Hesperidin - loaded PVA/alginate hydrogel: targeting NFκB/iNOS/COX-2/TNF-α inflammatory signaling pathway.

Introduction: Skin injuries represent a prevalent form of physical trauma, necessitating effective therapeutic strategies to expedite the wound healing process. Hesperidin, a bioflavonoid naturally occurring in citrus fruits, exhibits a range of pharmacological attributes, including antimicrobial, antioxidant, anti-inflammatory, anticoagulant, and analgesic properties. The main objective of the study was to formulate a hydrogel with the intention of addressing skin conditions, particularly wound healing. Methods: This research introduces a methodology for the fabrication of a membrane composed of a Polyvinyl alcohol - Sodium Alginate (PVA/A) blend, along with the inclusion of an anti-inflammatory agent, Hesperidin (H), which exhibits promising wound healing capabilities. A uniform layer of a homogeneous solution comprising PVA/A was cast. The process of crosslinking and the enhancement of hydrogel characteristics were achieved through the application of gamma irradiation at a dosage of 30 kGy. The membrane was immersed in a Hesperidin (H) solution, facilitating the permeation and absorption of the drug. The resultant system is designed to deliver H in a controlled and sustained manner, which is crucial for promoting efficient wound healing. The obtained PVA/AH hydrogel was evaluated for cytotoxicity, antioxidant and free radical scavenging activities, anti-inflammatory and membrane stability effect. In addition, its action on oxidative stress, and inflammatory markers was evaluated on BJ-1 human normal skin cell line. Results and Discussion: We determined the effect of radical scavenging activity PVA/A (49 %) and PVA/AH (87%), the inhibition of Human red blood cell membrane hemolysis by PVA/AH (81.97 and 84.34 %), hypotonicity (83.68 and 76.48 %) and protein denaturation (83.17 and 85.8 %) as compared to 250 µg/ml diclofenac (Dic.) and aspirin (Asp.), respectively. Furthermore, gene expression analysis revealed an increased expression of genes associated with anti-oxidant and anti-inflammatory properties and downregulated TNFα, NFκB, iNOS, and COX2 by 67, 52, 58 and 60%, respectively, by PVA/AH hydrogel compared to LPS-stimulated BJ-1 cells. The advantages associated with Hesperidin can be ascribed to its antioxidant and anti-inflammatory attributes. The incorporation of Hesperidin into hydrogels offers promise for the development of a novel, secure, and efficient strategy for wound healing. This innovative approach holds potential as a solution for wound healing, capitalizing on the collaborative qualities of PVA/AH and gamma irradiation, which can be combined to establish a drug delivery platform for Hesperidin.

Stabilization of the cubic, fast-ion conducting phase of Li7La3Sn2O12 garnet by gallium doping.

All-solid-state batteries present promising high-energy-density alternatives to conventional Li-ion chemistries, and Li-stuffed garnets based on Li7La3Zr2O12 (LLZO) remain a forerunner for candidate solid-electrolytes. One route to access fast-ion conduction in LLZO phases is to stabilize the cubic LLZO phase by doping on the Li sites with aliovalent ions such as Al3+ or Ga3+. Despite prior attempts, the stabilization of the cubic phase of isostructural Li7La3Sn2O12 (LLSO) by doping on the Li sites has up to now not been realised. Here, we report a novel cubic fast-ion conducting Li7La3Sn2O12-type phase stabilized by doping Ga3+ in place of Li. 0.3 mole of gallium per formula unit of LLSO were needed to fully stabilize the cubic garnet, allowing structural and electrochemical characterizations of the new material. A modified sol-gel synthesis approach is introduced in this study to realise Ga-doping in LLSO, which offers a viable route to preparing new Sn-based candidate solid-electrolytes for all-solid-state battery applications.

The membrane-cytoplasmic linker defines activity of FtsH proteases in Pseudomonas aeruginosa clone C.

Pandemic Pseudomonas aeruginosa clone C strains encode two inner-membrane associated ATP-dependent FtsH proteases. PaftsH1 is located on the core genome and supports cell growth and intrinsic antibiotic resistance, whereas PaftsH2, a xenolog acquired through horizontal gene transfer from a distantly related species, is unable to functionally replace PaftsH1. We show that purified PaFtsH2 degrades fewer substrates than PaFtsH1. Replacing the 31-amino acid-extended linker region of PaFtsH2 spanning from the C-terminal end of the transmembrane helix-2 to the first seven highly divergent residues of the cytosolic AAA+ ATPase module with the corresponding region of PaFtsH1 improves hybrid-enzyme substrate processing in vitro and enables PaFtsH2 to substitute for PaFtsH1 in vivo. Electron microscopy indicates that the identity of this linker sequence influences FtsH flexibility. We find membrane-cytoplasmic (MC) linker regions of PaFtsH1 characteristically glycine-rich compared to those from FtsH2. Consequently, introducing three glycines into the membrane-proximal end of PaFtsH2's MC linker is sufficient to elevate its activity in vitro and in vivo. Our findings establish that the efficiency of substrate processing by the two PaFtsH isoforms depends on MC linker identity and suggest that greater linker flexibility and/or length allows FtsH to degrade a wider spectrum of substrates. As PaFtsH2 homologs occur across bacterial phyla, we hypothesize that FtsH2 is a latent enzyme but may recognize specific substrates or is activated in specific contexts or biological niches. The identity of such linkers might thus play a more determinative role in the functionality of and physiological impact by FtsH proteases than previously thought.

Infectious aortic aneurysms: A case report and review of cases from the Middle East and North Africa (MENA) region.

An infectious aortic aneurysm is a rare disease entity. We report a challenging case of a 29-year-old male presenting with chest pain and constitutional symptoms. The patient was found to have three pseudoaneurysms of the aorta on imaging, significant pathological findings of necrotizing granulomatous lymphadenitis from a supraclavicular lymph node biopsy, and a highly suggestive clinical picture of tuberculous aortitis. He was referred to vascular surgery for intervention and discharged on antituberculous therapy for 6 months. To the best of our knowledge, only five cases of tuberculous aortic aneurysms have been reported from the Middle East and North Africa (MENA) region, all with favorable outcomes. A high index of suspicion, early detection, and prompt intervention are essential in managing such cases.

A precise estimation for vibrational energies of diatomic molecules using the improved Rosen-Morse potential.

In the context of the generalized fractional derivative, novel solutions to the D-dimensional Schrödinger equation are investigated via the improved Rosen-Morse potential (IRMP). By applying the Pekeris-type approximation to the centrifugal term, the generalized fractional Nikiforov-Uvarov method has been used to derive the analytical formulations of the energy eigenvalues and wave functions in terms of the fractional parameters in D-dimensions. The resulting solutions are employed for a variety of diatomic molecules (DMs), which have numerous uses in many fields of physics. With the use of molecular parameters, the IRMP is utilized to reproduce potential energy curves for numerous DMs. The pure vibrational energy spectra for several DMs are determined using both the fractional and the ordinary forms to demonstrate the effectiveness of the method utilized in this work. As compared to earlier investigations, it has been found that our estimated vibrational energies correspond with the observed Rydberg-Klein-Rees (RKR) data much more closely. Moreover, it is observed that the vibrational energy spectra of different DMs computed in the existence of fractional parameters are superior to those computed in the ordinary case for fitting the observed RKR data. Thus, it may be inferred that fractional order significantly affects the vibrational energy levels of DMs. Both the mean absolute percentage deviation (MAPD) and average absolute deviation (AAD) are evaluated as the goodness of fit indicators. According to the estimated AAD and MAPD outcomes, the IRMP is an appropriate model for simulating the RKR data for all of the DMs under investigation.

EDSS and infratentorial white matter lesion volume are considered predictors of fatigue severity in RRMS.

Fatigue is a common disabling symptom of relapsing remitting multiple sclerosis (RRMS). Many studies have linked grey matter atrophy to fatigue, but white matter lesion load (WM-LL) has received less attention. Here we assess the relation between fatigue and regional WM-LL volumetric measures. 63 patients with RRMS participated in this study; mean age was 31.9 ± 8.1 years. Each patient provided demographic details and was scored on the expanded disability status scale (EDSS) and fatigue severity scale (FSS). VolBrain, a fully automated, operator-independent tool was used to assess WM-LL and whole brain volume. The patients were classified into three groups: no fatigue (FSS < 4), low to moderate fatigue (FSS ≥ 4 ≤ 5) and high fatigue (FSS > 5). 33.3% of patients had no significant fatigue, 25.4% had mild-to-moderate fatigue, and 41.3% had significant fatigue. Age, disease duration, relapses, and EDSS were positively correlated to fatigue severity (P = 0.034, 0.002, 0.009 and 0.001 respectively). Whole brain volume, total and regional WM-LL (juxtacortical, periventricular, infratentorial) were also correlated with fatigue severity. Ordinal regression analysis for fatigue severity showed EDSS and infratentorial lesion volume were the best predictors. In conclusion, EDSS and infratentorial lesion volume (cerebellar and brainstem) are the best predictors of fatigue severity.

Chitosan Surface-Modified PLGA Nanoparticles Loaded with Cranberry Powder Extract as a Potential Oral Delivery Platform for Targeting Colon Cancer Cells.

Nutraceutical cranberry powder extract (CBPE) has distinct polyphenols inhibiting colon cancer growth and proliferation. However, its oral therapeutic efficacy is hindered because of its low permeability. This study aims to formulate chitosan surface-modified PLGA nanoparticles (CS-PLGA NPs) for encapsulating CBPE and modulating its release rate, permeation, cell targeting, and, therefore, its cytotoxicity. A full 23 factorial design is employed to scrutinize the effect of lactide/glycolide ratio, PLGA weight, and stabilizer concentrations on entrapment efficiency percentage (EE%), particle size (PS), polydispersity index (PDI), and zeta potential (ZP). The optimum formula (F4) shows spherical particles with a relatively high EE% (72.30 ± 2.86%), an appropriate size of 370.10 ± 10.31 nm, PDI; 0.398 ± 0.001, and ZP; -5.40 ± 0.21 mV. Alongside the ATR-FTIR outcomes, the chitosan surface-modified formula (CS-F4) demonstrates a significant increase in particle size (417.67 ± 6.77 nm) and a shift from negative to positive zeta potential (+21.63 ± 2.46 mV), confirming the efficiency of surface modification with chitosan. The intestinal permeability of F4 and CS-F4 is significantly increased by 2.19- and 3.10-fold, respectively, compared to the CBPE solution, with the permeability coefficient (Papp) being 2.05 × 10-4 cm/min and 2.91 × 10-4 cm/min, for F4 and CS-F4, respectively, compared to the CBPE solution, 9.36 × 10-5 cm/min. Moreover, CS-F4 evidences significant caspase-3 protein level expression stimulation and significant inhibition of vascular endothelial growth factor (VEGF) and signal transducer and activator of transcription-3 (STAT-3) protein expression levels, confirming the superiority of CS-F4 for targeting HT-29 cells. Briefly, CS-PLGA NPs could be regarded as a prosperous delivery system of CBPE with enhanced permeation, cell targeting, and antitumor efficacy.

The Virtual Surgical Management of Facial Fibrous Dysplasia.

PURPOSE: Fibrous dysplasia (FD) is a benign condition, which is characterized by the replacement of normal bone with fibrous tissue and the deposition of woven bone in an irregular manner. Surgical resection, careful corrective osteotomies as debulking, and recontouring procedures are frequently performed, but can be complicated by postoperative regrowth of the lesion. The main aim of this study was to introduce a computer-guided technique for a predetermined technique of bone contouring of craniofacial FD involving the facial bones. METHODS: This case report was conducted on an 18-year-old girl complaining of unilateral craniofacial dysplasia. Upon clinical examination and radiographic examination, a customized computer-generated bone contouring guide was designed using virtual surgical software for accurate contouring of excess bone in the cranial vault and frontal bone. This guide was virtually designed after importing the multislice computerized tomography scans into the virtual surgical planning software. It was generated based on the mirroring option of the unaffected normal side along the median sagittal plane. In the surgery, the guide was seated in place and 5 mm implant drills were inserted through the guide depth holes. Bone removal was made using surgical burs connecting the guiding depth holes. RESULTS: At the end of the follow-up, the patient showed acceptance of her external appearance with no signs of infection or dehiscence. CONCLUSION: This patient-specific cutting guide shows a promising solution for preplanned bone removal in cases with unilateral craniofacial FD.

'Poly phenolic phytoceutical loaded nano-bilosomes for enhanced caco-2 cell permeability and SARS-CoV 2 antiviral activity': in-vitro and insilico studies.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) predisposed to the emergence of worldwide catastrophe that impels the evolution of safe and effective therapeutic system. Polyphenols as resveratrol (RSV) exhibit a well evidenced antiviral activity. Unfortunately, like most phenolic nutraceuticals, RSV suffers from restrained solubility and massive degradation in GIT and liver which in turn prohibit its clinical use. Herein, PEGylated bilosomes (PBs) contain PEGylated edge activator along with the traditional components as (Span 60, cholesterol and bile salts) were proposed to boost both permeability and bioavailability of RSV. The investigation of the prominent effect of the diverse variables on the characteristics of the vesicles and picking of the optimum formula were conducted via construction of 23 factorial experiment. The appraisal of the formulae was conducted on the basis of entrapment efficiency percent (EE%), particle size (PS) and zeta potential (ZP). In addition, the spherical shaped optimal formula (F5) exhibited EE% of 86.1 ± 2.9%, PS of 228.9 ± 8.5 nm, and ZP of -39.8 ± 1.3 mV. The sorted optimum formula (F5) exhibited superior dissolution behaviors, and boosted Caco-2 cells cellular uptake by a round 4.7 folds relative to RSV dispersion. In addition, F5 demonstrated a complete in vitro suppression of SARS-CoV-2 at a concentration 0.48 µg/ml with 6.6 times enhancement in antiviral activity relative to RSV dispersion. The accomplished molecular modeling heavily provided proof for the possible interactions of resveratrol with the key residues of the SARS-CoV2 Mpro enzyme. Finally, F5 could be proposed as a promising oral panel of RSV for curation from SARS-CoV-2 infection.

The deleterious effect of xylene-induced ear edema in rats: Protective role of dexketoprofen trometamol transdermal invasomes via inhibiting the oxidative stress/NF-κB/COX-2 pathway.

Pain and inflammation could have a negative impact on a patient's quality of life and performance, causing them to sleep less. Dexketoprofen trometamol (DKT) is a water-soluble, nonselective NSAIDs. Because DKT is quickly eliminated in the urine after oral delivery, its efficacy is limited and must be taken repeatedly throughout the day. The main ambition of this work is to develop and characterize the potential of invasomes to enhance the transdermal transport of DKT to achieve efficient anti-inflammatory and pain management. The optimum formulation (C1) showed the least %RE (53.29 ± 2.68 %), the highest %EE (86.51 ± 1.05 %), and spherical nanosized vesicles (211.9 ± 0.57 nm) with (PDI) of 0.353 ± 0.01 and (ZP) of -19.15 ± 2.45 mV. DKT flux and deposition in stratum corneum, epidermal, and dermal skin layers were significantly augmented by 2.6 and 3.51 folds, respectively, from the optimum invasomal gel formulation (C1-G) compared to DKT conventional gel (DKT-G). The anti-inflammatory activity of C1-G was evaluated using a model of xylene-induced ear edema in rats. Xylene exposure upregulated the ear expression of COX-2 level and MPO activity. Xylene also significantly increased the ear NF-κB p65, TNF-α, IL-Iß, and MDA levels. Furthermore, xylene induced oxidative stress, as evidenced by a significant decrease in ear GSH and serum TAC levels. These impacts were drastically improved by applying C1-G compared to rats that received DKT-G and plain invasomal gel formulation (plain C1-G). The histopathological findings imparted substantiation to the biochemical and molecular investigations. Thereby, C1-G could be a promising transdermal drug delivery system to improve the anti-inflammatory and pain management of DKT.

The generalized fractional NU method for the diatomic molecules in the Deng-Fan model.

Abstract: A solution of the fractional N-dimensional radial Schrödinger equation (SE) with the Deng-Fan potential (DFP) is investigated by the generalized fractional Nikiforov-Uvarov (NU) method. The analytical formulas of energy eigenvalues and corresponding eigenfunctions for the DFP are generated. Furthermore, the current results are applied to several diatomic molecules (DMs) for the DFP as well as the shifted Deng-Fan potential (SDFP). For both the DFP and its shifted potential, the effect of the fractional parameter ( δ ) on the energy levels of various DMs is examined numerically and graphically. We found that the energy eigenvalues are gradually improved when the fractional parameter increases. The energy spectra of various DMs are also evaluated in three-dimensional space and higher dimensions. It is worthy to note that the energy spectrum raises as the number of dimensions increases. In addition, the dependence of the energy spectra of the DFP and its shifted potential on the reduced mass, screening parameter, equilibrium bond length and rotational and vibrational quantum numbers is illustrated. To validate our findings, the energy levels of the DFP and SDFP are estimated at the classical case ( δ = 1 ) for various DMs and found that they are entirely compatible with earlier studies. Graphical abstract: In this study, a new algorithm of the generalized fractional Nikiforov-Uvarov method is employed to obtain new solutions to the fractional N-dimensional radial Schrödinger equation with the Deng-Fan potential. In addition, the results are applied to several diatomic molecules. The impact of the fractional parameter on the energy levels of various diatomic molecules is investigated. We found that the energy of the diatomic molecule is more bounded at lower fractional parameter values than in the classical case.

Application of Nano-Inspired Scaffolds-Based Biopolymer Hydrogel for Bone and Periodontal Tissue Regeneration.

This review's objectives are to provide an overview of the various kinds of biopolymer hydrogels that are currently used for bone tissue and periodontal tissue regeneration, to list the advantages and disadvantages of using them, to assess how well they might be used for nanoscale fabrication and biofunctionalization, and to describe their production processes and processes for functionalization with active biomolecules. They are applied in conjunction with other materials (such as microparticles (MPs) and nanoparticles (NPs)) and other novel techniques to replicate physiological bone generation more faithfully. Enhancing the biocompatibility of hydrogels created from blends of natural and synthetic biopolymers can result in the creation of the best scaffold match to the extracellular matrix (ECM) for bone and periodontal tissue regeneration. Additionally, adding various nanoparticles can increase the scaffold hydrogel stability and provide a number of biological effects. In this review, the research study of polysaccharide hydrogel as a scaffold will be critical in creating valuable materials for effective bone tissue regeneration, with a future impact predicted in repairing bone defects.

A Novel Computational Tool for the Fractional-Order Special Functions Arising from Modeling Scientific Phenomena via Abu-Shady-Kaabar Fractional Derivative.

Recently, a generalized fractional derivative formulation, known as Abu-Shady-Kaabar fractional derivative, is studied in detail which produces satisfactory results that are consistent with conventional definitions of fractional derivative such as Caputo and Riemann-Liouville. To derive the fractional forms of special functions, the generalized fractional derivative is used. The findings demonstrate that the current findings are compatible with Caputo findings. In addition, the fractional solution to the Bessel equation is found. While modeling phenomena in engineering, physical, and health sciences, special functions can be encountered in most modeling scenarios related to electromagnetic waves, hydrodynamics, and other related models. Therefore, there is a need for a computational tool for computing special functions in the sense of fractional calculus. This tool provides a straightforward technique for some fractional-order special functions while modeling these scientific phenomena in science, medicine, and engineering.

Biochemical and molecular assessment of selenium forms for the alleviation of oxidative stress in senescent human fibroblasts.

Selenium enhances the cellular antioxidant capacity and alleviates oxidative stress. We investigated the transcriptional and enzymatic activities of selenium-dependent glutathione peroxidase 1 and thioredoxin reductase 1 (TrxR1), and levels of glutathione, hydrogen peroxide, lipid peroxides, and protein carbonyls in primary passage 5 (P5) and senescent passage 25 (P25) and 30 (P30) fibroblasts. Cells were incubated in either standard Dulbecco growth medium (CM1) containing normal plasma selenium levels (0.8 µmol/l), or in CM2, CM3, and CM4 containing 3 µmol/l (5 µmol/l for TrxR1) sodium selenite, L-hydroxyselenomethionine, or Se-methylselenocysteine, respectively. Gene transcripts and activities of both investigated enzymes as well as the levels of reduced glutathione were significantly increased in CM2-, CM3-, and CM4-incubated senescent P25 and P35 cells compared against those incubated in CM1. In congruence, although all oxidative stress parameters including oxidized glutathione were significantly lower in CM2-, CM3-, and CM4-incubated senescent cells compared against those incubated in CM1, such reductions were of significantly higher magnitude in CM3 and CM4 cells compared against those in CM2. In conclusion, organic L-hydroxyselenomethionine and Se-methylselenocysteine are equally more potent at alleviating oxidative stress in senescent cells than inorganic sodium selenite, and thus could be beneficial for use in elderly subjects and those with oxidative stress-associated disease.

Fe/Co-MOF Nanocatalysts: Greener Chemistry Approach for the Removal of Toxic Metals and Catalytic Applications.

This study describes the preparation of new bimetallic (Fe/Co)-organic framework (Bi-MOF) nanocatalysts with different percentages of iron/cobalt for their use and reuse in adsorption, antibacterial, antioxidant, and catalytic applications following the principles of green chemistry. The prepared catalysts were characterized using several techniques, including X-ray powder diffraction, Fourier transform infrared spectroscopy, transmission electron microscopy, and scanning electron microscopy. These techniques proved the formation of MOFs, and the average crystallite sizes were 25.3-53.1, 27.6-67.2, 3.0-18.9, 3.0-12.9, and 3.0-23.6 nm for the Fe-MOF, Co-MOF, 10%Fe:90%Co-MOF, 50%Fe:50%Co-MOF, and 90%Fe:10%Co-MOF samples, respectively. The nanoscale (Fe/Co) Bi-MOF catalysts as efficient heterogeneous solid catalysts showed high catalytic activity with excellent yields and short reaction times in the catalytic reactions of quinoxaline and dibenzoxanthene compounds, in addition to their antioxidant and antibacterial activities. Furthermore, the nanoscale (Fe/Co) Bi-MOF catalysts efficiently removed toxic metal pollutants (Pb2+, Hg2+, Cd2+, and Cu2+) from aqueous solutions with high adsorption capacity.

Comprehensive investigations of key mitochondrial metabolic changes in senescent human fibroblasts.

There is a paucity of detailed data related to the effect of senescence on the mitochondrial antioxidant capacity and redox state of senescent human cells. Activities of TCA cycle enzymes, respiratory chain complexes, hydrogen peroxide (H2O2), superoxide anions (SA), lipid peroxides (LPO), protein carbonyl content (PCC), thioredoxin reductase 2 (TrxR2), superoxide dismutase 2 (SOD2), glutathione peroxidase 1 (GPx1), glutathione reductase (GR), reduced glutathione (GSH), and oxidized glutathione (GSSG), along with levels of nicotinamide cofactors and ATP content were measured in young and senescent human foreskin fibroblasts. Primary and senescent cultures were biochemically identified by monitoring the augmented cellular activities of key glycolytic enzymes including phosphofructokinase, lactate dehydrogenase, and glycogen phosphorylase, and accumulation of H2O2, SA, LPO, PCC, and GSSG. Citrate synthase, aconitase, α-ketoglutarate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, isocitrate dehydrogenase, and complex I-III, IIIII, and IV activities were significantly diminished in P25 and P35 cells compared to P5 cells. This was accompanied by significant accumulation of mitochondrial H2O2, SA, LPO, and PCC, along with increased transcriptional and enzymatic activities of TrxR2, SOD2, GPx1, and GR. Notably, the GSH/GSSG ratio was significantly reduced whereas NAD+/NADH and NADP+/NADPH ratios were significantly elevated. Metabolic exhaustion was also evident in senescent cells underscored by the severely diminished ATP/ADP ratio. Profound oxidative stress may contribute, at least in part, to senescence pointing at a potential protective role of antioxidants in aging-associated disease.

Egyptian dermatologists attitude toward telemedicine amidst the COVID19 pandemic: a cross-sectional study.

BACKGROUND: Telemedicine involves distant exchange of medical information between health providers and patients via a telecommunication device with/without the aid of an audiovisual interactive assistance. The current COVID 19 pandemic impact on health services mandated an utmost readiness to implement telemedicine which in part is dependent on health care providers willingness to adopt such platforms. AIM: The aim of this cross sectional study was to assess knowledge and attitude toward telemedicine Egyptian dermatologists amidst the COVID 19 pandemic. PATIENTS AND METHODS: A cross sectional study was designed and data were collected using structured self-administered online questionnaires. RESULTS: Dermatologists had a good knowledge about telemedicine (mean 4.17 ± 1.63; p < .05). Of those completing the questionnaire, 193 (68.9%) were familiar with the term 'telemedicine' and 164 (58.6%) were familiar with tools like teleconferencing. The majority of responding dermatologists 227 (81.1%) were confident that the COVID 19 pandemic is a good opportunity to start applying telemedicine protocols however the majority 234 (83.6%) preferred using it on trial basis at first before full implementation. CONCLUSION: In conclusion an overall good attitude toward telemedicine was reported with a mean of 3.39 (p < .05). Further large scale studies are required to verify such findings.

Comprehensive investigations of key mitochondrial metabolic changes in senescent human fibroblasts

There is a paucity of detailed data related to the effect of senescence on the mitochondrial antioxidant capacity and redox state of senescent human cells.Activities of TCA cycle enzymes, respiratory chain complexes, hydrogen peroxide (H 2 O 2 ), superoxide anions (SA), lipid peroxides (LPO), protein carbonyl content (PCC), thioredoxin reductase 2 (TrxR2), superoxide dismutase 2 (SOD2), glutathione peroxidase 1 (GPx1), glutathione reductase (GR), reduced glutathione (GSH), and oxidized glutathione (GSSG), along with levels of nicotinamide cofactors and ATP content were measured in young and senescent human foreskin fibroblasts. Primary and senescent cultures were biochemically identified by monitoring the augmented cellular activities of key glycolytic enzymes including phosphofructokinase, lactate dehydrogenase, and glycogen phosphorylase, and accumulation of H2O2 , SA, LPO, PCC, and GSSG. Citrate synthase, aconitase, α-ketoglutarate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, isocitrate dehydrogenase, and complex I-III, IIIII, and IV activities were significantly diminished in P25 and P35 cells compared to P5 cells. This was accompanied by significant accumulation of mitochondrial H2O2 , SA, LPO, and PCC, along with increased transcriptional and enzymatic activities of TrxR2, SOD2, GPx1, and GR. Notably, the GSH/GSSG ratio was significantly reduced whereas NAD+ /NADH and NADP+ /NADPH ratios were significantly elevated. Metabolic exhaustion was also evident in senescent cells underscored by the severely diminished ATP/ ADP ratio. Profound oxidative stress may contribute, at least in part, to senescence pointing at a potential protective role of antioxidants in aging-associated disease.

The Potential Synergistic Activity of Zolmitriptan Combined in New Self-Nanoemulsifying Drug Delivery Systems: ATR-FTIR Real-Time Fast Dissolution Monitoring and Pharmacodynamic Assessment.

PURPOSE: The current work aimed to overcome the poor permeability and undesirable adverse effects of Zolmitriptan (ZMT) and to increase its efficacy in the treatment of acute migraine by exploiting the synergistic effect of the essential oil, lavender, to fabricate ZMT self-nanoemulsifying drug delivery systems (ZMT-SNEDDS). METHODS: ZMT-SNEDDS were fabricated based on full factorial design (32) to statistically assess the impact of oil and surfactant concentrations on the nanoemulsion globule size, zeta potential and percentage drug dissolution efficiency. An ATR-FTIR method was developed and validated for continuous real-time monitoring of ZMT dissolution and permeation. The dose of the optimized ZMT-SNEDDS used in the efficacy study was selected according to the acute toxicity study. The efficacy study was performed on migraineous rats induced by nitroglycerin and was evaluated by the activity cage and thermal tests, electroencephalogram, electroconvulsive stimulation, and biochemical analysis of brain tissue. Finally, histopathological and immunohistochemical examinations of the cerebra were carried out. RESULTS: Upon dilution, the optimized ZMT-SNEDDS (F5) exhibited nanosized spherical droplets of 19.59±0.17 nm with narrow size distribution, zeta potential (-23.5±1.17mV) and rapid emulsification characteristics. ATR-FTIR spectra elucidated the complete time course of dissolution and permeation, confirming F5 superior performance. Moreover, ZMT-SNEDDS (F5) showed safety in an acute toxicity study. ZMT concentration in rat brain tissues derived from F5 was lower compared to that of ZMT solution, yet its effect was better on the psychological state, algesia, as well as maintaining normal brain electrical activity and delayed convulsions. It counteracted the cerebral biochemical alternations induced by nitroglycerin, which was confirmed by histopathological examination. CONCLUSION: In a nutshell, these findings corroborated the remarkable synergistic efficacy and the high potency of lavender oil-based ZMT-SNEDDS in migraine management compared to the traditional zolmitriptan solution.

Efficacy and Safety of Topical Silymarin Versus Low Fluence 1064-nm Q Switched Nd:YAG Laser in the Treatment of Melasma: A Comparative Randomized Trial.

BACKGROUND AND OBJECTIVES: The management of melasma is challenging and requires multiple uses of available therapeutic options. To compare the short-term efficacy and safety of topical silymarin and low fluence 1064-nm Q-switched ND:YAG laser for treatment of melasma with dermoscopic follow-up. STUDY DESIGN/MATERIALS AND METHODS: Fifty female patients with melasma were included in this study. They were randomly divided into two groups. Group A: 25 patients were treated with six sessions of low fluence Q switched ND:YAG 1064-nm laser, and group B: 25 patients were treated with topical silymarin cream 1.4% with a 3-month treatment duration. Patients were evaluated clinically by the modified melasma area and severity index (mMASI) score. Dermoscopic examinations were performed before and after the treatment sessions. RESULTS: The severity of melasma, as evaluated dermoscopically and clinically by mMASI score, was significantly reduced after treatment in all patients with no recorded side effects. There was no statistically significant difference between both studied groups regarding the change in mMASI score and dermoscopic assessment of the patients after the treatment sessions. CONCLUSION: Both low fluence Q switched ND:YAG 1064-nm laser and topical silymarin cream appear to be safe and effective modalities in the treatment of melasma. © 2021 Wiley Periodicals LLC.