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Objective: Diabetic nephropathy is an unavoidable complication of chronic uncontrolled diabetes mellitus. The pathogenesis of diabetic nephropathy is multifactorial, and the development of an effective therapy remains to be elucidated. The aim of the present study was to assess the role of NOX2 and Nrf2 in the protective mechanism of thymoquinone (THQ) against streptozotocin (STZ)-induced diabetic nephropathy. Methods: Rats were injected with STZ (55 mg/kg) to induce diabetes. The diabetic rats were orally treated with THQ (10 mg/kg/day) for eight weeks. Results: STZ-treated rats exhibit an elevation of serum creatinine, serum urea, and creatinine clearance. The renal abnormalities were associated with increased NADPH oxidase isoform, NOX2 protein expression, and activity, along with elevated malondialdehyde (MDA). In addition, the tumor necrotic factor-alpha (TNF-α) level and nitric oxide (NO) bioavailability, as well as the transforming growth factor-beta (TGF)-β, were markedly increased. On the other hand, the nuclear factor-E2-related factor (Nrf2) protein expression was significantly reduced in diabetic rats compared to the control. However, treatment with THQ significantly reversed these alterations with subsequent ameliorating renal dysfunction and pathological abnormalities. Conclusion: The present study demonstrates that THQ could protect against STZ-induced diabetic nephropathy by modulating the Nrf2/NOX2 signaling pathway.

Abeer S Hassan,1 Amal Hofni,2 Mohammed AS Abourehab,3 Iman AM Abdel-Rahman4 1Department of Pharmaceutics, Faculty of Pharmacy, South Valley University, Qena, Egypt; 2Department of Pharmacology and Toxicology, Faculty of Pharmacy, South Valley University, Qena, Egypt; 3Department of Pharmaceutics and Industrial Pharmacy, College of Pharmacy, Minia University, Minia, Egypt; 4Department of Pharmacognosy, Faculty of Pharmacy, South Valley University, Qena, EgyptCorrespondence: Abeer S Hassan, Department of Pharmaceutics, Faculty of Pharmacy, South Valley University, Qena, Egypt, Tel +201012060262, Email abeer.saad@svu.edu.egIntroduction: Ginger extract (GE) has sparked great interest due to its numerous biological benefits. However, it suffers from limited skin permeability, which challenges its transdermal application. The target of the current work was to develop transethosomes as a potential nanovehicle to achieve enhanced transdermal delivery of GE through the skin.Methods: GE–loaded transethosomes were prepared by cold injection using different edge activators. The fabricated nanovesicles were evaluated for particle size, ζ-potential, encapsulation efficiency, and in vitro drug release. The selected formulation was then laden into the hydrogel system and evaluated for ex vivo permeability and in vivo anti-inflammatory activity in a carrageenan-induced rat-paw edema model.Results: The selected formulation comprised of sodium deoxycholate exhibited particle size of 188.3± 7.66 nm, ζ-potential of − 38.6± 0.08 mV, and encapsulation efficiency of 91.0%± 0.24%. The developed transethosomal hydrogel containing hydroxypropyl methylcellulose was homogeneous, pseudoplastic, and demonstrated sustained drug release. Furthermore, it exhibited improved flux (12.61± 0.45 μg.cm2/second), apparent skin permeability (2.43± 0.008× 10− 6 cm/second), and skin deposition compared to free GE hydrogel. In vivo testing and histopathological examination revealed that the GE transethosomal hydrogel exhibited significant inhibition of edema swelling compared to free GE hydrogel and ketoprofen gel. The animals that were treated with ginger transethosome hydrogel showed a significant decrement in reactive oxygen species and prostaglandin E2 compared to untreated animals.Conclusion: Transethosomes might be a promising new vehicle for GE for effective skin permeation and anti-inflammation. To the best of our knowledge, this work is the first utilization of transethosomes laden into hydrogel as a novel transdermal delivery system of GE.Graphical Abstract: Keywords: nanovesicles, transethosomes, ginger, ex vivo permeation, transdermal delivery, inflammation

The study was conducted to determine the effect of profitability, liquidity, leverage and firm size on the disclosure of Corporate Social Responsibility either partially or simultaneously. This study uses a quantitative descriptive approach, with the population being food and beverage sub-sector companies listed on the Indonesia Stock Exchange during the period 2017 to 2020. The sampling technique uses Probability Sample with purposive sampling method and obtains sample data of 9 companies and 36 sample data. Analysis of the data using SmartPLS software with the results of the study being that the variables of profitability, liquidity, leverage and company size did not affect the disclosure of Corporate Social Responsibility in food and beverage sub-sector companies listed on the Indonesia Stock Exchange for the 2017-2020 period. The value of the coefficient of determination is 46.5%. Hypothesis test obtained t arithmetic > t table or (9.139% > 0.985%). Thus H1,H2,H3 and H4 is rejected and Ho is accepted, meaning that there is no a significant influence of profitability, liquidity, leverage and firm size. Profitability, liquidity, leverage and firm size has no a significant effect on corporate social responsibility with the regression equation Y = -0,058X1 + 0,124X2 + 0.,428X3 – 0,08X4, The value of the coefficient of determination is 15,5% while the remaining 84,5% is influenced by other factors.

Methotrexate (MTX) is one of the most widely used cytotoxic chemotherapeutic agents, and it is used in the treatment of different autoimmune disorders. However, the clinical applications of MTX are limited by its hepatic toxicity. Hence, the present study was conducted to evaluate the efficacy of fasudil (Rho-Kinase inhibitor) in the amelioration of MTX hepatotoxicity and the possible underlying mechanisms. Experimentally, 32 male Sprague Dawley rats were used and divided into four groups: control, MTX (20 mg/kg, i.p., single dose), fasudil (10 mg/kg/day i.p.) for one week, and fasudil plus MTX. It was found that MTX significantly induced hepatitis and hepatocellular damage, as shown by abnormal histological findings and liver dysfunction (ALT and AST), with up-regulation of the inflammatory mediators NF-κB-p65 and IL-1β. Moreover, MTX remarkably disrupted oxidant/antioxidant status, as evidenced by malondialdehyde (MDA) up-regulation associated with the depletion of superoxide dismutase (SOD), catalase, and reduced glutathione (GSH) levels. Moreover, MTX reduced the hepatic expression of B-cell lymphoma 2 (Bcl-2). On the contrary, the i.p. administration of fasudil significantly ameliorated MTX hepatotoxicity by histopathological improvement, restoring oxidant/antioxidant balance, preventing hepatic inflammation, and improving the hepatic anti-apoptotic capability. Furthermore, fasudil hepatic concentration was determined for the first time using the validated RP-HPLC method. In conclusion, the present study revealed that fasudil has a reliable hepatoprotective effect against MTX hepatotoxicity with underlying antioxidant, anti-inflammatory, and anti-apoptotic mechanisms. It also introduced a new method for the determination of fasudil hepatic tissue concentration using the RP-HPLC technique.

The main objective of this project was to formulate novel decorated amphiphilic PLGA nanoparticles aiming for the selective delivery of the novel peptide (CK-10) to the cancerous/tumor tissue. Novel modified microfluidic techniques were used to formulate the nanoparticles. This technique was modified by using of Nano Assemblr associated with salting out of the organic solvent using K

This study aimed to examine the growth and production response of Allium fistolosum to the application of various doses of sago dregs compost and to determine the appropriate dose of sago dregs compost for it cultivation in polybags. This research was designed in Randomized Block Design (RAK) consisting of 4 doses of sago dregs compost treatments. The results showed that different doses of sago dregs compost had a significant effect on the growth and yield of Allium fistolosum. The dose of sago dregs compost with a dose of 600 g gave the highest yield on the parameters of observing plant height, stem diameter, and plant fresh weight.

Kota Yogyakarta adalah termasuk kota yang mempunyai kebudayaan serta tempat wisata yang beraneka ragam, hal tersebut menyebabkan banyak wisatawan yang ingin berkunjung dan berwisata di Yogyakarta, akan tetapi berdasrkan survey banyak dari wisatawan tersebut tidak menggunakan kendaraan khsusunya mobil pribadi ketika mengunjungi tempat objek wisata tersebut, sehingga diharuskan untuk me-rental mobil selama berada di Yogyakarta. Keterbatasaan wisatawan dalam melakukukan akses informasi tentang spesifikasi mobil dan rental mobil yang sesuai dengan kebutuhan menyebabkan masalah tersendiri untuk para wisatawan.Oleh karena itu dibutuhkan sebuah sistem pendukung keputusan untuk mendukung dan mempermudah wisatawan memilih suatu mobil dan tempat rental. Banyak metode sistem pendukung keputusan yang sering digunakan, antara lain metode Simple Additive Weighting (SAW). hasil akhir penelitian ini adalah sebuah sistem pendukung keputusan pemilihan mobil rental terbaik dengan hasil pengujian validasi sebesar 82%.Kata kunci: Wisatawan, Mobil, Rental, Simple Additive Weighting (SAW)

Endothelial dysfunction is a major contributor to the pathogenesis of vascular disease in diabetes mellitus and RhoA/Rho-kinase (ROCK) system appears to play a crucial role in this setting. The present study was conducted to investigate the effect of the selective ROCK inhibitor, fasudil, on diabetes-related endothelial dysfunction and elucidated its underlying mechanism(s). Diabetes was induced by a single intraperitoneal injection of streptozotocin (STZ, 50 mg/kg), and fasudil (5 mg/kg per day) was orally administered for 8 weeks. Our results showed that fasudil administration attenuated the increased activity/expression of ROCK (627.5 ± 27 vs. 247.8 ± 19.1) and the NADPH oxidase subunits, NOX2 and p47phox, in diabetic rat aorta. Fasudil could reduce the elevated tumor necrosis factor (TNF)-α (70.2 ± 14.1 vs. 25.3 ± 5.2) and transforming growth factor (TGF-β) levels and restored the deficit in antioxidant level of the diabetic aorta. Additionally, fasudil markedly improved the endothelial dysfunction in the diabetic aorta (73.8 ± 8.1 vs. 47.42 ± 8.69) and corrected the dysregulated endothelial nitric oxide (eNOS) expression. In conclusion, the present study demonstrates that fasudil effectively ameliorates the endothelial dysfunction in STZ-induced diabetic rats through inhibition of the Rho/ROCK pathway and thereby reducing the TNF-α-mediated NADPH oxidase activation.

Diabetic nephropathy is one of the most common causes of end-stage kidney disease. Aldosterone and angiotensin II appear to play a crucial role in the pathogenesis of this disease. The present study aimed to investigate effects of the combination therapy with spironolactone and candesartan on diabetic nephropathy and elucidate the underlying mechanism(s) involved. Diabetes was induced in rats by a single intraperitoneal injection of streptozotocin (STZ) (55 mg/kg). The diabetic rats were orally treated with spironolactone (50 mg/kg/day) and/or candesartan (1 mg/kg/day) for 8 weeks. Administration of STZ caused a marked elevation in the serum level of creatinine, urea and urinary albumin–creatinine ratio (ACR). This was associated with upregulated renal protein levels of nuclear factor-kappa B (NF-κB), transforming growth factor (TGF)-β, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) alongside increasing the renal superoxide anion (O2−) production, malondialdehyde (MDA) level and the systolic blood pressure. There was a marked decrease in nitric oxide (NO) bioavailability and antioxidant enzyme capacity. The combined therapy of spironolactone and candesartan significantly normalized the oxidative stress and fibrotic/inflammatory alterations. Additionally, the elevated blood pressure was attenuated by administration of candesartan alone or in combination. This was associated with improving the renal function parameters. The combined therapy exhibited more profound response compared to the monotherapy. In conclusion, our results demonstrate that the combined therapy of spironolactone and candesartan can confer an additive benefit over the use of either drug alone against STZ-induced diabetic nephropathy, presumably via attenuating the inflammatory responses and oxidative status markers.