Hanan Hassan Fouad

3-nitropropionic acid (3-NP) is a potent mitochondrial inhibitor mycotoxin. Systemic administration of 3-NP can induce Huntington's disease (HD)-like symptoms in experimental animals. Safranal (Safr) that is found in saffron essential oil has antioxidant, anti-inflammatory and anti-apoptotic actions. Candesartan (Cands) is an angiotensin receptor blocker that has the potential to prevent cognitive deficits. The present study aims to investigate the potential neuroprotective efficacy of Safr or Cands in 3-NP-induced rat model of HD. The experiments continued for nine consecutive days. Rats were randomly assigned into seven groups. The first group (Safr-control) was daily intraperitoneally injected with paraffin oil. The second group (Cands- and 3-NP-control) daily received an oral dose of 0.5% carboxymethylcellulose followed by an intraperitoneal injection of 0.9% saline. The third and fourth groups received a single daily dose of 50 mg/kg Safr (intraperitoneal) and 1 mg/kg Cands (oral), respectively. The sixth group was daily treated with 50 mg Safr kg/day (intraperitoneal) and was intraperitoneally injected with 20 mg 3-NP/ kg, from the 3rd till the 9th day. The seventh group was daily treated with 1 mg Cands /kg/day (oral) and was intraperitoneally injected with 20 mg 3-NP/ kg, from the 3rd till the 9th day. The present results revealed that 3-NP injection induced a considerable body weight loss, impaired memory and locomotor activity, reduced striatal monoamine levels. Furthermore, 3-NP administration remarkably increased striatal malondialdehyde and nitric oxide levels, whereas markedly decreased the total antioxidant capacity. Moreover, 3-NP significantly upregulated the activities of inducible nitric oxide synthase and caspase-3 as well as the Fas ligand, in striatum. On the contrary, Safr and Cands remarkably alleviated the above-mentioned 3-NP-induced alterations. In conclusion, Safr and Cands may prevent or delay the progression of HD and its associated impairments through their antioxidant, anti-inflammatory, anti-apoptotic and neuromodulator effects.

BACKGROUND: Amelioration of proteinuria is one of main treatment targets in patients with glomerulonephritis, yet the remission rates are suboptimal.

AIM OF THE STUDY: To examine the effect of the sodium-glucose transporter 2 inhibitor (empagliflozin) on proteinuria and kidney function progression, in patients with glomerulonephritis not due to diabetic kidney diseases.

SUBJECTS AND METHODS: Fifty patients were recruited. The entry criteria were diagnosis of glomerulonephritis, and proteinuria (proteinuria ≥ 500 mg⁄g) in spite of the use of the maximal tolerated dose of RAAS blocking agents together with specific immunosuppression treatment regimens. Group 1 (Empagliflozin arm): 25 patients who received 25 mg of empagliflozin once daily for 3 months as add-on to their regular treatment protocol (RAAS blockers and immunosuppression). Group 2 (Placebo arm): 25 patients treated with RAAS blockers and immunosuppression. The primary efficacy endpoints were the change in creatinine eGFR, and proteinuria 3 months after starting treatment.

RESULTS: Progression of proteinuria was lower with empagliflozin as compared to placebo (odds ratio, 0.65; 95% CI, 0.55 to 0.72, p = 0.002). Decline in eGFR was lower with empagliflozin as compared to placebo; however, this was statistically not significant (odds ratio, 0.84; 95% CI, 0.82 to 1.2, p = .31). The percentage change in proteinuria was greater with empagliflozin as compared to placebo (median, - 77 (- 97-105) vs - 48 (- 80-117).

CONCLUSION: Empagliflozin has a favorable effect on amelioration of proteinuria in patients with glomerulonephritis. Empagliflozin has tendency to preserve kidney function in patients with glomerulonephritis as compared to placebo; however, longer term studies are required.

Background: Corneal ulcer is the discontinuation of the surface epithelial layer of the cornea with variable amounts of the stroma affected. Recent research suggests that Extracellular Vesicles (EVs) of stem cells have the same effects on target cells that their parental stem cells act, these effects are brought on by paracrine signaling involves the release of cytokines and nucleic acids (DNA, mRNA, and miRNA) which may lead to alteration of the gene expression, proliferation, and differentiation of the recipient cells. Methodology: 24 male New Zealand albino rabbits were used in this study, divided randomly into 4 groups (6 rabbits per group), induction of corneal ulcers centrally in groups (I, II) and peripherally in (III, IV). Treated groups are (I, III) using topical lyophilized canine Mesenchymal Stem Cells derived EVs & control groups are (II, IV) using topical normal saline. Result: both treated groups appeared fluorescein negative at the 5th day and are characterized by rapid reepithelization significantly earlier than control groups which were still fluorescein positive. AS-OCT (Anterior Segment Optical Coherence Tomography) showed well-healed epithelium with intact and homogenous stroma on the 5th day in both treated groups, but control groups showed irregular arrangements of epithelial plaques and presented some abnormalities as stromal fibrosis and sub-epithelial cyst formation. Histopathology in both treated groups showed the development of a complete layer of epithelium within 1week which increased in rows at 2nd and 3rd weeks of treatment and the stromal edema decreased with time unlike control groups that showed weak fragmented epithelium development, sub-epithelial hemorrhage and vascularization. These findings prove that EVs have the ability to heal corneal wounds even if in the peripheral parts of the cornea that are deficient in limbal stem cells. Conclusion: In terms of safety, quality, regulatory concerns, and cost, EVs are superior to corneal transplantation and live stem cell therapy. © 2023 by the authors. Licensee ResearchersLinks Ltd, England, UK. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons. org/licenses/by/4.0/).