into 2 groups for daily intraperitoneal injection of AZD2014 (5 mg/kg, n=5) or vehicle (5 mL/kg, n=5) for 24 days. Tumor growth was assessed using calipers every 4 days and the tumor growth curve was drawn. After the final injection, the mice were euthanized and the tumors were dissected for measuring tumor weight and histopathological analysis with HE staining. Immunohistochemical staining was used to detect the expressions of Ki-67, cleaved caspase-3, CD31, and the epithelial-mesenchymal transition (EMT)-related proteins (Ecadherin, N-cadherin, and vimentin) in the tumor tissue. RESULTS: Daily treatment with AZD2014 significantly suppressed HCC growth as compared with the control group. HE staining showed significantly increased tumor necrosis in AZD2014-treated mice. AZD2014 treatment inhibited tumor cell proliferation, angiogenesis and EMT progression as shown by decreased expressions of Ki-67, CD31, N-cadherin, and vimentin and increased expression of E-cadherin in the tumor tissue, and significantly promoted tumor cell apoptosis as shown by an increased expression of cleaved caspase-3 in AZD2014-treated mice. CONCLUSIONS: AZD2014 is a highly potent antitumor agent for HCC in nude mice bearing HCC xenografts. AZD2014 can effectively inhibit tumor proliferation, angiogenesis and EMT progression and induce tumor cell necrosis and apoptosis.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Animales , Apoptosis , Benzamidas , Carcinoma Hepatocelular/tratamiento farmacológico , Línea Celular Tumoral , Proliferación Celular , Transición Epitelial-Mesenquimal , Xenoinjertos , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Diana Mecanicista del Complejo 1 de la Rapamicina , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Morfolinas , Pirimidinas , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Both hepatocellular carcinoma (HCC) and metabolic syndrome are closely associated with the composition of the gut microbiota (GM). Although it has been proposed that elements of the GM can be used as biomarkers for the early diagnosis of HCC, whether metabolic syndrome results in a misrepresentation of the results of the early diagnosis of HCC using GM remains unclear. We compared the differences in the faecal microbiota of 10 patients with primary HCC, six patients with type 2 diabetes mellitus (T2DM), seven patients with arterial hypertension, six patients with both HCC and T2DM, and 10 patients with both HCC and arterial hypertension, as well as 10 healthy subjects, using high-throughput sequencing of 16S rRNA gene amplicons. Our results revealed a significant difference in the GM between subjects with and without HCC. The 49 bacterial genera out of the 494 detected genera were significantly different between the groups. These results show that changes in the GM can be used to distinguish between subjects with and without HCC, and can resist interference of T2DM and arterial hypertension with the GM. The results of the present study provide an important basis for the clinical auxiliary diagnosis of HCC by detecting the GM.
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Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/microbiología , Heces/microbiología , Microbioma Gastrointestinal/genética , Neoplasias Hepáticas/microbiología , Síndrome Metabólico/microbiología , Adulto , Bacterias/genética , Biomarcadores , Carcinoma Hepatocelular/patología , Diabetes Mellitus Tipo 2/microbiología , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , ARN Ribosómico 16S/genéticaRESUMEN
Objective: To understand the auditory cortex resting-state fMRI features for adult post-lingual deafness.Method: The author performed functional connectivity analysis on the study subjects with resting-state fMRI,the region of interest(ROI) of which were based separately on the left and right sides of primary auditory cortex. The data were collected from 8 cases with severe or above sensorineurally post-lingual deafness,compared to a control group of 8 cases with normal hearing. Result: When ROI were based on the left A1 areas of all subjects, the main activating area in the control group was bilateral superior temporal gyrus(STG), while the post-lingual deafness group included the bilateral STG, pre-central gyri, left Transverse temporal gyrus(TTG), post-central gyri and right TTG (P<0.01); when ROI were based on the right A1 areas of all subjects, the main activating area in the control group was the bilateral STG, while the post-lingual deafness group included the bilateral STG, right preîcentral gyri and post-central gyr i(P<0.01). The data showed statistical significance(P<0.05). Conclusion: After hearing loss functional reorganization takes place in the brains of adults with post-lingual deafness, resulting in possible enhancement of visual sense, tactile sense and other sensory systems in order to compensate information acquisition in daily life. î.
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Corteza Auditiva , Sordera , Imagen por Resonancia Magnética , Adulto , Corteza Auditiva/diagnóstico por imagen , Corteza Auditiva/fisiopatología , Sordera/diagnóstico por imagen , Sordera/fisiopatología , Humanos , LenguaRESUMEN
Objective:To explore the value and significance of the combination of 3D printing and spiral CT three-dimensional reconstruction in the diagnosis and treatment of common mandibular fractures. Method:Forty patients with mandibular fracture were collected. They were randomly divided into traditional operation group and 3D printing combined with three-dimensional reconstruction operation group. The differences between the two groups were compared according to the operation time and the recovery of fracture. Result:The operation time and trauma of 3D printing combined with three-dimensional reconstruction group were significantly better than those of traditional operation group, and the former was better than the latter ï¼P<0.05ï¼. Conclusion: 3D printing combined with three-dimensional reconstruction operation method realized the concept of individualized, precise and minimally invasive comprehensive treatment, which is worthy of clinical promotion.
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Imagenología Tridimensional , Fracturas Mandibulares , Humanos , Impresión Tridimensional , Tomografía Computarizada EspiralRESUMEN
INTRODUCTION: A national survey on critical values in hematology of China laboratories was conducted to determine the current practice and assess the quality indicators so as to obtain a quality improvement. METHODS: Laboratories participating were asked to submit the general information, the practice of critical value reporting, and the status of timeliness of critical value reporting. RESULTS: A total of 862 laboratories submitted the results. The majority of participants have included white blood cell count, blood platelet count, hemoglobin, prothrombin time, and activated partial thromboplastin time in their critical value lists. Many sources are used for establishing a critical value policy, and some of the laboratories consult with clinicians. The unreported critical value rate, late critical value reporting rate, and clinically unacknowledged rate in China are relatively low, and the median of critical value reporting time is 8-9 minutes. CONCLUSION: There exists a wide variety for critical value reporting in hematology in China. Laboratories should establish a policy of critical value reporting suited for their own situations and consult with clinicians to set critical value lists. Critical values are generally reported in a timely manner in China, but some measures should be taken to further improve the timeliness of critical value reporting.
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Hematología/normas , Laboratorios de Hospital/normas , Atención Ambulatoria , China , Servicios Médicos de Urgencia , Encuestas de Atención de la Salud , Pruebas Hematológicas/métodos , Pruebas Hematológicas/normas , Humanos , Pacientes Internos , Mejoramiento de la Calidad , Indicadores de Calidad de la Atención de Salud , Factores de TiempoRESUMEN
PURPOSE: Investigation of magnetic susceptibility and chemical exchange as sources of MRI phase contrast between gray and white matter resulting from protein and iron content from subcellular fractions. METHODS: This study analyzes the iron and macromolecule content of different subcellular fractions from rat brain and their relation to the water-resonance frequency by NMR spectroscopy. Additionally, the contributions of susceptibility and exchange were determined with different NMR reference substances. RESULTS: Only weak correlations between iron (r = 0.4318, P = 0.76) or protein content (r = 0.4704, P = 0.70) and frequency shift were observed. After membrane depletion, the correlation for iron increased to r = -0.9006 (P = 0.0009), whereas the shift relative to protein content increased much less (r = -0.4982, P = 0.64). Exchange-driven frequency shifts were 1.283 ppb/(mg/ml) for myelin and 0.775 ppb/(mg/ml) for synaptosomes; susceptibility-driven shifts were -1.209 ppb/(mg/ml) for myelin and -0.368 ppb/(mg/ml) for synaptosomes. The ratios between susceptibility and exchange differ significantly from simple protein solutions. CONCLUSIONS: As a result of counteracting susceptibility and exchange and increased relative shifts in membrane-depleted fractions, we conclude that tissue microstructure accounts more for the in vivo phase contrast than in the situation of homogenized tissue. Thus, membranes may generate much of the in vivo MR phase contrast resulting from anisotropy. Magn Reson Med 77:2028-2039, 2017. © 2016 International Society for Magnetic Resonance in Medicine.
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Encéfalo/diagnóstico por imagen , Hierro/química , Imagen por Resonancia Magnética/métodos , Proteínas/química , Algoritmos , Animales , Anisotropía , Encéfalo/patología , Interpretación de Imagen Asistida por Computador/métodos , Espectroscopía de Resonancia Magnética , Microscopía de Contraste de Fase , Ratas , Ratas Wistar , Fracciones Subcelulares , Sustancia Blanca/metabolismoRESUMEN
Recently, the one-stage posterior approach for treating spinal tuberculosis (TB) has gained popularity. However, large bony defects after debridement remain a major challenge in posterior surgery. The present retrospective study aims to compare the clinical outcomes of posterior-only surgical management by titanium mesh versus iliac bone grafts for treating lumbosacral TB. This was a retrospective cohort study. From January 2006 to April 2012, 36 patients with lumbosacral TB were treated at our department. The 36 cases were divided into 2 groups: 17 patients in Group A (titanium mesh) underwent one-stage posterior internal fixation, debridement, and titanium mesh bone fusion. The 19 patients in Group B (iliac bone graft) underwent posterior instrumentation, debridement, and iliac bone graft in a single procedure. The clinical and radiographic results for the 2 groups were analyzed and compared. The mean year of patients was 49.9â±â15.4 months in group A and 55.5â±â12.6 months in group B. All patients were followed up for an average of 47.3â±â8.1 months (range 36-60 months). Spinal TB was completely cured and no intraspinal infection and central nervous system complications of TB infection occurred. Bone fusion was achieved 6.4â±â1.9 months in group A and 7.8â±â2.1 months in group B. There was no significant statistical difference in bone fusion between the 2 groups (Pâ>â.05). The Oswestry Disability Index score (ODI) significantly improved between the preoperative and the last visit in either group. However, no significant difference was observed between the 2 groups at last visit (Pâ>â.05). There were significant differences between groups regarding the postoperative lumbosacral angle and angle correction loss at the final follow-up (Pâ<â.05). The average operative complication rate of Group A was less than that of Group B. Both iliac bone and titanium mesh can effectively construct anterior column defects in posterior surgery. The titanium mesh has the advantage of minor surgical invasion, effective reconstruction of large defects, and ideal sagittal alignment in lumbosacral TB for patients with osteoporosis and poor iliac bone quality.
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Trasplante Óseo/métodos , Ilion/trasplante , Región Lumbosacra/cirugía , Mallas Quirúrgicas , Tuberculosis de la Columna Vertebral/cirugía , Trasplante Óseo/instrumentación , Estudios de Casos y Controles , Femenino , Humanos , Vértebras Lumbares/microbiología , Vértebras Lumbares/cirugía , Región Lumbosacra/microbiología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Sacro/microbiología , Sacro/cirugía , TitanioRESUMEN
Objective:To study the variation of the electrode impedance in different periods after cochlear implantation performed with round window insertion in steroid deposition, and to provide the basis for the postoperative debugging of the speech processor. Method:Detected the electrode impedance of 47 cochlear receivers after operation in steroid deposition from September 2014 to October 2015, compared the impedance values between different periods, and different groups according to their locations. Result:The average impedance of all the electrodes and the 3 subgroups are low after implantation (period A0), peaked at the first month (period A1), then decreased slowly, and then turned to be stable at the sixth month (period A3); the impedance values were no significantly different between the sixth month (period A3) and the twelfth month (period A4) while were significantly different between each of other two periods (P<0.05); the apical group had the highest impedance and the basal group had the lowest impedance in all the 5 periods. Conclusion:The local use of steroid can decrease the impedance of the electrode after implantation. The impedance value were the low during operation, peaked at the first month, then decreased slowly, and turned to be stable at the sixth month. As a result, the cochlear implant should be debugged at regular intervals in 6 months after operation to obtain the best hearing status.
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Implantación Coclear , Impedancia Eléctrica , Ventana Redonda/fisiología , Esteroides/administración & dosificación , Cóclea , Implantes Cocleares , Pérdida Auditiva , HumanosRESUMEN
OBJECTIVE: This study aimed to document the difference of immunophenotypes in peripheral blood mononuclear cells (PBMCs) between long-term stable liver transplant recipients and recipients with acute rejection. We also sought to identify whether there is any correlation between microRNA (miRNA) expression profile and the differential immunoprofile in these 2 groups to establish a specific miRNA biomarker to identify potential liver transplant recipients. METHODS: PBMCs were isolated from 53 stable liver transplant recipients (STA group) and 15 liver transplant recipients with repeated biopsy-proven rejection episodes admitted to our hospital. Immunoprofiles were analyzed by means of flow cytometry. Analysis of miRNA expression in the PBMCs was performed by means of real-time polymerase chain reaction. RESULTS: The immune profiling analysis showed increased frequency of peripheral natural killer cells and regulatory T cells in stable liver transplant recipients compared with the acute rejection recipients and healthy volunteers (P < .05). There was no significant difference in the immune cell levels (CD19(+) B cells, CD4(+) T cells, and CD8(+) T cells) in PBMCs among the transplant recipient groups and healthy control subjects. Three miRNAs, miR-18b, miR-340, and miR-106b, were up-regulated in the PBMCs of the STA recipients compared with recipients with acute rejection. CONCLUSIONS: These results suggest that miR-18b, miR-340, and miR-106b, which regulate the expression of specific immunophenotypes, can be used as potential biomarkers to identify long-term stable liver transplant recipients from recipients with acute rejection.
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Rechazo de Injerto/inmunología , Leucocitos Mononucleares/metabolismo , Trasplante de Hígado/efectos adversos , MicroARNs/sangre , Adulto , Anciano , Biomarcadores/sangre , Linfocitos T CD8-positivos/metabolismo , Femenino , Citometría de Flujo , Rechazo de Injerto/sangre , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena en Tiempo Real de la Polimerasa , Regulación hacia ArribaRESUMEN
Neuropsychiatric symptoms are common in Alzheimer's disease (AD) and other neurodegenerative disorders. Recent progress has been made with clinical trials, advancing new therapies for psychosis in Parkinson's disease (PD), agitation in AD, and apathy in AD. Definitions have emerged for agitation and apathy in patients with cognitive impairment, facilitating recruitment of clinical trial populations. Progress in clinical trial design and the agents being assessed promise to advance therapies for disabling symptoms and improve quality of life for patients and caregivers.
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Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/psicología , Ensayos Clínicos como Asunto , Trastornos Mentales/tratamiento farmacológico , Trastornos Mentales/psicología , Terapias en Investigación/tendencias , Enfermedad de Alzheimer/epidemiología , Apatía/efectos de los fármacos , Citalopram/farmacología , Citalopram/uso terapéutico , Ensayos Clínicos como Asunto/métodos , Trastornos del Conocimiento/tratamiento farmacológico , Trastornos del Conocimiento/epidemiología , Trastornos del Conocimiento/psicología , Humanos , Trastornos Mentales/epidemiología , Piperidinas/farmacología , Piperidinas/uso terapéutico , Proyectos de Investigación/tendencias , Terapias en Investigación/métodos , Resultado del Tratamiento , Urea/análogos & derivados , Urea/farmacología , Urea/uso terapéuticoRESUMEN
Lipoic acid synthase, which exists primarily in mitochondria, participates in the biosynthesis of intrinsic lipoic acid. The lipoic acid synthase gene in pig is known as LIAS. To further investigate the biological functions of the protein that is encoded by LIAS, we cloned the open read frame of porcine LIAS (GenBank No. JN797612.1) into the expression vector pET-28α(+). The resulting pET-28α(+)-Lias recombinant vector was introduced into the Escherichia coli BL21 (DE3) strain. With induction by isopropyl ß-D-1-thiogalactopyranoside, the recombinant E. coli strain can express the target protein that has a molecular weight of 41.58 kDa, which was confirmed by Western blotting.
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Expresión Génica , Sistemas de Lectura Abierta , Sulfurtransferasas/genética , Animales , Clonación Molecular , Escherichia coli/genética , Escherichia coli/metabolismo , Peso Molecular , Plásmidos/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Sulfurtransferasas/metabolismo , PorcinosRESUMEN
Biomarkers are characteristics that are objectively measured and evaluated as indicators of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention. Amyloid measures become abnormal early in the Alzheimer's disease process and have only weak correlations with disease progression and cognitive decline; cerebrospinal fluid tau, brain atrophy, and reduced cortical metabolism correlate with cognitive measures and disease progression. Combinations of biomarkers have higher correlations and are better predictors of future decline than single biomarkers. Current biomarkers do not account for all of the variance in Alzheimer's disease; a more complete repertoire of biomarkers that more comprehensively assay the disease process is needed.
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Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/metabolismo , Encéfalo/metabolismo , Encéfalo/patología , Enfermedad de Alzheimer/terapia , Péptidos beta-Amiloides/metabolismo , Animales , Biomarcadores/metabolismo , Manejo de la Enfermedad , HumanosRESUMEN
We amplified S14R protein gene cDNA of porcine, cloned it into a prokaryotic expression plasmid, and expressed it in Escherichia coli. A pair of primers was designed based on the cDNA sequence of the porcine S14R gene in GenBank. The target gene fragment from porcine liver tissue was amplified by RT-PCR. Confirmed by auto-sequencing, the target gene fragment was subcloned into an expression vector of pET28a. The pET28a-S14R construct was subsequently transformed into E. coli BL21 (DE3). This construct was verified by restriction endonuclease digestion and sequencing. Using isopropyl ß-D-1-thiogalactopyranoside induction, a new recombinant protein with the expected relative molecular mass of 24 kDa appeared. The result was identified by SDS-PAGE electrophoresis. Porcine S14R includes 549bp (GenBank No. JN793537), with an open reading frame of 549 bp coding 182 amino acids.
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Receptores Citoplasmáticos y Nucleares/genética , Sus scrofa/genética , Secuencia de Aminoácidos , Animales , Clonación Molecular , Escherichia coli , Expresión Génica , Datos de Secuencia Molecular , Receptores Citoplasmáticos y Nucleares/biosíntesis , Receptores Citoplasmáticos y Nucleares/química , Análisis de Secuencia de ADN , Homología de Secuencia de AminoácidoRESUMEN
Interkeukin-8 (IL-8) is an important inflammatory mediator. It is an angiogenic factor associated with inflammation and carcinogenesis. To date, research on IL-8 has been limited to its role as an indicator of inflammation. There has been no systematic research concerning IL-8 expression levels in the mouse mammary gland during pregnancy and lactation. Mouse mammary gland samples were collected on days 1, 6, 12, 18 of pregnancy and of lactation (6 mice per group). The expression levels of IL-8 mRNA were measured by semi-quantitative RT-PCR, with GAPDH as an internal control. IL-8 mRNA was highly expressed on day 1 of pregnancy in the mouse mammary glands (IL-8(IOD)/GAPDH(IOD) = 1.68), and then suddenly declined; it reached 0.74 and 0.71 on days 6 and 12 of pregnancy. On day 18 of pregnancy, it started to increase (IL-8(IOD)/GAPDH(IOD) = 1.02). However, the expression levels of IL-8 mRNA were not significant during pregnancy. During lactation, IL-8 expression level was lower than during pregnancy, but it stabilized at 0.32-0.41 (IL-8(IOD)/GAPDH(IOD)) from day 1 to day 18 of lactation, although the difference was not significant. We suggest that the changes in IL-8 expression level during development is related to its regulatory role in mouse mammary gland immunity.
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Interleucina-8/genética , Lactancia/metabolismo , Glándulas Mamarias Animales/metabolismo , Embarazo/metabolismo , ARN Mensajero/genética , Animales , Femenino , Expresión Génica , Regulación del Desarrollo de la Expresión Génica , Interleucina-8/metabolismo , Glándulas Mamarias Animales/inmunología , Ratones , ARN Mensajero/metabolismoRESUMEN
The aim of this study is to test the activity of a marine bioactive compound containing high-purity caviar-derived DNA, collagen elastin and protein extracts from sturgeon (LD-1227, Caviarlieri, Laboratoires Dom, Switzerland) to exert neuroprotective properties in an experimental setting while also being potential triggers of neurogenesis in a separate in vitro study. Supplementation with high-DHA mixture of LD-1227 was applied for 30 days to stress model rats. Both supplementations significantly mitigated the histological brain damage when analyzing hippocampal subregions and corticosterone level. However, LD-1227 was most significantly efficient in preventing SOD, Catalase and ascorbic acid decrease in brain tissue. Both supplementations stimulated neurogenesis in vitro and neuron markers in particular but og olygodendrocyte markers and glia increased only in LD-1227-enriched medium. Taken together, these data suggest that LD-1227 is able to significantly protect the brain structure redox system to higher degree than DHA. Moreover, from in vitro study it appears that marine bioactive compound, through it wide array of small unsaturated fatty acids, phospholipids and neurotransmitter precursors, is likely to influence neuronal and glial lineage to act differently from a DHA-rich mixture.
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Mezclas Complejas/farmacología , Proteínas de Peces/farmacología , Peces , Hipocampo/metabolismo , Enfermedades Neurodegenerativas/tratamiento farmacológico , Neurogénesis/efectos de los fármacos , Animales , Antígenos de Diferenciación/metabolismo , Células Cultivadas , Mezclas Complejas/química , Proteínas de Peces/química , Hipocampo/patología , Enfermedades Neurodegenerativas/metabolismo , Enfermedades Neurodegenerativas/patología , Ratas , Ratas Sprague-DawleyRESUMEN
MicroRNA (miRNA) are small single-stranded noncoding RNA with important roles in regulating innate immunity in nonruminants via transcriptional and posttranscriptional mechanisms. Mastitis causes significant losses in the dairy industry and a wealth of large-scale mRNA expression data from mammary tissue have provided fundamental insights into the tissue adaptations to pathogens. We studied the expression of 14 miRNA (miR-10a, -15b, -16a, -17, -21, -31, -145, -146a, -146b, -155, -181a, -205, -221, and -223) associated with regulation of innate immunity and mammary epithelial cell function in tissue challenged with Streptococcus uberis. Those data, along with microarray expression of 2,102 differentially expressed genes, were used for bioinformatics analysis to uncover putative target genes and the most affected biological pathways and functions. Three miRNA (181a, 16, and 31) were downregulated approximately 3- to 5-fold and miR-223 was upregulated approximately 2.5-fold in infected versus healthy tissue. Among differentially expressed genes due to infection, bioinformatics analysis revealed that the studied miRNA share in the regulation of a large number of metabolic (SCD, CD36, GPAM, and FASN), immune/oxidative stress (TNF, IL6, IL10, SOD2, LYZ, and TLR4), and cellular proliferation/differentiation (FOS and CASP4) target genes. This level of complex regulation was underscored by the coordinate effect revealed by bioinformatics on various cellular pathways within the Kyoto Encyclopedia of Genes and Genomes database. Most pathways associated with "cellular processes," "organismal systems," and "diseases" were activated by putative target genes of miR-31 and miR-16a, with an overlapping activation of "immune system" and "signal transduction." A pronounced effect and activation of miR-31 target genes was observed within "folding, sorting, and degradation," "cell growth and death," and "cell communication" pathways, whereas a marked inhibition of "lipid metabolism" occurred. Putative targets of miR-181a had a strong effect on FcγR-mediated phagocytosis, toll-like receptor signaling, and antigen processing and presentation, which were activated during intramammary infections. The targets of both miR-31 and miR-223 had an inhibitory effect on "lipid metabolism." Overall, the combined analyses indicated that changes in mammary tissue immune, metabolic, and cell growth-related signaling pathways during infection might have been mediated in part through effects of miRNA on gene transcription. Differential expression of miRNA supports the view from nonruminant cells/tissues that certain miRNA might be essential for the tissue's adaptive response to infection.
Asunto(s)
Glándulas Mamarias Animales/microbiología , Mastitis Bovina/microbiología , MicroARNs/genética , Infecciones Estreptocócicas/veterinaria , Streptococcus , Animales , Bovinos , Biología Computacional , Femenino , Regulación de la Expresión Génica/genética , Genes/genética , Inmunidad Innata/genética , Glándulas Mamarias Animales/metabolismo , Mastitis Bovina/genética , MicroARNs/análisis , Estrés Oxidativo/genética , Reacción en Cadena en Tiempo Real de la Polimerasa/veterinaria , Infecciones Estreptocócicas/genética , Infecciones Estreptocócicas/metabolismo , Infecciones Estreptocócicas/microbiologíaRESUMEN
This study aims to determine the effects of different alkaline supplementations on high protein diet-induced abnormalities affecting bone metabolism in rats which were also undergoing physical exercise of moderate intensity. Sixty elderly Sprague-Dawley rats were randomly divided into four groups of 10 rats each and treated for 16 weeks as follows: baseline control group fed normal food (C); acidic high-protein diet supplemented group (chronic acidosis, CA group), bicarbonate-based alkaline formula (Basenpulver, Named, Italy) supplemented chronic acidosis (BB-CA) and citrate-based alkaline supplement (CB-CA). Throughout the supplementation period, rats were put on a treadmill training mimicking a moderate level of exercise. In the CA group, 24-hour urinary calcium (Ca) and phosphorus (P) excretion were increased over 30 percent (p<0.05 vs normal diet controls). However serum Ca was not significantly changed. Femural and tibial BMD and BMC was significantly decreased in the CA group (p<0.05) but both alkaline supplementations prevented such phenomenon (p<0.05 vs CA), without significant difference between the two formulations although the BB-CA group showed significantly more preserved trabecular bone volume (p<0.05 vs CB-CA group). An increased level of over 50 percent of urinary Dpd observed in the CA group (p<0.001) was reverted to normal by both supplementations (p<0.001 vs CA group). The same applied to urinary net acid excretion (p<001) with BB-supplementation performing better than CB-supplementation (p<0.05). Moreover, while the latter did not modify Nterminal telopeptide value, BB-supplementation significantly normalized this parameter (p<0.05 vs CA group) which exercise and acidic protein diet had modified (p<0.01 vs control diet). Overall, the present study shows that a bicarbonate-based alkaline formula, when administered to a dose amenable to clinical use, may significantly protect bone structure in exercising aged animals to a greater extent than a quali/quantitavely similar citrate-based formula.