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Aim: The primary factor causing chronic renal failure is diabetic nephropathy (DN) worldwide. However, the current biomarkers for DN have limited diagnostic utility. Thus, this work aimed to clarify the implications of microRNA-200a (miR-200a) and microRNA-132 (miR-132) and their correlation with NF-κB (nuclear factor- kappa beta), and, TNF-α (tumor necrosis factor –alpha) signaling to identify biomarkers able to distinguish late-stage from early- stage DN. Methods: Fifty healthy controls, and 271 type 2 diabetic (T2D) patients (166 male plus 105 female) were enrolled. Participants were stratified into seven groups according to along with the estimated glomerular filtration rate (eGFR), glycated hemoglobin (HbA1c%), healthy controls, diabetes without DN (G1), diabetes with mild renal impairment (G2), and four DN grades (G3a, G3b, G4, and G5). Results: Compared to healthy controls, the DN groups exhibited linear increases in serum miR-200a, TNF-α, NF-κB, matrix metalloproteinase (MMP-9) and interleukin-6 (IL-6) levels and reductions in miR-132 serum expression. Among the patients, NF-κB and TNF-α produced a negative correlation with miR-132, while, positive correlation has been discovered with miR-200-a. The operating characteristic of the receiver curve (ROC), proved that, miR-200a also miR-132 had good diagnostic performance in distinguishing early from advanced DN. Conclusion: MiR-200a as well as miR-132 expression levels, and their correlations with NF-κB/TNF-alpha signaling, were able to differentiate between DN patients with lower eGFR, suggesting their utility as diagnostic and prognostic biomarkers.

Inflammation is a condition that is closely linked to diabetes mellitus type 2 (T2DM), short for T2DM several different antidiabetic medications have been produced to regulate hyperglycemia, with indications that these therapies may have anti-inflammatory effects along with their glucose-lowering efficacy. Thus, this research was planned to explore the impact of antidiabetic agents on the cytokine expression levels —interleukin (IL)-1β, IL-6, IL-17, and IL-37 when patients have T2DM.In this study, 168 eligible subject matter was split into two groups: 50 healthy individuals and 118 cases with T2DM, who were classified into two subgroups: 30 untreated patients and 88 patients treated with metformin-based therapy.The outcome exhibited a significant increase within HbA1c% and proinflammatory cytokines (i.e., IL-1β, IL- 6, and IL-17), whereas IL-37 decreased considerably in untreated cases with T2DM compared to those in subjects who are healthy. Furthermore, the results showed increased levels Regarding waist size, body mass index and assessment using that homeostasis model, cholesterol, triglycerides, low-density lipoprotein levels, and heart danger elements in untreated cases with T2DM in comparison with hygienic subjects. Notably, treated patients with T2DM revealed an ameliorative impact on HbA1c, IL-6, IL-17, IL-37, IL-1β levels and lipid profile compared with untreated patients with T2DM.Antidiabetic agents may have a beneficial activity on the inflammatory status by reducing blood glucose levels, hyperlipidemia, and proinflammatory cytokines. The anti-inflammatory activity of IL-37 can apply a potentially effective therapeutic goal in treating T2DM and its complications.

A growing body of studies suggests that Ca2+ signaling controls a variety of biological processes in brain elements. Activation of L-type voltage-operated Ca2+ channels (VOCCs) plays a role in the development of oligodendrocyte (OL) lineage loss, and indicates that the blocking of these channels may be an effective way to inhibit OL lineage cell loss. For this study, 10.5-day-old male Sprague–Dawley rats were used to generate cerebellar tissue slices. The slice tissues were cultured and randomly allocated to one of four groups (six each) and treated as follows: Group I, (sham control); Group II, 0.1% dimethyl sulfoxide (DMSO) only (vehicle control); Group III, injury (INJ); Group IV, (INJ and treatment with NIF). The injury was simulated by exposing the slice tissues to 20 min of oxygen–glucose deprivation (OGD). At 3 days post-treatment, the survival, apoptosis, and proliferation of the OL lineages were measured and compared. Results: In the INJ group, there was a decrease in mature myelin basic protein+ OLs (MBP+ OLs) and their precursors, NG2+ OPCs (Nerve-glia antigen 2+ oligodendrocyte precursor cell), compared with controls. A significant elevation was observed in the NG2+ OPCs and apoptotic MBP+ OLs as confirmed by a TUNEL assay. However, the cell proliferation rate was decreased in NG2+ OPCs. NIF increased OL survival as measured by apoptosis rate in both OL lineages and preserved the rate of proliferation in the NG2+ OPCs. Conclusions: Activation of L-type VOCCs may contribute to OL pathology in association with reduced mitosis of OPCs following brain injury as a strategy to treat demyelinating diseases.

Abstract Accumulating evidence indicates the role of endocrine disruptor bisphenol A (BPA) in many pathological conditions. Histone deacetylase (HDAC) inhibition has potential for the treatment of many diseases/abnormalities. Using a mouse BPA exposure model, this study investigated the hepatoprotective effects of the Food and Drug Administration–approved HDAC2 inhibitor valproic acid (VPA) against BPA-induced liver pathology. We randomly divided 30 adult male Swiss albino mice (8 weeks old; N = 6) into five groups: group 1, no treatment (sham control (SC)); group 2, only oral sterile corn oil (vehicle control (VC)); group 3, 4 mg/kg/day of oral BPA (single dose (BPA group)); group 4, 0.4% oral VPA (VPA group); and group 5, oral BPA + VPA (BPA + VPA group). At the age of 10 weeks, the mice were euthanized for biochemical and histological examinations. BPA promoted a significant decrease in the body weight (BW), an increase in the liver weight, and a significant increase in the levels of liver damage markers aspartate aminotransferase and alanine aminotransferase in the BPA group compared to SC, as well as pathological changes in liver tissue. We also found an increase in the rate of apoptosis among hepatocytes. In addition, BPA significantly increased the levels of oxidative stress indices, malondialdehyde, and protein carbonylation but decreased the levels of reduced glutathione (GSH) in the BPA group compared to SC. In contrast, treatment with the HDAC2 inhibitor VPA significantly attenuated liver pathology, oxidative stress, and apoptosis and also enhanced GSH levels in VPA group and BPA + VPA group. The HDAC2 inhibitor VPA protects mice against BPA-induced liver pathology, likely by inhibiting oxidative stress and enhancing the levels of antioxidant-reduced GSH.

Bisphenol A (BPA), a ubiquitous plasticizer, is capable of producing oxidative splenic injury, and ultimately led to spleen pathology. Further, a link between VitD levels and oxidative stress was reported. Hence the role of VitD in BPA-induced oxidative splenic injury was investigated in this study. Sixty male and female Swiss albino mice (3.5 weeks old) were randomly divided into control and treated groups 12 mice in each (six males and six females). The control groups were further divided into sham (no treatment) and vehicle (sterile corn oil), whereas the treatment group was divided into VitD (2,195 IU/kg), BPA (50 μg/kg), and BPA+VitD (50 μg/kg + 2,195 IU/kg) groups. For six weeks, the animals were dosed intraperitoneally (i.p). One week later, at 10.5 weeks old, mice were sacrificed for biochemical and histological analyses. Findings showed BPA triggered neurobehavioral abnormalities and spleen injury with increased apoptotic indices (e.g. DNA fragmentation) in both sexes. A significant increase was found in lipid peroxidation marker, MDA in splenic tissue, and leukocytosis. Conversely, VitD treatment altered this scenario into motor performance preservation, reducing oxidative splenic injury with a decrease in the percent apoptotic index. This protection was significantly correlated with preserving leukocyte counts and reduced MDA levels in both genders. It can be concluded from the above findings that VitD treatment has an ameliorative effect on oxidative splenic injury induced by BPA, highlighting the continuous crosstalk between oxidative stress and the VitD signaling pathway.

Ulcerative colitis (UC) is an inflammatory bowel disease with high morbidity. Acetic acid-induced damage of colonic mucosa in rats is a commonly used experimental animal model of UC. This research aimed to explore for the first time the ameliorative effect of dietary supplementation with fava bean on the incidence of UC in rats fed with sucrose containing diet. Rats were divided into five groups as follows: G1, control healthy rats; G2, colitic rats; G3, colitic rats fed diets containing 30% sucrose, G4, healthy rats fed diets containing 30% sucrose and G5, colitic rats fed diets containing 30% sucrose supplemented with dried ground fava bean. Colonic injury and inflammation were evaluated through a disturbance of oxidative biomarkers, a significant increase in inflammatory biomarkers and inflammatory cytokines, and histological abnormalities in colonic tissues accompanied by colonic mucosal DNA damage. Colitic rats fed on sucrose containing diet demonstrated additional histological, biochemical, and DNA alterations in colonic mucosa of rats. Dietary supplementation with dried ground fava bean significantly corrected the impaired oxidative and inflammatory biomarker levels and modulated histological features and DNA alterations. Finally, fava bean attenuated the oxidative damage and colonic injury induced by acetic acid, which confirmed its high anti-oxidant and anti-incendiary properties.

Cellular elements of maturing brain are vulnerable to insults, which lead to neurodevelopmental defects. There are no established treatments at present. Here we examined the efficacy of selective adenosine A2A receptor inhibitor SCH58261 to combat brain injury, particularly oligodendrocyte (OL) lineage cells, in young rats. Wistar rats (n = 24, 6.5 days old) were randomly divided into equal groups of four. The sham (SHAM) group received no treatment, the vehicle (VEHICLE) group received 0.1% dimethylsufoxide, the injury (INJ) group was exposed to oxygen-glucose deprivation insult, and the injury+SCH58261 (INJ+SCH58261) group was exposed to the insult and received 1 μM SCH58261. Immunocytochemical experiments revealed that there was a significant reduction in the populations of mature OL (MBP+ OLs) and immature OL precursors (NG2+ OPCs) in the INJ group compared to SHAM group. Furthermore, there was also a significant increase in the percent of apoptotic MBP+ OL and NG2+ OPC populations as evidenced by TUNEL assay. In addition, there was a significant reduction in the proliferation rate among NG2+ OPCs, which was confirmed by BrdU immunostaining. On the other hand, treatment with SCH58261 significantly enhanced survival, evidenced by the reduction in apoptotic indices for both cell types, and it is preserved the NG2+ OPC proliferation. Activation of adenosine A2A receptors may contribute to OL lineage cell loss in association with decreased mitotic behavior of OPCs in neonatal brains upon injury. Future investigations assessing ability of SCH58261 to regenerate myelin will provide insights into its wider clinical relevance.

Bisphenol A (BPA), an endocrine and metabolic disruptor, is widely used to manufacture polycarbonate plastics and epoxy resins. Accumulating evidence suggests that paternal BPA exposure adversely affects male germlines and results in atypical reproductive phenotypes that might persist for generations to come. Our study investigated this exposure on testicular architecture and sperm quality in mouse offspring, and characterised underlying molecular mechanism(s). A total of 18 immature male Swiss albino mice (3.5 weeks old) were randomly divided into three groups and treated as follows: Group I, no treatment (sham control); Group II, sterile corn oil only (vehicle control); Group III, BPA (400 μg/kg) in sterile corn oil. At 9.5 weeks old, F0 males were mated with unexposed females. F0 offspring (F1 generation) were monitored for postnatal development for 10 weeks. At 11.5 weeks old, the animals were sacrificed to examine testicular architecture, sperm parameters, including DNA integrity, and oxidative stress biomarkers. Results showed that BPA significantly induced changes in the body and testis weights of the F0 and F1 generation BPA lineages compared to F0 and F1 generation control lineages. A decrease in sperm count and motility with further, increased sperm abnormalities, no or few sperm DNA alterations and elevated levels of MDA, PC and NO were recorded. Similar effects were found in BPA exposed F0 males, but were more pronounced in the F0 offspring. In addition, BPA caused alterations in the testicular architecture. These pathological changes extended transgenerationally to F1 generation males’ mice, but the pathological changes were more pronounced in the F1 generation. Our findings demonstrate that the biological and health BPA impacts do not end in paternal adults, but are passed on to offspring generations. Hence, linking observed testis and sperm abnormalities in the F1 generation to BPA exposure of their parental line was evident in this work. The findings also illustrate that oxidative stress appears to be a molecular component of the testis and sperm pathologies.

Plant proteins can be an important alternative to animal proteins subject to minor modification to address sustainability issues. The impact of ultrasound application on the yield, techno-functional properties, and molecular characteristics of protein extracted from Moringa oleifera seeds was studied. For this purpose, a central composite design (CCD) was applied to optimize ultrasound-assisted extraction (UAE) parameters such as amplitude (25–75%), solute-to-solvent ratio (1:10–1:30), and pH (9–13) for obtaining the maximum protein yield. At the optimized conditions of 75% amplitude, 1:20 solute-to-solvent ratio, and 11 pH, a protein yield of 39.12% was obtained in the UAE process. Moreover, the best sonication time at optimized conditions was 20 min, which resulted in about 150% more extraction yield in comparison to conventional extraction (CE). The techno-functional properties, for instance, solubility, water (WHC)- and oil-holding capacity (OHC), and emulsifying and foaming properties of the protein obtained from UAE and CE were also compared. The functional properties revealed high solubility, good WHC and OHC, and improved emulsifying properties for protein obtained from UAE. Although protein from UAE provided higher foam formation, foaming stability was significantly lower.

This study assessed the possible protective role of green synthesized zinc oxide nanoparticles using Moringa olifera leaf extract (MO-ZNPs) in acrylamide (ACR)-induced reproductive dysfunctions in male rats. ACR (20 mg/kg b.wt/day) and/or MO-ZNPs (10 mg/kg b.wt/day) were given orally by gastric gavage for 60 days. Then, sperm parameters; testicular enzymes; oxidative stress markers; reproductive hormones including testosterone, luteinizing hormone (LH)-estradiol, and follicle-stimulating hormone (FSH) concentration; testis histology; steroidogenesis-related gene expression; and apoptotic markers were examined. The findings revealed that MO-ZNPs significantly ameliorated the ACR-induced decline in the gonadosomatic index and altered the pituitary–gonadal axis, reflected by decreased serum testosterone and FSH with increased estradiol and LH, and sperm analysis disruption. Furthermore, a notable restoration of the tissue content of antioxidants (catalase and reduced glutathione) but depletion of malondialdehyde was evident in MO-ZNPs+ACR-treated rats compared to ACR-exposed ones. In addition, MO-ZNPs oral dosing markedly rescued the histopathological changes and apoptotic caspase-3 reactions in the testis resulting from ACR exposure. Furthermore, in MO-ZNPs+ACR-treated rats, ACR-induced downregulation of testicular steroidogenesis genes and proliferating cell nuclear antigen (PCNA) immune-expression were reversed. Conclusively, MO-ZNPs protected male rats from ACR-induced reproductive toxicity by suppressing oxidative injury and apoptosis while boosting steroidogenesis and sex hormones.

Macroalgae are a valuable source of highly bioactive primary and secondary metabolites that may have useful bioapplications. To investigate the nutritional and nonnutritional contents of underexploited edible seaweeds, proximate composition, including protein, fat, ash, vitamins A, C, and E, and niacin, as well as important phytochemicals, including polyphenols, tannins, flavonoids, alkaloids, sterols, saponins, and coumarins, were screened from algal species using spectrophotometric methods. Ash content ranged from 3.15–25.23% for green seaweeds, 5–29.78% for brown algae, and 7–31.15% for red algae. Crude protein content ranged between 5 and 9.8% in Chlorophyta, 5 and 7.4% in Rhodophyta, and between 4.6 and 6.2% in Phaeophyceae. Crude carbohydrate contents ranged from 20 to 42% for the collected seaweeds, where green algae had the highest content (22.5–42%), followed by brown algae (21–29.5%) and red algae (20–29%). Lipid content was found to be low in all the studied taxa at approximately 1–6%, except for Caulerpa prolifera (Chlorophyta), which had a noticeable higher lipid content at 12.41%. These results indicated that Phaeophyceae were enriched with a high phytochemical content, followed by that of Chlorophyta and Rhodophyta. The studied algal species contained a high amount of carbohydrate and protein, indicating that they could be considered as a healthy food source.

Olanzapine (OLZ), one of the second-generation antipsychotics, is effective in stress accompanying with chronic psychiatric disease. But the effect of chronic long-standing use of OLZ administration on the liver and its association with metabolic side effects plus weight gain is still unclear. The objective of our study was to evaluate the antioxidant effect of Hypericum perforatum (HP) on OLZ-induced oxidative stress, biochemical disturbance, and histological alteration in the rat’s liver. Forty male wistar albino rats were allocated as follows: normal control rats (group 1), rats treated with OLZ at a dose of 27.0 mg/kg/day (group 2), group 3 (treated with HP at a dose of 81.0 mg/kg/day) and group 4 (received HP plus OLZ at the same doses). The results revealed that the OLZ-administration led to a significant elevation (***P < 0.001) in the levels of MDH, blood glucose, triglycerides, total cholesterol, liver function parameters and weight gain while a significant decrease (***P < 0.001) in activities of liver SOD and GSH was found. In addition to structural damage in the liver’s tissue. These findings were evaluated the toxic effects of chronic administration of OLZ. While HP supplementation caused a significant improvement (++P

Soybean has good nutritional and functional properties, which are essential for human physiology. Okara, a residue from soybean processing industries has a distinct profile of nutrients and phytochemicals. Therefore, the current study was planned to investigate the functional importance of okara. In the first phase of this study, okara was isolated from soybean and characterized in terms of protein, fat, ash, soluble dietary fiber, and insoluble dietary fiber. Furthermore, the okara flour was characterized using FT-IR (Fourier transform infrared spectroscopy), and micrograph images were obtained using SEM (scanning electron microscope). In the second phase of study, synbiotic (prebiotics + probiotics) yogurt was prepared with 3% concentrations of okara. Treatments were named as OFYo (control), OFY1 (probiotics), and OFY2 (3% okara + probiotics). Yogurt was subjected to physicochemical, antioxidant, microbiological, and sensory analysis. The addition of okara significantly affected nutritional and antioxidant attributes of yogurt (p < 0.05). The results indicated that adding 3% okara affected the protein, fat, water holding capacity, and color. Total phenolic contents, DPPH (2,2-diphenyl-1-picrylhydrazyl) activity and ABTS (2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) activity increased due to the addition of okara. Likewise, the highest total viable count (8.25 log CFU/mL) and probiotic count (8.98 log CFU/mL) were noted in yogurt with 3% okara. Okara has dietary fibers; this dietary fiber acts as a prebiotic source for probiotic L. Rhamnosus. This shows that okara has a different prebiotic potential. The addition of okara has promising potential for the development of functional food.

In this review, we discuss the advantages of vegetable sprouts in the development of food products as well as their beneficial effects on a variety of disorders. Sprouts are obtained from different types of plants and seeds and various types of leafy, root, and shoot vegetables. Vegetable sprouts are enriched in bioactive compounds, including polyphenols, antioxidants, and vitamins. Currently, different conventional methods and advanced technologies are used to extract bioactive compounds from vegetable sprouts. Due to some issues in traditional methods, increasingly, the trend is to use recent technologies because the results are better. Applications of phytonutrients extracted from sprouts are finding increased utility for food processing and shelf-life enhancement. Vegetable sprouts are being used in the preparation of different functional food products such as juices, bread, and biscuits. Previous research has shown that vegetable sprouts can help to fight a variety of chronic diseases such as cancer and diabetes. Furthermore, in the future, more research is needed that explores the extraordinary ways in which vegetable sprouts can be incorporated into green-food processing and preservation for the purpose of enhancing shelf-life and the formation of functional meat products and substitutes.

The current review investigates the effects of black seed (Nigella sativa) on human health, which is also used to encapsulate and oxidative stable in different food products. In recent decades, many extraction methods, such as cold pressing, supercritical fluid extraction, Soxhlet extraction, hydro distillation (HD) method, microwave-assisted extraction (MAE), ultrasound-assisted extraction, steam distillation, and accelerated solvent extraction (ASE) have been used to extract the oils from black seeds under optimal conditions. Black seed oil contains essential fatty acids, in which the major fatty acids are linoleic, oleic, and palmitic acids. The oxidative stability of black seed oil is very low, due to various environmental conditions or factors (temperature and light) affecting the stability. The oxidative stability of black seed oil has been increased by using encapsulation methods, including nanoprecipitation, ultra-sonication, spray-drying, nanoprecipitation, electrohydrodynamic, atomization, freeze-drying, a electrospray technique, and coaxial electrospraying. Black seed, oil, microcapsules, and their components have been used in various food processing, pharmaceutical, nutraceutical, and cosmetics industries as functional ingredients for multiple purposes. Black seed and oil contain thymoquinone as a major component, which has anti-oxidant, -diabetic, -inflammatory, -cancer, -viral, and -microbial properties, due to its phenolic compounds. Many clinical and experimental studies have indicated that the black seed and their by-products can be used to reduce the risk of cardiovascular diseases, chronic cancer, diabetes, oxidative stress, polycystic ovary syndrome, metabolic disorders, hypertension, asthma, and skin disorders. In this review, we are focusing on black seed oil composition and increasing the stability using different encapsulation methods. It is used in various food products to increase the human nutrition and health properties.

The catalytic activity of Sr2PdO3, prepared through the sol-gel citrate-combustion method for the oxygen evolution reaction (OER) in a 0.1 M HClO4 solution, was investigated. The electrocatalytic activity of Sr2PdO3 toward OER was assessed via the anodic potentiodynamic polarization and electrochemical impedance spectroscopy (EIS). The glassy carbon modified Sr2PdO3 (GC/Sr2PdO3) electrode exhibited a higher electrocatalytic activity, by about 50 times, in comparison to the unmodified electrode. The order of the reaction was close to unity, which indicates that the adsorption of the hydroxyl groups is a fast step. The calculated activation energy was 21.6 kJ.mol−1, which can be considered a low value in evaluation with those of the reported OER electrocatalysts. The Sr2PdO3 perovskite portrayed a high catalyst stability without any probability of catalyst poisoning. These results encourage the use of Sr2PdO3 as a candidate electrocatalyst for water splitting reactions.

La0.9Sr0.1FeO3 perovskite, prepared by the microwave-assisted method, was capped with cetyl trimethyl ammonium bromide (CTAB) cationic surfactant, and applied as a sorbent for the removal of the anionic Congo red (CR) dye from aqueous solutions. X-ray diffraction (XRD) patterns showed that the perovskite structure was not affected by capping; however, the particle size increased. There was a hipsochromic shift in the value of λmax of the CR absorption spectrum in the presence of CTAB, which indicated the formation of an oppositely charged dye–surfactant complex. The adsorption efficiency of CTAB-capped La0.9Sr0.1FeO3 was independent of the pH of the solution—equilibrium was reached after a few minutes. The value of the maximum adsorption capacity, qm, was 151.52 mg·g−1, which was 10-times higher than that of the pure perovskite. The proposed sorbent maintained its excellent sorption ability in the presence of the sample matrix; therefore, it can be regenerated and reused with unchanged performance.

Fish lipids are comprised of considerable quantities of polyunsaturated acids and are prone to oxidation, producing reactive oxygen species and hydroperoxides. This study aimed to evaluate the biochemical and structural alterations in Caco-2 cells following exposure to 100 μg/mL methyl linoleate or fish oil, and then radiated for 24, 48 or 72 h. Electron spin resonance spectroscopy detected free radicals in the lipid membrane, Raman microscopy observed biochemical alterations and atomic force microscopy identified changes in morphology, such as the breakdown of DNA bonds. The study showed that bioimaging and biochemical techniques can be effective at detecting and diagnosing cellular injuries incurred by lipid peroxidation.

Protein kinases orchestrate diverse cellular functions; however, their dysregulation is linked to metabolic dysfunctions, associated with many diseases, including cancer. Mitogen-Activated Protein (MAP) kinase is a notoriously oncogenic signaling pathway in human malignancies, where the extracellular signal-regulated kinases (ERK1/2) are focal serine/threonine kinases in the MAP kinase module with numerous cytosolic and nuclear mitogenic effector proteins. Subsequently, hampering the ERK kinase activity by small molecule inhibitors is a robust strategy to control the malignancies with aberrant MAP kinase signaling cascades. Consequently, new heterocyclic compounds, containing a sulfonamide moiety, were rationally designed, aided by the molecular docking of the starting reactant 1-(4-((4-methylpiperidin-1-yl)sulfonyl)phenyl)ethan-1-one (3) at the ATP binding pocket of the ERK kinase domain, which was relying on the molecular extension tactic. The identities of the synthesized compounds (4−33) were proven by their spectral data and elemental analysis. The target compounds exhibited pronounced anti-proliferative activities against the MCF-7, HepG-2, and HCT-116 cancerous cell lines with potencies reaching a 2.96 μM for the most active compound (22). Moreover, compounds 5, 9, 10b, 22, and 28 displayed a significant G2/M phase arrest and induction of the apoptosis, which was confirmed by the cell cycle analysis and the flow cytometry. Thus, the molecular extension of a small fragment bounded at the ERK kinase domain is a valid tactic for the rational synthesis of the ERK inhibitors to control various human malignancies.

Novel fused chromenes (4,7–11) and pyrimidines (12–16) were designed, synthesized, and evaluated for their mammary gland breast cancer (MCF-7), human colon cancer (HCT-116), and liver cancer (HepG-2) activities. The structural identity of the synthesized compounds was established according to their spectroscopic analysis, such as FT-IR, NMR, and mass spectroscopy. The preliminary results of the bioassay disclosed that some of the target compounds were proven to have a significant antiproliferative effect against the three cell lines, as compared to Doxorubicin, Vinblastine, and Colchicine, used as reference drugs. Particularly, compounds 7 and 14 exerted promising anticancer activity towards all cell lines and were chosen for further studies, such as cell cycle analysis, cell apoptosis, caspase 3/7 activity, DNA fragmentation, cell invasion, and migration. We found that these potent cytotoxic compounds induced cell cycle arrest at the S and G2/M phases, prompting apoptosis. Furthermore, these compounds significantly inhibit the invasion and migration of the different tested cancer cells. The structure-activity relationship (SAR) survey highlights that the antitumor activity of the desired compounds was affected by the hydrophobic or hydrophilic nature of the substituent at different positions.

Breast cancer is among the highest morbidity and mortality rates in women around the world. In the present investigation we aimed to synthesis novel nanosystem combining two naturally important anticancer agents with different mechanism of action namely Moringa oleifera and caffeine. Firstly, chemical analysis of Moringa oleifera extract and caffeine was done by gas chromatography-mass spectroscopy (GC-MS) in order to assess the main chemical compounds present and correlate between them and the possible anticancer effect. The novel nanosystem was characterized through dynamic light scattering techniques which revealed the stability and homogeneity of the prepared M. oleifera leaves extract/Caffeine loaded chitosan nanoparticles, while FTIR and transmission electron microscope (TEM) proved the shape and the successful incorporation of M. oleifera leaves extract/Caffeine onto the nanochitosan carrier. Our initial step was to assess the anticancer effect in vitro in cancer cell line MCF-7 which proved the significant enhanced effect of M. oleifera leaves extract/Caffeine nanosystem compared to M. oleifera leaves extract or caffeine loaded nanoparticles. Further studies were conducted in vivo namely tumor biomarkers, tumor volume, bioluminescence imaging, molecular and histopathological investigations. The present study proved the potent anticancer effect of the synthesized M. oleifera leaves extract/Caffeine loaded chitosan nanoparticles. Mo/Caf/CsNPs exhibited a large number of apoptotic cells within the tumor mass while the adipose tissue regeneration was higher compared to the positive control. The prepared nanoparticles downregulated the expression of Her2, BRCA1 and BRCA2 while mTOR expression was upregulated. The aforementioned data demonstrated the successful synergistic impact of Moringa and caffeine in decreasing the carcinoma grade., (© 2024. The Author(s).)

In this study, novel selective antitumor compounds were synthesized based on their fundamental pharmacophoric prerequisites associated with EGFR inhibitors. A molecular hybridization approach was employed to design and prepare a range of 4 H -chromene-3-carboxylates 7a - g , 8 , and 11a - e derivatives, each incorporating a sulfonamide moiety. The structures of these hybrid molecules were verified using comprehensive analytical and spectroscopic techniques. During the assessment of the newly synthesized compounds for their anticancer properties against three tumor cell lines (HepG-2, MCF-7, and HCT-116), compounds 7f and 7g displayed remarkable antitumor activity against all tested cell lines, outperforming the reference drug Cisplatin in terms of efficacy. Consequently, these promising candidates were selected for further investigation of their anti-EGFR, h CAII, and MMP-2 potential, which exhibited remarkable effectiveness against EGFR and MMP2 when compared to Sorafenib. Additionally, docking investigations regarding the EGFR binding site were implemented for the targeted derivatives in order to attain better comprehension with respect to the pattern in which binding mechanics occur between the investigated molecules and the active site, which illustrated a higher binding efficacy in comparison with Sorafenib.

Chitosan integrated nanoparticles of clotrimazole and Egyptian Vitis vinifera juice extract was evaluated in order to maximize the antifungal activity and reduce the gross side effects. In the present study Egyptian Thompson Seedless Vitis vinifera and Clotrimazole (Cz) loaded chitosan nanoparticles (NCs/VJ/Cz) showed a promising antifungal effect with average inhibition zone diameters of 74 and 72 mm against Candida albicans and Aspergillus niger respectively. NCs/VJ /Cz was stable with significant drug entrapment efficiency reached 94.7%; PDI 0.24; zeta potential value + 31 and average size 35.4 nm diameter. Ex vivo and in vivo evaluation of skin retention, permeation and wound repair potentialities of NCs/VJ /Cz ointment was examined by experimental rats with wounded skin fungal infection. Data proved the ability of NCs/VJ /Cz to gradually release the drugs in a sustained manner with complete wound healing effect and tissue repair after 7 days administration. As a conclusion NCs/VJ /Cz ointment can be used as a novel anti-dermatophytic agent with high wound healing capacity., Competing Interests: 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., (© 2021 The Author(s).)