Therapeutic effect of N, N-Diphenyl-1,4-phenylenediamine and adipose-derived stem cells coadministration on diabetic cardiomyopathy in type 1 diabetes mellitus-rat model.

Type 1 diabetes stem-cell-based treatment approach is among the leading therapeutic strategies for treating cardiac damage owing to the stem cells' regeneration capabilities. Mesenchymal stem cells derived from adipose tissue (AD-MSCs) have shown great potential in treating diabetic cardiomyopathy (DCM). Herein, we explored the antioxidant-supporting role of N, N'-diphenyl-1,4-phenylenediamine (DPPD) in enhancing the MSCs' therapeutic role in alleviating DCM complications in heart tissues of type 1 diabetic rats. Six male albinos Wistar rat groups have been designed into the control group, DPPD (250 mg/kg, i.p.) group, diabetic-untreated group, and three diabetic rat groups treated with either AD-MSCs (1 × 106 cell/rat, i.v.) or DPPD or both. Interestingly, all three treated diabetic groups exhibited a significant decrease in serum glucose, HbA1c, heart dysfunction markers (lactate dehydrogenase and CK-MP) levels, and lipid profile fractions (except for HDL-C), as well as some cardiac oxidative stress (OS) levels (MDA, AGEs, XO, and ROS). On the contrary, serum insulin, C-peptide, and various cardiac antioxidant levels (GSH, GST, CAT, SOD, TAC, and HO-1), beside viable cardiac cells (G0/G1%), were markedly elevated compared with the diabetic untreated group. In support of these findings, the histological assay reflected a marked enhancement in the cardiac tissues of all diabetic-treated groups, with obvious excellency of the AD-MSCs + DPPD diabetic-treated group. Such results strongly suggested the great therapeutic potentiality of either DPPD or AD-MSCs single injection in enhancing the cardiac function of diabetic rats, with a great noted enhancement superiority of DPPD and AD-MSCs coadministration.

Molecular detection of exosomal miRNAs of blood serum for prognosis of colorectal cancer.

Colorectal cancer (CRC) is the third most common cancer affecting people. The discovery of new, non-invasive, specific, and sensitive molecular biomarkers for CRC may assist in the diagnosis and support therapeutic decision making. Exosomal miRNAs have been demonstrated in carcinogenesis and CRC development, which makes these miRNAs strong biomarkers for CRC. Deep sequencing allows a robust high-throughput informatics investigation of the types and abundance of exosomal miRNAs. Thus, exosomal miRNAs can be efficiently examined as diagnostic biomarkers for disease screening. In the present study, a number of 660 mature miRNAs were detected in patients diagnosed with CRC at different stages. Of which, 29 miRNAs were differentially expressed in CRC patients compared with healthy controls. Twenty-nine miRNAs with high abundance levels were further selected for subsequent analysis. These miRNAs were either highly up-regulated (e.g., let-7a-5p, let-7c-5p, let-7f-5p, let-7d-3p, miR-423-5p, miR-3184-5p, and miR-584) or down-regulated (e.g., miR-30a-5p, miR-99-5p, miR-150-5p, miR-26-5p and miR-204-5p). These miRNAs influence critical genes in CRC, leading to either tumor growth or suppression. Most of the reported diagnostic exosomal miRNAs were shown to be circulating in blood serum. The latter is a novel miRNA that was found in exosomal profile of blood serum. Some of the predicted target genes of highly expressed miRNAs participate in several cancer pathways, including CRC pathway. These target genes include tumor suppressor genes, oncogenes and DNA repair genes. Main focus was given to multiple critical signaling cross-talking pathways including transforming growth factor ß (TGFß) signaling pathways that are directly linked to CRC. In conclusion, we recommend further analysis in order to experimentally confirm exact relationships between selected differentially expressed miRNAs and their predicted target genes and downstream functional consequences.

Chemical and spectroscopic characterization of (Artemisinin/Querctin/ Zinc) novel mixed ligand complex with assessment of its potent high antiviral activity against SARS-CoV-2 and antioxidant capacity against toxicity induced by acrylamide in male rats.

A novel Artemisinin/Quercetin/Zinc (Art/Q/Zn) mixed ligand complex was synthesized, tested for its antiviral activity against coronavirus (SARS-CoV-2), and investigated for its effect against toxicity and oxidative stress induced by acrylamide (Acy), which develops upon cooking starchy foods at high temperatures. The synthesized complex was chemically characterized by performing elemental analysis, conductance measurements, FT-IR, UV, magnetic measurements, and XRD. The morphological surface of the complex Art/Q/Zn was investigated using scanning and transmission electron microscopy (SEM and TEM) and energy dispersive X-ray analysis (XRD). The in vitro antiviral activity of the complex Art/Q/Zn against SARS-CoV-2 and its in vivo activity against Acy-induced toxicity in hepatic and pulmonary tissues were analyzed. An experimental model was used to evaluate the beneficial effects of the novel Art/Q/Zn novel complex on lung and liver toxicities of Acy. Forty male rats were randomly divided into four groups: control, Acy (500 mg/Kg), Art/Q/Zn (30 mg/kg), and a combination of Acy and Art/Q/Zn. The complex was orally administered for 30 days. Hepatic function and inflammation marker (CRP), tumor necrosis factor, interleukin-6 (IL-6), antioxidant enzyme (CAT, SOD, and GPx), marker of oxidative stress (MDA), and blood pressure levels were investigated. Histological and ultrastructure alterations and caspase-3 variations (immunological marker) were also investigated. FT-IR spectra revealed that Zn (II) is able to chelate through C=O and C-OH (Ring II) which are the carbonyl oxygen atoms of the quercetin ligand and carbonyl oxygen atom C=O of the Art ligand, forming Art/Q/Zn complex with the chemical formula [Zn(Q)(Art)(Cl)(H2O)2]⋅3H2O. The novel complex exhibited a potent anti-SARS-CoV-2 activity even at a low concentration (IC50 = 10.14 µg/ml) and was not cytotoxic to the cellular host (CC50 = 208.5 µg/ml). Art/Q/Zn may inhibit the viral replication and binding to the angiotensin-converting enzyme-2 (ACE2) receptor and the main protease inhibitor (MPro), thereby inhibiting the activity of SARS-CoV-2 and this proved by the molecular dynamics simulation. It alleviated Acy hepatic and pulmonary toxicity by improving all biochemical markers. Therefore, it can be concluded that the novel formula Art/Q/Zn complex is an effective antioxidant agent against the oxidative stress series, and it has high inhibitory effect against SARS-CoV-2.

Valorizing pomegranate wastes by producing functional silver nanoparticles with antioxidant, anticancer, antiviral, and antimicrobial activities and its potential in food preservation.

The food sector generates massive amounts of waste, which are rich in active compounds, especially polyphenols; therefore, valorizing these wastes is a global trend. In this study, we produce silver nanoparticles from pomegranate wastes, characterized by enhanced antioxidant, anticancer, antiviral, and antimicrobial properties and investigated their potential to maintain the fruit quality for sixty days in market. The pomegranate waste-mediated silver nanoparticles (PPAgNPs) were spherical shape (measured by TEM), 20 nm (Zeta sizer), negatively charged -25.98 mV (Zeta potential), and surrounded by active groups (FTIR). The PPAgNPs scavenged 94 % of DPPH radicals and inhibited the growth of pathogens, i.e., Staphylococcus aureus, Listeria monocytogenes, Campylobacter jejuni, Salmonella typhi and Candida with inhibition zones diameters (16-45 mm). They impeded the development of breast and colon cancer cell lines by 80 and 78 %, increased the activity of apoptosis marker caspase 3, and inhibited 82 % of COVID-19. The PPAgNPs were added to the rat diet at 80, 160, and 320 µg/kg levels. PPAgNPs administered at a concentration of 160 µg/kg in the rat diet resulted in the best growth performance, normal liver and kidney parameters (p = 0.029-0.038), lowered lipid profile, malondialdhyde (MDA), and raised glutathion reduced (GSH), total protein (TP). Also, the reduced gene expression of Interleukin 6 (IL-6) and Tumor necrosis factor alpha (TNF-α) in albino rats' serum indicates the anti-inflammatory effect of PPAgNPs. PPAgNPs developed a functional coating to preserve mandarin fruit for 60 days by dipping technique. The active coat containing PPAgNPs can effectively preserve the fruit for 60 days.

Protective impacts of Artemisia annua against hepatic toxicity induced by gentamicin.

The current study aimed to investigate the ameliorative effects of Artemisia annua (RA) extract on hepatic toxicity induced by gentamicin injection mice. Sixteen mice were divided into four groups; the control group received saline, the second group received 1% A. annua (RA) extract, third group injected 80 mg/kg gentamicin (GEN) intraperitoneally. The protective group treated with a combination of GEN and A. annua. All mice were treated for consecutive 15 days. Results confirmed that hepatic biomarkers (GPT, GCT, GOT, IL-6 and IL-1ß), all were altered after gentamycin injection. The histological analysis confirmed that gentamycin injected mice showed portal vein congestion, micro and macro steatosis, and nuclear pyknosis of hepatocytes. The protective group showed intact central vein with less microsteatosis of some hepatocytes. Immunochemistry analysis confirmed that the immunoreactivity of COX-2 gene showed negative impact in examined groups. Unlike, NF-κB gene exhibited diffuse positive expression in the gentamicin group. TGF-ß1 immunoreactivity was mild positive in control and highly upregulated in gentamicin treated mice, all were normalized after RA administration. In conclusion, RA showed a beneficial impact against gentamycin induced hepatic toxicity at cellular and biochemical levels by regulating proteins and inflammatory markers associated with liver activity.

Sugiol Masters Apoptotic Precision to Halt Gastric Cancer Cell Proliferation.

Sugiol, a natural compound with anticancer properties, has shown promise in various cancer types, but its potential in preventing gastric cancer remains uncertain. In this study, we aimed to examine the inhibitory effect of sugiol on human gastric cancer cell proliferation. Our findings demonstrate that sugiol effectively suppresses the proliferation of SNU-5 human gastric cancer cells, leading to apoptotic cell death. We assessed the chemo-preventive potential of sugiol via an MTT assay and confirmed the induction of oxidative stress using the H2DCFDA fluorescent dye. Treatment with sugiol at concentrations higher than 25 µM for 24 h resulted in an increase in intracellular levels of reactive oxygen species (ROS). This elevation of ROS levels inhibited cell-cycle progression and induced cell-cycle arrest at the G1 phase. Furthermore, our study revealed that sugiol reduces the viability and proliferation of SNU-5 cells in a dose-dependent manner. Importantly, ADME and toxicity analyses revealed that sugiol was effective and nontoxic at low doses. In parallel, we utilized the Swiss target prediction tool to identify potential targets for sugiol. Enzymes and nuclear receptors were identified as major targets. To gain insights into the molecular interactions, we performed structure-based molecular docking studies, focusing on the interaction between sugiol and STAT3. The docking results revealed strong binding interactions within the active site pocket of STAT3, with a binding affinity of -12.169 kcal/mole. Sugiol's -OH group, carbonyl group, and phenyl ring demonstrated hydrogen-bonding interactions with specific residues of the target protein, along with Vander Waals and hydrophobic interactions. These data suggest that sugiol has the potential to inhibit the phosphorylation of STAT3, which is known to play a crucial role in promoting the growth and survival of cancer cells. Targeting the dysregulated STAT3 signaling pathway holds promise as a therapeutic strategy for various human tumors. In combination with interventions that regulate cell cycle progression and mitigate the DNA damage response, the efficacy of these therapeutic approaches can be further enhanced. The findings from our study highlight the antiproliferative and apoptotic potential of sugiol against human gastric cancer cells (SNU-5). Moreover, the result underpins that sugiol's interactions with STAT3 may contribute to its inhibitory effects on cancer cell growth and proliferation. Further research is warranted to explore the full potential of sugiol as a therapeutic agent and its potential application in treating gastric cancer and other malignancies characterized by dysregulated STAT3 activity.

Characterization of Portulaca oleracea Whole Plant: Evaluating Antioxidant, Anticancer, Antibacterial, and Antiviral Activities and Application as Quality Enhancer in Yogurt.

Purslane (Portulaca oleracea L.) is rich in phenolic compounds, protein, and iron. This study aims to produce functional yogurt with enhanced antioxidant, anticancer, antiviral, and antimicrobial properties by including safe purslane extract in yogurt formulation; the yogurt was preserved for 30 days at 4 °C, and then biochemical fluctuations were monitored. The purslane extract (PuE) had high phenolic compounds and flavonoids of 250 and 56 mg/mL, respectively. Therefore, PuE had considerable antioxidant activity, which scavenged 93% of DPPH˙, inhibited the viability of MCF-7, HCT, and HeLa cell lines by 84, 82, and 80%, respectively, and inhibited 82% of the interaction between the binding between Spike and ACE2 compared to a SARS-CoV-2 inhibitor test kit. PuE (20-40 µg/mL) inhibited the growth of tested pathogenic bacteria and Candida strains, these strains isolated from spoild yogurt and identified at gene level by PCR. Caffeic acid glucoside and catechin were the main phenolic compounds in the HPLC profile, while the main flavor compound was carvone and limonene, representing 71% of total volatile compounds (VOCs). PuE was added to rats' diets at three levels (50, 150, and 250 µg/g) compared to butylated hydroxyanisole (BHA). The body weight of the rats fed the PuE diet (250 µg/g) increased 13% more than the control. Dietary PuE in rats' diets lowered the levels of low-density lipoprotein (LDL) levels by 72% and increased the levels of high-density lipoprotein (HDL) by 36%. Additionally, liver parameters in rats fed PuE (150 µg/g) decreased aspartate aminotransferase (AST), alanine aminotransferase (ALT), and malondialdehyde (MDA) levels by 50, 43, and 25%, respectively, while TP, TA, and GSH were increased by 20, 50, and 40%, respectively, compared to BHA. Additionally, PuE acts as a kidney protector by lowering creatinine and urea. PuE was added to yogurt at three concentrations (50, 150, and 250 µg/g) and preserved for 30 days compared to the control. The yogurt's pH reduced during storage while acidity, TSS, and fat content increased. Adding PuE increased the yogurt's water-holding capacity, so syneresis decreased and viscosity increased, which was attributed to enhancing the texture properties (firmness, consistency, and adhesiveness). MDA decreased in PuE yogurt because of the antioxidant properties gained by PuE. Additionally, color parameters L and b were enhanced by PuE additions and sensorial traits, i.e., color, flavor, sugary taste, and texture were enhanced by purslane extract compared to the control yogurt. Concerning the microbial content in the yogurt, the lactic acid bacteria (LAB) count was maintained as a control. Adding PuE at concentrations of 50, 150, and 250 µg/g to the yogurt formulation can enhance the quality of yogurt.

Phytochemical Characterization of Saudi Mint and Its Mediating Effect on the Production of Silver Nanoparticles and Its Antimicrobial and Antioxidant Activities.

The green synthesis of nanoparticles (NPs) is attracting enormous attention as a new area of study that encompasses the development and discovery of new agents for their utilization in different fields, such as pharmaceuticals and food. Nowadays, the use of plants, particularly medicinal plants, for the creation of NPs has emerged as a safe, ecofriendly, rapid, and simple approach. Therefore, the present study aimed to use the Saudi mint plant as a medicinal plant for the synthesis of silver nanoparticles (AgNPs) and to evaluate the antimicrobial and antioxidant activities of AgNPs compared to mint extract (ME). A phenolic and flavonoid analysis that was conducted by using HPLC indicated the presence of numerous compounds in the ME. Through an HPLC analysis, chlorogenic acid at a concentration of 7144.66 µg/mL was the main detected component in the ME, while catechin, gallic acid, naringenin, ellagic acid, rutin, daidzein, cinnamic acid, and hesperetin were identified in varying concentrations. AgNPs were synthesized by using ME and were confirmed via UV-visible spectroscopy at 412 nm of the maximum absorption. The mean diameter of the synthesized AgNPs was measured by TEM to be 17.77 nm. Spectra obtained by using energy-dispersive X-ray spectroscopy indicated that silver was the main element formation in the created AgNPs. The presence of various functional groups, analyzed by using Fourier transform infrared spectroscopy (FTIR), indicated that the mint extract was responsible for reducing Ag+ to Ag0. The spherical structure of the synthesized AgNPs was confirmed by X-ray diffraction (XRD). Furthermore, the ME showed reduced antimicrobial activity (a zone of inhibition of 30, 24, 27, 29, and 22 mm) compared with the synthesized AgNPs (a zone of inhibition of 33, 25, 30, 32, 32, and 27 mm) against B. subtilis, E. faecalis, E. coli, P. vulgaris, and C. albicans, respectively. The minimum inhibitory concentration of the AgNPs was lower than that of the ME for all of the tested micro-organisms, except for P. vulgaris. The MBC/MIC index suggested that the AgNPs revealed a higher bactericidal effect compared to the ME. The synthesized AgNPs exhibited antioxidant activity with a reduced IC50 (IC50 of 8.73 µg/mL) compared to that of the ME (IC50 of 13.42 µg/mL). These findings demonstrate that ME could be applied as a mediator for AgNPs synthesis and natural antimicrobial and antioxidant agents.

Enhanced Solubility and Biological Activity of Dexibuprofen-Loaded Silica-Based Ternary Solid Dispersions.

The current study was designed to formulate ternary solid dispersions (TSDs) of dexibuprofen (Dex) by solvent evaporation to augment the solubility and dissolution profile, in turn providing gastric protection and effective anti-inflammatory activity. Initially, nine formulations (S1 to S9) of binary solid dispersions (BSDs) were developed. Formulation S1 comprising a 1:1 weight ratio of Dex and Syloid 244FP® was chosen as the optimum BSD formulation due to its better solubility profile. Afterward, 20 TSD formulations were developed using the optimum BSD. The formulation containing Syloid 244FP® with 40% Gelucire 48/16® (S18) and Poloxamer 188® (S23) successfully enhanced the solubility by 28.23 and 38.02 times, respectively, in pH 6.8, while dissolution was increased by 1.99- and 2.01-fold during the first 5 min as compared to pure drug. The in vivo gastroprotective study in rats suggested that the average gastric lesion index was in the order of pure Dex (8.33 ± 2.02) > S1 (7 ± 1.32) > S18 (2.17 ± 1.61) > S23 (1.83 ± 1.04) > control (0). The in vivo anti-inflammatory study in rats revealed that the percentage inhibition of swelling was in the order of S23 (71.47 ± 2.16) > S18 (64.8 ± 3.79) > S1 (54.14 ± 6.78) > pure drug (18.43 ± 2.21) > control (1.18 ± 0.64) after 6 h. ELISA results further confirmed the anti-inflammatory potential of the developed formulation, where low levels of IL-6 and TNF alpha were reported for animals treated with S23. Therefore, S23 could be considered an effective formulation that not only enhanced the solubility and bioavailability but also reduced the gastric irritation of Dex.

Pharmaceutical Development of Intraperitoneal Arachis hypogaea as a Renal Protective Agent.

BACKGROUND: Kidneys are among the vital organs of the human body; therefore, damage from any exogenous/endogenous agent may put human life at risk. Arachis hypogaea (AH) contains different free radical scavenging flavonoids, stilbenes, and tannins. This research aimed to elucidate the possible nephroprotective mechanism of AH methanolic crude extract (AHcr) and n-hexane oil fraction (AHO) against gentamycin-induced nephrotoxicity. METHODS: After the extraction of the crude oil of the plant, they were tested against a Gentamycin (GM)-treated group of Swiss Albino mice for their nephroprotective action. Animals were divided into six (6) equal groups with five (5) animals in each group. These groups were: control group (0.5 mL normal saline via intraperitoneal -i.p), gentamycin group (gentamycin 100 mg/kg i.p), Silymarin + gentamycin group (Silymarin 50 mg/kg and gentamycin 100 mg/kg i.p), plant extract (AHcr1) and gentamycin group (AHcr1 250 mg/kg and gentamycin 100 mg/kg i.p), AHcr2 + gentamycin group (AHcr2; 500 mg/kg and gentamycin 100 mg/kg i.p) and the hexane oil fraction (AHO) + gentamycin (AHO 1 mL/kg and GM 100 mg/kg i.p). After completion of doses, animals were sacrificed for the collection of blood to further investigate biochemical changes and histopathological changes in kidney tissues. RESULTS: Serum creatinine, urea, and blood urea nitrogen significantly increased (p < 0.001) in the gentamycin-treated group as compared to the control group. The elevated level of serum creatinine, urea, and blood urea nitrogen was decreased significantly (p < 0.001) in groups treated with AHcr and AHO compared to the gentamycin group. Similarly, the histopathological study of kidney tissues from the gentamycin group showed tubular necrosis, vacuolation, and fibrosis. CONCLUSIONS: The effect of crude extract and hexane soluble fraction of AH caused a significant reversal of gentamycin-induced nephrotoxicity.

Utilization of a nanostructured lipid carrier encapsulating pitavastatin-Pinus densiflora oil for enhancing cytotoxicity against the gingival carcinoma HGF-1 cell line.

Oral squamous cell carcinoma (OSCC) is the most common epithelial tumor of the oral cavity. Gingival tumors, a unique type of OSCC, account for 10% of these malignant tumors. The antineoplastic properties of statins, including pitavastatin (PV), and the essential oil of the Pinus densiflora leaf (Pd oil) have been adequately reported. The goal of this investigation was to develop nanostructured lipid carriers (NLCs) containing PV combined with Pd oil and to determine their cytotoxicity against the cell line of human gingival fibroblasts (HGF-1). A central composite quadratic design was adopted to optimize the nanocarriers. The particle size and stability index of the nano-formulations were measured to evaluate various characteristics. TEM analysis, the entrapment efficiency, dissolution efficiency, and the cytotoxic efficiency of the optimized PV-loaded nanostructured lipid carrier drug delivery system (PV-Pd-NLCs) were evaluated. Then, the optimal PV-Pd-NLCs was incorporated into a Carbopol 940® gel base and tested for its rheological features and its properties of release and cell viability. The optimized NLCs had a particle size of 98 nm and a stability index of 89%. The gel containing optimum PV-Pd-NLCs had reasonable dissolution efficiency and acceptable rheological behavior and acquired the best cytotoxic activity against HGF-1 cell line among all the formulations developed for the study. The in vitro cell viability studies revealed a synergistic effect between PV and Pd oil in the treatment of gingival cancer. These findings illustrated that the gel containing PV-Pd-NLCs could be beneficial in the local treatment of gingival cancer.

Thymoquinone protects the testes of hypothyroid rats by suppressing pro-inflammatory cytokines and oxidative stress and promoting SIRT1 testicular expression.

Background: Hypothyroidism has been linked to many testicular structural and dysfunctional changes in males. Thymoquinone (TQ) has shown a potent testicular protective effect through its antioxidant, anti-inflammatory, antiapoptotic, fertility-enhancing, and endocrine modulatory activities. Objectives: This study aimed to investigate the efficacy of TQ in preserving the testicular structure of a model of experimentally induced hypothyroidism in rats and identify the mechanism behind this effect. Materials and methods: Propylthiouracil (PTU) was used to induce hypothyroidism in adult male Wistar rats, who were then treated with TQ (50 mg/kg/body weight) for 4 weeks and compared to the untreated rats. Thyroid hormonal profile, oxidants/antioxidants profile, and serum testosterone levels were assessed. Gene expression and immune expression of SIRT1 and pro-inflammatory cytokines TNF-α and NF-κB were also assessed in the testicular tissue. Results: TQ administration successfully improved PTU-induced disturbance in the thyroid hormonal profile (T3, T4, and TSH), serum testosterone level, and pancreatic antioxidants compared to the untreated hypothyroid group. TQ significantly downregulated (p = 0.001, p ˂ 0.001) TNF-α and NF-κB transcription, while it significantly upregulated (p = 0.01) SIRT1 transcription in the testes of hypothyroid rats. TQ markedly relieved the histopathological testicular changes induced by PTU and significantly increased (p = 0.002, p = 0.01) the sectional area of seminiferous tubules and germinal epithelial height, respectively. TUNEL-positive apoptotic germinal cells were significantly decreased (p ˂ 0.001), while PCNA-positive proliferating germinal cells and androgen receptor expression were significantly increased (p ˂ 0.001) in the testes of TQ-treated hypothyroid rats. Conclusion: Thymoquinone could limit the hypothyroidism-induced structural changes in the testis, mostly through the upregulation of SIRT1 expression, which seems to mediate its promising antioxidant, anti-inflammatory and antiapoptotic effects that were evident in this study. Therefore, TQ is recommended as an adjuvant safe supplement in managing hypothyroidism, especially in males.

Pomegranate Pomace Extract with Antioxidant, Anticancer, Antimicrobial, and Antiviral Activity Enhances the Quality of Strawberry-Yogurt Smoothie.

Valorizing the wastes of the food industry sector as additives in foods and beverages enhances human health and preserves the environment. In this study, pomegranate pomace (PP) was obtained from the company Schweppes and exposed to the production of polyphenols and fiber-enriched fractions, which were subsequently included in a strawberry-yogurt smoothie (SYS). The PP is rich in carbohydrates and fibers and has high water-absorption capacity (WAC) and oil-absorption capacity (OAC) values. The LC/MS phenolic profile of the PP extract indicated that punicalagin (199 g/L) was the main compound, followed by granatin B (60 g/L) and pedunculagin A (52 g/L). Because of the high phenolic content of PP extract, it (p ≤ 0.05) has high antioxidant activity with SC50 of 200 µg/mL, besides scavenging 95% of DPPH radicals compared to ascorbic acid (92%); consequently, it reduced lung cancer cell lines' viability to 86%, and increased caspase-3 activity. Additionally, it inhibited the growth of pathogenic bacteria and fungi i.e., L. monocytogenes, P. aeruginosa, K. pneumonia, A. niger, and C. glabrata, in the 45-160 µg/mL concentration range while killing the tested isolates with 80-290 µg/mL concentrations. These isolates were selected based on the microbial count of spoiled smoothie samples and were identified at the gene level by 16S rRNA gene sequence analysis. The interaction between Spike and ACE2 was inhibited by 75.6%. The PP extract at four levels (0.4, 0.8, 1.2, and 1.4 mg/mL) was added to strawberry-yogurt smoothie formulations. During 2 months storage at 4 °C, the pH values, vitamin C, and total sugars of all SYS decreased. However, the decreases were gradually mitigated in PP-SYS because of the high phenolic content in the PP extract compared to the control. The PP-SYS3 and PP-SYS4 scored higher in flavor, color, and texture than in other samples. In contrast, acidity, fat, and total soluble solids (TSS) increased at the end of the storage period. High fat and TSS content are observed in PP-SYS because of the high fiber content in PP. The PP extract (1.2 and 1.6 mg/mL) decreases the color differences and reduces harmful microbes in PP-SYS compared to the control. Using pomegranate pomace as a source of polyphenols and fiber in functional foods enhances SYS's physiochemical and sensory qualities.

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.

Development of Novel 1,3-Disubstituted-2-Thiohydantoin Analogues with Potent Anti-Inflammatory Activity; In Vitro and In Silico Assessments.

Inflammation is the main cause of several autoimmune diseases, including type I diabetes, rheumatoid arthritis, bullous pemphigoid, paraneoplastic pemphigoid, and multiple sclerosis. Currently, there is an urgent demand for the discovery of novel anti-inflammatory drugs with potent activity but also safe for long-term application. Toward this aim, the present study reported the design, synthesis, and characterization of a set of novel 1,3-disubstituted-2-thiohydantoins derivatives. The anti-inflammatory activity of synthesized compounds was assessed against murine leukemia cell line (RAW264.7) by evaluating the cytotoxicity activity and their potency to prevent nitric oxide (NO) production. The results revealed that the synthesized compounds possess a considerable cytotoxic activity together with the ability to reduce the NO production in murine leukemia cell line (RAW264.7). Among synthesized compounds, compound 7 exhibited the most potent cytotoxic activity with IC50 of 197.68 µg/mL, compared to celecoxib drug (IC50 value 251.2 µg/mL), and demonstrated a significant ability to diminish the NO production (six-fold reduction). Exploring the mode of action responsible for the anti-inflammatory activity revealed that compound 7 displays a significant and dose-dependent inhibitory effect on the expression of pro-inflammatory cytokines IL-1ß. Furthermore, compound 7 demonstrated the ability to significantly reduce the expression of the inflammatory cytokines IL-6 and TNF-α at 50 µg/mL, as compared to Celecoxib. Finally, detailed molecular modelling studies indicated that compound 7 exhibits a substantial binding affinity toward the binding pocket of the cyclooxygenase 2 enzyme. Taken together, our study reveals that 1,3-disubstituted-2-thiohydantoin could be considered as a promising scaffold for the development of potent anti-inflammatory agents.

Evaluation of Green Silver Nanoparticles Fabricated by Spirulina platensis Phycocyanin as Anticancer and Antimicrobial Agents.

Green nanotechnology has attracted attention worldwide, especially in treating cancer and drug-resistant section 6 microbes. This work aims to investigate the anticancer activity of green silver nanoparticles synthesized by Spirulina platensis phycocyanin (SPAgNPs) on two cancer cell lines: Lung cancer cell line (A-549) and breast cancer cell line (MCF-7), compared to the normal human lung cell line (A138). We also aimed to investigate the bactericidal activity against Staphylococcus aureus ATCC29737, Bacillus cereus ATCC11778, Escherichia coli ATCC8379, and Klebsiella pneumonia, as well as the fungicidal activity against Candida albicans (ATCC6019) and Aspergillus niger. The obtained SPAgNPs were spherical and crystalline with a size of 30 nm and a net charge of -26.32 mV. Furthermore, they were surrounded by active groups responsible for stability. The SPAgNPs scavenged 85% of the DPPH radical with a relative increase of approximately 30% over the extract. The proliferation of cancer cells using the MTT assay clarified that both cancer cells (A-549 and MCF-7) are regularly inhibited as they grow on different concentrations of SPAgNPs. The maximum inhibitory effect of SPAgNPs (50 ppm) reached 90.99 and 89.51% against A-549 and MCF7, respectively. Regarding antimicrobial activity, no inhibition zones occurred in bacterial or fungal strains at low concentrations of SPAgNPs and the aqueous Spirulina platensis extract. However, at high concentrations, inhibition zones, especially SPAgNPs, were more potent for all tested microorganisms than their positive controls, with particular reference to Staphylococcus aureus, since the inhibition zones were 3.2, 3.8, and 4.3 mm, and Bacillus cereus was 2.37 mm when compared to tetracycline (2.33 mm). SPAgNPs have more potent antifungal activity, especially against Aspergillus niger, compared to their positive controls. We concluded that SPAgNPs are powerful agents against oxidative stress and microbial infection.

Assessment of Binary Agarose-Carbopol Buccal Gels for Mucoadhesive Drug Delivery: Ex Vivo and In Vivo Characterization.

Agarose (AG) is a naturally occurring biocompatible marine seaweed extract that is converted to hydrocolloid gel in hot water with notable gel strength. Currently, its mucoadhesion properties have not been fully explored. Therefore, the main aim of this study was to evaluate the mucoadhesive potential of AG binary dispersions in combination with Carbopol 934P (CP) as mucoadhesive gel preparations. The gels fabricated via homogenization were evaluated for ex vivo mucoadhesion, swelling index (SI), dissolution and stability studies. The mucoadhesive properties of AG were concentration dependent and it was improved by the addition of CP. Maximum mucoadhesive strength (MS) (27.03 g), mucoadhesive flow time (FT) (192.2 min), mucoadhesive time in volunteers (MT) (203.2 min) and SI (23.6% at 4 h) were observed with formulation F9. The mucoadhesive time investigated in volunteers (MT) was influenced by AG concentration and was greater than corresponding FT values. Formulations containing 0.3%, w/v AG (F3 and F9) were able to sustain the release (~99%) for both drugs till 3 h. The optimized formulation (F9) did not evoke any inflammation, irritation or pain in the buccal cavity of healthy volunteers and was also stable up to 6 months. Therefore, AG could be considered a natural and potential polymer with profound mucoadhesive properties to deliver drugs through the mucosal route.

Ameliorative Effect of Pomegranate Peel Extract (PPE) on Hepatotoxicity Prompted by Iron Oxide Nanoparticles (Fe2O3-NPs) in Mice.

An evaluation of the ameliorative effect of pomegranate peel extract (PPE) in counteracting the toxicity of iron oxide nanoparticles (Fe2O3-NPs) that cause hepatic tissue damage is focused on herein. Forty male albino mice were haphazardly grouped into four groups as follows: the first control group was orally gavage daily with physiological saline; the second group received 100 mg/kg of PPE by the oral route day after day; the third group received 30 mg/kg Fe2O3-NPs orally; and the fourth group received both PPE and Fe2O3-NPs by the oral route, the same as the second and third sets. Later, after the completion of the experiment, we collected the liver, blood, and bone marrow of bone specimens that were obtained for further laboratory tests. For instance, exposure to Fe2O3-NPs significantly altered serum antioxidant biomarkers by decreasing the levels of total antioxidant capacity (TAC), catalase (CAT), and glutathione s-transferase (GST). Additionally, it caused changes in the morphology of hepatocytes, hepatic sinusoids, and inflammatory Kupffer cells. Furthermore, they significantly elevated the number of chromosomal aberrations including gaps, breaks, deletions, fragments, polyploidies, and ring chromosomes. Moreover, they caused a significant overexpression of TIMP-1, TNF-α, and BAX mRNA levels. Finally, the use of PPE alleviates the toxicity of Fe2O3-NPs that were induced in the hepatic tissues of mice. It is concluded that PPE extract has mitigative roles against the damage induced by Fe2O3-NPs, as it serves as an antioxidant and hepatoprotective agent. The use of PPE as a modulator of Fe2O3-NPs' hepatotoxicity could be considered as a pioneering method in the use of phytochemicals against the toxicity of nanoparticles.

Ginger Is a Potential Therapeutic for Chronic Toxoplasmosis.

Background:Toxoplasma gondii (T. gondii) is an opportunistic parasite that causes serious diseases in humans, particularly immunocompromised individuals and pregnant women. To date, there are limited numbers of therapeutics for chronic toxoplasmosis which necessitate the discovery of effective and safe therapeutics. In the present study, we aimed to evaluate the antitoxoplasmosis potential of ginger extract in mice with experimentally induced chronic toxoplasmosis. Results: Treatment with ginger extract significantly reduced cysts count in the brains of T. gondii-infected mice with a marked alleviation of edema and inflammation, and a reversal of neuronal injury. Moreover, ginger extract treatment reduced inflammation in liver and lungs and protected hepatocytes from infection-induced degeneration. Consistently, apoptosis was significantly mitigated in the brains of ginger extract-treated mice compared to infected untreated animals or spiramycin-treated animals. Methods: Four groups of Swiss albino mice (10 mice each) were used. The first group was not infected, whereas 3 groups were infected with Me49 T. gondii strains. One infected group remained untreated (infected untreated), whereas the other two infected groups were treated with either ginger extract (250 mg/kg) or spiramycin (positive control; 100 mg/kg), respectively. The therapeutic potential of ginger extract was evaluated by calculation of the parasite burden in infected animals, and examination of the infected tissues for reduced pathologic changes. Conclusions: Our results showed for the first time that ginger extract exhibited marked therapeutic effects in mice with chronic T. gondii infection which indicates that it can be used as a safe and effective treatment for chronic toxoplasmosis.

Antidiabetic Drug Sitagliptin with Divalent Transition Metals Manganese and Cobalt: Synthesis, Structure, Characterization Antibacterial and Antioxidative Effects in Liver Tissues.

Metals and their complexes have an increasing number of medical applications. Sitagliptin (STG) acts as an antidiabetic drug. Mn(II) and Co(II) complexes were studied and characterized based on physical characterization, FT-IR, DG/TG, XRD, ESM, and TEM. Data revealed that STG acts as a bidentate ligand through the oxygen atom of a carbonyl group and the nitrogen atom of an amino group. Magnetic measurement data revealed that the Mn/STG metal complex has a square planner geometry. The experiment was performed on 40 male albino rats who were divided into four groups: the control group, STG group, group treated with STG/Mn, and group treated with Co/STG. Biomarkers for hepatic enzymes and antioxidants were found in the blood, and hepatic tissue histology was evaluated. STG in combination with Mn and Co administration showed potent protective effects against hepatic biochemical alterations induced by STG alone, as well as suppressing oxidative stress and structural alterations. These complexes prevented any stress and improved hepatic enzymatic levels more than STG alone. The STG/Mn complex was highly effective against Bacillus subtilis and Streptococcus pneumonia, while STG/Co was highly effective against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureas. Therefore, STG combined with Mn and Co produced a synergistic effect against oxidative stress and improved the histological structure of the liver tissues. STG metal complexes with Mn and Co showed the most potential ameliorative antioxidant and hepatoprotective effects.