Green Synthesis of Zinc Oxide Nanoparticles from Althaea officinalis Flower Extract Coated with Chitosan for Potential Healing Effects on Diabetic Wounds by Inhibiting TNF-α and IL-6/IL-1ß Signaling Pathways.

Background: Diabetes Mellitus is a multisystem chronic pandemic, wound inflammation, and healing are still major issues for diabetic patients who may suffer from ulcers, gangrene, and other wounds from uncontrolled chronic hyperglycemia. Marshmallows or Althaea officinalis (A.O.) contain bioactive compounds such as flavonoids and phenolics that support wound healing via antioxidant, anti-inflammatory, and antibacterial properties. Our study aimed to develop a combination of eco-friendly formulations of green synthesis of ZnO-NPs by Althaea officinalis extract and further incorporate them into 2% chitosan (CS) gel. Method and Results: First, develop eco-friendly green Zinc Oxide Nanoparticles (ZnO-NPs) and incorporate them into a 2% chitosan (CS) gel. In-vitro study performed by UV-visible spectrum analysis showed a sharp peak at 390 nm, and Energy-dispersive X-ray (EDX) spectrometry showed a peak of zinc and oxygen. Besides, Fourier transforms infrared (FTIR) was used to qualitatively validate biosynthesized ZnO-NPs, and transmission electron microscope (TEM) showed spherical nanoparticles with mean sizes of 76 nm and Zeta potential +30mV. The antibacterial potential of A.O.-ZnO-NPs-Cs was examined by the diffusion agar method against Gram-positive (Staphylococcus aureus and Bacillus subtilis) and Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa). Based on the zone of inhibition and minimal inhibitory indices (MIC). In addition, an in-silico study investigated the binding affinity of A.O. major components to the expected biological targets that may aid wound healing. Althaea Officinalis, A.O-ZnO-NPs group showed reduced downregulation of IL-6, IL-1ß, and TNF-α and increased IL-10 levels compared to the control group signaling pathway expression levels confirming the improved anti-inflammatory effect of the self-assembly method. In-vivo study and histopathological analysis revealed the superiority of the nanoparticles in reducing signs of inflammation and wound incision in rat models. Conclusion: These biocompatible green zinc oxide nanoparticles, by using Althaea Officinalis chitosan gel ensure an excellent new therapeutic approach for quickening diabetic wound healing.

Scheimpflug-Based Tomographic Risk Factors for the Development of Acute Corneal Hydrops in Keratoconus.

PURPOSE: The purpose of this study was to assess the risk factors that predispose patients with keratoconus to develop acute corneal hydrops (ACH), including both clinical and tomographic risk factors. We additionally describe tomographic changes of the cornea over time after ACH. METHODS: We retrospectively reviewed patients with keratoconus who were followed at our institution from January 2015 to May 2023. Control eyes, defined as eyes with advanced keratoconus (stage IV Amsler-Krumeich classification on initial examination) were compared with eyes that developed ACH. Demographic, clinical, and tomographic factors were investigated. Visual acuity, keratometry, and corneal thickness were assessed at each follow-up visit to monitor progression over time. RESULTS: Twenty-three eyes of 19 patients developed ACH over the follow-up period. The incidence of known clinical associations including seasonal allergies, eye rubbing, snoring, asthma, and eczema was similar between the hydrops and control groups. There was a higher incidence of Down syndrome in the hydrops group ( P = 0.04). Eyes that developed hydrops had similar best corrected visual acuity on initial examination, but had steeper keratometry ( P = 0.003) and thinner corneas ( P < 0.001) than controls at baseline. After hydrops, progressive corneal flattening and reduced maximum keratometry occurred over time. However, final best corrected visual acuity was worse compared with initial examination before hydrops ( P = 0.03), as well as compared with control eyes ( P < 0.001). CONCLUSIONS: Risk factors of developing ACH include steep keratometry and thin corneas as well as Down syndrome. Although corneal flattening will occur after resolution of acute corneal edema, visual acuity worsened after ACH.

Revolutionizing Psoriasis Topical Treatment: Enhanced Efficacy Through Ceramide/Phospholipid Composite Cerosomes Co-Delivery of Cyclosporine and Dithranol: In-Vitro, Ex-Vivo, and in-Vivo Studies.

Purpose: Improving the treatment of psoriasis is a serious challenge today. Psoriasis is an immune-mediated skin condition affecting 125 million people worldwide. It is commonly treated with cyclosporine-A (CsA) and dithranol (DTH). CsA suppresses the activation of T-cells, immune cells involved in forming psoriatic lesions. Meanwhile, DTH is a potent anti-inflammatory and anti-proliferative drug that effectively reduces the severity of psoriasis symptoms such as redness, scaling, and skin thickness. CsA and DTH belong to BCS class II with limited oral bioavailability. We aim to develop a drug delivery system for topical co-delivery of CsA and DTH, exploring its therapeutic potential. Methods: Firstly, we developed a niosomal drug delivery system based on ceramide IIIB to form Cerosomes. Cerosomes were prepared from a mixture of Ceramide, hyaluronic acid, and edge activator using a thin-film hydration technique. To co-deliver CsA and DTH topically for the treatment of psoriasis. These two hydrophobic drugs encapsulated into our synthesized positively charged particle cerosomes. Results:  Cerosomes had an average particle size of (222.36 nm± 0.36), polydispersity index of (0.415±0.04), Entrapment Efficiency of (96.91%± 0.56), and zeta potential of (29.36±0.38mV) for selected formula. In vitro, In silico, in vivo, permeation, and histopathology experiments have shown that cerosomes enhanced the skin penetration of both hydrophobic drugs by 66.7% compared to the CsA/DTH solution. Imiquimod (IMQ) induced psoriatic mice model was topically treated with our CsA/DTH cerosomes. We found that our formulation enhances the skin penetration of both drugs and reduces psoriasis area and severity index (PASI score) by 2.73 times and 42.85%, respectively, compared to the CsA/DTH solution. Moreover, it reduces the levels of proinflammatory cytokines, TNF-α, IL-10, and IL-6 compared to CsA/DTH solution administration. Conclusion: The Cerosomes nano-vesicle-containing CsA/DTH represents a more promising topical treatment for psoriasis, giving new hope to individuals with psoriasis, compared to commercial and other conventional alternatives.

Spontaneous Reattachment of a Detached Sutured Descemet-Stripping Automated Endothelial Keratoplasty Graft.

Introduction: This is a case report of a spontaneous reattachment of Descemet-stripping automated endothelial keratoplasty (DSAEK). This graft was primarily sutured, and 20% sulfur hexafluoride (SF6) was injected into the anterior chamber, followed by graft detachment and spontaneous reattachment, 3 months later. Case Presentation: A 78-year-old male presented with DSAEK graft detachment, which was the patient's second DSAEK (the first also did not adhere). During the second surgery, the DSAEK graft was sutured and 20% SF6 was injected intraoperatively. Graft reattachment occurred without any intervention or repositioning 3 months after the 2nd DSAEK surgery. Conclusion: Spontaneous DSEAK late graft reattachment is possible, particularly in the setting of an anchoring suture. In some patients, waiting can be an option that can spare the patient the possible risks of graft repositioning, rebubbling, or repeating the DSAEK. Suturing the DSAEK graft primarily may have served as an anchor to keep the graft approximate and aid in attachment. A graft suture can be considered in the setting of a previously failed DSAEK due to DSAEK graft detachment.