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Background: Orlistat (Orli) is an anti-obesity medication that has been approved by the US Food and Drug Administration. It has relatively limited oral bioavailability with promising inhibitory effects on cell proliferation as well as reducing the growth of tumors., Aims: This investigation was done to evaluate the potential protective effect of Tamoxifen/Orlistat nanocrystals alone or in combination against Solid Ehrlich Carcinoma (SEC) and to clarify the possible underlying influences., Materials and Methods: The liquid antisolvent precipitation technique (bottom-up technology) was utilized to manufacture Orlistat Nanocrystals. To explore potential causes for the anti-tumor action, female Swiss Albino mice bearing SEC were randomly assigned into five equal groups (n = 6). Group 1: Tumor control group, group 2: Tam group: tamoxifen (0.01 g/kg, IP), group 3: Free-Orli group: orlistat (0.24 g/kg, IP), group 4: Nano-Orli: orlistat nanocrystals (0.24 g/kg, IP), group 5: Tam-Nano-Orli: Both doses of Tam and Nano-Orli. All treatments were administered for 16 days., Key Findings: The untreated mice showed development in the tumor volume and weight. As well as histopathology results from these mice revealed many tumor large cells as well as solid sheets of malignant cells. Also, untreated mice showed raised VEGF and TGF-1beta content. Moreover, results of gene expression in the SEC-bearing mice noted upregulation in HIF-1α, MMP-9, Bcl-2, and P27 gene expression and downregulation of TXNIP, BAX, and P53 gene expression. On the other hand, administrated TAM, Free-Orli, Nano-Orli, and a combination of Tam-Nano-Orli distinctly suppressed the tumor effects on estimated parameters with special reference to Tam-Nano-Orli., Significance: The developed Tamoxifen/Orlistat nanocrystals combination could be considered a promising approach to augment antitumor effects., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest., (Copyright © 2024. Published by Elsevier Masson SAS.)

Hesperidin (Hes) protects different organs from damage by acting as a potent antioxidant and anti-inflammatory. This study aims to evaluate the gastroprotective effects of free hesperidin and its chitosan nanoparticles (HNPs) against ethanol-induced gastric ulcers in rats, hypothesizing that HNPs will enhance bioavailability and therapeutic efficacy due to improved solubility and targeted delivery. HNPs were synthesized via ion gelation and characterized using TEM, SEM, and zeta potential analyses. Key assessments included gastric acidity, histological analysis, and markers of inflammation, oxidative stress, and apoptosis. HNPs significantly decreased gastric acidity, reduced inflammatory and apoptotic markers, and enhanced antioxidant enzyme activities compared to free hesperidin and esomeprazole. Furthermore, Sirt-1, PGC-1α, HO-1, and FOXO1 gene expression were also evaluated. HNPs raised Sirt-1, PGC-1α, HO-1, and downregulated FOXO1, and they suppressed the activities of NF-κB p65, COX-2, IL-1β, CD86, FOXO1 P53, and caspase-3 and increased Sirt-1 activity. HNPs treatment notably restored antioxidant enzyme activity, reduced oxidative stress and inflammatory markers, and improved histological outcomes more effectively than free hesperidin and esomeprazole. These results indicate that chitosan nanoparticles significantly enhance the gastroprotective effects of hesperidin against ethanol-induced gastric ulcers, potentially offering a more effective therapeutic strategy. Further research should explore the clinical applications of HNPs in human subjects., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Alamoudi, El-Masry, El-Nagar, El Zahaby, Elmorshedy, Gaballa, Alshawwa, Alsunbul, Alharthi and Ibrahim.)

Hesperidin (Hes) functions as a strong antioxidant and anti-inflammatory to guard against damage to the heart, liver, and kidneys. Nevertheless, due to its restricted solubility and bioavailability, a delivery method is required for it to reach a specific organ. In this study, ion gelation was used to synthesize a chitosan/hesperidin nanoformulation. Numerous characterization techniques, such as zeta potential, particle size, XRD, TEM, SEM, and FTIR analyses, were used to corroborate the synthesis of hesperidin nanoparticles (Hes-NPs). Male albino mice were given a pretreatment dose of 100 mg/kg, PO, of Hes or Hes-NPs, which was administered daily for 14 days before the induction of doxorubicin nephrotoxicity on the 12th day. Kidney function (urea and creatinine levels) was measured. Lipid peroxidation (MDA) and antioxidant enzyme (CAT and SOD) activities were estimated. TNF-α, IL-1β, and VEGF content; histopathological examination of kidney tissue; and immunohistochemical staining of NF-κB, Caspase-3, BAX, Bcl-2, and TGF-β1 were evaluated. The gene expressions of Sirt-1 , Bcl-2 , VEGF , HIF1-α , and Kim-1 were also considered. The results showed that pretreatment with Hes or Hes-NPs reduced doxorubicin's nephrotoxic effects, with Hes-NPs showing the greatest reduction. Kidney enzyme and MDA content were lowered in response to the Hes or Hes-NP pretreatment, whereas antioxidant enzyme activities were increased. Hes or Hes-NP pretreatment suppressed the levels of TNF-α, IL-1β, VEGF, NF-κB, Caspase-3, BAX, and TGF-β1; however, pretreatment increased Bcl-2 protein levels. Furthermore, the gene expressions of Sirt-1 , Bcl-2 , VEGF , HIF1-α , and Kim-1 were considerably higher with Hes-NP than with Hes treatment. These results suggest that Hes-NP treatment might reduce DOX-induced nephrotoxicity in mice via modulating Sirt-1/HIF1-α/VEGF/NF-κB signaling to provide antioxidant, anti-inflammatory, and anti-apoptotic effects.

Cyclophosphamide (CP) is an anticancer drug that causes infertility disorders. This study was designed to evaluate a nanoformulation of chitosan with an ethanolic extract from Spirulina platensis in terms of its protection against cyclophosphamide-induced ovarian toxicity. Nine groups of female Wistar rats were randomly assigned as follows: 1: control vehicle, 2: chitosan polymer, 3: telmisartan, 4: Spirulina platensis extract, 5: nanoformulation of the Spirulina platensis , and 6: single injection of CP; groups 7, 8, and 9 received the same treatments as those used in groups 3, 4, and 5, respectively, with a single dose of CP (200 mg/kg, I.P). The results displayed that the CP treatment decreased estradiol, progesterone, anti-mullerian hormone, and GSH content, and it downregulated PPAR-γ, Nrf-2, and HO-1 gene expression. In addition, the CP treatment caused an increase in the FSH, LH, and MDA levels. In the same manner, the protein expression of caspase-3, NF-kB, and TNF-α was upregulated in response to the CP treatment, while PPAR-γ was downregulated in comparison with the control. The rats treated with SPNPs exhibited a substantial reduction in the detrimental effects of oxidative stress and inflammation of the ovarian tissue. This study's conclusions showed that SPNPs counteracted the effects of CP, preventing the death of ovarian follicles and restoring the gonadotropin hormone balance and normal ovarian histological appearance.

One flavonoid glycoside with demonstrated therapeutic potential for several illnesses, including cancer, is hesperidin. However, because of its limited bioavailability and solubility, it is only marginally absorbed, necessitating a delivery mechanism to reach the intended therapeutic target. Additionally, the cytoskeleton of crustaceans yields chitosan, a naturally occurring biopolymer with mucoadhesive properties that has been used to improve the absorption of advantageous chemical substances like flavonoids. Chitosan/hesperidin nanoparticles (Hes-Nanoparticles) were made using the ion gelation technique. The synthesis of Hes-Nanoparticles was confirmed by several characterization methods, including the swelling test, zeta potential, particle size, FTIR, XRD, TEM, and SEM. DPPH and ABTS were used to demonstrate radical scavenging activity in antioxidant assays of chitosan, hesperidin, and the synthesized Hes-Nanoparticles. In addition, by a viability assay against MDA-MB-231, the anticancer efficacies of chitosan, hesperidin, and the synthesized Hes-Nanoparticles were assessed. Furthermore, annexin-V/PI double staining and the cycle of cell analysis were determined by flow cytometry. The results displayed that Hes-Nanoparticles have higher antioxidant activity than chitosan and hesperidin alone. Also, it has been demonstrated that Hes-Nanoparticles are more effective in early cell cycle arrest, suppressing the viability of cancer cells, and increasing cell apoptosis than chitosan and hesperidin alone. In conclusion, Hes-Nanoparticles demonstrated more antioxidant and antitumor activities than chitosan and hesperidin alone. Moreover, it has been established that Hes-Nanoparticles, in a highly soluble form, increase activity in contrast to the poorly soluble form of hesperidin alone.

Background: Cardiotoxicity is one of the limiting side effects of the commonly used anticancer agent cyclophosphamide (Cyclo)., Materials and Methods: The possible protective effects of telmisartan and nanoformulated Spirulina platensis (Sp) methanolic extract against Cyclo-induced cardiotoxicity were examined in this study. Experimental groups of rats were randomly divided into nine groups as control vehicle, control polymer, telmisartan (TEL, 10 mg/kg), free Sp extract (300 mg/kg), nano Sp extract (100 mg/kg), Cyclo (200 mg/kg), TEL + Cyclo, free Sp + Cyclo, and nano Sp + Cyclo. The groups with Cyclo combinations were treated in the same manner as their corresponding ones without Cyclo, with a single dose of Cyclo on day 18., Results: The results indicate that Cyclo causes significant cardiotoxicity, manifesting in the form of notable increases of 155.49%, 105.74%, 451.76%, and 826.07% in the serum levels of glutamic oxaloacetic transaminase (SGOT), lactate dehydrogenase (LDH), creatine kinase MB (CK-MB), and cardiac troponin I (cTnI) enzyme activities, respectively, as compared to the control. In addition, the cardiac glutathione (GSH) content and activity of glutathione peroxidase-1 (GPX-1) enzyme decreased by 65.94% and 73.85%, respectively. Treatment with nano Sp extract showed the most prominent restorations of the altered biochemical, histopathological, and immunohistochemical features as compared with those by TEL and free Sp; moreover, reductions of 30.64% and 43.02% in the p-AKT content as well as 60.43% and 75.30% of the endothelial nitric oxide synthase (eNOS) immunoreactivity were detected in the TEL and free Sp treatment groups, respectively. Interestingly, nano Sp boosted the autophagy signal via activation of beclin-1 (36.42% and 153.4%), activation of LC3II (69.13% and 195%), downregulation of p62 expressions (39.68% and 62.45%), and increased gene expressions of paraoxonase-1 (PON-1) (90.3% and 225.9%) compared to the TEL and free Sp treatment groups, respectively., Conclusion: The findings suggest the protective efficiency of telmisartan and nano Sp extract against cardiotoxicity via activations of the antioxidant, antiapoptotic, and autophagy signaling pathways., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Almukainzi, El-Masry, Ibrahim, Saad, El Zahaby, Saleh and El-Nagar.)

An FDA-approved kinase inhibitor called sorafenib (SOR) is used to treat primary kidney and liver cancer as well as to stop the spread of advanced breast cancer. Side effects from SOR, such as palmar-plantar erythrodysesthesia syndrome, can negatively impact an individual's quality of life. There are a lot of data supporting the importance of lycopene (LYC) in preventing cancer. The antitumor properties of the combination of sorafenib and lycopene were examined in this study. A viability test against MDA-MB-231 was used to assess the anticancer efficacy of sorafenib, lycopene, and their combination in vitro. Moreover, a cell cycle analysis and Annexin-V/PI double staining were performed by using flow cytometry. In addition, the protein level of JNK-1, ERK-1, Beclin-1, P38, and P53 of the MDA-MB-231 cell line was estimated using ELISA kits. In addition, mice with SEC were divided into four equal groups at random ( n = 10) to investigate the possible processes underlying the in vivo antitumor effect. Group IV (SEC-SOR-LYC) received SOR (30 mg/kg/day, p.o.) and LYC (20 mg/kg/day, p.o.); Group I received the SEC control; Group II received SEC-SOR (30 mg/kg/day, p.o.); and Group III received SEC-LYC (20 mg/kg/day, p.o.). The findings demonstrated that the combination of sorafenib and lycopene was superior to sorafenib and lycopene alone in causing early cell cycle arrest, suppressing the viability of cancer cells, and increasing cell apoptosis and autophagy. Likewise, the combination of sorafenib and lycopene demonstrated inhibition of the levels of Bcl-2, Ki-67, VEGF, IL-1β, and TNF-α protein. Otherwise, the quantities of the proteins BAX, P53, and caspase 3 were amplified. Furthermore, the combined treatment led to a substantial increase in TNF-α , caspase 3 , and VEGF gene expression compared to the equivalent dosages of monotherapy. The combination of sorafenib and lycopene enhanced apoptosis and reduced inflammation, as seen by the tumor's decreased weight and volume, hence demonstrating its potential anticancer effect.

Background: Phaeophyceae species are enticing interest among researchers working in the nanotechnology discipline, because of their diverse biological activities such as anti-inflammatory, antioxidant, anti-microbial, and anti-tumor. In the present study, the anti-cancer properties of Polycladia crinita extract and green synthesized Polycladia crinita selenium nanoparticles (PCSeNPs) against breast cancer cell line (MDA-MB-231) and solid Ehrlich carcinoma (SEC) were investigated. Methods: Gas chromatography-mass spectroscopy examinations of Polycladia crinita were determined and various analytical procedures, such as SEM, TEM, EDX, and XRD, were employed to characterize the biosynthesized PCSeNPs. In vitro, the anticancer activity of free Polycladia crinita and PCSeNPs was evaluated using the viability assay against MDA-MB-231, and also cell cycle analysis by flow cytometry was determined. Furthermore, to study the possible mechanisms behind the in vivo anti-tumor action, mice bearing SEC were randomly allocated into six equal groups (n = 6). Group 1: Tumor control group, group 2: free SeNPs, group 3: 25 mg/kg Polycladia crinita , group 4: 50 mg/kg Polycladia crinita , group 5: 25 mg/kg PCSeNPs, group 6: 50 mg/kg PCSeNPs. Results: Gas chromatography-mass spectroscopy examinations of Polycladia crinita extract exposed the presence of many bioactive compounds, such as 4-Octadecenoic acid-methyl ester, Tetradecanoic acid, and n-Hexadecenoic acid. These compounds together with other compounds found, might work in concert to encourage the development of anti-tumor activities. Polycladia crinita extract and PCSeNPs were shown to inhibit cancer cell viability and early cell cycle arrest. Concentrations of 50 mg/kg of PCSeNPs showed suppression of COX-2, NF-кB, VEGF, ki-67, Notch 1, and Bcl-2 protein levels. Otherwise, showed amplification of the caspase 3, BAX, and P53 protein levels. Moreover, gene expression of caspase 3, caspase 9, Notch 1, cyclin D1, NF-кB, IL-6, and VEGF was significantly more effective with PCSeNPs than similar doses of free extract. Conclusion: The PCSeNPs mediated their promising anti-cancerous action by enhancing apoptosis and mitigating inflammation, which manifested in promoting the total survival rate and the tumor volume decrease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Alotaibi, El-Masry, Selim, El-Bouseary, El-Sheekh, Makhlof and El-Nagar.)

Background: Orlistat (ORL) is an effective irreversible inhibitor of the lipase enzyme, and it possesses anticancer effects and limited aqueous solubility. This study was designed to improve the aqueous solubility, oral absorption, and tissue distribution of ORL via the formulation of nanocrystals (NCs)., Methods: ORL-NC was prepared using the liquid antisolvent precipitation method (bottom-up technology), and it demonstrated significantly improved solubility compared with that of the blank crystals (ORL-BCs) and untreated ORL powder. The biodistribution and relative bioavailability of ORL-NC were investigated via the radiolabeling technique using Technetium-99m ( 99m Tc). Female Swiss albino mice were used to examine the antitumor activity of ORL-NC against solid Ehrlich carcinoma (SEC)-induced hepatic damage in mice., Results: The prepared NCs improved ORL's solubility, bioavailability, and tissue distribution, with evidence of 258.70% relative bioavailability. In the in vivo study, the ORL-NC treatment caused a reduction in all tested liver functions (total and direct bilirubin, AST, ALT, and ALP) and improved modifications in liver sections that were marked using hematoxylin and eosin staining (H&E) and immunohistochemical staining (Ki-67 and ER-α) compared with untreated SEC mice., Conclusions: The developed ORL-NC could be considered a promising formulation approach to enhance the oral absorption tissue distribution of ORL and suppress the liver damage caused by SEC.

Marine algal extracts exhibit a potent inhibitory effect against several enveloped and non-enveloped viruses. The infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has several adverse effects, including an increased mortality rate. The anti-COVID-19 agents are still limited; this issue requires exploring novel, effective anti-SARS-CoV-2 therapeutic approaches. This study investigated the antiviral activity of an aqueous extract of Ulva lactuca , which was collected from the Gulf of Suez, Egypt. The aqueous extract of Ulva lactuca was characterized by high-performance liquid chromatography (HPLC), Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and Energy Dispersive X-ray (EDX) analyses. According to the HPLC analysis, the extract comprises several sugars, mostly rhamnose (32.88%). The FTIR spectra showed numerous bands related to the functional groups. EDX analysis confirmed the presence of different elements, such as oxygen (O), carbon (C), sulfur (S), magnesium (Mg), potassium (K), calcium (Ca), and sodium (Na), with different concentrations. The aqueous extract of U. lactuca (0.0312 mg/mL) exhibited potent anti-SARS-CoV-2 activity via virucidal activity, inhibition of viral replication, and interference with viral adsorption (% inhibitions of 64%, 33.3%, and 31.1%, respectively). Consequently, ulvan could be a promising compound for preclinical study in the drug development process to combat SARS-CoV-2.

Bromoxynil octanoate (BO) is a herbicide necessary for plant growth and production. However, it may cause damage to environment and humans. This study aimed to investigate the potential testicular toxicity of BO and its possible underlying mechanisms. Male Albino (Sprague Dawley) rats were administered BO in different doses (5, 10, 20, and 40 mg/kg/BW; P.O.) daily for 21 days. Testicular function was evaluated by determining count and viability of epididymal sperm, and testosterone. In addition, the following parameters were assessed; MDA, NO, and H 2 O 2 as oxidative stress markers; SOD, CAT, GPx, GST, and GSH as antioxidant markers; NF-ĸB-P65 and IL-18 as inflammatory markers; caspase-9 and caspase-3 as apoptotic markers; gene expression of NF-ĸB-P65, TNF-α, BAX, Bcl-2, and caspase-3; and histopathological examination of epididymis and testis sections. The results showed a significant (P < 0.05) increase in MDA, NO, H 2 O 2 , IL-18, and caspase-9 content, NF-ĸB-P65, TNF-α, Bax, and Caspase-3 expression as compared to control. Furthermore, the count and viability of epididymal sperm, testosterone level, SOD, CAT, GPx, GST, and GSH content, and Bcl-2 expression showed a significant (P < 0.05) decrease as compared to control. In conclusion BO-induced testicular damage by altering oxidation, inflammation, and apoptosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Taking into consideration, the challenges faced by the environment and agro-ecosystem make increased for suggestions more reliable methods to help increase food security and deal with difficult environmental problems. Environmental factors play a critical role in the growth, development, and productivity of crop plants. Unfavorable changes in these factors, such as abiotic stresses, can result in plant growth deficiencies, yield reductions, long-lasting damage, and even death of the plants. In reflection of this, cyanobacteria are now considered important microorganisms that can improve the fertility of soils and the productivity of crop plants due to their different features like photosynthesis, great biomass yield, ability to fix the atmospheric N 2, capability to grow on non-arable lands, and varied water sources. Furthermore, numerous cyanobacteria consist of biologically active substances like pigments, amino acids, polysaccharides, phytohormones, and vitamins that support plant growth enhancement. Many studies have exposed the probable role of these compounds in the alleviation of abiotic stress in crop plants and have concluded with evidence of physiological, biochemical, and molecular mechanisms that confirm that cyanobacteria can decrease the stress and induce plant growth. This review discussed the promising effects of cyanobacteria and their possible mode of action to control the growth and development of crop plants as an effective method to overcome different stresses., Competing Interests: Competing InterestsThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© The Author(s) 2023.)

Background: Numerous pesticides and herbicides used in excess cause oxidative stress in plants. These chemicals protect plants from weeds and pests, but they also have very negative side effects, making them common abiotic stressors. One of the most significant nutritional crops in the world is the wheat plant. Conditions of herbicide stress have a negative impact on the plant's phonological phases and metabolic pathways. Plants primarily make an effort to adjust to the environment and develop oxidative homeostasis, which supports stress tolerance., Methods: When controlling broadleaf weeds that emerge after cereal crop plants have been planted, bromoxynil is frequently used as a selective-contact herbicide. This study looked at the effects of the cyanobacteria Arthrospira platensis and Nostoc muscorum aqueous extracts, tryptophan, and bromoxynil (Bh) alone or in combination on wheat plant growth parameters. Both tryptophan and cyanobacterial extract were used as chemical and natural safeners against Bh application. The antioxidant activity and transcriptome studies using qRT-PCR were assayed after 24, 48, 72, 96 h, and 15 days from Bh application in the vegetation stage of wheat plants (55 days old)., Results: In comparison with plants treated with Bh, wheat plants treated with cyanobacteria and tryptophan showed improvements in all growth parameters. Following application of Bh, wheat plants showed reduced glutathione content, as well as reduced antioxidant enzyme activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione-s-transferase. The combination of different treatments and Bh caused alleviation of the harmful effect induced by Bh on the measured parameters. Additionally, the expression of glutathione synthase and glutathione peroxidase, in addition to those of three genes ( Zeta , Tau , and Lambda ) of the GST gene family, was significantly upregulated when using Bh alone or in combination with different treatments, particularly after 24 h of treatment., Conclusion: The current study suggests using cyanobacterial extracts, particularly the A. platensis extract, for the development of an antioxidant defense system against herbicide toxicity, which would improve the metabolic response of developed wheat plants.