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.

Nifuroxazide attenuates indomethacin-induced renal injury by upregulating Nrf2/HO-1 and cytoglobin and suppressing NADPH-oxidase, NF-κB, and JAK-1/STAT3 signals.

Indomethacin (INDO) is an NSAID with remarkable efficacy and widespread utilization for alleviating pain. Nevertheless, renal function impairment is an adverse reaction linked to INDO usage. Nifuroxazide (NFX), an oral nitrofuran antibiotic, is frequently employed as an intestinal anti-infective agent. Our study aimed to investigate the renoprotective effects of NFX against INDO-induced nephrotoxicity and explore the protection mechanisms. Four groups of rats were allocated to (I) the normal control, (II) the NFX-treated (50 mg/kg), (III) INDO control (20 mg/kg), and (IV) NFX + INDO. NFX attenuates renal impairment in INDO-induced renal injury, proved by decreasing serum levels of urea, creatinine, uric acid, and NGAL while the albumin was elevated. NFX mitigates renal oxidative stress by decreasing MDA levels and restoring the antioxidants' GSH and SOD levels mediated by upregulating Nrf2, HO-1, and cytoglobin pathways. NFX mitigated renal inflammation and effectively decreased MPO, IL-1ß, and TNF-α levels in the rat's kidney mediated by significant downregulation of NADPH-oxidase and NF-κB expression and suppression of JAK-1 and STAT3 phosphorylation. NFX mitigates renal apoptosis by decreasing the expression of cleaved caspase-3 expression. In conclusion, NFX treatment prevents INDO nephrotoxicity by regulating Nrf2/HO-1, cytoglobin, NADPH-oxidase, NF-κB, and JAK-1/STAT3 signals.

Assessment of Biochemical and Neuroactivities of Cultural Filtrate from Trichoderma harzianum in Adjusting Electrolytes and Neurotransmitters in Hippocampus of Epileptic Rats.

BACKGROUND: Epilepsy is a serious chronic neurological disorder, which is accompanied by recurrent seizures. Repeated seizures cause physical injuries and neuronal dysfunction and may be a risk of cancer and vascular diseases. However, many antiepileptic drugs (AEDs) have side effects of mood alteration or neurocognitive function, a reduction in neuron excitation, and the inhibition of normal activity. Therefore, the present study aimed to evaluate the effect of secondary metabolites of Trichoderma harzianum cultural filtrate (ThCF) when adjusting different electrolytes and neurotransmitters in the hippocampus of epileptic rats. METHODS: Cytotoxicity of ThCF against LS-174T cancer cells was assessed using a sulforhodamine B (SRB) assay. Quantitative estimation for some neurotransmitters, electrolytes in sera or homogenate of hippocampi tissues, and mRNA gene expression for ion or voltage gates was assessed by quantitative Real-Time PCR. RESULTS: Treatment with ThCF reduces the proliferative percentage of LS-174T cells in a concentration-dependent manner. ThCF administration improves hyponatremia, hyperkalemia, and hypocalcemia in the sera of the epilepticus model. ThCF rebalances the elevated levels of many neurotransmitters and reduces the release of GABA and acetylcholine-esterase. Also, treatments with ThCF ameliorate the downregulation of mRNA gene expression for some gate receptors in hippocampal homogenate tissues and recorded a highly significant elevation in the expression of SCN1A, CACNA1S, and NMDA. CONCLUSION: Secondary metabolites of Trichoderma (ThCF) have cytotoxic activity against LS-174T (colorectal cancer cell line) and anxiolytic-like activity through a GABAergic mechanism of action and an increase in GABA as inhibitory amino acid in the selected brain regions and reduced levels of NMDA and DOPA. The present data suggested that ThCF may inhibit intracellular calcium accumulation by triggering the NAADP-mediated Ca2+ signaling pathway. Therefore, the present results suggested further studies on the molecular pathway for each metabolite of ThCF, e.g., 6-pentyl-α-pyrone (6-PP), harzianic acid (HA), and hydrophobin, as an alternative drug to mitigate the side effects of AEDs.

Development of canagliflozin nanocrystals sublingual tablets in the presence of sodium caprate permeability enhancer: formulation optimization, characterization, in-vitro, in silico, and in-vivo study.

Canagliflozin (CFZ) is a sodium-glucose cotransporter-2 inhibitor (SGLT2) that lowers albuminuria in type-2 diabetic patients, cardiovascular, kidney, and liver disease. CFZ is classified as class IV in the Biopharmaceutical Classification System (BCS) and is characterized by low permeability, solubility, and bioavailability, most likely attributed to hepatic first-pass metabolism. Nanocrystal-based sublingual formulations were developed in the presence of sodium caprate, as a wetting agent, and as a permeability enhancer. This formulation is suitable for children and adults and could enhance solubility, permeability, and avoid enterohepatic circulation due to absorption through the sublingual mucosa. In the present study, formulations containing various surfactants (P237, P338, PVA, and PVP K30) were prepared by the Sono-homo-assisted precipitation ion technique. The optimized formula prepared with PVP-K30 showed the smallest particle size (157 ± 0.32 nm), Zeta-potential (-18 ± 0.01), and morphology by TEM analysis. The optimized formula was subsequently formulated into a sublingual tablet containing Pharma burst-V® with a shorter disintegration time (51s) for the in-vivo study. The selected sublingual tablet improved histological and biochemical markers (blood glucose, liver, and kidney function), AMP-activated protein kinase (AMPK), and protein kinase B (AKT) pathway compared to the market formula, increased CFZ's antidiabetic potency in diabetic rabbits, boosted bioavailability by five-fold, and produced faster onset of action. These findings suggest successful treatment of diabetes with CFZ nanocrystal-sublingual tablets.

Development of thermosensitive hydrogel of Amphotericin-B and Lactoferrin combination-loaded PLGA-PEG-PEI nanoparticles for potential eradication of ocular fungal infections: In-vitro, ex-vivo and in-vivo studies.

The most prevalent conditions among ocular surgery and COVID-19 patients are fungal eye infections, which may cause inflammation and dry eye, and may cause ocular morbidity. Amphotericin-B eye drops are commonly used in the treatment of ocular fungal infections. Lactoferrin is an iron-binding glycoprotein with broad-spectrum antimicrobial activity and is used for the treatment of dry eye, conjunctivitis, and ocular inflammation. However, poor aqueous stability and excessive nasolacrimal duct draining impede these agens' efficiency. The aim of this study was to examine the effect of Amphotericin-B, as an antifungal against Candida albicans, Fusarium, and Aspergillus flavus, and Lactoferrin, as an anti-inflammatory and anti-dry eye, when co-loaded in triblock polymers PLGA-PEG-PEI nanoparticles embedded in P188-P407 ophthalmic thermosensitive gel. The nanoparticles were prepared by a double emulsion solvent evaporation method. The optimized formula showed particle size (177.0 ± 0.3 nm), poly-dispersity index (0.011 ± 0.01), zeta-potential (31.9 ± 0.3 mV), and entrapment% (90.9 ± 0.5) with improved ex-vivo pharmacokinetic parameters and ex-vivo trans-corneal penetrability, compared with drug solution. Confocal laser scanning revealed valuable penetration of fluoro-labeled nanoparticles. Irritation tests (Draize Test), Atomic force microscopy, cell culture and animal tests including histopathological analysis revealed superiority of the nanoparticles in reducing signs of inflammation and eradication of fungal infection in rabbits, without causing any damage to rabbit eyeballs. The nanoparticles exhibited favorable pharmacodynamic features with sustained release profile, and is neither cytotoxic nor irritating in-vitro or in-vivo. The developed formulation might provide a new and safe nanotechnology for treating eye problems, like inflammation and fungal infections.

Contralateral Eye Study of Topography Guided versus Q Value Adjusted Photorefractive Keratectomy in Myopia and Myopic Astigmatism.

PURPOSE OF THE STUDY: To compare visual outcome, higher order aberrations (HOAs) of topography guided and Q value adjusted ablation in the fellow eye of patients undergoing photorefractive keratectomy (PRK) for the correction of myopia and myopic astigmatism. METHODS: Prospective randomized controlled interventional clinical study. The eyes of 52 patients undergoing PRK for myopia and astigmatism were included, that is, 104 eyes in total. In each patient, eyes were randomly allocated to group I: one eye received topography guided PRK using Contoura ablation software, or group II: the other eye received Q value adjusted PRK using Custom Q ablation software. FOLLOW-UP: Six months. RESULTS: At the end of 6 months, LogMAR UDVA was -0.04 ± 0.12 and -0.05 ± 0.11 (p = 0.688), while LogMAR CDVA was -0.06 ± 0.09 and -0.06 ± 0.1 in group I and group II, respectively (p = 0.972). Both groups showed a progressive oblate shift with time. This oblate shift was insignificantly less in group I by Topolyzer at 6mm, 15° and 30° at 6 months (p = 0.102, p = 0.138, p = 0.245, respectively). Topolyzer identified a significant difference between the change in coma and trefoil in both groups at 6 months (p<0.001 and p = 0.001, respectively). This was caused by the significant worsening of coma in group II (p<0.001) and the significant improvement of trefoil in group I (p = 0.007). No significant difference was found between groups in the change of ISV or ABR (p = 0.955 and 0.982, respectively). Ablation depth is a significant predictor of ΔQ at 6mm, 15° and 30° (p = 0.009, 0.039 and 0, respectively). No significant difference was found in the Strehl ratio or contrast sensitivity, although they were insignificantly better in group I (p = 0.785 and p = 0.745, respectively). CONCLUSION: TG PRK and CQ PRK yielded similar results regarding UDVA, CDVA, MRSE, safety, predictability and contrast sensitivity. Both groups showed a progressive oblate shift, which was less in the TG group but the difference was statistically insignificant. TG PRK showed significantly improved trefoil HOA as compared to CQ PRK.

Evaluation of Insulin Resistance Induced Brain Tissue Dysfunction in Obese Dams and their Neonates: Role of Ipriflavone Amelioration.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is associated with activation of liver fibrogenesis and predisposes to cirrhosis and associated morbi-mortality. A high fat high cholesterol diet (HFD) was provided to female albino rats to establish a NASH model. It is well known that the offspring of obese mothers have an increased risk of obesity and diabetes. The present study aimed at evaluating the ameliorative effects of ipriflavone (IP) as a natural food supplement on lipid metabolism, improving insulin sensitivity, reducing oxidative stress and inflammation, modifying metabolic risk factors and/or reduce brain damage, in both neonates and their dams. MATERIALS AND METHODS: The present aim was achieved by evaluating the oxidative stress and antioxidant defense system biomarkers, as thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH), catalase, and superoxide dismutase (SOD) activities. In addition, the neurotransmitter acetylcholine (Ach) and acetylcholine esterase (AchE) activities, as well as levels of the apolipoprotein E4 (APOE4); ß-secretase, hyper phosphor-tau and ß-amyloid 42; 3-hydroxy- 3-methyl glutaryl coenzyme A reductase (HMG CoA R)" and COX-II by immunoblotting assays in the brain tissue of neonates and their dams in all the studied groups. RESULTS: A very significant amelioration in acetylcholine and acetylcholine esterase neurotransmitters, Alzheimer's makers (ß-amyloid), antioxidants (reduced glutathione (GSH) contents, catalase (CAT) and superoxide dismutase (SOD); and inflammatory cytokines in NASH model is observed upon administrating ipriflavone (IP) as a natural food supplement. The multifunctional activities of ipriflavone as an antioxidant, anti-inflammatory and anti-insulin resistance drug were discussed and correlated with other investigations. CONCLUSION: Regarding steatohepatitis, the present study confirmed the anti-inflammatory effects of the ipriflavone (IP). Therefore, future studies should focus on hepatic fatty acid uptake, hepatic lipogenesis, and fatty acid oxidation and the role of IP in regulating hepatic fat metabolism. In addition, natural products like IP could be combined with the highly used pharmaceutical drugs to reduce the side effects of nonalcoholic steatohepatitis, and minimize progression of dementia. Moreover, the present study supports further attempts to heal the neural dysfunction via antioxidant and anti-inflammatory cascade activities using ipriflavone (IP).

Ultrasound biomicroscopy as a diagnostic tool in infants with primary congenital glaucoma.

PURPOSE: Studying the role of ultrasound biomicroscopy (UBM) in detection of anterior segment changes in infants with primary congenital glaucoma (PCG). METHODS: Cross-sectional study that included 25 eyes of 15 patients suffering from PCG and a control group of 15 eyes of ten age- and sex-matched participants. Diagnosis of PCG was based on clinical data (intraocular pressure, corneal diameter, fundus examination and amplitude-modulation scan measurement of axial length). UBM examination was done for all participants for measurement of central corneal thickness, anterior chamber depth, lens thickness, iris thickness (measured 2 mm from the iris root and again at the thickest point near the pupil), zonular length, posterior chamber depth, and angle of anterior chamber. Qualitative evaluation was done for abnormal angle membranes, iris insertion level, and ciliary processes position and configuration. RESULTS: Mean age ± standard deviation was 10.32±3.59 months in the study group and 14.54±5.9 months in the control group. The central corneal thickness, anterior chamber depth, zonular length, and angle of anterior chamber were significantly larger in the study group than in the control group, with mean values 700±190 µm, 3.55±0.32 mm, 1.02±0.15 mm, and 58.47°±5.57°, respectively. The posterior chamber depth had a mean of 0.33±0.06 mm, which was significantly smaller than that of the control group. In the study group, the mean iris thickness 2 mm from the iris root was 0.32±0.04 mm, the mean iris thickness at the thickest point near the pupil was 0.38±0.08 mm, and the mean lens thickness was 3.32±0.18 mm. These three parameters were smaller than the control group but the difference was insignificant. Loss of normal iris configuration was detected in all eyes of the study group. Anterior iris insertion was detected in 56% of the eyes in the study group, and abnormal angle membrane was found in 12%. CONCLUSION: UBM is a useful tool for detection of anterior segment changes in PCG, which is helpful especially in cases with opaque cornea or cases with borderline clinical findings.