Lateral Abdominal Wall Hematoma Mimicking Aortic Dissection Presentation: A Case Report.

Lateral abdominal wall hematoma is a rare clinical entity but a great mimicker of other diseases' clinical presentations. In this case report, we present a 42-year-old male patient with a constellation of signs and symptoms that were mistaken for aortic dissection before the lateral abdominal wall hematoma diagnosis was confirmed with computed tomography (CT) imaging. Uncontrolled hypertension and persistent cough were most likely predisposing factors; the patient was managed conservatively and discharged in a stable condition.

Green synthesis of zinc oxide nanoparticles using ethanolic extract of Gliricidia sepium (Jacq.) kunth. Ex. Walp., stem: Characterizations and their gastroprotective effect on ethanol-induced gastritis in rats.

The study presents a significant advancement in drug delivery and therapeutic efficacy through the successful synthesis of Gliricidia sepium(Jacq.) Kunth. ex. Walp., stem zinc oxide nanoparticles(GSS ZnONPs). The phenolic compounds present in Gliricidia sepium stem (GSS) particularly vanillic acid, apegnin-7-O-glucoside, syringic acid, and p-coumaric acid which were identified by HPLC. These compounds shown antioxidant and anti-inflammatory properties. GSS ZnONPs demonstrate pronounced gastroprotective effects against ethanol-induced gastritis, evidenced by the reduction in gastric lesions and mucosal injury upon its treatment. Histopathological evaluation and immunohistochemical analysis of nuclear factor erythroid 2-related factor 2 (Nrf2) expression further validate these results, revealing the amelioration of ethanol-induced gastritis and improved gastric tissue condition due to their treatment. Noteworthy is the dose-dependent response of GSS ZnONPs, showcasing their efficacy even at lower doses against ethanol-induced gastritis which is confirmed by different biomarkers. These findings have substantial implications for mitigating dosage-related adverse effects while preserving therapeutic benefits, offering a more favorable treatment approach. This study aims to investigate the potential gastroprotective activity of GSS ZnONPs against gastritis.

Enhancement of Female Rat Fertility via Ethanolic Extract from Nigella sativa L. (Black Cumin) Seeds Assessed via HPLC-ESI-MS/MS and Molecular Docking.

The characteristic chemical composition of Nigella seeds is directly linked to their beneficial properties. This study aimed to investigate the phytochemical composition of Nigella sativa seeds using a 100% ethanolic extract using HPLC-ESI-MS/MS. Additionally, it explored the potential biological effects of the extract on female rat reproduction. Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH), Estrogen (E2), and Progesterone (P4) hormone levels were also assessed, along with the morphological and histological effects of the extract on ovarian, oviductal, and uterine tissues. Molecular docking was performed to understand the extract's activity and its role in regulating female reproduction by assessing its binding affinity to hormonal receptors. Twenty metabolites, including alkaloids, saponins, terpenes, flavonoids, phenolic acids, and fatty acids, were found in the ethanolic extract of N. sativa seeds through the HPLC-ESI-MS/MS study. The N. sativa seed extract exhibited strong estrogenic and LH-like activities (p < 0.05) with weak FSH-like activity. Furthermore, it increased the serum levels of LH (p < 0.05), P4 hormones (p < 0.001), and E2 (p < 0.0001). Molecular docking results displayed a strong interaction with Erß, LH, GnRH, and P4 receptors, respectively. Based on these findings, N. sativa seeds demonstrated hormone-like activities, suggesting their potential as a treatment for improving female fertility.

New pyrazolylindolin-2-one based coumarin derivatives as anti-melanoma agents: design, synthesis, dual BRAFV600E/VEGFR-2 inhibition, and computational studies.

Malignant melanoma is the most invasive skin cancer with the highest risk of death. The inhibition of BRAFV600E appears relevant for overcoming secondary resistance developed during melanoma treatment. BRAFV600E triggers angiogenesis via modification of the expression of angiogenic inducers, which play a crucial role in the metastasis of melanoma. Accordingly, the dual inhibition of the BRAFV600E/VEGFR-2 signaling pathway is considered a rational approach in the design of anti-melanoma candidates. In this study, a new class of pyrazolylindolin-2-one linked coumarin derivatives as dual BRAFV600E/VEGFR-2 inhibitors targeting A375 melanoma cells was designed. Target compounds were tailored to occupy the pockets of BRAFV600E and VEGFR-2. Most of the synthesized compounds demonstrated potent mean growth inhibitory activity against A375 cells. Compound 4j was the most active cytotoxic derivative, displaying an IC50 value at a low micromolar concentration of 0.96 µM with a significant safety profile. Moreover, 4j showed dual potent inhibitory activity against BRAFV600E and VEGFR-2 (IC50 = 1.033 and 0.64 µM, respectively) and was more active than the reference drug sorafenib. Furthermore, derivative 4j caused significant G0/G1 cell cycle arrest, induced apoptosis, and inhibited the migration of melanoma cells. Molecular docking showed that compound 4j achieved the highest ΔG value of -9.5 kcal mol-1 against BRAFV600E and significant ΔG of -8.47 kcal mol-1 against VEGFR-2. Furthermore, the structure-activity relationship study revealed that TPSA directly contributed to the anticancer activity of the tested compounds.

Neuroprotective potential of Erigeron bonariensis ethanolic extract against ovariectomized/D-galactose-induced memory impairments in female rats in relation to its metabolite fingerprint as revealed using UPLC/MS.

Erigeron bonariensis is widely distributed throughout the world's tropics and subtropics. In folk medicine, E. bonariensis has historically been used to treat head and brain diseases. Alzheimer's disease (AD) is the most widespread form of dementia initiated via disturbances in brain function. Herein, the neuroprotective effect of the chemically characterized E. bonariensis ethanolic extract is reported for the first time in an AD animal model. Chemical profiling was conducted using UPLC-ESI-MS analysis. Female rats underwent ovariectomy (OVX) followed by 42 days of D-galactose (D-Gal) administration (150 mg/kg/day, i.p) to induce AD. The OVX/D-Gal-subjected rats received either donepezil (5 mg/kg/day) or E. bonariensis at 50, 100, and 200 mg/kg/day, given 1 h prior to D-Gal. UPLC-ESI-MS analysis identified 42 chemicals, including flavonoids, phenolic acids, terpenes, and nitrogenous constituents. Several metabolites, such as isoschaftoside, casticin, velutin, pantothenic acid, xanthurenic acid, C18-sphingosine, linoleamide, and erucamide, were reported herein for the first time in Erigeron genus. Treatment with E. bonariensis extract mitigated the cognitive decline in the Morris Water Maze test and the histopathological alterations in cortical and hippocampal tissues of OVX/D-Gal-subjected rats. Moreover, E. bonariensis extract mitigated OVX/D-Gal-induced Aß aggregation, Tau hyperphosphorylation, AChE activity, neuroinflammation (NF-κBp65, TNF-α, IL-1ß), and apoptosis (Cytc, BAX). Additionally, E. bonariensis extract ameliorated AD by increasing α7-nAChRs expression, down-regulating GSK-3ß and FOXO3a expression, and modulating Jak2/STAT3/NF-ĸB p65 and PI3K/AKT signaling cascades. These findings demonstrate the neuroprotective and memory-enhancing effects of E. bonariensis extract in the OVX/D-Gal rat model, highlighting its potential as a promising candidate for AD management.

Citrus clementine Peel Essential Oil Ameliorates Potassium Dichromate-Induced Lung Injury: Insights into the PI3K/AKT Pathway.

Acute Lung Injury (ALI) is a life-threatening syndrome that has been identified as a potential complication of COVID-19. There is a critical need to shed light on the underlying mechanistic pathways and explore novel therapeutic strategies. This study aimed to examine the potential therapeutic effects of Citrus clementine essential oil (CCEO) in treating potassium dichromate (PDC)-induced ALI. The chemical profile of CCEO was created through GC-MS analysis. An in vivo study in rats was conducted to evaluate the effect of CCEO administrated via two different delivery systems (oral/inhalation) in mitigating acute lung injury (ALI) induced by intranasal instillation of PDC. Eight volatile compounds were identified, with monoterpene hydrocarbons accounting for 97.03% of the identified constituents, including 88.84% of D-limonene. CCEO at doses of 100 and 200 mg/kg bw exhibited antioxidant and anti-inflammatory properties. These significant antioxidant properties were revealed through the reduction of malondialdehyde (MDA) and the restoration of reduced glutathione (GSH). In addition, inflammation reduction was observed by decreasing levels of cytokines tumor necrosis factor-α and tumor growth factor-ß (TNF-α and TGF-ß), along with an increase in phosphatidylinositide-3-kinase (PI3K) and Akt overexpression in lung tissue homogenate, in both oral and inhalation routes, compared to the PDC-induced group. These results were supported by histopathological studies and immunohistochemical assessment of TGF-ß levels in lung tissues. These findings revealed that CCEO plays an integral role in relieving ALI induced by intranasal PDC and suggests it as a promising remedy.

Applying an internal transcribed spacer as a single molecular marker to differentiate between Tetraselmis and Chlorella species.

In the realm of applied phycology, algal physiology, and biochemistry publications, the absence of proper identification and documentation of microalgae is a common concern. This poses a significant challenge for non-specialists who struggle to identify numerous eukaryotic microalgae. However, a promising solution lies in employing an appropriate DNA barcoding technique and establishing comprehensive databases of reference sequences. To address this issue, we conducted a study focusing on the molecular characterization and strain identification of Tetraselmis and Chlorella species, utilizing the internal transcribed spacer (ITS) barcode approach. By analyzing the full nuclear ITS region through the Sanger sequencing approach, we obtained ITS barcodes that were subsequently compared with other ITS sequences of various Tetraselmis and Chlorella species. To ensure the reliability of our identification procedure, we conducted a meticulous comparison of the DNA alignment, constructed a phylogenetic tree, and determined the percentage of identical nucleotides. The findings of our study reveal the significant value of the ITS genomic region as a tool for distinguishing and identifying morphologically similar chlorophyta. Moreover, our results demonstrate that both the ITS1 and ITS2 regions are capable of effectively discriminating isolates from one another; however, ITS2 is preferred due to its greater intraspecific variation. These results underscore the indispensability of employing ITS barcoding in microalgae identification, highlighting the limitations of relying solely on morphological characterization.

Protective Action Mechanisms of Launaea mucronata Extract and Its Nano-Formulation against Nephrotoxicity in Rats as Revealed via Biochemical, Histopathological, and UPLC-QTOF-MS/MS Analyses.

Plants belonging to the Launaea genus have been extensively utilized ethnopharmacologically to treat a variety of diseases, including kidney disorders. Chromium is a common industrial pollutant that has been linked to kidney disease. The present work was designed for the investigation of the UPLC-QTOF-MS/MS metabolite profile of the L. mucronate ethanolic extract (LME), along with assessing the mechanistic protective actions of LME and its nano-silver formulation (LMNS) against K2Cr2O7-induced nephrotoxicity in rats. LMNE was successfully biosynthesized and confirmed using UV-Visible (UV-Vis) spectroscopy and transmission electron microscopy (TEM). The nephroprotective effects of LME and LMNE was assessed in rats exposed to potassium dichromate (K2Cr2O7, 15 mg/kg BW) to cause nephrotoxicity. LME and LMNS, separately, were administered twice daily for 14 days at doses of 200 and 400 mg/kg BW, respectively. The kidney function, catalase, UGT, Nrf2, PGE2, Cox-2, ERK, and MAPK levels in renal tissue were all assessed, along with histopathological examinations for exploring their ameliorative effects. Forty-five bioactive metabolites were annotated belonging to flavonoids, phenolic and organic acids, coumarins, and fatty acids. Metabolite profiling revealed that chlorogenic acid, apigenin, and luteolin glycosides were the main phenolics, with chlorogenic acid-O-hexoside reported for the first time in LME. The findings revealed that the serum kidney function indicators (urea and creatinine) were markedly elevated in K2Cr2O7-intoxicated rats. Furthermore, inflammatory indicators (COX-2 and PGE2), MAPK, and ERK were all markedly elevated in kidney tissue, whereas catalase, UGT, and Nrf2 levels were downregulated. Histological and immunohistochemical assays confirmed the toxic effects of K2Cr2O7 in the kidneys. In contrast, the administration of LME and LMNS prior to K2Cr2O7 considerably improved the architecture of the renal tissue, while also restoring levels of most biochemical markers. Functioning via the inhibition of the MAPK/ERK pathway, activating Nrf2, and modifying the antioxidant and metabolic enzymes, LME and LMNS exerted their nephroprotective effects against K2Cr2O7-induced toxicity.

Exploring Exogenous Indole-3-acetic Acid's Effect on the Growth and Biochemical Profiles of Synechocystis sp. PAK13 and Chlorella variabilis.

Microalgae have garnered scientific interest for their potential to produce bioactive compounds. However, the large-scale industrial utilization of microalgae faces challenges related to production costs and achieving optimal growth conditions. Thus, this study aimed to investigate the potential role of exogenous indole-3-acetic acid (IAA) application in improving the growth and production of bioactive metabolites in microalgae. To this end, the study employed different concentrations of exogenously administered IAA ranging from 0.36 µM to 5.69 µM to assess its influence on the growth and biochemical composition of Synechocystis and Chlorella. IAA exposure significantly increased IAA levels in both strains. Consequentially, improved biomass accumulation in parallel with increased total pigment content by approximately eleven-fold in both strains was observed. Furthermore, the application of IAA stimulated the accumulation of primary metabolites. Sugar levels were augmented, providing a carbon source that facilitated amino acid and fatty acid biosynthesis. As a result, amino acid levels were enhanced as well, leading to a 1.55-fold increase in total amino acid content in Synechocystis and a 1.42-fold increase in Chlorella. Total fatty acids content increased by 1.92-fold in Synechocystis and by 2.16-fold in Chlorella. Overall, the study demonstrated the effectiveness of exogenously adding IAA as a strategy for enhancing the accumulation of microalgae biomass and biomolecules. These findings contribute to the advancement of microalgae-based technologies, opening new avenues to produce economically important compounds derived from microalgae.

Glycine differentially improved the growth and biochemical composition of Synechocystis sp. PAK13 and Chlorella variabilis DT025.

The potential of microalgae to produce valuable compounds has garnered considerable attention. However, there are various challenges that hinder their large-scale industrial utilization, such as high production costs and the complexities associated with achieving optimal growth conditions. Therefore, we investigated the effects of glycine at different concentrations on the growth and bioactive compounds production of Synechocystis sp. PAK13 and Chlorella variabilis cultivated under nitrogen availability. Glycine supplementation resulted in increased biomass and bioactive primary metabolites accumulation in both species. Sugar production, particularly glucose content, significantly improved in Synechocystis at 3.33 mM glycine (1.4 mg/g). This led to enhanced organic acid, particularly malic acid, and amino acids production. Glycine stress also influenced the concentration of indole-3-acetic acid, which was significantly higher in both species compared to the control. Furthermore, fatty acids content increased by 2.5-fold in Synechocystis and by 1.36-fold in Chlorella. Overall, the exogenous application of glycine is a cheap, safe, and effective approach to enhancing sustainable microalgal biomass and bioproducts production.

Seasonal Changes in the Biochemical Composition of Dominant Macroalgal Species along the Egyptian Red Sea Shore.

Macroalgae are significant biological resources in coastal marine ecosystems. Seasonality influences macroalgae biochemical characteristics, which consequentially affect their ecological and economic values. Here, macroalgae were surveyed from summer 2017 to spring 2018 at three sites at 7 km (south) from El Qusier, 52 km (north) from Marsa Alam and 70 km (south) from Safaga along the Red Sea coast, Egypt. Across all the macroalgae collected, Caulerpa prolifera (green macroalgae), Acanthophora spicifera (red macroalgae) and Cystoseira myrica, Cystoseira trinodis and Turbinaria ornata (brown macroalgae) were the most dominant macroalgal species. These macroalgae were identified at morphological and molecular (18s rRNA) levels. Then, the seasonal variations in macroalgal minerals and biochemical composition were quantified to determine the apt period for harvesting based on the nutritional requirements for commercial utilizations. The chemical composition of macroalgae proved the species and seasonal variation. For instance, minerals were more accumulated in macroalgae C. prolifera, A. spicifera and T. ornata in the winter season, but they were accumulated in both C. myrica and C. trinodis in the summer season. Total sugars, amino acids, fatty acids and phenolic contents were higher in the summer season. Accordingly, macroalgae collected during the summer can be used as food and animal feed. Overall, we suggest the harvesting of macroalgae for different nutrients and metabolites in the respective seasons.

Antibacterial, Antifungal, and Anticancer Effects of Camel Milk Exosomes: An In Vitro Study.

Camel milk (CM) has potent antibacterial and antifungal effects and camel milk exosomes (CM-EXO) have been shown to inhibit the proliferation of a large variety of cancer cells including HepaRG, MCF7, Hl60, and PANC1. However, little is known regarding the effects of CM-EXO on bacteria, fungi, HepG2, CaCo2, and Vero cells. Therefore, this study aimed to evaluate the antibacterial, antifungal, and anticancer effects of CM-EXO. EXOs were isolated from CM by ultracentrifugation and characterized by transmission electron microscope and flow cytometry. Unlike CM, CM-EXO (6 mg/mL) had no bactericidal effects on Gram-positive bacteria (Staphylococcus aureus, Micrococcus luteus, and Enterococcus feacalis) but they had bacteriostatic effects, especially against Gram-negative strains (Escherichia coli, Pseudomonas aeruginosa, and Proteus mirabilis), and fungistatic effects on Candida albicans. HepG2, CaCo2, and Vero cells were respectively treated with CM-EXOs at low (6.17, 3.60, 75.35 µg/mL), moderate (12.34, 7.20, 150.70 µg/mL), and high (24.68, 14.40, 301.40 µg/mL) doses and the results revealed that CM-EXOs triggered apoptosis in HepG2 and CaCo2 cells, but not in normal Vero cells, as revealed by high Bax expression and caspase 3 activities and lower expression of Bcl2. Interestingly, CM-EXOs also induced the elevation of intracellular reactive oxygen species and downregulated the expression of antioxidant-related genes (NrF2 and HO-1) in cancer cells but not in normal cells. CM-EXOs have antibacterial and antifungal effects as well as a selective anticancer effect against HepG2 and CaCo2 cells with a higher safety margin on normal cells.

Gene expression analysis and the risk of relapse in favorable histology Wilms' tumor.

Introduction and Objectives: Wilms' tumor (WT) relapse occurs in 15% of patients. We aim to investigate the association between the expression of several genetic markers and WT relapse risk. Materials and methods: The study included 51 children treated for WT at a tertiary center between 2001 and 2019: 23 patients had disease relapse (group A) and 28 remained relapse-free after at least 2 years of follow-up (group B). Patients with syndromic, bilateral synchronous or anaplastic WT were excluded. Autologous renal tissue from 20 patients served as control. Total RNA was isolated from tumor tissue and control. Gene expression levels of WT1, HIF1α, b-FGF, c-MYC and SLC22A18 were assessed using quantitative RT-PCR and normalized to GAPDH. Immunohistochemical staining for WT1 and gene expression levels were compared between the study groups. Results: Median patient age was 3 (IQR = 2-5) years and 36 (70.6%) had stage I disease. Baseline characteristics were similar between study groups. Relapse occurred at a median of 6.8 (2.8-24.7) months, predominantly in the lungs (11/23, 47.8%). Tumors that relapsed expressed significantly higher levels of WT1, HIF1α, b-FGF and c-MYC and lower levels of SLC22A18 (p < 0.001). Strong immunohistochemical staining for WT1 was seen in 73.9% of group A and 14.29% of group B (p < 0.001). These associations retained statistical significance irrespective of patient and tumor characteristics. Conclusions: Higher expression levels of WT1, HIF1 α, b-FGF and c-MYC and lower level of SLC22A18 are associated with increased risk of WT relapse. These genetic markers can serve as future prognostic predictors and help stratify patients for treatment.

Remote Ischaemic Conditioning in STEMI Patients in Sub-Saharan AFRICA: Rationale and Study Design for the RIC-AFRICA Trial.

PURPOSE: Despite evidence of myocardial infarct size reduction in animal studies, remote ischaemic conditioning (RIC) failed to improve clinical outcomes in the large CONDI-2/ERIC-PPCI trial. Potential reasons include that the predominantly low-risk study participants all received timely optimal reperfusion therapy by primary percutaneous coronary intervention (PPCI). Whether RIC can improve clinical outcomes in higher-risk STEMI patients in environments with poor access to early reperfusion or PPCI will be investigated in the RIC-AFRICA trial. METHODS: The RIC-AFRICA study is a sub-Saharan African multi-centre, randomized, double-blind, sham-controlled clinical trial designed to test the impact of RIC on the composite endpoint of 30-day mortality and heart failure in 1200 adult STEMI patients without access to PPCI. Randomized participants will be stratified by whether or not they receive thrombolytic therapy within 12 h or arrive outside the thrombolytic window (12-24 h). Participants will receive either RIC (four 5-min cycles of inflation [20 mmHg above systolic blood pressure] and deflation of an automated blood pressure cuff placed on the upper arm) or sham control (similar protocol but with low-pressure inflation of 20 mmHg and deflation) within 1 h of thrombolysis and applied daily for the next 2 days. STEMI patients arriving greater than 24 h after chest pain but within 72 h will be recruited to participate in a concurrently running independent observational arm. CONCLUSION: The RIC-AFRICA trial will determine whether RIC can reduce rates of death and heart failure in higher-risk sub-optimally reperfused STEMI patients, thereby providing a low-cost, non-invasive therapy for improving health outcomes.

Ameliorative Effects of Camel Milk and Its Exosomes on Diabetic Nephropathy in Rats.

Contradictory results were obtained regarding the effects of extracellular vesicles such as exosomes (EXOs) on diabetes and diabetic nephropathy (DN). Some studies showed that EXOs, including milk EXOs, were involved in the pathogenesis of DN, whereas other studies revealed ameliorative effects. Compared to other animals, camel milk had unique components that lower blood glucose levels. However, little is known regarding the effect of camel milk and its EXOs on DN. Thus, the present study was conducted to evaluate this effect on a rat model of DN induced by streptozotocin. Treatment with camel milk and/or its EXOs ameliorated DN as evidenced by (1) reduced levels of kidney function parameters (urea, creatinine, retinol-binding protein (RBP), and urinary proteins), (2) restored redox balance (decreased lipid peroxide malondialdehyde (MDA) and increased the activity of antioxidants enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx)), (3) downregulated expression of DN-related genes (transforming growth factor-beta 1 (TGFß1), intercellular adhesion molecules 1 (ICAM1), and transformation specific 1 (ETS1), integrin subunit beta 2 (ITGß2), tissue inhibitors of matrix metalloproteinase 2 (TIMP2), and kidney injury molecule-1 (KIM1)), and (4) decreased renal damage histological score. These results concluded that the treatment with camel milk and/or its EXOs could ameliorate DN with a better effect for the combined therapy.

Does immunohistochemical staining of P53, Ki 67 and cyclin A accurately predict Wilms tumor recurrence and survival?

Objective: To evaluate whether p53, cyclin A and ki67 immunohistochemical (IHC) assay can be used as predictors for Wilms' tumor (WT) unfavorable outcomes. Methods: It is a non-concurrent cohort study including patients who underwent nephrectomy for WT from January 2000 to December 2015 in a tertiary referral center. Over a 5- year follow-up, unfavorable events, including relapse and cancer-specific mortality (CSM), were recorded. P53, cyclin A, and ki67 IHC assay were carried out for formalin-fixed paraffin-embedded WT samples. Results: After excluding those who did not meet the inclusion criteria, 75 patients were enrolled. Of the patients, 15/75 (20%) experienced WT relapse while 11/75 (14.6%) died of WT over five years. Unfavorable histology (UFH), including prominent blastemal components and anaplasia, was found in 15/75 (20%) children.Cyclin A immunopositivity was associated with high rates of relapse and CSM. P53 and ki67 positive IHC assay did not show any statistically significant association with unfavorable outcomes. Other risk factors e.g. advanced staging, UFH, extracapsular extension, tumor rupture, lymphadenopathy, and venous thrombosis were not associated with poor prognosis. However, the presence of residual tumors was accompanied by lower survival rates. Conclusion: Cyclin A IHC assay can be used as a predictor of WT recurrence and CSM. Further studies with prospective patterns and a larger sample size are needed.Abbreviations: WT: Wilms' tumor, UFH: unfavorable histology, IHC: immunohistochemical, PI: proliferation index, RFS: relapse-free survival, CSS: cancer-specific survival, FH: favorable histology, CSM: cancer-specific mortality, CDK: cyclin-dependent kinase.

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.

Design, synthesis, anti-inflammatory evaluation and molecular docking of novel thiophen-2-ylmethylene-based derivatives as potential TNF-α production inhibitors.

Inflammation is considered to be an alarming signal for the progress of varied biological complications. Based on the previous reports in the literature that proved the noticeable efficacy of thiophene scaffold as well as nitrogen heterocyclic based compounds against acute and chronic inflammatory disease, a new set of thiophen-2-ylmethylene-based derivatives incorporated with various nitrogenous heterocyclic rings was synthesized and evaluated for their in vivo anti-inflammatory efficiency via applying formalin-induced paw edema bioassay using celecoxib as a standard drug. Compounds 6 and 11a displayed fast onset as well as long duration of anti-inflammatory potency better than that of celecoxib. However, compounds 4a, 7a, 7b and 9b exhibited moderate anti-inflammatory efficiency compared with celecoxib. Ulcerogenic activity and histopathology studies were also carried out. Moreover, the analgesic evaluation of some bioactive candidates revealed that compound 6 showed a promising and long acting analgesic effect exceeding that of the reference drug. While, compounds 4a and 7a displayed mild analgesic activity. Furthermore, the inhibitory effects of some potent anti-inflammatory derivatives on the production of tumor necrosis factor-alpha (TNF-α) were tested. The obtained results revealed that compounds 6 and 11a displayed a remarkable inhibitory effect on the production of TNF-α greater than that of celecoxib. Otherwise, compounds 4a and 7a showed nearly the same inhibitory effect as celecoxib. Finally, the molecular docking study was performed for the tested derivatives 4a, 4b, 6, 7a, 9a and 11a to understand the binding interactions with the active site of TNF-α.

In vivo assessment of the durable, green and in situ bio-functional cotton fabrics based carboxymethyl chitosan nanohybrid for wound healing application.

Herein, a newly developed approach for durable antibacterial cotton fabrics coated carboxymethyl chitosan (CMCs) via ionic crosslinking driven by cationization of cotton surface (CC) with 3-chloro-2-hydroxyl propyl-trimethyl ammonium chloride (CHTAC) was achieved. In this regard, the novelty was extended to impart a highly antibacterial activity through harnessing of the as-functionalized CMCs/CC for in situ preparation of AgNPs, without using of hazardous reductants. The antibacterial activity of the in situ prepared AgNPs onto CMCs/CC as well as the in vivo study on the rat lab were investigated to evaluate their healing efficiency, pathological tissues and biomarkers. Results affirmed that the treatment of CC with 10% of CMCs was adequate to achieve the highest swelling ratio which, in turns, is able to in situ deposition of AgNPs with a size range of 2-10 nm onto CC/CMCs rendering them a highly durable antibacterial activity against both Gram +Ve and Gram -Ve bacteria, which had a bacterial reduction of 98% to 86% after 20 washing cycles. Furthermore, the in vivo study revealed effectively the advantageous uses of the cotton functionalized with AgNPs compared to CC/CMCs in wound healing via alleviating the oxidative stress and promoting hyaluronic acid in wounded skin as well as increasing RUNX2 in healed skin tissues.

Fisetin alleviates thioacetamide-induced hepatic fibrosis in rats by inhibiting Wnt/ß-catenin signaling pathway.

BACKGROUND: Liver fibrosis is a chronic wound-healing response to liver injury of various origins and represents a major health problem. OBJECTIVE: The current study endeavored to investigate the repressing effect of fisetin on hepatic fibrosis induced by thioacetamide (TAA) in rats. MATERIALS AND METHODS: Rats were injected with TAA (200 mg/kg) intraperitoneally twice per week for 6 weeks to induce liver fibrosis. Fisetin (50 and 100 mg/kg/day) or silymarin (50 mg/kg/day) were given orally on a daily basis along with TAA. Liver function parameters, oxidative stress, inflammatory and fibrogenic biomarkers as well as wnt3a, ß-catenin, glycogen synthase kinase 3 (GSK-3ß) and cyclin D1 were estimated. Histoapthological and immunohistochemical examinations were performed. RESULTS: Fisetin restored normal liver functions, increased reduced glutathione (GSH) level and decreased malondialdehyde (MDA), as well as inflammatory biomarkers including; tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6). Additionally, it lessened transforming growth factor ß1 (TGF-ß1), collagen I and tissue inhibitor of metalloproteinase-1 (TIMP-1) levels as well as elevated matrix metalloproteinase-9 (MMP-9) hepatic content. Furthermore, fisetin significantly suppressed wnt3a gene expression associated with decreased ß-catenin and increased GSK-3ß levels. Moreover, fisetin decreased the progress of histologic hepatic fibroplasia and diminished hepatic expression of α-SMA and cyclin D1. CONCLUSION: Fisetin curbed liver fibrosis and exhibited superior activity over silymarin through inhibition of hepatic stellate cells (HSCs) activation and proliferation via suppressing the Wnt/ß-catenin pathway, modulating MMP-9 and TIMP-1, and inhibiting multiple profibrogenic factors, besides its antioxidant and anti-inflammatory effects. Therefore, fisetin is a promising therapeutic candidate for hepatic fibrosis.