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Kidney organoids - 3D representations of kidneys made either from pluripotent or tissue stem cells - have been available for well over a decade. Their application could confer notable benefits over longstanding in vivo approaches with the potential for clinically aligned human cells and reduced ethical burdens. They been used, at a proof-of-concept level, in development in disease modeling (including with patient-derived stem cells), and in screening drugs for efficacy/toxicity. They differ from real kidneys: they represent only foetal-stage tissue, in their simplest forms they lack organ-scale anatomical organization, they lack a properly arranged vascular system, and include non-renal cells. Cell specificity may be improved by better techniques for differentiation and/or sorting. Sequential assembly techniques that mimic the sequence of natural development, and localized sources of differentiation-inducing signals, improve organ-scale anatomy. Organotypic vascularization remains a challenge: capillaries are easy, but the large vessels that should serve them are absent from organoids and, even in cultured real kidneys, these large vessels do not survive without blood flow. Transplantation of organoids into hosts results in their being vascularized (though probably not organotypically) and in some renal function. It will be important to transplant more advanced organoids, with a urine exit, in the near future to assess function more stringently. Transplantation of human foetal kidneys, followed by nephrectomy of host kidneys, keeps rats alive for many weeks, raising hope that, if organoids can be produced even to the limited size and complexity of foetal kidneys, they may one day be useful in renal replacement.
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Diferenciación Celular , Riñón , Organoides , Organoides/citología , Humanos , Riñón/citología , AnimalesRESUMEN
Introduction: The objective of this study was to evaluate the usefulness of the serum biomarkers myeloperoxidase (MPO), paraoxonase (PON), and plasma asprosin in acute myocardial infarction (AMI) diagnosis and assess their compatibility with routinely screened cardiac biomarkers. Methods: This study was conducted using a prospective cross-sectional design and included 90 patients, consisting of 60 patients diagnosed with AMI (30 with ST-segment elevation and 30 with non-ST-segment elevation on ECG) and 30 controls (without a diagnosis of AMI). Changes in the levels of cardiac biomarkers (Hs-cTnI, CK, CK-MB), lipid profile (TC, TG, LDL, HDL), MPO, PON, asprosin, and routine biochemical parameters of patients were evaluated. Furthermore, receiver operating characteristic curve analysis revealed the diagnostic value of Hs-cTnI, MPO, PON, and asprosin in predicting AMI. Binary logistic regression analysis of cardiac marker concentrations was used to predict the presence of AMI. In contrast, multinomial logistic regression analysis was conducted to predict the type of AMI and the control group. Results: The median levels of MPO and plasma asprosin were found to be higher in the patient group (3.22 [interquartile range {IQR}: 2.4-4.4] ng/ml and 10.84 [IQR: 8.8-17.8] ng/ml, respectively) than in the control group (2.49 [IQR: 1.9-2.9] ng/ml and 4.82 [IQR: 4.6-8.0] ng/ml, respectively) (p = 0.001 and p < 0.001, respectively). The median levels of PON were 8.94 (IQR: 7.6-10.4) ng/ml in the patient group and 10.44 (IQR: 9.1-20.0) ng/ml in the control group (p < 0.001). In the binary logistic regression model, compared with the control group, a 1 ng/ml increase in MPO level increased the odds of having AMI by 3.61 (p = 0.041, 95% CI: 1.055-12.397), whereas a 1 ng/ml increase in asprosin level increased the odds of having AMI by 2.33 (p < 0.001, 95% CI: 1.479-3.683). In the multinominal logistic regression model, compared with the control group, a 1 ng/ml increase in the MPO level increased the odds of having NSTEMI by 4.14 (p = 0.025, 95% CI: 1.195-14.350), whereas a 1 ng/ml increase in asprosin concentrations increased the odds of having NSTEMI by 2.35 (p < 0.001, 95% CI: 1.494-3.721). Conclusion: Herein, MPO and asprosin concentrations increased with Hs-cTnI, and a decrease in PON concentration indicated that oxidant-antioxidant parameters and adipokines were related to AMI pathogenesis.
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OBJECTIVE: This study aimed to reveal the relationship between obesity and asprosin (fibrillin-1) in patients undergoing bariatric surgery and to investigate the role of asprosin in obesity etiopathogenesis. METHODS: The study included 37 patients who underwent laparoscopic sleeve gastrectomy for severe obesity and 37 patients who underwent laparoscopic cholecystectomy for cholelithiasis in the study and control groups, respectively. Blood samples were collected from the patients in the preoperative period to measure biochemical parameters. Blood samples were collected at 6 months postoperatively from the patients in the study group to compare their pre- and postoperative serum asprosin levels. RESULTS: A significant intergroup difference in terms of mean asprosin levels in adipose tissue was noted (p = 0.001). A comparison of preoperative and postoperative 6-month serum asprosin levels in the study group showed significant differences (p = 0.021). The area under the curve of asprosin tissue levels was 78.1%, and the cutoff value was 217.34 ng/g of protein, with a sensitivity and specificity of 73.0%. Tissue levels of asprosin were found to increase the risk of obesity by a factor of 1.018 (odds ratio; 95% CI: 1.008-1.027). CONCLUSIONS: Serum asprosin levels decreased significantly at 6 months after bariatric surgery. Adipose tissue of patients with obesity showed high asprosin levels and immunoreactivity. In conclusion, asprosin levels in adipose tissue were considered a potential independent risk factor in obesity etiopathogenesis.
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Cirugía Bariátrica , Obesidad Mórbida , Tejido Adiposo/metabolismo , Gastrectomía , Humanos , Obesidad/metabolismo , Obesidad Mórbida/cirugíaRESUMEN
Circadian rhythms are a series of endogenous autonomous 24-h oscillations generated by the circadian clock. At the molecular level, the circadian clock is based on a transcription-translation feedback loop, in which BMAL1 and CLOCK transcription factors of the positive arm activate the expression of CRYPTOCHROME (CRY) and PERIOD (PER) genes of the negative arm as well as the circadian clock-regulated genes. There are three PER proteins, of which PER2 shows the strongest oscillation at both stability and cellular localization level. Protein-protein interactions (PPIs) or interactome of the circadian clock proteins have been investigated using classical methods such as two-dimensional gel electrophoresis, immunoprecipitation-coupled mass spectrometry, and yeast-two hybrid assay where the dynamic and weak interactions are difficult to catch. To identify the interactome of PER2 we have adopted proximity-dependent labeling with biotin and mass spectrometry-based identification of labeled proteins (BioID). In addition to known interactions with such as CRY1 and CRY2, we have identified several new PPIs for PER2 and confirmed some of them using co-immunoprecipitation technique. This study characterizes the PER2 protein interactions in depth, and it also implies that using a fast BioID method with miniTurbo or TurboID coupled to other major circadian clock proteins might uncover other interactors in the clock that have yet to be discovered.
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Relojes Circadianos , Proteínas Circadianas Period , Factores de Transcripción ARNTL/genética , Factores de Transcripción ARNTL/metabolismo , Proteínas CLOCK/genética , Proteínas CLOCK/metabolismo , Relojes Circadianos/genética , Proteínas Circadianas Period/genética , Proteínas Circadianas Period/metabolismo , Proteoma/metabolismoRESUMEN
The aim of this study was to investigate the possible protective effects of chrysin on oxidative status and histological alterations against carbon tetrachloride (CCl4)-induced liver and kidney tissue in rats. The animals were randomly divided into four groups; the control, chrysin (100 mg/kg), CCl4 (0.5 ml/kg) and chrysin + CCl4 groups. Liver and kidney injuries were assessed by biochemical and histopathological examinations. The levels of malondialdehyde (MDA), reduced glutathione (GSH), and superoxide dismutase (SOD) activity were measured in tissues. Serum tumor necrosis factor-α (TNF-α), aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea, and creatinine levels were also measured in blood samples. MDA, serum TNF-α, AST, ALT, urea, and creatinine levels (p < 0.05) were significantly higher, and SOD activity and GSH level were significantly (p < 0.05) lower in the CCl4 group than in the control group. Treatment with chrysin in the chrysin + CCl4 group decreased MDA, AST, ALT, creatinine, and TNF-α levels (p < 0.05), and increased SOD activity, GSH levels (p < 0.05), and serum TNF-α levels (p < 0.05). In addition, body weight change (BWC) (p < 0.05) and feed intake (FI) were significantly lower (p < 0.001) in the CCl4 group than in the control group. Moreover, treatment with chrysin increased BWC and FI in the chrysin + CCl4 group compared with that in the CCl4 group. These findings also confirmed by histopathological examination. The chrysin treatment ameliorated the CCl4-induced biochemical and pathological alterations. These results demonstrated that chrysin provided amelioration on the rat liver and kidney tissues CCl4-induced injury by increasing the antioxidant activity.
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Tetracloruro de Carbono , Flavonoides , Alanina Transaminasa/metabolismo , Animales , Antioxidantes , Aspartato Aminotransferasas/metabolismo , Tetracloruro de Carbono/toxicidad , Flavonoides/metabolismo , Riñón/metabolismo , Hígado/metabolismo , Estrés Oxidativo , Extractos Vegetales , RatasRESUMEN
AIM: To investigate the effects of trauma type and survival on biochemical parameters including blood urea, creatinine, and glucose levels on patients with traumatic brain injury (TBI). MATERIAL AND METHODS: The medical records of 102 patients with TBIs who were admitted to the emergency department and/ or hospitalized in the neurosurgery department between 2016 and 2019 were examined retrospectively. RESULTS: Types of trauma included: 19 cases of subarachnoid hemorrhage, 25 cases of subdural hemorrhage, 9 cases of epidural hemorrhage, 28 cases of intracerebral hemorrhage, 4 cases of multiple hemorrhage, and 12 cases with other hemorrhages. We examined the effects of trauma type and survival on a total of 17 blood test parameters, but only three (blood urea, creatinine, and glucose) showed significance for the overall model, meaning that either trauma type or survival or an interaction between the two had significant effects on these three blood parameters. CONCLUSION: Our findings imply that the risk of fatality due to TBI might be deduced from observation of the patient?s blood urea and glucose levels as these two parameters differed significantly in fatal versus surviving cases. Blood urea and creatinine levels were different for different trauma types and may be useful in distinguishing the type of injury.
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Biomarcadores/sangre , Glucemia/análisis , Lesiones Traumáticas del Encéfalo/sangre , Creatinina/sangre , Urea/sangre , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
OBJECTIVES: Diclofenac sodium (DS) is a widely used nonsteroidal anti-inflammatory drug. Although its high doses are known to cause toxic effects in many tissues including liver and kidney, the effects on the cardiovascular system (CVS) have not been fully elucidated yet. Therefore, this study aimed to investigate the effect of DS on CVS. METHODS: The Control group did not receive medication; however, a single dose of 240 mg/kg DS was administered orally to the DS group. Electrocardiography (ECG) measurements were performed in all animals before (0thhour) and after (1st,6th,12th,24thhour) intoxication. After 24 h, All animals were sacrificed. Biochemical (malondialdehyde [MDA], and glutathione (GSH), Apelin, Elabela, Meteorin, Endoglin, Keap1, and Nrf2) and histopathological analyzes were performed on heart tissue samples. RESULTS: ECG results showed that there was a statistically significant increase in QTc, QRS, and heart rate at the 12th and 24th hours in the DS group. The biochemical analysis showed that GSH, Apelin, Keap1, and NRF2 values decreased significantly while Meteorin and Endoglin levels increased in the DS group. When histopathological results were evaluated, distinct lesions were observed in the DS group. CONCLUSION: In conclusion, high doses of DS intake can cause adverse effects on and damage to CVS.
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Antiinflamatorios no Esteroideos/toxicidad , Diclofenaco/toxicidad , Frecuencia Cardíaca/efectos de los fármacos , Corazón/efectos de los fármacos , Miocardio/metabolismo , Animales , Apelina/efectos de los fármacos , Apelina/metabolismo , Sistema Cardiovascular/efectos de los fármacos , Electrocardiografía , Endoglina/efectos de los fármacos , Endoglina/metabolismo , Glutatión/efectos de los fármacos , Glutatión/metabolismo , Proteína 1 Asociada A ECH Tipo Kelch/efectos de los fármacos , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Malondialdehído/metabolismo , Miocardio/patología , Factor 2 Relacionado con NF-E2/efectos de los fármacos , Factor 2 Relacionado con NF-E2/metabolismo , Proteínas del Tejido Nervioso/efectos de los fármacos , Proteínas del Tejido Nervioso/metabolismo , Hormonas Peptídicas/efectos de los fármacos , Hormonas Peptídicas/metabolismo , RatasRESUMEN
The aim of this study was to investigate the protective effects of pomegranate extract and tangeretin alone or in combination in DMBA-induced rat breast cancer model. A total of 68 female rats were randomly divided into 8 groups. The first 4 groups were designed as controls for cancer and treatment groups, and the control groups were composed of only control (C), Pomegranate (P), Tangeretin (T), and Pomegranate+Tangeretin (P+T) groups. The other four groups were designed as cancer and treatment groups and were composed of DMBA (D) and DMBA+Pomegranate (D+P), DMBA+Tangeretin (D+T), DMBA+Pomegranate+Tangeretin (D+P+T) groups. Tumor markers and angiogenesis parameters were studied from plasma samples obtained from rats. Histopathological, immunohistochemical, and TUNEL analyses and expressions of proteins affecting apoptosis and cell cycle were determined in breast tissue samples. In the DMBA group, plasma CA15-3, CEA, VEGF, MMP-9, and NF-κB levels were significantly increased compared to the controls, but significant decreases were observed in these parameters except MMP-9 in the treatment groups. It was observed that p53 and Bax expressions significantly increased in both D+P and D+P+T groups compared to the DMBA group, and these findings were supported by Tunel and immunohistochemical findings. Cyclin D1 expressions were found to be significantly decreased only in the D+T group and supported by TUNEL and immunohistochemical findings. Immunohistochemical ER-α and Ki-67 immune reactivities were significantly decreased in all treatment groups compared to the DMBA group. Our results showed that combined application of pomegranate extract and tangeretin may be more beneficial in preventing breast cancer development.
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Flavonas/farmacología , Neoplasias Mamarias Experimentales/prevención & control , Extractos Vegetales/farmacología , Granada (Fruta)/química , 9,10-Dimetil-1,2-benzantraceno/efectos adversos , Animales , Apoptosis/efectos de los fármacos , Carcinógenos , Quimioprevención , Combinación de Medicamentos , Receptor alfa de Estrógeno/metabolismo , Femenino , Flavonas/química , Antígeno Ki-67/metabolismo , Neoplasias Mamarias Experimentales/patología , FN-kappa B/metabolismo , Extractos Vegetales/química , Ratas , Ratas Sprague-Dawley , Proteína p53 Supresora de Tumor/metabolismo , Proteína X Asociada a bcl-2/metabolismoRESUMEN
INTRODUCTION: Accidental head injuries are known to cause serious traumatic brain injury (TBI). Children younger than 2 years of age build a separate group that is more difficult to assess clinically. Investigations targeting TBIs in pediatric cases, particularly in those between 0 and 2 years of age, are limited. OBJECTIVE: In this study, we reviewed a number of severe accidental head injuries in a cohort of children aged 0-2 years to evaluate the relative incidence, distribution, and clinical success in determining the nature of the cases in the Kars Province of Turkey. METHODS: The study targeted 26 -cases who presented to the Emergency Department of Kars Harakani Hospital for TBI between 2017 and 2019 through retrospective chart review. RESULTS AND CONCLUSIONS: Among the children who presented to the emergency clinic, 2 were newborns, 7 were <1 year of age, and the remaining 17 cases were between 1 and 2 years old. The number of male and female patients was equal, and 5 fatality cases were observed. The most frequent cause of head trauma were falls. We deduced that 6 cases had subarachnoid hemorrhage, 2 cases had subdural hemorrhage, 3 cases had epidural hemorrhage, and 4 cases had contusion. We compared the mean level of the two blood parameters hemoglobin (HGB) and hematocrit (HCT) between fatal and surviving cases and detectedthat both values decreased dramatically in exitus cases. The higher fatality rate in the present study could be attributed to the fact that we targeted only the severe TBI cases. Severe TBI in children younger than 2 years results in a life-threating situation. The risk of fatality might be deduced from the reduction of the HGB and HCT levels as it is significantly lower in fatal cases than in surviving cases.
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Lesiones Traumáticas del Encéfalo/epidemiología , Accidentes por Caídas/estadística & datos numéricos , Accidentes de Tránsito/estadística & datos numéricos , Preescolar , Contusiones/epidemiología , Traumatismos Craneocerebrales/epidemiología , Femenino , Hematoma Epidural Craneal/epidemiología , Hematoma Subdural/epidemiología , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Estudios Retrospectivos , Hemorragia Subaracnoidea/epidemiología , Turquía/epidemiologíaRESUMEN
OBJECTIVE: Protective effects of ischemic postconditioning (PostC) decrease/disappear with age and chronic heart diseases. Similarly, low serum melatonin levels have been reported in the same risk groups. The aims of this study were to investigate the effects of melatonin on the protection of PostC in ischemia-reperfusion (I/R)-induced infarct size and roles of uncoupling protein (UCP) 3, irisin, and nuclear factor kappa B (NFkB) levels. METHODS: Rats were pinealectomized (Px) or sham operated (non-Px) 2 months before the I/R studies. The left main coronary artery was occluded for 30 min followed by 120 min reperfusion. PostC was induced with three cycles of R/I (10 s each) after ischemia. RESULTS: The infarct size was found to be significantly higher in Px rats (54.68±1.5%) than in the control group (35.1±2.5%). PostC and melatonin administrations to non-Px rats significantly reduced the infarct size. On the other hand, PostC did not create a significant effect in Px rats, but protection was provided when PostC was co-administrated with melatonin. While significant decreases were detected in the UCP3 levels, irisin and NFkB levels increased with I/R and Px. Treatment with PostC and melatonin in non-Px groups and their co-administration in Px groups were found to return all the genes close to normal levels. CONCLUSION: The physiological and pharmacological concentrations of melatonin may play a role in the protection of PostC. In cases when physiological melatonin is reduced, such as aging and heart diseases, this protection may decrease, and this effect may be restored by melatonin replacement. PostC and melatonin may regulate energy metabolism and inflammatory mediators and protect mitochondria by affecting the UCP3, irisin, and NFkB levels.
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Poscondicionamiento Isquémico , Melatonina/uso terapéutico , Daño por Reperfusión Miocárdica/prevención & control , Proteína Desacopladora 3/sangre , Animales , Modelos Animales de Enfermedad , Masculino , Melatonina/administración & dosificación , Daño por Reperfusión Miocárdica/sangre , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND: The aim of this study was to evaluate the therapeutic effects of thalidomide and etanercept on lipopolysaccharide (LPS)-induced sepsis in a rat model. METHODS: Thirty male Wistar Albino rats were divided into 5 groups: Control, LPS, LPS+Thalidomide, LPS+Etanercept, and LPS+Thalidomide+Etanercept. The control group was given a 1 mL intraperitoneal (i.p.) injection of 0.9% saline solution. For endotoxic treatment, the rats were injected with a single i.p. dose of LPS (Escherichia coli 0111: B4 (5 mg/kg). Thalidomide (0.5 mg/kg) and etanercept (1 mg/kg) were administered i.p. to the therapeutic groups. Hepatic tissue tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1) and platelet-derived growth factor (PDGF) levels were determined by enzyme-linked immunosorbent assay and malondialdehyde (MDA) levels and total oxidant status (TOS) were measured using appropriate methods. RESULTS: In vivo results exhibited elevated liver tissue TNF-α, IL-6, ICAM-1, PDGF, MDA, and TOS levels in the LPS-treated animals compared with the controls. The analysis of liver tissue supported the findings of biochemical alterations and indicated a therapeutic role for thalidomide and etanercept. Treatment of septic animals with these agents resulted in a remarkable decrease in the selected proinflammatory cytokines, angiogenic factors, and reactive oxygen parameters. CONCLUSION: Restoration of cytokine balance and oxidant status to normal levels following treatment with selected therapeutic agents suggests that thalidomide and etanercept can help to avoid the potentially devastating effects of sepsis.
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Etanercept/farmacología , Lipopolisacáridos/efectos adversos , Sepsis/metabolismo , Talidomida/farmacología , Animales , Citocinas/análisis , Citocinas/metabolismo , Modelos Animales de Enfermedad , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Ratas , Ratas WistarRESUMEN
Apelin is a peptide hormone defined as a ligand for G-protein clamped receptor (APJ) receptor. It is indicated in the literature both apelin and APJ are synthesized on the peripheral tissues including the renal tissues. Which roles does the apelin play on the renal tissue has not been completely illuminated yet. This study is designed to determine the possible protective effect of apelin-13 on the kidney I/R injury. Adult male Sprague-Dawley rats were used in this study. In the sham group, right kidneys of the animals were dissected. In the I/R group, right kidney was dissected and ischemia of 45 min was performed, and then reperfusion was applied for 3 h. In the treatment groups, three different doses of apelin were injected at the beginning of the ischemia unlike the I/R group. BUN, Cre, Na, K, Cl, total protein and albumin from serum samples were determined and TNF-α, IL-1ß, IL-6, TAS and TOS parameters were read with ELISA reader. MDA, SOD, CAT and GSH-Px enzyme activations from renal tissues were measured. In comparison with the sham and I/R groups, while the serum BUN, CRE, CI and TNF-α levels showed an increase in the groups on which the apelin-13 was applied, Na, total protein, albumin, TAS levels decreased. Serum TOS level of other groups showed an increase by comparison with the sham group. Our results showed that apelin-13 applied after I/R increased the antioxidant enzyme activity in a dose dependent manner, prevented the lipid oxidation and improved the renal functions.