Search Results (25)

Cisplatin is a widely utilized chemotherapy drug effective against various cancers, yet its use is often constrained by severe toxicity to healthy organs, including the liver, kidneys, and spleen. This study explored the protective role of Chlorella vulgaris, a microalga known for its antioxidant and anti-inflammatory properties, against cisplatin-induced organ damage. The research focused on modulating oxidative stress, inflammation, and the Nrf2 signaling pathway. The experimental design included four groups: a control group receiving saline, a cisplatin group administered 1.34 mg/kg weekly for three months, a C. vulgaris group receiving 150 mg/kg daily, and a combined cisplatin/Chlorella vulgaris group. Cisplatin treatment significantly elevated oxidative stress markers, such as lipid peroxidation and nitric oxide, while increasing pro-inflammatory cytokines (TNF-α, IL-12, IL-6) and reducing antioxidant capacity. Additionally, liver and kidney function markers were markedly impaired, and histopathological analysis revealed structural damage in the liver, kidneys, and spleen. Conversely, C. vulgaris supplementation mitigated these effects, restoring oxidative stress markers, cytokine levels, and organ function to near-normal values. Microscopic examination confirmed that Chlorella vulgaris effectively prevented cisplatin-induced structural damage. Notably, while cisplatin increased Nrf2 expression as an adaptive response to oxidative stress, C. vulgaris attenuated this effect, reflecting its potent antioxidant capabilities. Full article

The protective potentials of Tribulus terrestris (TT) and L-arginine (L-Arg) against reproductive toxicity induced by fipronil (FPN) in male rats were investigated. A total of 36 male rats were allocated into six groups: control, TT, L-Arg, FPN, FPN + TT, and FPN + L-Arg groups. The body and sex organ weights, semen criteria, serum testosterone levels, and testicular oxidative stress were determined. Sexual behavior, testicular and penile androgen receptor (AR), penile nitric oxide synthase (NOS), immunohistochemistry of proliferating cell nuclear antigen (PCNA), and histopathology were also assessed. FPN disrupted reproductive health by influencing the expression and activity of NOS and AR, leading to compromised erectile function, sexual dysfunction, and hormonal imbalance. Significant improvements in body weight, reproductive organ weights, the expression of NOS and AR, and testosterone levels were observed in the TT- and L-Arg-treated groups. Behavioral assessments indicated improved sexual performance in the TT- and L-Arg-treated groups. Histopathological studies of the testes and penis tissue, immunohistochemical expression of PCNA in testicular tissues, and biochemical analyses further confirmed the protective effects of TT and L-Arg. Collectively, these findings highlighted the potential of TT and L-Arg in counteracting FPN-induced reproductive impairments. Full article

Imidacloprid (IMI) is a widely used insecticide known for its high selectivity toward insects. Ellagic acid (EA) is a plant-derived polyphenolic compound recognized for its therapeutic potential and favorable safety profile in the treatment of various diseases. This study aimed to evaluate the therapeutic effects of EA, formulated as novasomes (NOV), against IMI-induced thyroid dysfunction and to investigate the underlying mechanisms. Rats were divided into four equal groups: control, EA-NOV, IMI, and IMI + EA-NOV. Thyroid function was assessed by measuring free triiodothyronine (T3), free thyroxine (T4), and thyroid-stimulating hormone (TSH) levels. Thyroid tissues were examined to evaluate histopathological alterations, as well as to assess the oxidative/antioxidant pathway (Nrf2, SOD, TAC, MDA), inflammatory pathway (IL-1β, TNF-α, NF-κB), apoptotic pathway (Bcl, BAX), and autophagy pathway (PI3K/Akt/mTOR, P53, Beclin-1). Exposure to IMI resulted in impaired thyroid function, the upregulated gene expression of the PI3K/Akt/mTOR pathway, and downregulated P53 expression. Additionally, immunohistochemical staining revealed Beclin-1-mediated autophagy, alongside increased apoptosis, oxidative stress, and elevated levels of inflammatory cytokines. Conversely, EA improved thyroid function and ameliorated histopathological alterations by enhancing autophagy-inducing pathways. Additionally, the alleviation of oxidative stress was evidenced by the increased immunohistochemical staining of Nrf2, which promoted the synthesis and activity of antioxidant enzymes and reduced apoptotic and inflammatory markers. This study proposes the use of EA as a potential protective, naturally occurring phytoceutical against IMI-induced thyroid dysfunction, primarily through the modulation of PI3K/Akt/mTOR-mediated autophagy. Full article

Identifying suitable sites for urban, industrial, and tourist development is important, especially in areas with increasing population and limited land availability. Kharga Oasis, Egypt, stands out as a promising area for such development, which can help reduce overcrowding in the Nile Valley and Delta. However, soil and various environmental factors can affect the suitability of civil engineering projects. This study used Geographic Information Systems (GISs) and a multi-criteria decision-making approach to assess the suitability of Kharga Oasis for construction activities. Geotechnical parameters were obtained from seismic velocity data, including Poisson’s ratio, stress ratio, concentration index, material index, N-value, and foundation-bearing capacity. A comprehensive analysis of in situ and laboratory-based geological and geotechnical data from 24 boreholes examined soil plasticity, water content, unconfined compressive strength, and consolidation parameters. By integrating geotechnical, geomorphological, geological, environmental, and field data, a detailed site suitability map was created using the analytic hierarchy process to develop a weighted GIS model that accounts for the numerous elements influencing civil project design and construction. The results highlight suitable sites within the study area, with high and very high suitability classes covering 56.87% of the land, moderate areas representing 27.61%, and unsuitable areas covering 15.53%. It should be noted that many settlements exist in highly vulnerable areas, emphasizing the importance of this study. This model identifies areas vulnerable to geotechnical and geoenvironmental hazards, allowing for early decision-making at the beginning of the planning process and reducing the waste of effort. The applied model does not only highlight suitable sites in the Kharga Oasis, Egypt, but, additionally, it provides a reproducible method for efficiently assessing land use suitability in other regions with similar geological and environmental conditions around the world. Full article

Doxorubicin (DOX) cancer therapy induces serious cardiotoxicity as a side effect. This study aimed to investigate the cardioprotective effects of grape seed extract (GSE) and L-Carnitine (L-CA) against DOX-induced cardiac toxicity in male rats. Six groups of male albino rats were used: G1 (control); G2 (GSE), given grape seed extract (100 mg/kg b.wt.) orally for 35 days; G3 (L-CA) (150 mg/kg b.wt.); Group 4 (DOX-induced cardiotoxicity), given DOX (10 mg/kg b.wt., i.p.) on the 28th day of the experiment; G5 (GSE + DOX), given GSE and DOX as previously mentioned; and G6 (L-CA + DOX), given L-CA and DOX as previously mentioned. Electrocardiographic evaluation, lipid profile, lipid peroxidation and antioxidants, serum cardiac markers, and inflammatory markers were estimated. Histopathological evaluation of cardiac tissue was also examined. Key findings showed that DOX induced ECG abnormalities lipid peroxidation, reduced antioxidants, and elevated cardiac and inflammatory markers. GSE and L-CA significantly ameliorated ECG abnormalities, reduced lipid peroxidation, improved antioxidant enzymes and serum cardiac markers, and reduced inflammation. These findings suggest that GSE and L-CA exhibit substantial cardioprotective effects in DOX-induced cardiotoxicity via their antioxidant and anti-inflammatory potentials. Full article

The current research investigated the use of gelatin nanoparticles (GNPs) for enhancing the cytotoxic effects of nivolumab, an immune checkpoint inhibitor. The unique feature of GNPs is their biocompatibility and functionalization potential, improving the delivery and the efficacy of immunotherapeutic drugs with fewer side effects compared to traditional treatments. This exploration of GNPs represents an innovative direction in the advancement of nanomedicine in oncology. Nivolumab-loaded GNPs were prepared and characterized. The optimum formulation had a particle size of 191.9 ± 0.67 nm, a polydispersity index of 0.027 ± 0.02, and drug entrapment of 54.67 ± 3.51%. A co-culture experiment involving A549 target cells and effector Jurkat cells treated with free nivolumab solution, and nivolumab-loaded GNPs, demonstrated that the latter had significant improvements in inhibition rate by scoring 87.88 ± 2.47% for drug-loaded GNPs against 60.53 ± 3.96% for the free nivolumab solution. The nivolumab-loaded GNPs had a lower IC₅₀ value, of 0.41 ± 0.01 µM, compared to free nivolumab solution (1.22 ± 0.37 µM) at 72 h. The results indicate that administering nivolumab-loaded GNPs augmented the cytotoxicity against A549 cells by enhancing effector Jurkat cell activity compared to nivolumab solution treatment. Full article

Miconazole nitrate (MCNR), an antifungal drug, is used to treat superficial infections. The objective of the current study was to assess the antifungal effectiveness of MCNR-loaded transethosomal gel (MNTG) against Candida albicans in an in vivo rat model. The outcomes were compared with those of the miconazole nitrate gel (MNG) and marketed Daktarin^® cream (2%) based on histopathological and hematological studies. The results of the skin irritation test revealed the safety profile of the MNTG. The MNTG demonstrated the greatest antifungal activity in the histological analysis and the visible restoration of the skin, and the rats revealed an apparent evidence of recovery. Compared to the untreated group, the treated group’s lymphocyte and white blood cells counts increased, but their eosinophil counts decreased. In conclusion, MNTG exhibited the greatest antifungal activity, which might be connected to the improved skin permeability of the transethosome’s nanosized vesicles. Therefore, it could be considered a promising carrier for topical usage and the treatment of cutaneous candidiasis. More clinical research needs to be performed in order to demonstrate its effectiveness and safe usage in humans. Full article

Although primary open-angle glaucoma (POAG) is a major cause of blindness worldwide, patients’ immune response and its relation to the disease course have not been fully unraveled in terms of analyses of circulating B-cell subsets, as well as the association of these subsets with the severity of POAG clinical features. Subjects and Methods: Flow cytometry was used to determine B-cell subset frequencies from 30 POAG patients grouped by hierarchical cluster analysis or the mean deviation (MD) of the visual field (VF) and correlated with the patients’ clinical and pathological data, as well as with BSF-2(IL-6) and CSIF:TGIF(IL-10), which were quantified in peripheral blood samples of patients and controls by ELISA. Results: The total B-cell frequency was increased in the POAG group in comparison to the control group (n = 30). Frequencies of specific B-cell subsets, such as double-negative (DN) and naïve B-cell subsets, were increased in relation to the severity of the POAG disease. However, the unswitched memory B compartment subset decreased in the POAG group. Other non-typical B-cell subsets such as DN B cells also showed significant changes according to the POAG disease severity course. These differences allow us to identify POAG severity-associated inflammatory clusters in patients with specifically altered B-cell subsets. Finally, ocular parameters, biomarkers of inflammation, and other glaucoma-related or non-clinical scores exhibited correlations with some of these B-cell subpopulations. Conclusion: The severity of the POAG disease course is accompanied by changes in the B-cell subpopulation, namely, DN B cells. Furthermore, the existing relationship of the B-cell subset frequencies with the clinical and the inflammatory parameters BSF-2(IL-6), CSIF:TGIF(IL-10), and the BSF-2(IL-6) to CSIF:TGIF(IL-10) ratio suggests that these B lymphocyte cells could serve as potential molecular bio-markers for assessing POAG disease severity and/or progression. Full article

Recently, myriad studies have defined the versatile abilities of gasotransmitters and their synthesizing enzymes to play a “Maestro” role in orchestrating several oncological and non-oncological circuits and, thus, nominated them as possible therapeutic targets. Although a significant amount of work has been conducted on the role of nitric oxide (NO) and carbon monoxide (CO) and their inter-relationship in the field of oncology, research about hydrogen sulfide (H₂S) remains in its infancy. Recently, non-coding RNAs (ncRNAs) have been reported to play a dominating role in the regulation of the endogenous machinery system of H₂S in several pathological contexts. A growing list of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are leading the way as upstream regulators for H₂S biosynthesis in different mammalian cells during the development and progression of human diseases; therefore, their targeting can be of great therapeutic benefit. In the current review, the authors shed the light onto the biosynthetic pathways of H₂S and their regulation by miRNAs and lncRNAs in various oncological and non-oncological disorders. Full article

Syzygium cumini L. is an evergreen tree belonging to family Myrtaceae, employed for different traditional uses like diabetes, inflammation, and fever. The current study aimed to compare the chemical compositions of the essential oils (EOs) isolated from different organs of Syzygium cumini (leaves (Scl), fruits (Scf), seeds (Scs), and bark (Scb)) using a GC/MS analysis. Also, a chemometric analysis was applied to explore the main similarities and differences among different organs using a Principal Component Analysis (PCA) and a hierarchal cluster analysis (HCA). Furthermore, in vitro antiaging activities were investigated via anti-collagenase, anti-elastase, and anti-hyaluronidase assays. The GC-MS analysis revealed 82 compounds representing 92.13%, 99.42%, 100%, and 92.97% in Scl, Scf, Scs, and Scb, respectively. The predominant components were α-pinene, β-pinene, (E)-β-caryophyllene, α-caryophyllene, caryophyllene oxide, and α-humulene epoxide II with variable percentages. All EOs were positioned on positive PC1, except for Scs, which was positioned on the negative side in a separate quadrant. The HCA dendrogram displayed the closeness of Scl and Scb, which was not clearly recognized in the PCA score plot. Moreover, the Scs oils were totally discriminated from other parts. The Scl and Scs oils showed superior anti-collagenase, anti-elastase, and anti-hyaluronidase activities. Thus, S. cumini oils should be considered for cosmetic preparations to retard skin aging manifestations. Full article

Miconazole nitrate (MCNR) is a BCS class II antifungal drug with poor water solubility. Although numerous attempts have been made to increase its solubility, formulation researchers struggle with this significant issue. Transethosomes are promising novel nanocarriers for improving the solubility and penetration of drugs that are inadequately soluble and permeable. Thus, the objective of this study was to develop MCNR-loaded transethosomal gel in order to enhance skin permeation and antifungal activity. MCNR-loaded transethosomes (MCNR-TEs) were generated using the thin film hydration method and evaluated for their zeta potential, particle size, polydispersity index, and entrapment efficiency (EE%). SEM, FTIR, and DSC analyses were also done to characterize the optimized formulation of MCNR-TEs (MT-8). The optimized formulation of MCNR-TEs was incorporated into a carbopol 934 gel base to form transethosomal gel (MNTG) that was subjected to ex vivo permeation and drug release studies. In vitro antifungal activity was carried out against Candida albicans through the cup plate technique. An in vivo skin irritation test was also performed on Wistar albino rats. MT-8 displayed smooth spherical transethosomal nanoparticles with the highest EE% (89.93 ± 1.32%), lowest particle size (139.3 ± 1.14 nm), polydispersity index (0.188 ± 0.05), and zeta potential (−18.1 ± 0.10 mV). The release profile of MT-8 displayed an initial burst followed by sustained release, and the release data were best fitted with the Korsmeyer-Peppas model. MCNR-loaded transethosomal gel was stable and showed a non-Newtonian flow. It was found that ex vivo drug permeation of MNTG was 48.76%, which was significantly higher than that of MNPG (plain gel) (p ≤ 0.05) following a 24-h permeation study. The prepared MCNR transethosomal gel exhibited increased antifungal activity, and its safety was proven by the results of an in vivo skin irritation test. Therefore, the developed transethosomal gel can be a proficient drug delivery system via a topical route with enhanced antifungal activity and skin permeability. Full article

Phthalates are widely distributed in our environment due to their usage in many industries, especially in plastic production, which has become an essential part of daily life. This investigation aimed to assess the potential remedial influence of lutein, a naturally occurring carotenoid, on phthalate-triggered damage to the liver and kidneys. When di-(2-ethylhexyl) phthalate (DEHP) was administered to male albino rats over sixty straight days at a dosage of 200 mg/kg body weight, it resulted in a significant increase in the serum activity of liver enzymes (AST, ALT, and GGT), alpha-fetoprotein, creatinine, and cystatin-C, as well as disruptions in the serum protein profile. In addition, intoxication with DEHP affected hepato-renal tissues’ redox balance. It increased the content of some proinflammatory cytokines, nuclear factor kappa B (Nf-κB), and apoptotic marker (caspase-3); likewise, DEHP-induced toxicity and decreased the level of anti-apoptotic protein (Bcl-2) in these tissues. Lutein administration at a dose level of 40 mg/kg b.w efficiently facilitated the changes in serum biochemical constituents, hepato-renal oxidative disturbance, and inflammatory, apoptotic, and histopathological alterations induced by DEHP intoxication. In conclusion, it can be presumed that lutein is protective as a natural carotenoid against DEHP toxicity. Full article

Tofacitinib is an antirheumatic drug characterized by a short half-life and poor permeability, which necessitates the development of sustained release formulation with enhanced permeability potential. To achieve this goal, the free radical polymerization technique was employed to develop mucin/chitosan copolymer methacrylic acid (MU-CHI-Co-Poly (MAA))-based hydrogel microparticles. The developed hydrogel microparticles were characterized for EDX, FTIR, DSC, TGA, X-ray diffraction, SEM, drug loading; equilibrium swelling (%), in vitro drug release, sol–gel (%) studies, size and zeta potential, permeation, anti-arthritic activities, and acute oral toxicity studies. FTIR studies revealed the incorporation of the ingredients into the polymeric network, while EDX studies depicted the successful loading of tofacitinib into the network. The thermal analysis confirmed the heat stability of the system. SEM analysis displayed the porous structure of the hydrogels. Gel fraction showed an increasing tendency (74–98%) upon increasing the concentrations of the formulation ingredients. Formulations coated with Eudragit (2% w/w) and sodium lauryl sulfate (1% w/v) showed increased permeability. The formulations equilibrium swelling (%) increased (78–93%) at pH 7.4. Maximum drug loading and release (%) of (55.62–80.52%) and (78.02–90.56%), respectively, were noticed at pH 7.4, where the developed microparticles followed zero-order kinetics with case II transport. Anti-inflammatory studies revealed a significant dose-dependent decrease in paw edema in the rats. Oral toxicity studies confirmed the biocompatibility and non-toxicity of the formulated network. Thus, the developed pH-responsive hydrogel microparticles seem to have the potential to enhance permeability and control the delivery of tofacitinib for the management of rheumatoid arthritis. Full article

Free-radical polymerization technique was adopted to fabricate a stimuli-responsive intelligent quince/mucin co-poly (methacrylate) hydrogel for the controlled delivery of acyclovir sodium. The developed hydrogel matrices were appraised using different parameters, such as drug loading (%), swelling kinetics, pH- and electrolyte-responsive swelling, and sol–gel fraction. Drug-excipient compatibility study, scanning electron microscopy, thermal analysis, powder X-ray diffraction (PXRD) analysis, in vitro drug release studies, drug release kinetics and acute oral toxicity studies were conducted. The results of drug loading revealed an acyclovir sodium loading of 63–75% in different formulations. The hydrogel discs exhibited pH-responsive swelling behavior, showing maximum swelling in a phosphate buffer with a pH of 7.4, but negligible swelling was obvious in an acidic buffer with a pH of 1.2. The swelling kinetics of the developed hydrogel discs exhibited second-order kinetics. Moreover, the hydrogel discs responded to the concentration of electrolytes (CaCl₂ and NaCl). The results of the FTIR confirm the formation of the hydrogel via free-radical polymerization. However, the major peaks of acyclovir remain intact, proving drug-excipient compatibility. The results of the SEM analysis reveal the porous, rough surface of the hydrogel discs with multiple cracks and pores over the surface. The results of the PXRD disclose the amorphous nature of the fabricated hydrogel. The dissolution studies showed a minor amount of acyclovir sodium released in an acidic environment, while an extended release up to 36 h in the phosphate buffer was observed. The drug release followed Hixen–Crowell’s kinetics with Fickian diffusion mechanism. The toxicity studies demonstrated the non-toxic nature of the polymeric carrier system. Therefore, these results signify the quince/mucin co-poly (methacrylate) hydrogel as a smart material with the potential to deliver acyclovir into the intestine for an extended period of time. Full article

Recently, population growth and resource depletion have been matched by a growing demand for self-sustaining communities. Numerous studies promote sustainable solutions to the concerns of climate change and food scarcity. This study aims at creating an automated Economic Land Utilization Optimization Model (ELUOM) that identifies sustainable and cost-effective agricultural practices. Soil, water & climatic characteristics of over 400 crops are gathered in a relational database to build the model. Evolutionary algorithms are utilized to filter the database based on user input. Optimization process is then performed on all possible utilization plans of the filtered crops to maximize the 20-year return while minimizing water consumption. The model is verified on a case study in Giza, Egypt where it shows the potential of increasing the return/m³ of water by 370% versus current practices. This research also studies the application of ELOUM on a vacant plot in the American university in Cairo, Egypt. Full article