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1.
J Med Case Rep ; 15(1): 509, 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34645501

RESUMO

INTRODUCTION: Meningiomas are the most commonly encountered intracranial tumors, usually showing indolent behavior. Extra-axial spreading and distant metastases are seldom detected in these tumors, and lung metastasis from a low-grade meningioma is a rare event. CASE PRESENTATION: This case report aimed to present the clinical, imaging, and pathological features of a 37-year-old Caucasian pregnant woman with bilateral lung metastases incidentally detected during preoperative workup ahead of surgery for a primary intracranial meningioma. The possible metastatic routes and risk factors of dissemination to the pulmonary circulation were discussed as well. CONCLUSION: Metastasis must be considered in patients with intracranial meningiomas accompanied by venous sinus invasion and extension through the calvarium. Thorough paraclinical investigations are suggested in such cases.

3.
Iran J Med Sci ; 46(5): 383-394, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34539013

RESUMO

Background: Osteoarthritis (OA) is a degenerative joint disease that causes a variety of adverse health effects. Considering the need to identify additional effective therapeutic options for OA therapy, we investigated the effect of co-injection of apigenin and synovial membrane-derived mesenchymal stem cells (SMMSCs) on OA in male rats' knee joints. Methods: The study was performed in 2019 at the Department of Pharmacology, Shiraz University of Medical Sciences, Shiraz, Iran. Anterior cruciate ligament transection (ACLT) was used to induce OA. For three weeks, male Sprague-Dawley rats (eight groups, n=6 each) were treated once-weekly with intra-articular injections of apigenin alone or in combination with SMMSC (three million cells), phosphate-buffered saline, or hyaluronic acid. After three months, the interleukin 1 beta (IL-1ß), tumor necrosis factor-alpha (TNF-α), superoxide dismutase (SOD), and malondialdehyde (MDA) levels were measured in the cartilage homogenate. The expression of extracellular matrix (ECM) components including collagen 2a1, aggrecan, IL-1ß, TNF-α, inducible nitric oxide synthase (iNOS), transcription factor SOX-9, and matrix metalloproteinases 3 and 13 were assessed using real-time polymerase chain reaction (RT-PCR) analysis. Radiological evaluation and histopathological assessment were used to evaluate the knees. Results: Levels of TNF-α (P=0.009), MDA (P>0.001), and IL-1ß (P<0.001) decreased and the level of SOD increased (P=0.004) in the apigenin 0.3 µM with SMMSCs group. RT-PCR analysis indicated that IL-1ß in the apigenin 0.3 µM with SMMSCs group reduced significantly (P<0.001). This group also exhibited increased expression levels of SOX-9, collagen 2a1, and aggrecan (P<0.001). Conclusion: Apigenin may have supplementary beneficial effects on cell therapy in a rat model of OA due to its possible effect on the reduction of oxidative stress, suppression of inflammation, and promotion of production of ECM components.

4.
Toxicon ; 202: 60-66, 2021 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-34562495

RESUMO

A new guaianolide sesquiterpene lactone with cytotoxic properties was isolated from Euphorbia microsphaera Boiss. To determine the highest active fraction and isolate bioactive compounds, a bioassay guided fractionation approach was used. The general toxicity properties of the plant's extracts and fractions (fr1-10) were assessed against Artemia salina, Oryzeaphilus mercator, and Tribolium castaneum. Cytotoxic activities were investigated against normal human foreskin fibroblasts and two malignant cell lines, including human breast cancer (MCF-7) and human fibrosarcoma cells (HT1080) using the MTT assay at different time points of 24, 48, and 72 h. Single crystal X-ray diffraction (SC-XRD) and mass spectrometry data were used to determine the structure of the active guaianolide sesquiterpene lactone (3aR,4S,4aS,5R,7aS,9aS)-5-hydroxy-5,8-dimethyl-3-methylene-2-oxo-2,3,3a,4,4a,5,6,7,7a, 9a decahydroazuleno [6,5-b] furan-4-yl acetate (named aryanin). Chloroformic fraction 7 (fr7, LC50 = 93.50 µg/mL for general toxicity) had the highest toxicity result, with a mortality rate of more than 50% for both insect species after 12 h at 15 mg/mL. The highest cytotoxicity of aryanin was observed on 24 h treated MCF-7 with an IC50 of 13.81 µg/mL. After 24 h, the inhibition of MCF-7 cell proliferation was 92%-94% at concentrations of 25-50 µg/mL, respectively. On MCF-7, the IC50 was found to be 49.35 µg/mL after 72 h. This compound had a considerable cytotoxicity (IC50 ≤ 12.5 µg/mL, 24 h) on human foreskin fibroblasts. In contrast to the MCF-7 cell line, the proliferation of human foreskin fibroblasts was increased after 72 h.


Assuntos
Antineoplásicos Fitogênicos , Neoplasias da Mama , Euphorbia , Fibrossarcoma , Sesquiterpenos , Neoplasias da Mama/tratamento farmacológico , Feminino , Humanos , Lactonas , Células MCF-7
5.
Acta Histochem ; 123(7): 151775, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34450327

RESUMO

BACKGROUND: Tissue engineering is considered as a promising tool for remodeling the native cells microenvironment. In the present study, the effect of alginate hydrogel and collagen microspheres integrated with extracellular matrix components were evaluated in the decrement of apoptosis in human pancreatic islets. MATERIALS/METHODS: For three-dimensional culture, the islets were encapsulated in collagen microspheres, containing laminin and collagen IV and embedded in alginate scaffold for one week. After that the islets were examined in terms of viability, apoptosis, genes and proteins expression including BAX, BCL2, active caspase-3, and insulin. Moreover, the islets function was evaluated through glucose-induced insulin and C-peptide secretion assay. In order to evaluate the structure of the scaffolds and the morphology of the pancreatic islets in three-dimensional microenvironments, we performed scanning electron microscopy. RESULTS: Our findings showed that the designed hydrogel scaffolds significantly improved the islets viability using the reduction of activated caspase-3 and TUNEL positive cells. CONCLUSIONS: The reconstruction of the destructed matrix with alginate hydrogels and collagen microspheres might be an effective step to promote the culture of the islets.

6.
J Control Release ; 337: 1-13, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34271033

RESUMO

Renal ischemia/reperfusion (I/R) injury is responsible for significant mortality and morbidity during renal procedures. Nitric oxide (NO) deficiency is known to play a crucial role in renal I/R injury; however, low stability and severe toxicity of high concentrations of NO have limited its applications. Herein, we developed an in-situ forming Fmoc-dipheylalanine hydrogel releasing s-nitroso-n-acetylpenicillamine (FmocFF-SNAP) for renal I/R injury. Fmoc-FF hydrogel comprising of ß-sheet nanofibers was prepared through the pH-titration method. It was then characterized by electron microscopy, pyrene assay, and circular dichroism techniques. Mechanical properties of Fmoc-FF hydrogel (thixotropy and syringeability) were investigated by oscillatory rheology and texture analysis. To assess the therapeutic efficiency in the renal I/R injury model, expression of inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) was measured in various samples (different concentrations of free SNAP and FmocFF-SNAP, unloaded Fmoc-FF, and sham control) by real-time RT-PCR, ROS production, serum biomarkers, and histopathological evaluations. According to the results, Fmoc-FF self-assembly in physiologic conditions led to the formation of an entangled nanofibrous and shear-thinning hydrogel. FmocFF-SNAP exhibited a sustained NO release over 7 days in a concentration-dependent manner. Importantly, intralesional injection of FmocFF-SNAP caused superior recovery of renal I/R injury when compared to free SNAP in terms of histopathological scores and renal function indices (e.g. serum creatinine, and blood urea nitrogen). Compared to the I/R control group, biomarkers of oxidative stress and iNOS expression were significantly reduced possibly due to the sustained release of NO. Interestingly, the eNOS expression showed a significant enhancement reflecting the regeneration of the injured endothelial tissue. Thus, the novel FmocFF-SNAP can be recommended for the alleviation of renal I/R injury.

7.
Biodes Manuf ; : 1-22, 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34306798

RESUMO

Abstract: The development of natural biomaterials applied for hard tissue repair and regeneration is of great importance, especially in societies with a large elderly population. Self-assembled peptide hydrogels are a new generation of biomaterials that provide excellent biocompatibility, tunable mechanical stability, injectability, trigger capability, lack of immunogenic reactions, and the ability to load cells and active pharmaceutical agents for tissue regeneration. Peptide-based hydrogels are ideal templates for the deposition of hydroxyapatite crystals, which can mimic the extracellular matrix. Thus, peptide-based hydrogels enhance hard tissue repair and regeneration compared to conventional methods. This review presents three major self-assembled peptide hydrogels with potential application for bone and dental tissue regeneration, including ionic self-complementary peptides, amphiphilic (surfactant-like) peptides, and triple-helix (collagen-like) peptides. Special attention is given to the main bioactive peptides, the role and importance of self-assembled peptide hydrogels, and a brief overview on molecular simulation of self-assembled peptide hydrogels applied for bone and dental tissue engineering and regeneration.

8.
Toxicol Lett ; 349: 12-29, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34089816

RESUMO

The cholestatic liver injury could occur in response to a variety of diseases or xenobiotics. Although cholestasis primarily affects liver function, it has been well-known that other organs such as the kidney could be influenced in cholestatic patients. Severe cholestasis could lead to tissue fibrosis and organ failure. Unfortunately, there is no specific therapeutic option against cholestasis-induced organ injury. Hence, finding the mechanism of organ injury during cholestasis could lead to therapeutic options against this complication. The accumulation of potentially cytotoxic compounds such as hydrophobic bile acids is the most suspected mechanism involved in the pathogenesis of cholestasis-induced organ injury. A plethora of evidence indicates a role for the inflammatory response in the pathogenesis of several human diseases. Here, the role of nuclear factor-kB (NFkB)-mediated inflammatory response is investigated in an animal model of cholestasis. Bile duct ligated (BDL) animals were treated with sulfasalazine (SSLZ, 10 and 100 mg/kg, i.p) as a potent inhibitor of NFkB signaling. The NFkB proteins family activity in the liver and kidney, serum and tissue levels of pro-inflammatory cytokines, tissue biomarkers of oxidative stress, serum markers of organ injury, and the liver and kidney histopathological alterations and fibrotic changes. The oxidative stress-mediated inflammatory-related indices were monitored in the kidney and liver at scheduled time intervals (3, 7, and 14 days after BDL operation). Significant increase in serum and urine markers of organ injury, besides changes in biomarkers of oxidative stress and tissue histopathology, were evident in the liver and kidney of BDL animals. The activity of NFkB proteins (p65, p50, p52, c-Rel, and RelB) was significantly increased in the liver and kidney of cholestatic animals. Serum and tissue levels of pro-inflammatory cytokines (IL-1ß, IL-2, IL-6, IL-7, IL-12, IL-17, IL-18, IL-23, TNF-α, and INF-γ) were also higher than sham-operated animals. Moreover, TGF- ß, α-SMA, and tissue fibrosis (Trichrome stain) were evident in cholestatic animals' liver and kidneys. It was found that SSLZ (10 and 100 mg/kg/day, i.p) alleviated cholestasis-induced hepatic and renal injury. The effect of SSLZ on NFkB signaling and suppression of pro-inflammatory cytokines could play a significant role in its protective role in cholestasis. Based on these data, NFkB signaling could receive special attention to develop therapeutic options to blunt cholestasis-induced organ injury.


Assuntos
Anti-Inflamatórios/farmacologia , Colestase/tratamento farmacológico , Citocinas/metabolismo , Mediadores da Inflamação/metabolismo , Nefropatias/prevenção & controle , Rim/efeitos dos fármacos , Cirrose Hepática/prevenção & controle , Fígado/efeitos dos fármacos , NF-kappa B/antagonistas & inibidores , Sulfassalazina/farmacologia , Animais , Colestase/metabolismo , Colestase/patologia , Ducto Colédoco/cirurgia , Modelos Animais de Doenças , Regulação para Baixo , Rim/metabolismo , Rim/patologia , Nefropatias/metabolismo , Nefropatias/patologia , Ligadura , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Masculino , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais
9.
Int J Vitam Nutr Res ; : 1-10, 2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34162225

RESUMO

Nutritional interventions can be valuable for the prevention of postmenopausal osteoporosis. This study aimed to investigate the effects of kefir fortified with omega-3 and vitamin C on the bone and uterus parameters of ovariectomized rats. Seventy-seven female Sprague-Dawley rats were ovariectomized or sham-operated. The ovariectomized rats were assigned to six groups and received 1 ml/day of distilled water (OVX group), milk, kefir, kefir fortified with omega-3 (kefir+ω3), kefir fortified with vitamin C (kefir+vit-C) or kefir fortified with omega-3 and vitamin C (kefir+ω3+vit-C) for 12 weeks. The sham group also received 1ml/day of distilled water. Subsequently, bone mineral content (BMC) and bone mineral density (BMD) of various bones were assessed. Femurs and uteri were harvested for bone ash analysis and histopathological examinations, respectively. Sera were analyzed for carboxy-terminal cross-linked telopeptide of type 1 collagen, procollagen type 1 amino-terminal propeptide, calcium, phosphorous, tumor necrosis factor-α (TNF-α) and total antioxidant capacity levels. Ovariectomy resulted in significant reduction in bone density (P<0.05). Kefir+ω3+vit-C significantly improved BMC of lumbar spine (0.699±0.027 g compared with 0.580±0.018 in the OVX group), and kefir, kefir+vit-C and kefir+ω3+vit-C significantly increased BMD of tibia (0.118±0.003 g/cm2, 0.119±0.001 and 0.120±0.004 compared with 0.102±0.005 in the OVX group). Moreover, ovariectomy markedly elevated TNF-α level, which was significantly reversed by kefir+ω3+vit-C. Significant atrophy of the uterus was observed following ovariectomy, although the uterus parameters did not change by any of the interventions. In conclusion, kefir fortified with omega-3 and vitamin C may have protective effects against bone loss through suppressing inflammation.

10.
Biotechnol Lett ; 43(8): 1659-1673, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33934256

RESUMO

OBJECTIVE: An attractive cell source for stem cell-based therapy are WJ-MSCs. Hence, tracking WJ-MSCs using non-invasive imaging procedures (such as MRI) and contrast agents (Zn0.5Ni0.5Fe2O4, NFNPs) are required to evaluate cell distribution, migration, and differentiation. RESULTS: Results showed that the bare and dextrin-coated NFNPs were internalized inside the WJ-MSCs and had no effect on the cell viability, proliferation, apoptosis, karyotyping, and morphology of WJ-MSCs up to 125 µg/mL. Besides, treated WJ-MSCs were differentiated into osteo/adipocyte-like cells. The expression of RUNX 2, SPP 1 (P < 0.05), and OCN (P > 0.05) genes in the WJ-MSCs treated with dextrin-coated NFNPs was higher than the untreated WJ-MSCs; and the expression of CFD, LPL, and PPAR-γ genes was reduced in WJ-MSCs treated with both NFNPs in comparison with the untreated WJ-MSCs (P > 0.05). CONCLUSION: Overall, results showed that dextrin-coated NFNPs had no adverse effect on the cellular characteristics, proliferation, and differentiation of WJ-MSCs, and suggesting their potential clinical efficacy.

11.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-34023475

RESUMO

BACKGROUND: Acute hepatitis A is usually a self-limited viral disease but can be severe and even fatal in special groups of patients including those with chronic liver disease and recipients of liver transplantation. To take appropriate preventive measures, it is important to determine the immune status against the hepatitis A virus in patients at risk of grave clinical outcomes following infection. To assess the need for immunization against hepatitis A, we aimed to determine the immune status against hepatitis A in a population of liver transplant recipients. We also investigated the association between hepatitis A immune status and demographic factors such as age and sex, underlying liver disease, source of drinking water, geographical area of residence and socioeconomic status. METHODS: This cross-sectional study was performed on 242 recipients of allogenic liver transplants at Abu Ali Sina Organ Transplant Hospital in Shiraz, Iran, between January 2017 and April 2017. The level of immunity was assessed using hepatitis A antibody detection kits. RESULTS: The rate of immunity against hepatitis A was detected as 88.8% in our study population. In the multivariable logistic regression model, younger age (OR=1.175, P<0.001) and higher education level (OR=2.142, P=0.040) were the main determinants of non-immune status. However, hepatitis A immunity was independent of gender, monthly family income, water supply source, residential area and underlying liver disorder. CONCLUSION: Although a significant proportion of liver transplant recipients in this study showed evidence of natural immunity to hepatitis A, a considerable proportion of younger patients and those with a higher level of education were non-immune. The results of this study signify the importance of screening for hepatitis A immunity in this at-risk population of patients and the need for vaccinating non-immune patients.

12.
Tissue Cell ; 72: 101539, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33838351

RESUMO

BACKGROUND: The use of growth factors in tissue engineering is often challenging due to their instability and short half-life. The delivery of growth factors with nanocarriers can eliminate these problems. In the present study, we introduced an alginate oxide particle in acellular collagen-alginate composite hydrogel platform for the immobilization and controlled release of VEGF and bFGF to promote angiogenesis. METHODS: The particles were prepared by the oxidation of sodium alginate. Then, they were embedded in collagen-alginate hydrogel. Cytocompatibility of the construct with the human umbilical vein endothelial cells was analyzed through a live/dead assay and scanning electron microscopy. In vitro evaluation of VEGF and bFGF Release Kinetics was done. Moreover, the function of the constructs was confirmed through the chick chorioallantoic membrane assay. RESULTS: The engineered constructs maintained the human umbilical vein endothelial cells viability, which indicates the non-toxicity of the tested constructs. The presence of VEGF-loaded particles could improve the Total Branching Points in the chick chorioallantoic membrane assay. In this regard, Total Branching Points was significantly improved in the VEGF group compared to the control group (p = 0.010) and FGF group (p = 0.023). CONCLUSION: The results demonstrated the potential role of these particles in regenerative medicine to improve angiogenesis.

14.
J Food Biochem ; 45(4): e13702, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33694182

RESUMO

The aim of this study was to investigate the anti-androgenic effects of astaxanthin (AST) on human prostatic cancer cell growth, and its impact on androgen receptor (AR) signaling using prostate cancer (PCa) cell line LNCaP. LNCaP cells were treated with AST alone and in combination with CH223191 and flutamide (Flu) in the presence and absence of testosterone. MTT assay, cellular prostate-specific antigen (PSA) and dihydrotestosterone (DHT) production, mRNA levels of CYP1A1, PSA, Kallikrein-Related Peptidase 2 (KLK2), Transmembrane Serine Protease 2 (TMPRSS2), and AR genes were measured as endpoints. The expression of CYP1A1, PSA, KLK2, TMPRSS2, and AR mRNA levels was decreased which results in reducing the production of PSA and DHT in the presence of testosterone. Our data clearly demonstrate that AST has a potential ability to suppress the human prostate LNCaP cells growth at high concentrations. AST was able to repress the testosterone-induced transcription of AR-target genes. PRACTICAL APPLICATIONS: Astaxanthin is a natural compound with the most potent antioxidant activity among other antioxidants. In the current study, ASX suppressed the LNCaP cells at high concentrations. Furthermore, AST inhibited testosterone-induced transcriptional activation of androgen-related genes. AST induced the expression of CYP1A1, which is able to metabolize the steroid hormones. It seems that AST can act as AhR exogenous ligand by induction of CYP1A1, which results in testosterone metabolism and consequent suppression of AR genes. So that, AST could prevent the growth of testosterone-dependent PCa cells, downregulate downstream genes in testosterone pathways, and enhance the metabolism of testosterone via AhR pathway. Collectively, AST could be considered as a potential candidate for the treatment of PCa.


Assuntos
Antagonistas de Androgênios , Androgênios , Antagonistas de Androgênios/farmacologia , Androgênios/farmacologia , Linhagem Celular Tumoral , Humanos , Masculino , Receptores Androgênicos/genética , Receptores de Hidrocarboneto Arílico , Xantofilas/farmacologia
15.
Expert Opin Biol Ther ; 21(5): 687-696, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33646060

RESUMO

OBJECTIVE: The current study assesses the effects of platelet-rich plasma-fibrin glue (PRP-FG) dressing along with oral vitamin E and C on wound healing and biochemical markers in patients with non-healing diabetic foot ulcers (non-healing DFU). METHODS: This randomized controlled trial was performed on 25 patients with non-healing DFU. Patients were treated with PRP-FG dressing plus oral vitamin E and C (intervention group) or PRP-FG dressing plus placebo (control group) for 8 weeks. RESULTS: Eight weeks after treatment, six wounds in the intervention group and two wounds in the control group were completely closed, and also wound size significantly reduced in both intervention and control groups (p < 0.05). This reduction in wound size was significantly greater in the intervention group compared to the control group (p = 0.019). Also, a significant decrease in prooxidant-antioxidant balance (PAB) , ESR, and hs-CRP was observed in the intervention group compared to the control group (p < 0.05). CONCLUSION: Our results showed that PRP-FG dressing along with oral vitamin E and C could be used to increase wound healing in patients with non-healing DFU by enhancing the wound healing process and reducing oxidative stress. TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT04315909).

16.
Naunyn Schmiedebergs Arch Pharmacol ; 394(6): 1301-1314, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33538845

RESUMO

Bile duct obstruction or cholestasis can occur by several diseases or xenobiotics. Cholestasis and the accumulation of the bile constituents in the liver primarily damage this organ. On the other hand, extrahepatic organs are also affected by cholestasis. The kidney is the most affected tissue during cholestatic liver injury. Cholestasis-associated renal injury is known as cholemic nephropathy (CN). Several lines of evidence specify the involvement of oxidative stress and mitochondrial impairment in the pathogenesis of CN. The current study aimed to assess the role of silymarin as a potent antioxidant on CN-induced oxidative stress and mitochondrial dysfunction in the kidney. Bile duct ligated (BDL) rats were treated with silymarin (10 and 100 mg/kg, oral) for seven consecutive days. A significant increase in reactive oxygen species (ROS), lipid peroxidation, protein carbonylation, and oxidized glutathione (GSSG) levels were evident in the kidney of BDL animals. Moreover, reduced glutathione (GSH) content and total antioxidant capacity were significantly decreased in the kidney of cholestatic rats. Mitochondrial depolarization, decreased mitochondrial dehydrogenases activity, mitochondrial permeabilization, and depleted ATP stores were detected in the kidney mitochondria isolated from BDL animals. Kidney histopathological alterations, as well as serum and urine levels of renal injury biomarkers, were also significantly different in the BDL group. It was found that silymarin treatment significantly ameliorated CN-induced renal injury. The antioxidant effects of silymarin and its positive impact on mitochondrial indices seem to play a significant role in its renoprotective effects during cholestasis.

17.
Exp Clin Transplant ; 2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33622218

RESUMO

Coronavirus disease 2019 has affected more than 4 million people throughout the world since December 2019. It seems this infection has been the most insidious virus of the coronavirus family. This virus causes severe respiratory failure and symptoms in patients and can result in death. Designing a restrict protocol to deal with infections from severe acute respiratory syndrome coronavirus type 2 is critical in cell therapy institutes. In this review, we present the important aspects related to this virus in cell therapy protocols.

18.
Artigo em Inglês | MEDLINE | ID: mdl-32767922

RESUMO

BACKGROUND: Several studies have assessed the association between the vitamin D receptor (VDR) polymorphism and the risk of metabolic syndrome (MetS). However, the results were inconsistent and inconclusive. Therefore, we conducted a meta-analysis to clarify the exact association between the vitamin D receptor (VDR) polymorphisms and the risk of MetS. METHODS: All accessible studies reporting the association between the FokI (rs2228570) or/and TaqI (rs731236) or/and BsmI (rs1544410) or/and ApaI (rs7975232 polymorphisms of the Vitamin D Receptor and susceptibility to MetS published prior to February 2019 were systematically searched in Web of Science, Scopus, and PubMed. After that, Odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were estimated to evaluate the strength of the association in five genetic models. RESULTS: A total of 9 articles based on four gene variations, and comprising 3348 participants with 1779 metabolic syndrome patients were included. The overall results suggested a significant association between BsmI (rs1544410) polymorphism and MetS susceptibility in recessive model (OR, 0.72, 95% CI, 0.55-0.95, fixed effect model), allelic model (OR, 0.83, 95% CI, 0.72-0.95, fixed effect model), and bb vs BB (OR, 0.65, 95% CI, 0.46-0.93, fixed effect). However, no significant association was identified between TaqI (rs731236) polymorphism, ApaI (rs7975232) polymorphism, and FokI (rs2228570) polymorphism and MetS. CONCLUSION: This meta-analysis suggested an association between the BsmI (rs1544410) polymorphism and MetS. Indeed, BsmI (rs1544410) acts as a protective factor in the MetS. As a result, the VDR gene could be regarded as a promising pharmacological and physiological target in the prevention or treatment of the MetS.

19.
Biol Trace Elem Res ; 199(5): 1908-1918, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-32712907

RESUMO

Lithium is abundantly administered against bipolar disorder. On the other hand, the lithium-induced renal injury is a clinical complication which commonly reveals as drug-induced diabetes insipidus. However, lithium-induced cytotoxicity might also play a role in the adverse effects of this drug on the kidney. There is no clear cellular and molecular mechanism(s) for lithium-induced nephrotoxicity. The current study was designed to assess the effect of lithium on kidney tissue oxidative stress biomarkers and mitochondrial function and its relevance to drug-induced nephrotoxicity and electrolyte imbalance. Rats were treated with lithium (lithium carbonate, 25 and 50 mg/kg/day, i.p., for 28 consecutive days). Kidney mitochondria were also isolated from rats and exposed to increasing concentrations of lithium (0.01-10 mM). Serum and urine biomarkers of kidney injury, kidney tissue markers of oxidative stress, and renal histopathological changes were assessed. Moreover, several mitochondrial indices were monitored. Lithium-induced renal injury revealed a significant increase in urine and serum biomarkers of renal impairment. Lithium caused an increase in the kidney reactive oxygen species (ROS) level and lipid peroxidation (LPO). Renal glutathione (GSH) reservoirs were also depleted, and tissue antioxidant capacity decreased in lithium-treated animals. Significant tissue histopathological changes, including necrosis, Bowman capsule dilation, and interstitial inflammation, were evident in lithium-treated animals. On the other hand, significant alterations in kidney mitochondrial function were detected in lithium-treated groups. These data mention oxidative stress, mitochondrial dysfunction, and cellular energy crisis as the potential primary mechanisms for lithium-induced renal injury.


Assuntos
Lítio , Mitocôndrias , Animais , Antioxidantes/metabolismo , Rim/metabolismo , Peroxidação de Lipídeos , Lítio/toxicidade , Mitocôndrias/metabolismo , Estresse Oxidativo , Ratos , Espécies Reativas de Oxigênio/metabolismo
20.
Soft Matter ; 17(1): 57-67, 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33001116

RESUMO

Fmoc-dipeptides are a class of short aromatic peptides featuring eminent supramolecular self-assembly, which is due to the aromaticity of the Fmoc group, which improves the association of peptide building blocks. This study aimed to introduce a new dipeptide hydrogel scaffold, Fmoc-phenylalanine-valine (Fmoc-FV), for 3D culture of various cells. Peptide hydrogel scaffolds were prepared by the pH-titration method in various concentrations and temperatures, and characterized by spectroscopic methods, including circular dichroism, attenuated total reflection FT-IR and fluorimetry. Mechanical behaviors such as thixotropy and temperature-sensitivity were investigated by oscillatory rheology. The Fmoc-FV hydrogels were then applied in 3D-culture of WJ-MSCs (mesenchymal stem cells), HUVECs (normal endothelial cells), and MDA-MB231 (tumor cell line) by live-dead fluorescence microscopy and Alamar blue viability assay experiments. The results confirmed that the ß-sheet structure is principally interlocked by π-π stacking of the Fmoc groups and entangled nanofibrous morphologies as revealed by FE-SEM. Fmoc-FV self-assembly in physiologic conditions resulted in a thermo-sensitive and shear-thinning hydrogel. Notably, the Fmoc-FV hydrogel exhibited cell type-dependent biological activity, so higher cell proliferation was attained in HUVEC or MDA-MB231 cells than WJ-MSCs, indicating a possible need for incorporating cell-adhesion ligands in the Fmoc-FV hydrogel matrix. Therefore, the structural and biological properties of the Fmoc-dipeptide hydrogels are inter-related and can affect their applications in 3D cell culture and regenerative medicine.


Assuntos
Células-Tronco Mesenquimais , Nanofibras , Células Endoteliais , Hidrogéis , Fenilalanina , Espectroscopia de Infravermelho com Transformada de Fourier , Valina
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