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.

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.

Potential Anticancer Activity of Juniperus procera and Molecular Docking Models of Active Proteins in Cancer Cells.

Medicinal plants provide a wide range of active compounds that can be exploited to create novel medicines with minimal side effects. The current study aimed to identify the anticancer properties of Juniperus procera (J. procera) leaves. Here, we demonstrate that J. procera leaves' methanolic extract suppresses cancer cells in colon (HCT116), liver (HepG2), breast (MCF-7), and erythroid (JK-1) cell lines. By applying GC/MS, we were able to determine the components of the J. procera extract that might contribute to cytotoxicity. Molecular docking modules were created that used active components against cyclin-dependent kinase 5 (Cdk5) in colon cancer, aromatase cytochrome P450 in the breast cancer receptor protein, the -N terminal domain in the erythroid cancer receptor of the erythroid spectrin, and topoisomerase in liver cancer. The results demonstrate that, out of the 12 bioactive compounds generated by GC/MS analysis, the active ingredient 2-imino-6-nitro-2H-1-benzopyran-3-carbothiamide proved to be the best-docked chemical with the chosen proteins impacted by DNA conformational changes, cell membrane integrity, and proliferation in molecular docking studies. Notably, we uncovered the capacity of J. procera to induce apoptosis and inhibit cell growth in the HCT116 cell line. Collectively, our data propose that J. procera leaves' methanolic extract has an anticancer role with the potential to guide future mechanistic studies.

Epithelial Cell Adhesion Molecule (EpCAM) Expression Can Be Modulated via NFκB.

The epithelial cell adhesion molecule (EpCAM) is considered an essential proliferation signature in cancer. In the current research study, qPCR induced expression of EpCAM was noted in acute lymphoblastic leukemia (ALL) cases. Costunolide, a sesquiterpene lactone found in crepe ginger and lettuce, is a medicinal herb with anticancer properties. Expression of EpCAM and its downstream target genes (Myc and TERT) wasdownregulated upon treatment with costunolide in Jurkat cells. A significant change in the telomere length of Jurkat cells was not noted at 72 h of costunolide treatment. An in silico study revealed hydrophobic interactions between EpCAM extracellular domain and Myc bHLH with costunolide. Reduced expression of NFκB, a transcription factor of EpCAM, Myc, and TERT in costunolide-treated Jurkat cells, suggested that costunolide inhibits gene expression by targeting NFκB and its downstream targets. Overall, the study proposes that costunolide could be a promising therapeutic biomolecule for leukemia.

Transcriptomic Analysis of Conserved Telomere Maintenance Component 1 (CTC1) and Its Association with Leukemia.

Telomere length (TEL) regulation is important for genome stability and is governed by the coordinated role of shelterin proteins, telomerase (TERT), and CST (CTC1/OBFC1/TEN1) complex. Previous studies have shown the association of telomerase expression with the risk of acute lymphoblastic leukemia (ALL). However, no data are available for CST association with the ALL. The current pilot study was designed to evaluate the CST expression levels in ALL. In total, 350 subjects were recruited, including 250 ALL cases and 100 controls. The subjects were stratified by age and categorized into pediatrics (1-18 years) and adults (19-54 years). TEL and expression patterns of CTC1, OBFC1, and TERT genes were determined by qPCR. The univariable logistic regression analysis was performed to determine the association of gene expression with ALL, and the results were adjusted for age and sex in multivariable analyses. Pediatric and adult cases did not reflect any change in telomere lengths relative to controls. However, expression of CTC1, OBFC1, and TERT genes were induced among ALL cases. Multivariable logistic regression analyses showed association of CTC1 with ALL in pediatric [ß estimate (standard error (SE)= -0.013 (0.007), p = 0.049, and adults [0.053 (0.023), p = 0.025]. The association of CTC1 remained significant when taken together with OBFC1 and TERT in a multivariable model. Furthermore, CTC1 showed significant association with B-cell ALL [-0.057(0.017), p = 0.002) and T-cell ALL [-0.050 (0.018), p = 0.008] in pediatric group while no such association was noted in adults. Together, our findings demonstrated that telomere modulating genes, particularly CTC1, are strongly associated with ALL. Therefore, CTC1 can potentially be used as a risk biomarker for the identification of ALL in both pediatrics and adults.

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.

Optimization of Supercritical Carbon Dioxide Extraction of Saussurea costus Oil and Its Antimicrobial, Antioxidant, and Anticancer Activities.

Saussurea costus is a medicinal plant with different bioactive compounds that have an essential role in biomedicine applications, especially in Arab nations. However, traditional extraction methods for oils can lead to the loss of some volatile and non-volatile oils. Therefore, this study aimed to optimize the supercritical fluid extraction (SFE) of oils from S. costus at pressures (10, 20, and 48 MPa). The results were investigated by GC/MS analysis. MTT, DPPH, and agar diffusion methods assessed the extracted oils' anticancer, antioxidant, and antimicrobial action. GC/MS results showed that elevated pressure from 10 to 20 and 48 MPa led to the loss of some valuable compounds. In addition, the best IC50 values were recorded at 10 MPa on HCT, MCF-7, and HepG-2 cells at about 0.44, 0.46, and 0.74 µg/mL, respectively. In contrast, at 20 MPa, the IC50 values were about 2.33, 6.59, and 19.0 µg/mL, respectively, on HCT, MCF-7, and HepG-2 cells, followed by 48 MPa, about 36.02, 59.5, and 96.9 µg/mL. The oil extract at a pressure of 10 MPa contained much more of á-elemene, dihydro-à-ionone, patchoulene, á-maaliene, à-selinene, (-)-spathulenol, cedran-diol, 8S,13, elemol, eremanthin, á-guaiene, eudesmol, ç-gurjunenepoxide-(2), iso-velleral, and propanedioic acid and had a higher antioxidant activity (IC50 14.4 µg/mL) more than the oil extract at 20 and 48 MPa. In addition, the inhibitory activity of all extracts was higher than gentamicin against all tested bacteria. One of the more significant findings from this study is low pressure in SFE enhancement, the extraction of oils from S. costus, for the first time. As a result, the SFE is regarded as a good extraction technique since it is both quick and ecologically friendly. Furthermore, SFE at 10 MPa increased the production and quality of oils, with high antioxidant activity and a positive effect on cancer cells and pathogens.

Protective effect of Bosutinib with caspase inhibitors on human K562 cells.

Introduction: Cancer therapy has become increasingly focused on molecularly targeted medications. Despite the fact that multi-cytotoxic medication regimens have proven to be highly effective, many investigations in targeted treatments have focused on a single agent. The precise molecular mechanism of action of second-generation BCR-ABL tyrosine kinase inhibitors, which includes different targets and pathways, can help rationalize therapy in chronic myelogenous leukemia (CML) and other diseases affected by BCR-ABL tyrosine kinase inhibitors (TKIs). Aim: The purpose of this study was to analyze if bosutinib (BOS) combined with Boc-D-FMK effectively suppressed proliferation and induced apoptosis in K562 cells to a lesser extent, implying that bosutinib is an effective leukemia treatment and that its combination with Boc-D-FMK is a mild chemotherapeutic agent against leukemia. Methods: In this study, bosutinib was obtained together with other materials to perform a cell culture experiment with human cell lines, as well as additional drug treatment. Furthermore, cell viability (MTT assay) and flow cryometry such as viability and cell cycle assays are performed. The target profile of the dual SRC/ABL inhibitor bosutinib was studied in this study as a first kinase inhibitor to target K562 cells, which has recently been linked to the proliferation of myelogenous leukaemia cells, these results suggest the effectiveness of inhibitory activity on cell viability/proliferation, alone generated a potent value of 250 nM (39.27 ± 1.17) for 48 h as optimal dose. Results: The cytotoxic effect of bosutinib on the K562 cell line was assessed in vitro using the MTT assay, and the cytotoxicity was further clarified using cell viability and cell cycle assays. Guava Cell Assay software validated the activation of apoptosis. Sub-G1, G0/G1, S, and G2/M phases are depicted. Cell cycle research revealed that K562 cells treated with bosutinib accumulated much more in the sub-G1 phase, which was later validated by a drop peak at the G2/M phase. Conclusion: In conclusion, the nature of bosutinib's reduction of cancer cell growth may open the door to future research into the development of green synthesis medicines, particularly for cancer treatment.

Apigenin attenuates molecular, biochemical, and histopathological changes associated with renal impairments induced by gentamicin exposure in rats.

Gentamicin (GM) is an aminoglycoside antibiotic used to treat bacterial infections. However, its application is accompanied by renal impairments. Apigenin is a flavonoid found in many edible plants with potent therapeutic values. This study was designed to elucidate the therapeutic effects of apigenin on GM-induced nephrotoxicity. Animals were injected orally with three different doses of apigenin (5 mg kg-1 day-1, 10 mg kg-1 day-1, and 20 mg kg-1 day-1). Apigenin administration abolished the alterations in the kidney index and serum levels of kidney-specific functions markers, namely blood urea nitrogen and creatinine, and KIM-1, NGAL, and cystatin C following GM exposure. Additionally, apigenin increased levels of enzymatic (glutathione reductase, glutathione peroxidase, superoxide dismutase, and catalase) and non-enzymatic antioxidant proteins (reduced glutathione) and decreased levels of lipid peroxide, nitric oxide, and downregulated nitric oxide synthase-2 in the kidney tissue following GM administration. At the molecular scope, apigenin administration was found to upregulate the mRNA expression of Nfe2l2 and Hmox1 in the kidney tissue. Moreover, apigenin administration suppressed renal inflammation and apoptosis by decreasing levels of interleukin-1ß, tumor necrosis factor-alpha, nuclear factor kappa-B, Bax, and caspase-3, while increasing B-cell lymphoma-2 compared with those in GM-administered group. The recorded data suggests that apigenin treatment could be used to alleviate renal impairments associated with GM administration.

Antiulcer activity of proanthocyanidins is mediated via suppression of oxidative, inflammatory, and apoptotic machineries.

Gastric ulcer (GU) is a lesion in the gastric mucosa associated with excessive oxidative damage, inflammatory response, apoptotic events, and irritation which may develop into cancer. However, medications commonly used in GU treatment cannot normalize gastric mucosa, while causing several adverse effects. Proanthocyanidins (PAs) are dietary flavonoids with numerous biological and pharmacological activities. In the current investigation, we studied the potential anti-ulcerative activity of PAs against acidified ethanol (HCl/ethanol)-caused gastric ulceration. Fifty male albino Wistar rats were allocated into five equal groups: control, HCl/ethanol (3 mL/kg), lansoprazole (LPZ, 30 mg/kg) + HCl/ethanol, and PAs (100 and 250 mg/kg) + HCl/ethanol. LPZ and PAs were applied one week before gastric ulcer induction. PAs pretreatment notably reduced gastric mucosal macroscopic and microscopic pathological changes in a dose-dependent manner. Additionally, PAs activated the innate antioxidant molecules including glutathione and its derived antioxidants (glutathione peroxidase and glutathione reductase), along with superoxide dismutase and catalase, while attenuating pro-oxidant formation, including malondialdehyde and nitric oxide. Interestingly, PAs supplementation at a higher dose suppressed gastric inflammatory and apoptotic responses, as demonstrated by the reduced levels of interleukin-1ß, interleukin-6, tumor necrosis factor alpha, high-mobility group box 1, cyclooxygenase 2, prostaglandin E2, nuclear factor kappa-B, Bcl-2-associated X protein, and caspase-3, while B cell lymphoma 2 was elevated. Hence, PAs could exhibit antiulcer activity by protecting gastric tissue from the development of oxidative damage, inflammatory responses, and apoptosis events associated with ulceration. PRACTICAL IMPLICATIONS: Gastric ulcer is a lesion in the gastric mucosal layer associated with excessive inflammatory response, apoptotic events, oxidative damage, and irritation, and may develop into cancer with about 5%-10% morbidity rate. However, medications commonly used in GU treatment cannot normalize gastric mucosa, while causing several adverse effects. Therefore, new therapeutic approaches are needed to treat or prevent gastric ulceration. Proanthocyanidins (PAs, condensed tannins) are dietary flavonoids found in abundance in different plant species, including their fruits, bark, and seeds. Due to their potent antioxidative activity, PAs have been applied to prevent or treat oxidative stress-related diseases, including cancer, as well as metabolic, neurodegenerative, cardiovascular, and inflammatory disorders. Here, we examine the potential therapeutic role of proanthocyanidins (PAs) against acidified ethanol-induced gastric ulcer in rats through evaluating oxidative challenge, inflammatory response, apoptotic events, and histopathological changes in the gastric tissue.

Protocatechuic acid abrogates oxidative insults, inflammation, and apoptosis in liver and kidney associated with monosodium glutamate intoxication in rats.

Monosodium glutamate (MSG), a commonly used flavor enhancer, has been reported to induce hepatic and renal dysfunctions. In this study, the palliative role of protocatechuic acid (PCA) in MSG-administered rats was elucidated. Adult male rats were assigned to four groups, namely control, MSG (4 g/kg), PCA (100 mg/kg), and the last group was co-administered MSG and PCA at aforementioned doses for 7 days. Results showed that MSG augmented the hepatic and renal functions markers as well as glucose, triglycerides, total cholesterol, and low-density lipoprotein levels. Moreover, marked increases in malondialdehyde levels accompanied by declines in glutathione levels and notable decreases in the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase were observed in MSG-treated group. The MSG-mediated oxidative stress was further confirmed by downregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) gene expression levels in both tissues. In addition, MSG enhanced the hepatorenal inflammation as witnessed by increased inflammatory cytokines (interleukin-1b and tumor necrosis factor-α) and elevated nuclear factor-κB (NF-κB) levels. Further, significant increases in Bcl-2-associated X protein (Bax) levels together with decreases in B-cell lymphoma 2 (Bcl-2) levels were observed in MSG administration. Histopathological screening supported the biochemical and molecular findings. In contrast, co-treatment of rats with PCA resulted in remarkable enhancement of the antioxidant cellular capacity, suppression of inflammatory mediators, and apoptosis. These effects are possibly endorsed for activation of Nrf-2 and suppression of NF-kB signaling pathways. Collectively, addition of PCA counteracted MSG-induced hepatorenal injuries through modulation of oxidative, inflammatory and apoptotic alterations.

Rivaroxaban Modulates TLR4/Myd88/NF-Kß Signaling Pathway in a Dose-Dependent Manner With Suppression of Oxidative Stress and Inflammation in an Experimental Model of Depression.

Depression is a common mental illness leading to upset or anxiety, with a high incidence rate in the world. Depression can lead to suicidal thoughts and behavior. The present study aimed to evaluate the effect of the direct oral anticoagulant rivaroxaban (RVX), in the model of depression induced by chronic unpredicted mild stress (CUMS) in rats. Fifty-six male Wister rats were randomly divided into seven experimental groups (8 rats/group); Group 1: Control group given vehicle per oral (p.o.), Group 2: RVXL-control group (received rivaroxaban 20 mg/kg/day, p.o..), Group 3: RVXH-control group (received rivaroxaban 30 mg/kg/day, p.o.), Group 4: chronic unpredictable mild stress (CUMS) group, Group 5: FLX-treated CUMS group (received fluoxetine 10 mg/kg/day, p.o..), Group 6: RVXL-treated CUMS group (received rivaroxaban 20 mg/kg/day, p.o.), and Group 7: RVXH-treated CUMS group (received rivaroxaban 30 mg/kg/day, p.o.). The rats received the drugs from the first day of the experiment and continued till 4 weeks-the duration of the study. The following were measured: monoamine neurotransmitters, malondialdehyde (MDA), total nitrite/nitrate (NOx), reduced glutathione (GSH), superoxide dismutase (SOD), Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), nuclear factor-kappa B (NF-κB), tumor necrosis factor-α (TNF-α), brain-derived neurotrophic factor (BDNF), and vascular endothelial growth factor-A (VEGF-A). A forced swimming test (FST) was done. Furthermore, histological changes and glial fibrillary acidic protein (GFAP) immunoexpression were evaluated. CUMS showed a significant decrease in hypothalamic neurotransmitters, hippocampal GSH, SOD, BNDF, and VEGF-A with a significant increase in hippocampal MDA, NOx, NF-kß, Myd88, TLR4, TNF-α, and GFAP immunoexpression. RVX showed significant improvement in all parameters (p -value < 0.0001). In conclusion, RVX in a dose-dependent manner possesses potent ameliorative effects against depression by reducing the oxidative stress and inflammatory process, through the regulation of the TLR4/Myd88/NF-kß signaling pathway.

Epidemiological, Morphometric, and Molecular Investigation of Cystic Echinococcosis in Camel and Cattle From Upper Egypt: Current Status and Zoonotic Implications.

Cystic echinococcosis has been considered one of the major parasitic zoonoses which is associated with severe economic losses. The present study was undertaken to investigate the occurrence, organ distribution, cyst fertility, and viability of cystic echinococcosis in slaughtered camels and cattle from various abattoirs in Assiut Governorate, Egypt. The work also involved morphological, morphometric, and molecular identification of the parasite. The occurrence of hydatid cysts was investigated in total number of 100 lungs of camels and 574 liver and lungs of cattle admitted to three slaughterhouses at Assiut Governorate, Egypt. Moreover, several individual variable factors, including organ involvement, age, sex, and hydatid cyst characteristics, were studied to identify their possible association with the occurrence of the disease. Genomic DNA was extracted from the hydatid cysts, followed by molecular identification of the parasite through amplification of ribosomal DNA internal transcribed spacer (ITS) regions. Hydatid cysts were found in 6 camels (6%) out of 100 inspected camels, while 5 hydatid cysts (0.87%) were detected in a total number of 574 cattle examined. The parasite was detected exclusively in lungs of camels, while lungs were the main organ infected by the parasite in cattle and one hydatid cyst was found in the liver (0.17%). In camel, 66.7, 16.65, and 16.65%of detected cysts were fertile, sterile, and calcified, respectively, while in cattle, these percentages were 60, 20, and 20%, respectively. None of the studied variable factors were significantly associated with the occurrence of the disease in camels, with the exception that all cysts were found in the lung. Conversely, we found a significant association (P < 0.05) between the age and sex of the slaughtered cattle and the occurrence of hydatid cysts. In this respect, the rate of infection was higher in female cattle and those cattle more than 5 years (P < 0.05). The morphological, morphometric, and molecular studies confirmed the presence of the parasite. Taken together, our results concluded that camels and cattle play a potential role in maintaining the transmission cycle of this zoonotic parasite.

Antioxidant and Anti-Inflammatory Potential of Thymoquinone and Lycopene Mitigate the Chlorpyrifos-Induced Toxic Neuropathy.

CPF (chlorpyrifos) is an organophosphate pesticide used in agricultural and veterinary applications. Our experiment aimed to explore the effects of thymoquinone (TQ) and/or lycopene (LP) against CPF-induced neurotoxicity. Wistar rats were categorized into seven groups: first group served as a control (corn oil only); second group, TQ (10 mg/kg); third group, LP (10 mg/kg); fourth group, CPF (10 mg/kg) and deemed as CPF toxic control; fifth group, TQ + CPF; sixth group, (LP + CPF); and seventh group, (TQ + LP + CPF). CPF intoxication inhibited acetylcholinesterase (AchE), decreased glutathione (GSH) content, and increased levels of malondialdehyde (MDA), an oxidative stress biomarker. Furthermore, CPF impaired the activity of antioxidant enzymes including superoxide dismutase (SOD) and catalase (CAT) along with enhancement of the level of inflammatory mediators such as tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1ß. CPF evoked apoptosis in brain tissue. TQ or LP treatment of CPF-intoxicated rats greatly improved AchE activity, oxidative state, inflammatory responses, and cell death. Co-administration of TQ and LP showed better restoration than their sole treatment. In conclusion, TQ or LP supplementation may alleviate CPF-induced neuronal injury, most likely due to TQ or LPs' antioxidant, anti-inflammatory, and anti-apoptotic effects.

Enhanced Antibacterial Potential of Amoxicillin against Helicobacter pylori Mediated by Lactobionic Acid Coated Zn-MOFs.

H. pylori (Helicobacter pylori) causes a common chronic infectious disease and infects around 4.4 billion people worldwide. H. pylori was classified as a member of the primary class of stomach cancer (stomach adenocarcinoma). Hence, this study was conducted to design a novel lactobionic acid (LBA)-coated Zn-MOFs to enhance bactericidal activity of Amoxicillin (AMX) against H. pylori. The synthesized Zn-MOFs were characterized by various techniques which included Dynamic Light Scattering (DLS), Fourier Transform Infrared (FT-IR) Spectroscopy, Powder X-ray diffraction, scanning electron microscope, and atomic force microscope. They were capable of encapsulating an increased amount of AMX and investigated for their efficacy to enhance the antibacterial potential of their loaded drug candidate. Interestingly, it was found that LBA-coated Zn-MOFs significantly reduced the IC50, MIC, and MBIC values of AMX against H. pylori. Morphological investigation of treated bacterial cells further authenticated the above results as LBA-coated Zn-MOFs-treated cells underwent complete distortion compared with non-coated AMX loaded Zn-MOFs. Based on the results of the study, it can be suggested that LBA-coated Zn-MOFs may be an effective alternate candidate to provide new perspective for the treatment of H. pylori infections.

Computational and Preclinical Evidence of Anti-ischemic Properties of L-Carnitine-Rich Supplement via Stimulation of Anti-inflammatory and Antioxidant Events in Testicular Torsed Rats.

Ischemia-reperfusion injury is a urological emergency condition that could lead to necrosis, testicular damage subfertility, and infertility. The purpose of this study was to identify changes taking place in the rat testis at short-term (4 hr) as well as long-term (7 days) reperfusion following testicular torsion and to evaluate the effects of Proxeed Plus (PP), L-carnitine-rich antioxidant supplement, on preventing these changes using the biochemical parameters and histopathology. Thirty adult male rats were divided into five groups: in groups, 1-4 testicular ischemia was achieved by rotating the left testis 720° clockwise for 4 h and dividing into the sham, torsion/detorsion (T/D), T/D+1000 mg/kg BW PP, and T/D+5000 mg/kg BW PP groups, respectively. PP was administered intraperitoneally 30 min before detorsion while group 5 served as the normal control. All rats were sacrificed 4 h after detorsion. The same experimental design was set up, and animals were sacrificed after 7 days of detorsion. The testicular levels of human cyclooxygenase-2; tumor necrosis factor; interleukins-1ß, 6, and 10; hydrogen peroxide; malonaldehyde; superoxide dismutase; catalase; glutathione transferase; glutathione peroxidase; glutathione reductase; and histopathological damage were evaluated. Our results revealed that rats in the torsion/detorsion group exhibited elevated testicular levels of oxidative markers and proinflammatory cytokines, low levels of antioxidant enzymes, and severe histological alterations relative to the control and sham groups. Treatments with 1000 and 5000 mg/kg BW of PP for 4 hr and 7 days significantly (p < 0.05) decreased the levels of the proinflammatory and oxidative markers while increasing the spermatogenesis, testicular levels of antioxidant enzymes, and anti-inflammatory cytokine (IL-10) in a dose-dependent manner. This suggested that PP exhibited anti-inflammatory and antioxidant activities against I/R testes thus serving as an effective supplement to protect against testicular assault.

Pharmacological Screening of Viola odorata L. for Memory-Enhancing Effect via Modulation of Oxidative Stress and Inflammatory Biomarkers.

Purpose: Alzheimer disease (AD) is a progressive neurodegenerative disorder that is caused by neuroinflammation and oxidative stress. The present study aimed to characterize and then investigate the memory-enhancing potential of Viola odorata methanolic extract in lipopolysaccharide (LPS)-treated mice. Methods: V. odorata characterization was done by using the GCMS technique. Neuroinflammation was induced by the intracerebroventricular administration of LPS at a dose of 12 µg. Animals were divided randomly into six groups (n = 10). Group I was normal control, which was given vehicle. Group II was disease control, which received LPS (12 µg) via the intracerebroventricular route. Group III was standard, which was administered with donepezil (3 µg) orally for 21 days. Groups IV-VI were the treatment groups, which were administered with the extract at 100, 200, and 400 mg/kg dose levels orally respectively for 21 days. Groups III-VI received LPS (12 µg) on the first day along with their treatments. During the treatment, the animals were assessed for memory retention by employing different behavioral paradigms namely elevated plus maze, passive avoidance, foot shock and open field. Various mediators [endogenous antioxidants, neurotransmitters, and acetylcholinesterase (AChE)] involved in the pathogenesis of AD were quantified by using the UV spectrophotometric method. Results: Extract-treated groups showed a remarkable improvement in cognitive impairment in all behavioral paradigms. Oxidative stress biomarkers, that is, superoxide dismutase, catalase, and glutathione were raised dose-dependently in the treatment groups with a dose-dependent decrease in the malonaldehyde and AChE levels in the brains of the treated animals. The treatment groups showed decreased levels of inflammatory biomarkers, that is, tumor necrosis factor-alpha, nuclear factor kappa light-chain enhancer of activated ß-cells, and cyclo-oxygenase, which supports the therapeutic effectiveness of the treatment. Conclusion: Based on behavioral, oxidative stress biomarker, and neuroinflammatory data, it is concluded that V. odorata possesses memory-enhancing activity and may prove a beneficial role in the management of AD.

Protective efficacy of thymoquinone or ebselen separately against arsenic-induced hepatotoxicity in rat.

Arsenic (As) exposure is associated with adverse health outcomes to the living organisms. In the present study, the hepato-protective ability of thymoquinone (TQ), the active principle of Nigella sativa seed, or ebselen (Eb), an organoselenium compound, against As intoxication in female rats was investigated. For this purpose, animals were allocated randomly into control, As (20 mg/kg), TQ (10 mg/kg), Eb (5 mg/kg), As+TQ, and As+Eb groups that were orally administered for 28 consecutive days. Arsenic exposure resulted in hepatic oxidative damage which was evidenced by marked decreases in antioxidant parameters (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione (GSH)) concomitant with high malondialdehyde (MDA) level. Furthermore, As toxicity induced significant elevations in liver accumulation of As, serum hepatic indices (aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and total bilirubin (TB)), and apoptotic marker (B cell lymphoma 2(Bcl2), Bcl-2-associated X protein (Bax), and caspase 3) levels. Additionally, notable increments in hepatic fibrotic markers (epidermal growth factor (EFG) and transforming growth factor beta 1 (TGF-ß1)) associated with high nitric oxide, interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), and myeloperoxidase (MPO) levels were noticed following As intoxication. Biochemical findings were well-supported by hepatic histopathological screening. The co-treatment of As-exposed rats with TQ or Eb considerably improved liver function and antioxidant status together with lessened hepatic As content, inflammation, apoptosis, and fibrosis. The overall outcomes demonstrated that TQ or Eb ameliorates As-induced liver injury through their favorable antioxidant, anti-inflammatory, anti-apoptotic, and fibrolytic properties.

Concise review: workshop review: understanding and assessing the risks of stem cell-based therapies.

The field of stem cell therapeutics is moving ever closer to widespread application in the clinic. However, despite the undoubted potential held by these therapies, the balance between risk and benefit remains difficult to predict. As in any new field, a lack of previous application in man and gaps in the underlying science mean that regulators and investigators continue to look for a balance between minimizing potential risk and ensuring therapies are not needlessly kept from patients. Here, we attempt to identify the important safety issues, assessing the current advances in scientific knowledge and how they may translate to clinical therapeutic strategies in the identification and management of these risks. We also investigate the tools and techniques currently available to researchers during preclinical and clinical development of stem cell products, their utility and limitations, and how these tools may be strategically used in the development of these therapies. We conclude that ensuring safety through cutting-edge science and robust assays, coupled with regular and open discussions between regulators and academic/industrial investigators, is likely to prove the most fruitful route to ensuring the safest possible development of new products.