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Type 2 Diabetes mellitus (T2DM) has the potential to impair cardiac function and cause heart failure. We aimed to study the cardioprotective influence of Galactin-3 (Gal-3) inhibitor; modified citrus pectin (MCP) in isoprenaline induced myocardial infarction (MI) in T2DM rats. Forty rats were allocated into 4 groups; groups I and II served as control. T2DM was provoked in groups III and IV by serving them high fat diet followed by a single low dose of Streptozotocin (STZ), then group IV were administered MCP in drinking water for 6 weeks. Groups III and IV were then subcutaneously injected isoprenaline hydrochloride once daily on the last 2 successive days to induce MI. MCP restored echocardiographic parameters with significant decline in Gal-3 area % in cardiac tissue alongside protection against cardiac remodelling. our data showed that there is a protective potential for Gal-3 inhibitor (MCP) against cardiac injury in isoprenaline induced MI in T2DM.
Type 2 Diabetes mellitus (T2DM) has the potential to impair cardiac function and cause heart failure (HF).Gal-3 inhibition with MCP for 6 weeks caused effective protection against cardiac fibrosis, LV dysfunction, and ensuing heart failure progress in type 2 diabetic rats with an isoprenaline-induced myocardial infarction.The defending effect of Gal-3 inhibitor; MCP seems to be exerted by modulating cardiac cell response to injury, through decreasing incidence of cardiac inflammation, oxidative stress, apoptosis and decreased cardiac Gal-3 immuno-reactivity.
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BACKGROUND: The inconvenience of social and behavioural deficits after cerebral ischaemia reperfusion (I/R) injury is still not well documented. AIM: We aimed to study the protective effect of preconditioning swimming exercise combined with melatonin against cerebral I/R induced injury. METHODOLOGY: Sixty rats were allocated into 6 groups; groups I and II served as control. Groups 3,4,5,6 subjected to bilateral carotid ligation for 30 minutes (min.) followed by reperfusion. Group 3 left untreated while groups 4 and 6; underwent swimming exercise 30 min/day, five days a week for three weeks before the surgery. Groups 5 and 6 treated with melatonin 30 minutes before the operation, then, all rats in groups 4, 5,6 were subjected to I/R. After that, groups 5 and 6 treated with 2nd dose of melatonin 30 minutes after reperfusion. RESULTS: Combined strategy exhibited the most neuroprotective effect through prevention of cerebral I/R induced inflammation, oxidative stress and apoptosis with subsequent improvement in socio behaviour deficits and enhanced Glial cell proliferative capacity. CONCLUSION: The protective contribution of combined strategy is associated with modulation in Macrophage-stimulating 1/mitogen-activated protein kinase/extracellular signal-regulated kinase (MST1/MAPK/ERK) pathway which may explain, at least in part, its protective potential.
Preconditioning swimming exercise combined with melatonin protected against cerebral I/R induced socio-behavioural deficit.Cerebral I/R induced pathophysiological alterations in Prefrontal cortical neurons (PFC) are prevented by combined Preconditioning swimming exercise and melatoninCombined Preconditioning swimming exercise/melatonin in cerebral I/R modulates MST1/MAPK/ERK signalling pathwayCombined Preconditioning swimming exercise/melatonin inhibit inflammation, oxidative stress and apoptosis, thus enhance Glial cell proliferative capacity in I/R induced injury in PFC neurons.
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BACKGROUND: Preeclampsia (PE) poses a substantial risk to prenatal and maternal health. Folic acid (FA) and methylenetetrahydrofolate reductase (MTHFR) play roles in DNA methylation and genomic integrity maintenance, with MTHFR polymorphisms potentially impacting PE occurrence. Human microRNA 149 (miR-149) remains underexplored in PE despite its involvement in folate metabolism. This study seeks to evaluate serum miR-149 levels with the MTHFR C677T polymorphism for diagnosing PE. METHODS: Seventy females aged 28-40 gestational weeks were divided into control and Preeclampsia groups. Serum miR-149 and MTHFR gene levels were evaluated using real-time PCR. RESULTS: Preeclamptic patients showed significantly lower serum miR-149 levels than healthy controls (P ≤ 0.01). PE cases showed a higher frequency of the TT genotype and T allele of the C677T polymorphism (OR = 0.181, 2.882, respectively), implicating them as genetic risk factors. The CT genotype also increased PE risk (OR = 0.26), while no significant difference was observed in the CC genotype. CONCLUSION: Merging miR-149 and MTHFR polymorphism assessment improves discrimination between healthy and PE groups, offering valuable insights into PE pathogenesis and potential diagnostic strategies.
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Background: Ageing is a key risk factor for cardiovascular disease and is linked to several alterations in cardiac structure and function, including left ventricular hypertrophy and increased cardiomyocyte volume, as well as a decline in the number of cardiomyocytes and ventricular dysfunction, emphasizing the pathological impacts of cardiomyocyte ageing. Dental pulp stem cells (DPSCs) are promising as a cellular therapeutic source due to their minimally invasive surgical approach and remarkable proliferative ability. Aim: This study is the first to investigate the outcomes of the systemic transplantation of DPSCs in a D-galactose (D-gal)-induced rat model of cardiac ageing. Methods. Thirty 9-week-old Sprague-Dawley male rats were randomly assigned into three groups: control, ageing (D-gal), and transplanted groups (D-gal + DPSCs). D-gal (300 mg/kg/day) was administered intraperitoneally daily for 8 weeks. The rats in the transplantation group were intravenously injected with DPSCs at a dose of 1 × 106 once every 2 weeks. Results: The transplanted cells migrated to the heart, differentiated into cardiomyocytes, improved cardiac function, upregulated Sirt1 expression, exerted antioxidative effects, modulated connexin-43 expression, attenuated cardiac histopathological alterations, and had anti-senescent and anti-apoptotic effects. Conclusion: Our results reveal the beneficial effects of DPSC transplantation in a cardiac ageing rat model, suggesting their potential as a viable cell therapy for ageing hearts.
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Polpa Dentária , Galactose , Miócitos Cardíacos , Ratos Sprague-Dawley , Animais , Masculino , Ratos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/transplante , Miócitos Cardíacos/efeitos dos fármacos , Polpa Dentária/citologia , Transplante de Células-Tronco/métodos , Envelhecimento/fisiologia , Sirtuína 1/metabolismo , Diferenciação Celular/efeitos dos fármacos , Conexina 43/metabolismo , Modelos Animais de Doenças , Células-Tronco/metabolismo , Células-Tronco/citologia , Apoptose/efeitos dos fármacosRESUMO
Programmed cell death protein-1 (PD-1) is an immune checkpoint protein, PD-1 interaction with PD ligand-1 (PD-L1) is essential for maintaining immunological tolerance. The study aimed to study and compare the levels of PD-1 and PD-L1 in lesional and nonlesional skin of lichen planus (LP) patients and compare these levels to normal healthy controls to assess their role in the pathogenesis of LP. This case-control study involved 30 patients with LP and 30 healthy age-and sex-matched controls. After clinical assessment of the severity by LP severity index score (LPSI), skin biopsies were taken from lesional and nonlesional skin of LP patients and from normal skin in healthy controls for assessment of the tissue levels of PD-1 and PD-L1 by ELISA. The tissue levels of both PD-1 and PD-L1 were significantly higher in healthy controls than in both lesional and nonlesional skin of LP patients (P < 0.001). Also, significantly higher PD-l and PD-L1 levels in nonlesional skin than in lesional skin of LP patients were reported (P < 0.001). No significant correlations were found between lesional and nonlesional PD-1, PD-L1 levels, or LPSI score. Based on the fact that PD-1/PD-L1 interaction is important to maintain tolerance and protection against autoimmune diseases, in addition to our study results that revealed lower levels of PD-1/PD-L1 in LP skin than in healthy skin, we can conclude that PD-1/PDL-1 may be incriminated in the pathogenesis of LP. ClinicalTrials.govID: NCT04892381.
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Antígeno B7-H1 , Líquen Plano , Humanos , Antígeno B7-H1/metabolismo , Estudos de Casos e Controles , Líquen Plano/metabolismo , Ligantes , Receptor de Morte Celular Programada 1RESUMO
Multiple sclerosis (MS) is a complex autoimmune condition affecting the central nervous system characterized by axonal damage, demyelination, and chronic inflammation. Multiple molecular and cellular components mediate neuroinflammation in MS. In human macrophages and microglia, miRNA-155 is an essential proinflammatory noncoding RNA that regulates phenotypic and functional polarization properties. This study was conducted to detect the plasma level of miRNA-155 in RRMS and assess its relationship with inflammatory and anti-inflammatory mediators. The study included 60 MS patients and 30 healthy controls. Real-time quantitative polymerase chain reaction was utilized to detect miRNA-155, iNOS, and SMAD2, whereas ELISA was used to determine TNF-α, IFN-É£, TGF-ß, and IL-10 levels. There was no significant difference in miRNA-155, SMAD2, and iNOS expression in MS patients compared to control subjects. In addition, there was a statistically significant increase in TNF-α, INF-É£, and TGF-ß levels. IL-10 levels did not differ significantly between MS patients and healthy controls. There was a positive correlation between miRNA-155 and TNF-α (p < 0.000, r = 0.922), INF-É£ (p < 0.000, r = 0.81), and iNOS (p < 0.000, r = 0.916) and inverse correlation between miRNA-155 and IL-10 (p < 0.000, r = -0.928), TGF-ß (p < 0.000, r = -0.904) and SMAD2 (p < 0.000, r = -0.848). We conclude that expression of miRNA-155 in MS may modulate macrophage/microglia polarization by increasing the secretion of TNF-α, IFN-É£ & iNOS and decreasing anti-inflammatory mediators IL10 and TGF-ß.
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MicroRNAs , Esclerose Múltipla , Humanos , Interleucina-10 , Fator de Necrose Tumoral alfa/metabolismo , Mediadores da Inflamação/metabolismo , Fator de Crescimento Transformador beta , Anti-Inflamatórios/uso terapêutico , MicroRNAs/genéticaRESUMO
Polycystic ovary syndrome (PCOS) is a common endocrine, reproductive, and metabolic disorder affecting females. The management of PCOS is challenging and current interventions are not enough to deal with all consequences of this syndrome. We explored the beneficial effect of combined sodium glucose co transporter-2 inhibitor (SGLT-2i); (empagliflozin) and metformin on hormonal and metabolic parameters in an animal model of PCOS and insulin resistance (IR). Forty adult female Wistar rats divided into five groups: control, PCOS-IR, PCOS-IR treated with metformin, PCOS-IR treated with empagliflozin, and PCOS-IR treated with combined metformin and empagliflozin. Single modality treatment with metformin or empagliflozin yielded significant improvement in body mass index, insulin resistance, lipid profile, sex hormones, inflammatory markers, and ovarian cystic follicles. Combined metformin with empagliflozin expressed further significant improvement in sex hormones, inflammatory markers with disappearance of ovarian cystic follicles. The superior significant improvement with combined treatment over the single modality was in line with significant improvement in the ovarian AMPKα-SIRT1 expression.
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Resistência à Insulina , Metformina , Síndrome do Ovário Policístico , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Ratos , Feminino , Animais , Metformina/farmacologia , Metformina/uso terapêutico , Síndrome do Ovário Policístico/tratamento farmacológico , Síndrome do Ovário Policístico/metabolismo , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Ratos Wistar , Insulina , Hormônios Esteroides GonadaisRESUMO
BACKGROUND: Vital pulp therapy, based on the use of stem cells, has promising research and therapeutic applications in dentistry. It is essential to understand the direct effect of capping materials on the dental pulp stem cells of primary teeth, which contribute to the healing powers of the tooth. The aim of this study is to evaluate the effect of different capping materials (Calcium Hydroxide (DyCal®) - Glass Ionomer (Fuji IX®) and light-cured resin modified calcium silicate (TheraCal LC®)) on the viability, proliferation, and differentiation of stem cells from human exfoliated deciduous teeth (SHEDs). METHODS: SHEDs were isolated from extracted primary teeth, then divided into four groups and each of the capping materials were applied to the stem cells as follows: group I the controls, group II with Ca(OH)2, group III with the GIC, and group IV with the Theracal LC. For all groups assessment of viability and proliferation rate was done using the MTT cell proliferation assay. Also, Differentiation was evaluated by measuring the gene expression of Alkaline phosphatase enzyme activity (ALP) and Dentin matrix protein-1 (DMP1) through quantitative real-time PCR. Morphological assessment was conducted using Alizarin Red S staining. All evaluations were performed after 7 and 14 days of culture. RESULTS: TheraCal LC showed the highest values of proliferation, which was significant only compared to the control group after 2 weeks (p = 0.012). After one week, TheraCal LC showed the highest significant values of ALP and DMP1 compared to all other groups (p < 0.001). CONCLUSION: The three materials under study are biocompatible, maintain viability, and stimulate the proliferation and differentiation of SHEDs. However, TheraCal LC allows better proliferation of SHEDs than Dycal Ca(OH)2 and Fuji IX GIC.
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Compostos de Cálcio , Hidróxido de Cálcio , Humanos , Hidróxido de Cálcio/farmacologia , Hidróxido de Cálcio/uso terapêutico , Compostos de Cálcio/farmacologia , Silicatos/farmacologia , Diferenciação Celular , Células-Tronco , Dente Decíduo , Proliferação de Células , Polpa DentáriaRESUMO
Environmental factors, such as sleep restriction, contribute to polycystic ovary syndrome (PCOS) by causing hyperinsulinemia, hyperandrogenism, insulin resistance, and oligo- or anovulation. This study aimed to evaluate the effects of circadian rhythm disruption on reproductive and metabolic functions and investigate the potential therapeutic benefits of MitoQ10 and hot tub therapy (HTT). Sixty female rats were divided into six groups: control, MitoQ10, HTT, and three groups with PCOS induced by continuous light exposure(L/L). The reproductive, endocrine, and structural manifestations ofL/L-induced PCOS were confirmed by serum biochemical measurements, ultrasound evaluation of ovarian size, and vaginal smear examination at week 14. Subsequently, the rats were divided into the L/L (untreated), L/L+MitoQ10-treated, andL/L+HTT-treated groups. At the end of week 22, all rats were sacrificed. Treatmentwith MitoQ10 or HTT partially reversed the reproductive, endocrine, and structural features of PCOS, leading to a decreased amplitude of isolated uterine contractions, ovarian cystic changes and size, and endometrial thickness. Furthermore, both interventions improved the elevated serum levels of anti-Mullerian hormone (AMH), kisspeptin, Fibulin-1, A disintegrin and metalloproteinase with thrombospondin motifs 19 (ADAMTS-19), lipid profile, homeostatic model assessment for insulin resistance (HOMA-IR), oxidative stress markers, androgen receptors (AR) and their transcription target genes, FKBP52 immunostaining in ovarian tissues, and uterine estrogen receptor alpha (ER-α) and PRimmunostaining. In conclusion, MitoQ10 supplementation and HTT demonstrated the potential for ameliorating metabolic, reproductive, and structural perturbations associated with PCOS induced by circadian rhythm disruption. These findings suggest a potential therapeutic role for these interventions in managing PCOS in women.
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Hiperandrogenismo , Resistência à Insulina , Síndrome do Ovário Policístico , Humanos , Feminino , Ratos , Animais , Síndrome do Ovário Policístico/diagnóstico , Síndrome do Ovário Policístico/terapia , Temperatura Alta , Ritmo Circadiano , Hiperandrogenismo/terapiaRESUMO
OBJECTIVE: To investigate the changes of the ventilatory function tests and the oxidative stress biomarkers among silica-exposed foundry workers. METHODS: The exposed group included 70 workers in an iron foundry. The nonexposed group included 40 subjects from Kasralainy outpatient clinic. Both groups were subjected to history taking, clinical examination, chest radiograph, spirometry, urinary silica, serum malondialdehyde (MDA), glutathione peroxidase (GPx), and 8-hydroxydeoxyguanosine (8-HdG). RESULTS: Higher urinary silica, serum MDA and serum 8-HdG, whereas lower serum GPx and ventilatory functions were detected in the exposed group compared with the controls. All parameters correlated with urinary silica. The exposed silicotic subgroup had increased work duration, urinary silica, serum MDA, and serum 8-HdG, and decreased serum GPx and ventilatory functions compared with non-silicotic subgroup. CONCLUSION: Oxidative stress biomarkers were abnormal with impairment of ventilatory functions among silica-exposed workers.
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Exposição Ocupacional , Dióxido de Silício , Humanos , Dióxido de Silício/toxicidade , Exposição Ocupacional/efeitos adversos , Malondialdeído , Estresse Oxidativo , BiomarcadoresRESUMO
AIMS: Oxidative stress also plays an important role in the pathogenesis of diabetic neuropathy (DN). Both resveratrol (RES) and exercise (EX) have potent anti-oxidative benefits. Low levels of nerve growth factor (NGF) and SIRT1 (a member of sirtuin family) have been reported in patients with DN. The current study has been designed to investigate the role of serum NGF and SIRT1 on DN-induced hyperalgesia and motor incoordination and to evaluate the possible protective role of RES and/or EX. MAIN METHODS: A total of 40 male adult albino rats divided into five groups; control, DN, DN + RES, DN + EX, and DN + RES and EX. DN was confirmed by sensorimotor disturbance and diminished nerve conduction velocity (NCV). NGF and SIRT1 levels were measured by western blot. Calcitonin gene-related peptide (CGRP) was measured by PCR. Myofibrillar degeneration and inflammation scores were revealed via H&E microscopic analysis of the gastrocnemius muscle. Immunohistochemical evaluation of caspase3 and TNF-α was performed in the lumber segment of spinal cord and gastrocnemius muscle sections. Ultrastructural evaluation of sciatic nerve axonal degeneration has also been assessed. KEY FINDINGS: DN group showed decreased SIRT1 level, decreased NGF level and correlated with CGRP level and Na+/K+ ATPase. Treatment with RES and/or EX resulted in improvement of sensorimotor disturbance. DN characterized by reduced SOD level, whereas RES and/or EX could limit oxidative damage by up-regulation Bcl2, Akt and GAP-43 and down-regulation of caspase3 and TNF-α. In conclusion, increased level of SIRT1and NGF by incorporation of RES (natural supplementation) and EX (life style modification) could improve the neuroinflammatory state in DN.
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Neuropatias Diabéticas , Exercício Físico , Doenças Musculares , Resveratrol , Masculino , Peptídeo Relacionado com Gene de Calcitonina , Neuropatias Diabéticas/tratamento farmacológico , Neuropatias Diabéticas/metabolismo , Neuropatias Diabéticas/terapia , Doenças Musculares/tratamento farmacológico , Doenças Musculares/terapia , Fator de Crescimento Neural/metabolismo , Resveratrol/farmacologia , Sirtuína 1/metabolismo , Fator de Necrose Tumoral alfa , Ratos , Complicações do Diabetes/tratamento farmacológico , Complicações do Diabetes/metabolismo , Complicações do Diabetes/terapia , Proteína GAP-43/metabolismo , AnimaisRESUMO
INTRODUCTION: TLRs are fundamental elements in the orchestration of the innate immune system. These receptors seem to be responsible for the inflammation and fibrosis in chronic dacryocystitis. The aim of the present study was to investigate the role of the toll-Like receptors (TLR2 and TLR4) signaling pathway and its downstream effector chemokine genes in the pathogenesis of chronic dacryocystitis. METHODS: This study was conducted on 20 patients diagnosed with chronic dacryocystitis and underwent external dacryocystorhinostomy. Estimation of gene expression of TLR2, TLR4, CCL2, CCL4, CXCL3, CXCR4, and c-FOS genes in the lacrimal sac tissues was performed together with the assessment of the inflammatory markers TNFα, IL-1ß, IFN-γ, and IL-22. Histopathological examination of the lacrimal sac walls using hematoxylin and eosin (H&E) stain, in addition to immunohistochemical staining of the CD68 and CD163 macrophage markers, was also performed. RESULTS: Our results showed that TLR2, TLR4, and c-FOS gene expressions were significantly increased in the chronic dacryocystitis group with a subsequent increase in their downstream effector chemokine genes CCL2, CCL4, and CXCL3. This up-regulation of genes was accompanied by macrophage shift of polarization toward the M1 pro-inflammatory phenotype (increased CD68 and decreased CD163 expression), leading to increased levels of the pro-inflammatory cytokines (TNF- α, IL-1ß and IFN-γ) and decreased anti-inflammatory marker IL-22 with chronic dacryocystitis. CONCLUSION: It is essential to fine-tune TLR activation through emerging therapeutic approaches. Targeting TLR signaling at the level of receptors or downstream adaptor molecules represents a new challenge for treating chronic dacryocystitis.
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Quimiocina CCL2 , Dacriocistite , Humanos , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Receptor 2 Toll-Like/genética , Receptor 2 Toll-Like/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Genes fos , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Células Cultivadas , Receptores Toll-Like/genética , Receptores Toll-Like/metabolismo , Transdução de Sinais , Macrófagos/metabolismo , Quimiocinas/genética , Quimiocinas/metabolismo , Dacriocistite/genética , Dacriocistite/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Fenótipo , Quimiocinas CXC/genética , Quimiocinas CXC/metabolismoRESUMO
Diabetic nephropathy (DN) is one of the devastating complications in diabetes mellitus (DM). Glucagon-like peptide-1 (GLP-1) is one of the incretins secreted from L cells in the intestine. Crocin (a carotenoid component of saffron) has antioxidants properties. We investigated the renal effects of Exendin-4 as a GLP-1 agonist and Crocin in DN.Thirty male rats were divided into five groups: control, type II DM, type II DM + Exendin-4, type II DM + Crocin and type II DM + Exendine-4 + Crocin. At the end of the experimental period, systolic and diastolic blood pressures were measured, and GFR was calculated. Blood and urine samples were collected for biochemical analysis. Tissue samples were collected from the kidney for histological examination and biochemical measurements of protein expression.Treatment with GLP-1 agonist or Crocin caused a significant improvement in renal function. Better results were achieved with simultaneous administration of both drugs with inhibition of notch signalling pathway and the related proteins.
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Diabetes Mellitus Experimental , Nefropatias Diabéticas , Ratos , Masculino , Animais , Nefropatias Diabéticas/metabolismo , Peptídeo 1 Semelhante ao Glucagon , Exenatida/farmacologia , Exenatida/uso terapêutico , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Carotenoides/farmacologia , Carotenoides/uso terapêutico , Modelos AnimaisRESUMO
BACKGROUND: Pemphigus diseases are a subgroup of autoimmune bullous diseases characterized by autoantibodies against desmogleins and occasionally desmocollins. Desmocollin 3 is the main desmocollin isoform that contributes to cell adhesion in the epidermis. OBJECTIVE: To evaluate the presence and level of anti-desmocollin 3 antibodies in pemphigus diseases, and to investigate whether their presence is associated with a specific type, presentation, or clinical pattern. METHODS: Forty patients with pemphigus diseases and forty healthy controls were enrolled. Medical history, clinical examination, and pemphigus disease area index (PDAI) scoring were recorded for all patients. Serum samples were collected from both groups for assessment of anti-desmocollin 3 antibody reactivity by ELISA. RESULTS: The presence of anti-desmocollin 3 antibodies was significant among patients with pemphigus compared with controls (P=0.003). The level of anti-desmocollin 3 antibodies was also significantly higher in patients with pemphigus compared with controls (P=0.01). There was no significant relationship between the presence of anti-desmocollin 3 antibodies and any of the clinical presentations of pemphigus (type, severity, duration, activity, presence of annular pattern, or site of affection - mucosal, cutaneous, on the scalp, palmoplantar, or flexural). CONCLUSION: Anti-desmocollin 3 antibodies are upregulated in pemphigus diseases and can contribute to the pathogenesis of pemphigus. No specific clinical type, presentation, or pattern was found to be associated with the presence of anti-desmocollin 3 antibodies.
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Autoanticorpos , Desmocolinas , Pênfigo , Regulação para Cima , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Autoanticorpos/sangue , Autoanticorpos/imunologia , Estudos de Casos e Controles , Desmocolinas/imunologia , Ensaio de Imunoadsorção Enzimática , Pênfigo/imunologiaRESUMO
Systemic treatments for rheumatoid arthritis are associated with many side effects. This study aimed to minimize the side effects associated with the systemic administration of leflunomide (LEF) by formulating LEF-loaded emulsomes (EMLs) for intra-articular administration. Additionally, EMLs were loaded with supramagnetic nanoparticles (SPIONs) to enhance joint localization, where a magnet was placed on the joint area after intra-articular administration. Full in vitro characterization, including colloidal characteristics, entrapment efficiency, and in vitro release were conducted besides the in vivo evaluation in rats with adjuvant-induced arthritis. In vivo study included joint diameter measurement, X-ray radiographic analysis, RT-PCR analysis, Western blotting, ELISA for inflammatory markers, and histopathological examination of dissected joints. The particle size and entrapment efficiency of the selected LEF SPION EMLs were 198.2 nm and 83.7%, respectively. The EMLs exhibited sustained release for 24 h. Moreover, in vivo evaluation revealed LEF SPION EMLs to be superior to the LEF suspension, likely due to the increase in LEF solubility by nanoencapsulation that improved the pharmacological effects and the use of SPION that ensured the localization of EMLs in the intra-articular cavity upon administration.
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We aimed to determine the level of miRNAs 16 and 135a in lifelong premature ejaculation (LPE) patients versus controls. Moreover, we evaluated the potential interplay between the studied miRNAs and fluoxetine in these patients after utilizing fluoxetine daily for 3 months. The study involved 60 consecutive LPE patients and 20 healthy age matched individuals as controls. The median miRNA16 was significantly higher in the controls (1.02) compared to the patients (0.31) (p < 0.001). Moreover, the median miRNA-135a was significantly higher in the controls compared to the patients 1.02 and 0.35, p < 0.001, respectively. In addition, the median pre-treatment miRNA16 in the responders was 0.29 that significantly increased to 0.66 (p < 0.001). The median pre-treatment miRNA-135a in the responders was 0.27 that significantly increased to 0.65 (p < 0.001). Furthermore, considering EXP(ß) for the odds ratio evaluation, with a 95% degree of confidence, a 1 fold increase in pre-treatment miRNA 135a fold change decreases the odds for being responsive to SSRI by 0.028. Meanwhile, there was non-significant association between fluoxetine responsiveness and age, pre-treatment miRNA 16, pre-treatment PEDT and pre-treatment IELT. The current study had shown that a lower pre-treatment miRNA 135a was significantly associated with response to fluoxetine.
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Fluoxetina , MicroRNAs , Ejaculação Precoce , Estudos de Casos e Controles , Ejaculação/fisiologia , Fluoxetina/uso terapêutico , Humanos , Masculino , Ejaculação Precoce/tratamento farmacológico , Ejaculação Precoce/genética , Fatores de TempoRESUMO
Scientific efforts have been made for a better understanding of the pathogenesis of hepatocellular carcinoma (HCC). We investigated the possible role of miR-192/nuclear factor-κB (NF-κB)/transforming growth factor-ß (TGF-ß)/E-cadherin in hepatic tumorigenesis. We expected a modulatory impact of thymoquinone. Thirty adult male rats were assigned into 3 groups (n = 10); (1) Control group. Group (2): Experimental HCC induced by intraperitoneal injection of diethylnitrosamine (DENA) followed by carbon tetrachloride (CCl4). Group (3): Thymoquinone 20 mg kg-1/oral supplementation starting from the model induction to the end of the 8th week. The HCC (DENA-CCL4) model was confirmed by elevated serum levels of alpha-fetoprotein and transaminases (ALT, AST) and by histopathological examination which denoted marked cellular atypia and features of neoplasia. Suppressed hepatic miR-192 and E-cadherin expression were detected in the HCC (DENA-CCL4) group accompanied by elevated tumor necrosis factor (TNF-α), interleukin (IL6)/NF-κB & TGF-ß1. Thymoquinone treatment protected the rat livers from hepatic tumorigenesis. Thymoquinone diminished (P < 0.001) alpha-fetoprotein and improved ALT, AST. It preserved hepatic miR-192 and normal E-cadherin expression. Thymoquinone-treated rats showed abrogated TNF-α, IL6/NF-κB/TGF-ß. Thymoquinone increased cell apoptosis markers Bax/Bcl2 and diminished cellular atypia. Pearson's correlations revealed positive association between miR-192 expression and E-cadherin and Bax/Bcl2 as well, and it was negatively correlated to alpha-fetoprotein, NF-κB and TGF-ß and the cellular atypia score. In conclusion, thymoquinone protected the liver tissues through preserving miR-192 and E-cadherin and aborting NF-κB & TGF-ß signaling. The current results highlight a new role for thymoquinone in preventing hepatic tumorigenesis.
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We used nicorandil, a K-ATP channel opener, to study the role of these channels in the amelioration of renal ischemia/reperfusion (I/R)-induced pancreatic injury, and the possible involvement of PI3K/Akt/mTOR signaling pathway. Forty-two male Wistar rats were included in this study, six were sacrificed for extraction of bone marrow mesenchymal stem cells (BM-MSCs) and conducting the in-vitro work, the others were included in vivo study and equally divided into six groups. Group 1 (sham control), but groups 2-6 were subjected to bilateral renal I/R: Group 2 (I/R); Group 3 (I/R-NC), treated with nicorandil; Group 4 (I/R-MSCs), treated with BM-MSCs; Group 5 (I/R-MSCC), treated with nicorandil-preconditioned BM-MSCs; Group 6 (I/R-NC-MSCC), treated with both systemic nicorandil and preconditioned BM-MSCC. Renal injury and subsequent pancreatic damage were detected in the I/R group by a significant increase in serum urea, creatinine, fasting glucose, and pancreatic enzymes. The pancreatic tissues showed a reduction in cellularity and a significant decrease in the expression of the cell survival pathway, PI3K/Akt/mTOR, in the I/R group compared to the control. Preconditioning MSCs with nicorandil significantly enhanced the proliferation assay and decreased their apoptotic markers. Indeed, combined systemic nicorandil and nicorandil-preconditioning maintained survival of MSC in the pancreatic tissue and amelioration of apoptotic markers and pancreatic TNF-α production. Histologically, all treated groups revealed better pancreatic architecture, and increased area % of anti-insulin antibody and CD31, which were all best observed in the NC-MSCC group. Thus, using K-ATP channel opener was efficient to enhance PI3K/Akt/mTOR expression levels (in vivo and in vitro).