Correction: Ammar et al. Protective Effects of Naringenin from Citrus sinensis (var. Valencia) Peels against CCl4-Induced Hepatic and Renal Injuries in Rats Assessed by Metabolomics, Histological and Biochemical Analyses. Nutrients 2022, 14, 841.

In the original publication [...].

Metabolomics approach of Symphyotrichum squamatum ethanol extract and its nano-Ag formulation protective effect on gastric ulcer via bio-chemical and pathological analyses.

ContextGastric ulcer (GU) a widely distributed ailment is associated with many causes, including alcohol consumption.Materials and MethodsChemical profiling of Symphyotrichum squamatum ethanol extract (SSEE) was established via ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-qTOF-MS) and employed in a silver nano-formulation (SSEE-N-Ag). SSEE and SSEE-N-Ag antiulcer activities were estimated against ethanol-induced rats by biochemical, histological, and metabolomics assessments. Reduced glutathione, total antioxidant capacity and prostaglandin E2 levels and gastric mucosa histopathological examination were analysed. The rats' metabolome changing alongside action pathways were elucidated via metabolite profile coupled to multivariate data analysis.ResultsUPLC-MS profiling of SSEE identified 75 components belonging to various classes. Compared with control, EtOH-treated rats showed decreased of tissue GSH, TAC and PGE2 by 62.32%, 51.85% and 47.03% respectively. SSEE and SSEE-N-Ag administration mitigated biochemical and histopathological alterations. Serum metabolomics analysis revealed for changes in several low molecular weight metabolites with ulcer development. These metabolites levels were restored to normal post-administration of SSEE-N-Ag. SSEE-N-Ag as mediated via modulating numerous metabolic pathways such as lipids, pyrimidine, energy metabolism and phosphatidylinositol signalling. This study provides novel insight for metabolic mechanisms underlying gastric ulcer relieving effect.ConclusionPresent results revealed potential antiulcer effect of SSEE and SSEE-N-Ag by decreasing ulcer-associated syndromes, supporting their anti-ulcerogenic action.

Chemical Profile of Cyperus laevigatus and Its Protective Effects against Thioacetamide-Induced Hepatorenal Toxicity in Rats.

Cyperus species represent a group of cosmopolitan plants used in folk medicine to treat several diseases. In the current study, the phytochemical profile of Cyperus laevigatus ethanolic extract (CLEE) was assessed using UPLC-QTOF-MS/MS. The protective effect of CLEE at 50 and 100 mg /kg body weight (b.w.) was evaluated on hepatorenal injuries induced by thioacetamide (100 mg/kg) via investigation of the extract's effects on oxidative stress, inflammatory markers and histopathological changes in the liver and kidney. UPLC-QTOF-MS/MS analysis of CLEE resulted in the identification of 94 compounds, including organic and phenolic acids, flavones, aurones, and fatty acids. CLEE improved the antioxidant status in the liver and kidney, as manifested by enhancement of reduced glutathione (GSH) and coenzyme Q10 (CoQ10), in addition to the reduction in malondialdehyde (MDA), nitric oxide (NO), and 8-hydroxy-2'-deoxyguanosine (8OHdG). Moreover, CLEE positively affected oxidative stress parameters in plasma and thwarted the depletion of hepatorenal ATP content by thioacetamide (TAA). Furthermore, treatment of rats with CLEE alleviated the significant increase in plasma liver enzymes, kidney function parameters, and inflammatory markers. The protective effect of CLEE was confirmed by a histopathological study of the liver and kidney. Our results proposed that CLEE may reduce TAA-hepatorenal toxicity via its antioxidant and anti-inflammatory properties suppressing oxidative stress.

Eicosapentaenoic acid loaded silica nanoemulsion attenuates hepatic inflammation through the enhancement of cell membrane components.

BACKGROUND: Liver inflammation is a multistep process that is linked with cell membrane fatty acids composition. The effectiveness of eicosapentaenoic acid (EPA) undergoes an irreversible change during processing due to their unsaturated nature; so the formation of nanocarrier for EPA is crucial for improving EPA's bioavailability and pharmacological properties. OBJECTIVE: In this study we aimed to evaluate the efficiency of EPA alone or loaded silica nanoemulsion on the management of hepatic inflammation induced by diethyl nitrosamine (DEN) through the enhancement of the cell membrane structure and functions. METHODS: The new formula of EPA was prepared to modify the properties of EPA. Forty-eight male Wistar albino rats were classified into: control, EPA, EPA loaded silica nanoemulsion (EPA-NE), DEN induced hepatic inflammation; DEN induced hepatic inflammation treated with EPA or EPA -NE groups. Plasma tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1ß), liver hydroxyproline (Hyp) content, and liver oxidant and anti-oxidants were estimated. Urinary 8- hydroxyguanozine (8- OHdG) and erythrocyte membrane fatty acids fractions were estimated by High-performance liquid chromatography (HPLC). Also, histopathology studies were done to verify our hypothesis. RESULTS: It was appeared that administration of EPA, in particular EPA loaded silica nanoemulsion, ameliorated the inflammatory response, increased the activity of the anti-oxidants, reduced levels of oxidants, and improved cell membrane structure compared to hepatic inflammation induced by DEN group. Histopathological examination confirmed these results. CONCLUSION: EPA and notably EPA loaded silica nanoemulsion strongly recommended as a promising supplement in the management of hepatic inflammation.

Osteogenic enhancement of modular ceramic nanocomposites impregnated with human dental pulp stem cells: an approach for bone repair and regenerative medicine.

BACKGROUND/AIM: Human dental pulp-derived mesenchymal stem cells (hDP-MSCs) are a promising source of progenitor cells for bone tissue engineering. Nanocomposites made of calcium phosphate especially hydroxyapatite (HA) offer an impressive solution for orthopedic and dental implants. The combination of hDP-MSCs and ceramic nanocomposites has a promising therapeutic potential in regenerative medicine. Despite the calcium phosphate hydroxyapatite (HA)-based nanocomposites offer a good solution for orthopedic and dental implants, the heavy load-bearing clinical applications require higher mechanical strength, which is not of the HA' properties that have low mechanical strength. Herein, the outcomes of using fabricated ceramic nanocomposites of hydroxyapatite/titania/calcium silicate mixed at different ratios (C1, C2, and C3) and impregnated with hDP-MSCs both in in vitro cultures and rabbit model of induced tibial bone defect were investigated. Our aim is to find out a new approach that would largely enhance the osteogenic differentiation of hDP-MSCs and has a therapeutic potential in bone regeneration. SUBJECTS AND METHODS: Human DP-MSCs were isolated from the dental pulp of the third molar and cultured in vitro. Alizarin Red staining was performed at different time points to assess the osteogenic differentiation. Flow cytometer was used to quantify the expression of hDP-MSCs unique surface markers. Rabbits were used as animal models to evaluate the therapeutic potential of osteogenically differentiated hDP-MSCs impregnated with ceramic nanocomposites of hydroxyapatite/tatiana/calcium silicate (C1, C2, and C3). Histopathological examination and scanning electron microscopy (SEM) were performed to evaluate bone healing potential in the rabbit induced tibial defects three weeks post-transplantation. RESULTS: The hDP-MSCs showed high proliferative and osteogenic potential in vitro culture. Their osteogenic differentiation was accelerated by the ceramic nanocomposites' scaffold and revealed bone defect's healing in transplanted rabbit groups compared to control groups. Histopathological and SEM analysis of the transplanted hDP-MSCs/ceramic nanocomposites showed the formation of new bone filling in the defect area 3 weeks post-implantation. Accelerate osseointegration and enhancement of the bone-bonding ability of the prepared nanocomposites were also confirmed by SEM. CONCLUSIONS: The results strongly suggested that ceramic nanocomposites of hydroxyapatite/ titania /calcium silicate (C1, C2, and C3) associated with hDP-MSCs have a therapeutic potential in bone healing in a rabbit model. Hence, the combined osteogenic system presented here is recommended for application in bone tissue engineering and regenerative medicine.

Renoprotective and Cardioprotective Potential of Moricandia sinaica (Boiss.) against Carbon Tetrachloride-Induced Toxicity in Rats.

The goal of the current study was to assess the nephroprotective and cardioprotective potential of Moricandia sinaica methanol extract (MOR-1), as well as its butanol (MOR-2) and aqueous (MOR-3) fractions against carbon tetrachloride (CCl4)-induced nephro and cardio-toxicity. Cardiac function was assessed using the biochemical parameters lactate dehydrogenase (LDH) and creatinine kinase (CK). Renal function was examined using the biochemical parameters creatinine and uric acid. The levels of nonprotein sulfhydryls (NPSH) and malondialdehyde (MDA) were used as markers of oxidative strain. A dose of 100 and 200 mg/kg of butanol fraction given prior to CCl4 treatment significantly (p < 0.05 - 0.001) protected against elevated LDH and CK levels. Similarly, treatment with silymarin (10 mg/kg) and butanol fraction (100 and 200 mg/kg) significantly (p < 0.05 - 0.001) boosted total protein levels compared to CCl4 treatment alone. The silymarin (10 mg/kg) and butanol fraction (100 and 200 mg/kg) also provided a significant (p < 0.05 - 0.001) protective effect for MDA levels. Methanol extract (MOR-1) and butanol (MOR-2) showed significant results and were recommended for further pharmacological and screening for active constituents.

Cytoprotective potentialities of carvacrol and its nanoemulsion against cisplatin-induced nephrotoxicity in rats: development of nano-encasulation form.

Cisplatin (Cisp) is a widely distributed chemotherapeutic drug for cancers. Nephrotoxicity is one of the most common side effects of the use of this drug. Carvacrol (CV) is a common natural compound in essential oils and extracts of medicinal plants with potent in vivo and in vitro bioactivities. The work was extended to achieve the target of investigation of the protective potentialities of CV and its nanoemulsion as a cytoprotective drug against Cisp-induced nephrotoxicity in albino rats. CV-nanoemulsion was prepared by a hydrophilic surfactant polysorbate 80 (Tween 80) and deionized water. The TEM image of the particle distribution prepared nanoemulsion is mainly spherical in shape with particle size varying between 14 and 30 nm. Additionally, the Cisp administration caused the increasing of the levels of urea and creatinine in the blood and serum. These increasing of urea and creatinine levels caused consequently the turbulence of the oxidative stress as well as the rising of hs-CRP, IL-6, and TNF-α levels in the serum. Also, histopathological changes of the kidney tissue were observed. These changes back to normal by treatment with CV-nanoemulsion. Expression levels of nephrotoxicity-related genes including LGALS3, VEGF, and CAV1 in kidney tissue using qRT-PCR were measured. The results revealed that the expression of LGALS3, VEGF and CAV1 genes was highly significantly increased in only Cisp treated group when compared with other treated groups. While, these genes expressions were significantly decreased in Cisp + CV treated group when compared with Cisp treated rats (P < 0.001). In addition, there were no significant differences between Cisp + nano-CV treated group and both negative control and nanoemulsion alone groups but it was not significant. In addition, the Western blot of protein analysis results showed that the LGALS3 and CAV1 are highly expressed only in Cisp + CV treated group compared with other groups. There was no significant difference between Cisp + nano-CV treated animals and negative control for both mRNA and protein expression. Based on these results, CV was combined with calcium alginate; a more stable capsule is formed, allowing for the formation of a double wall in the microcapsule. These results supported the therapeutic effect of CV and its nano-emulsion as cytoprotective agents against Cisp nephrotoxicity.

Protective Effects of Naringenin from Citrus sinensis (var. Valencia) Peels against CCl4-Induced Hepatic and Renal Injuries in Rats Assessed by Metabolomics, Histological and Biochemical Analyses.

Citrus fruits are grown worldwide for their special nutritive and several health benefits. Among citrus bioactives, naringenin, a major flavanone, exhibits a potential hepatoprotective effect that is not fully elucidated. Herein, serum biochemical parameters and histopathological assays were used to estimate the hepatoprotective activity of naringenin, isolated from Citrus sinensis (var. Valencia) peels, in CCl4-induced injury in a rat model. Further, GC-MS-based untargeted metabolomics was used to characterize the potential metabolite biomarkers associated with its activity. Present results revealed that naringenin could ameliorate the increases in liver enzymes (ALT and AST) induced by CCl4 and attenuate the pathological changes in liver tissue. Naringenin decreased urea, creatinine and uric acid levels and improved the kidney tissue architecture, suggesting its role in treating renal disorders. In addition, naringenin increased the expression of the antiapoptoic cell marker, Bcl-2. Significant changes in serum metabolic profiling were noticed in the naringenin-treated group compared to the CCl4 group, exemplified by increases in palmitic acid, stearic acid, myristic acid and lauric acids and decrease levels of alanine, tryptophan, lactic acid, glucosamine and glucose in CCl4 model rats. The results suggested that naringenin's potential hepato- and renoprotective effects could be related to its ability to regulate fatty acids (FAs), amino acids and energy metabolism, which may become effective targets for liver and kidney toxicity management. In conclusion, the current study presents new insights into the hepato- and renoprotective mechanisms of naringenin against CCl4-induced toxicity.

Gastro-protective effect of Artemisia Sieberi essential oil against ethanol-induced ulcer in rats as revealed via biochemical, histopathological and metabolomics analysis.

CONTEXT: Gastric ulcer is regarded as one of the main clinical ailments with high morbidity and mortality rates. MATERIALS AND METHODS: Gastro-protective effect of Artemisia sieberi essential oil (AS-EO) in ethanol-induced rats was evaluated via biochemical, histopathological and large-scale metabolomics analyses. Glutathione (GSH), total antioxidant capacity (TAC), prostaglandin (PGE2) and tumour necrosis factor α (TNF-α) alongside with histopathological examination of gastric mucosa were analysed. Metabolites profiling coupled to Global Natural Products Social molecular networking platform (GNPS) and multivariate data analyses to reveal for changes in rats metabolome with treatments and involved action mechanisms. RESULTS: Pre-treatment with 100 and 200 mg/kg of AS-EO in EtOH-treated rats restored all parameters towards normal status compared to disease model. AS-EO alleviated the histological and pathological damage of gastric tissue caused by ethanol. Metabolites profiling revealed an increase in uracil, cholesterol and fatty acids/fatty acyl amides levels in ulcer rats and restored to normal levels post AS-EO intervention. These results indicated the efficacy of AS-EO in a dose-dependent manner, and to exert protective effects in ulcer rat model by targeting several metabolic pathways viz. lipid, energy, and nucleotide metabolisms. CONCLUSION: AS-EO adds to the known uses of genus Artemisia as anti-ulcerogenic agent by attenuating oxidative stress and inflammatory responses associated with an ulcer. Several novel biomarkers for ulcer progression in rats were identified and have yet to be confirmed in human models.

1,8 Cineole and Ellagic acid inhibit hepatocarcinogenesis via upregulation of MiR-122 and suppression of TGF-ß1, FSCN1, Vimentin, VEGF, and MMP-9.

Hepatocellular carcinoma (HCC) is one of the most burdened tumors worldwide, with a complex and multifactorial pathogenesis. Current treatment approaches involve different molecular targets. Phytochemicals have shown considerable promise in the prevention and treatment of HCC. We investigated the efficacy of two natural components, 1,8 cineole (Cin) and ellagic acid (EA), against diethylnitrosamine/2-acetylaminofluorene (DEN/2-AAF) induced HCC in rats. DEN/2-AAF showed deterioration of hepatic cells with an impaired functional capacity of the liver. In addition, the levels of tumor markers including alpha-fetoprotein, arginase-1, alpha-L-fucosidase, and ferritin were significantly increased, whereas the hepatic miR-122 level was significantly decreased in induced-HCC rats. Interestingly, treatment with Cin (100mg/kg) and EA (60mg/kg) powerfully restored these biochemical alterations. Moreover, Cin and EA treatment exhibited significant downregulation in transforming growth factor beta-1 (TGF-ß1), Fascin-1 (FSCN1), vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), and epithelial-mesenchymal transition (EMT) key marker, vimentin, along with a restoration of histopathological findings compared to HCC group. Such effects were comparable to Doxorubicin (DOX) (2mg/kg); however, a little additive effect was evident through combining these phytochemicals with DOX. Altogether, this study highlighted 1,8 cineole and ellagic acid for the first time as promising phytochemicals for the treatment of hepatocarcinogenesis via regulating multiple targets.

Hepatoprotective effect of Raspberry ketone and white tea against acrylamide-induced toxicity in rats.

The current investigation was accomplished to evaluate the hepatoprotective effect of White tea and Raspberry Ketone against toxicity induced by acrylamide in rats. Sixty adult male rats were divided randomly into group (I) control; group (II) rats received RK with dose (6 mg/kg/day); Group III: rats received 5 ml of WT extract/kg/day; Group IV rats received AA (5 mg/kg/day); Group V: rats administrated with both AA (5 mg/kg/day) and RK (6 mg/kg/day) and Group VI: rats administrated AA (5 mg/kg/day) and 5 ml of WT extract/kg/day. The biochemical assays exhibited a significant increase in serum levels of Adiponectin, AST, ALT, ALP of the group treated with acrylamide if compared to the control group and an improvement in their levels of groups V and VI. The histopathological and immunohistochemical findings confirm the biochemical observations. In conclusion, the present investigation proved that the supplementation of WT and RK enhanced the liver histology, immunohistochemistry and biochemistry against the oxidative stress induced by acrylamide.

Gastroprotection against Rat Ulcers by Nephthea Sterol Derivative.

Different species belonging to the genus Nephthea (Acyonaceae) are a rich resource for bioactive secondary metabolites. The literature reveals that the gastroprotective effects of marine secondary metabolites have not been comprehensively studied in vivo. Hence, the present investigation aimed to examine and determine the anti-ulcer activity of 4α,24-dimethyl-5α-cholest-8ß,18-dihydroxy,22E-en-3ß-ol (ST-1) isolated from samples of a Nephthea species. This in vivo study was supported by in silico molecular docking and protein-protein interaction techniques. Oral administration of ST-1 reduced rat stomach ulcers with a concurrent increase in gastric mucosa. Molecular docking calculations against the H+/K+-ATPase transporter showed a higher binding affinity of ST-1, with a docking score value of -9.9 kcal/mol and a pKi value of 59.7 nM, compared to ranitidine (a commercial proton pump inhibitor, which gave values of -6.2 kcal/mol and 27.9 µM, respectively). The combined PEA-reactome analysis results revealed promising evidence of ST-1 potency as an anti-ulcer compound through significant modulation of the gene set controlling the PI3K signaling pathway, which subsequently plays a crucial role in signaling regarding epithelialization and tissue regeneration, tissue repairing and tissue remodeling. These results indicate a probable protective role for ST-1 against ethanol-induced gastric ulcers.

Renoprotective and therapeutic effects of newly water, ethanol, and butanol ginseng fractions in hypertensive and chronic kidney disease with L-NAME.

The present study investigated the protective and treatment effects of different ginseng fractions against L-NAME-induced renal toxicity in rats. The data obtained demonstrated that L-NAME significantly increased creatinine, urea, KIM-1, and lipocalin-2 levels in serum; and also increased renal MDA and eNOS levels compared with the control group. Three bioactive fractions were newly extracted from ginseng, analyzed by GC-MS analysis, and were examined for antimicrobial, prebiotic, and histological activities. All ginseng fractions improved such histological changes, as reflected by significant reductions in creatinine, urea, KIM-1, and LCN-2 levels in serum, and renal MDA and eNOS contents in tissue homogenate. The water ginseng fraction (WGF) has the highest prebiotic index of 4.7 toward Lactobacillus reuteri, and can improve the renal functions more than butanol ginseng fraction (BGF) and ethanol ginseng fraction (EGF). These three ginseng fractions significantly reversed L-NAME-induced depletion in the TNF-α gene expression level. Interestingly, WGF was able to improve the renal functions more than BGF and EGF. L-NAME led to alterations in the histological structure and functions of renal tissue of rats and ginseng supplementation could offer greater protection against these changes. Moreover, the WGF exhibited superior renoprotection properties when compared with the other two fractions: BGF and EGF, and the reference drug losartan.

Shoot aqueous extract of Manihot esculenta Crantz (cassava) acts as a protective agent against paracetamol-induced liver injury.

Manihot esculenta Crantz (Euphorbiaceae), known as cassava, is a widely cultivated plant, considered one of the main sources of food in the tropical and subtropical regions of Africa and Asia. The aim of the present study was the evaluation of the antioxidant and anti-inflammatory effects of cassava shoot aqueous extract (CSAE) on liver injury induced by paracetamol and investigation of its effect on hyperhomocysteinemia. CSAE was administered to male albino rats classified into seven groups: control, treated, and prophylactic groups. A significant reduction in liver enzymes, malondialdehyde, and homocysteine were observed when compared to the paracetamol group, together with an increase in paraoxonase-1. Histopathological and histochemical results indicated that CSAE effectively ameliorate these parameters. Two main flavonol glycosides, quercetin 3-O-rutinoside and kaempferol 3-O-rutinoside, in addition to a minor myricetin 3-O-rutinoside, were identified in CSAE. CSAE showed a therapeutic potential against paracetamol-induced liver injury probably through antioxidant activity of its flavonol glycosides.

Functional yogurt aims to protect against the aflatoxin B1 toxicity in rats.

Recently, the rise of mycotoxin contamination in food materials was found to be due to several factors, including climatic changes' impact. Therefore, the aim of this study was to provide a novel food product that allows the reduction of aflatoxin impact in animal tissues. Chicory root-extract (CRE) was evaluated for its active components, antioxidant potency, and antimicrobial activity. The CRE was utilized to produce functional yogurt (FY) that was evaluated in-vivo using experimental rats. The CRE showed high antioxidant activity and recorded valuable content of the active components. Results also showed a high antimicrobial effect against toxigenic fungal strains. The results have reflected the efficiency of the FY to suppress aflatoxin impacts in the animal tissues and biochemical parameters of rats-serum. An enhancement was recorded inliver and kidney functions for rats taking FY with the presence of aflatoxin. It was concluded that consumption of the FY assisted in suppression of the oxidative stress in rats-tissues.

Topical Wound Healing Activity of Myricetin Isolated from Tecomaria capensis v. aurea.

Wounds and burn injury are major causes of death and disability worldwide. Myricetin is a common bioactive flavonoid isolated naturally from the plant kingdom. Herein, a topical application of naturally isolated myricetin from the shoots of Tecomaria capensis v. aurea on excisional wound healing that was performed in albino rats. The wounded rats were treated every day with 10 and 20% myricetin for 14 days. During the experiment, the wound closure percentage was estimated at days 0, 7, and 14. Effects of myricetin on the inflammatory cytokines (tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and cluster of differentiation 68 (CD68) in the serum were evaluated using immunosorbent assay kits. The percentage of wound closure and contraction was delayed in wounded rats (67.35%) and was remarkably increased after treatment of wounded rats with myricetin; the treatment with 20% myricetin was the most potent (98.76%). Histological findings exhibited that 10% myricetin caused the formation of a large area of scarring at the wound enclosure and stratified squamous epithelium without the formation of papillae as in the control group. Treatment with 20% myricetin exhibited less area of scarring at the wound enclosure as well as re-epithelialization with a high density of fibroblasts and blood capillaries in the wound. Level elevations of serum pro-inflammatory cytokines, IL-1ß, and TNF-α and macrophage CD68 were decreased in wounded rats treated with myricetin. Thus, it can be suggested that the enhancements in inflammatory cytokines as well as systemic reorganization after myricetin treatment may be recommended to play a crucial part in the promotion of wound healing. The findings suggest that treatment with a higher dose of myricetin was better in improving wound curing in rats. It could serve as a potent anti-inflammatory agent and can be used as an adjunctive or alternative agent in the future.

UPLC-qTOF-MS Phytochemical Profile and Antiulcer Potential of Cyperus conglomeratus Rottb. Alcoholic Extract.

Cyperus has been commonly used as a multi-use medicinal plant in folk medicine worldwide. The objectives of our study were to determine the different metabolites in the Cyperus conglomeratus Rottb. methanol extract, and to assess its in vivo gastroprotective effect in ethanol-induced gastric ulcer model in rats. Serum levels of galactin-3 and TNF-α were employed as biochemical markers. To pinpoint for active agents, comprehensive metabolites profiling of extract via UPLC-qTOF-MS/MS was employed. A total of 77 chromatographic peaks were detected, of which 70 were annotated. The detected metabolites were categorized into phenolic acids and their derivatives, flavonoids, stilbenes, aurones, quinones, terpenes, and steroids. Rats were divided into six groups; healthy control, ulcer control, standard drug group, and 25, 50, 100 mg/kg of C. conglomeratus treated rats. Pre-treatment with C. conglomeratus alcohol extract significantly reduced galactin-3, and TNF-α in ethanol-induced ulcer model at 25, 50, and 100 mg/kg. Further histopathological and histochemical studies revealed moderate erosion of superficial epithelium, few infiltrated inflammatory cells, and depletion of gastric tissue glycoprotein in the ulcer group. Treatment with the extract protected the gastric epithelial cells in a dose-dependent manner. It could be concluded that C. conglomeratus extract provides significant gastroprotective activity in ethanol-induced gastric ulcer and ought to be included in nutraceuticals in the future for ulcer treatment.

ATR-IR and EPR spectroscopy for following the membrane restoration of isolated cortical synaptosomes in aluminium-induced Alzheimer's disease - Like rat model.

Synaptosomal membrane peroxidation and alteration in its biophysical properties are associated with Aluminium (Al) toxicity that may lead to cognitive dysfunction and Alzheimer's disease (AD) like pathogenesis. Here we investigated the therapeutic potential of Lepedium sativum (LS) as a natural anti-inflammatory, antioxidant and as acetyl cholinesterase inhibitor in treating Al induced AD-like in rat model. We utilized ATR-IR spectroscopy to follow the restoration in the damaged membrane structure of isolated rat cortical synaptosomes and its biophysical properties, electron paramagnetic resonance (EPR) spin trapping to follow NADPH oxidase activity (NOX), and EPR spin labelling in response to LS treatment after Al intoxication. We measured the concentration of Ca2+ ions in rat cortical tissue by inductively coupled plasma (ICP), the brain atrophy/curing and hydrocephalus by magnetic resonance imaging (MRI) besides light microscope histopathology. Our results revealed significant increase in synaptosomal membrane rgidification, order, lipid packing, reactive oxygen species (ROS) production and Ca2+ ion concentration as a result of Al intoxication. The dramatic increase in Ca2+ ion concentration detected in AD group associated with the increase in synaptic membrane polarity and EPR-detected order S-parameter suggest that release of synaptic vesicles into synaptic cleft might be hindered. LS treatment reversed these changes in synaptic membranes, and rescued an observed deficit in the exploratory behaviour of AD group. Our results also strongly suggest that the synaptosomal membrane phospholipids that underwent free radical attacks mediated by AlCl3, due to greater NOX activity, was prevented in the LS group. The results of ATR-IR and EPR spectroscopic techniques recommend LS as a promising therapeutic agent against synaptic membrane alterations opening a new window for AD drug developers.

The Effect of the Fractional Carbon Dioxide Laser on Improving Minoxidil Delivery for the Treatment of Androgenetic Alopecia.

Introduction: Recently, laser treatment for hair loss has become very popular. Laser-assisted drug delivery (LAD) is an evolving technology with potentially broad clinical applications. This work aims at inspecting the effect of the fractional carbon dioxide laser (CO2 ) on improving the delivery of minoxidil in patients with androgenetic alopecia and detecting the role of the fractional CO2 laser in its treatment. Methods: We enrolled 45 Egyptians with male androgenetic alopecia (MAGA); clinical grading was assessed based on Norwood-Hamilton classification. The patients were divided into 3 groups: the first group (combined group) received the fractional CO2 laser session followed by topical application of minoxidil and also in between sessions; the second group received fractional CO2 laser sessions only and 6 sessions with 2-week intervals were performed; the third group applied topical minoxidil only for 3 months. Global photographs and dermoscopic assessments were performed before treatment and 3 months after the treatment. Results: Several dermoscopic findings were detected, including peripilar sign, hair diversity, yellow spot, white dots, and arborizing red lines. The number of double hair units significantly increased after the treatment in the combined group. The mean number of hair after the treatment in the 3 groups significantly increased, mostly in the combined group. The hair thickness (thin & thick) significantly increased after the treatment in the combined group and the fractional group; however, in the minoxidil group, only thin hair thickness increased. In all the 3 groups, there was a significant improvement in hair count and thickness. Conclusion: The ablative fractional CO2 laser alone or combined with minoxidil may serve as an additional treatment for MAGA.

Combination of Human Amniotic Fluid Derived-Mesenchymal Stem Cells and Nano-hydroxyapatite Scaffold Enhances Bone Regeneration.

BACKGROUND: Human amniotic fluid-derived stem cells (hAF-MSCs) have a high proliferative capacity and osteogenic differentiation potential in vitro. The combination of hAF-MSCs with three-dimensional (3D) scaffold has a promising therapeutic potential in bone tissue engineering and regenerative medicine. Selection of an appropriate scaffold material has a crucial role in a cell supporting and osteoinductivity to induce new bone formation in vivo. AIM: This study aimed to investigate and evaluate the osteogenic potential of the 2nd-trimester hAF-MSCs in combination with the 3D scaffold, 30% Nano-hydroxyapatite chitosan, as a therapeutic application for bone healing in the induced tibia defect in the rabbit. SUBJECT AND METHODS: hAF-MSCs proliferation and culture expansion was done in vitro, and osteogenic differentiation characterisation was performed by Alizarin Red staining after 14 & 28 days. Expression of the surface markers of hAF-MSCs was assessed using Flow Cytometer with the following fluorescein-labelled antibodies: CD34-PE, CD73-APC, CD90-FITC, and HLA-DR-FITC. Ten rabbits were used as an animal model with an induced defect in the tibia to evaluate the therapeutic potential of osteogenic differentiation of hAF-MSCs seeded on 3D scaffold, 30% Nano-hydroxyapatite chitosan. The osteogenic differentiated hAF-MSCs/scaffold composite system applied and fitted in the defect region and non-seeded scaffold was used as control. The histopathological investigation was performed at 2, 3, & 4 weeks post-transplantation and scanning electron microscope (SEM) was assessed at 2 & 4 weeks post-transplantation to evaluate the bone healing potential in the rabbit tibia defect. RESULTS: Culture and expansion of 2nd-trimester hAF-MSCs presented high proliferative and osteogenic potential in vitro. Histopathological examination for the transplanted hAF-MSCs seeded on the 3D scaffold, 30% Nano-hydroxyapatite chitosan, demonstrated new bone formation in the defect site at 2 & 3 weeks post-transplantation as compared to the control (non-seeded scaffold). Interestingly, the scaffold accelerated the osteogenic differentiation of AF-MSCs and showed complete bone healing of the defect site as compared to the control (non-seeded scaffold) at 4 weeks post-transplantation. Furthermore, the SEM analysis confirmed these findings. CONCLUSION: The combination of the 2nd-trimester hAF-MSCs and 3D scaffold, 30% Nano-hydroxyapatite chitosan, have a therapeutic perspective for large bone defect and could be used effectively in bone tissue engineering and regenerative medicine.