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.

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.

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.

Infection pattern, case fatality rate and spread of Lassa virus in Nigeria.

BACKGROUND: Lassa fever (LF) is a zoonotic infectious disease of public concern in Nigeria. The infection dynamics of the disease is not well elucidated in Nigeria. This study was carried out to describe the pattern of infection, case fatality rate and spread of lassa virus (LASV) from 2017 to 2020. METHODS: Weekly epidemiological data on LF from December, 2016 to September, 2020 were obtained from Nigeria Centre for Disease Control. The number of confirmed cases and deaths were computed according to months and states. Descriptive statistics was performed and case fatality rate was calculated. Distribution and spread maps of LF over the four years period was performed on ArcMap 10.7. RESULTS: A total of 2787 confirmed cases and 516 deaths were reported in Nigeria from December, 2016 to September, 2020. Increase in number of cases and deaths were observed with 298, 528, 796 and 1165 confirmed cases and 79, 125, 158 and 158 deaths in 2017, 2018, 2019 and 2020 respectively. Over 60% of the cases were reported in two states, Edo and Ondo states. The LF cases spread from 19 states in 2017 to 32 states and Federal Capital Territory (FCT) in 2020. Ondo state (25.39%) had the highest of deaths rate from LF over the four years. Case fatality rate (CFR) of LF was highest in 2017 (26.5%) with CFR of 23.7, 19.6 and 13.4% in 2018, 2019 and 2020 respectively. The peak of infection was in the month of February for the four years. Infections increases at the onset of dry season in November and decline till April when the wet season sets-in. CONCLUSION: There is an annual increase in the number of LASV infection across the states in Nigeria. There is need to heighten control strategies through the use of integrated approach, ranging from vector control, health education and early diagnosis.

Luteolin protects against lead acetate-induced nephrotoxicity through antioxidant, anti-inflammatory, anti-apoptotic, and Nrf2/HO-1 signaling pathways.

Lead (Pb) is one of the most common heavy metal pollutants affecting living organisms. It induces nephrotoxicity with significant alterations in renal structure and function. Luteolin (LUT) a flavonoid present in various plant products is well known for exhibiting numerous pharmacological properties. We evaluated the protective efficacy of LUT against Pb-induced renal injury in male Wistar rats. Four experimental groups: control, LUT (50 mg/kg, orally), PbAc (20 mg/kg, i.p.), LUT + PbAc (at the aforementioned doses) were maintained for 7 days. PbAc administration significantly increased renal Pb accumulation, urea, and creatinine levels in serum, and induced renal histological alterations. Additionally, compared to the control rats, PbAc-treated rats exhibited significantly low levels of antioxidant enzyme activity and expression (SOD, CAT, GPx and GR), as well as high MDA levels. Moreover, PbAc exposure downregulated Nfe212 and Homx1 mRNA expression and significantly increased inflammatory marker (TNF-α, IL-1ß and NO) levels in renal tissue. PbAc significantly upregulated the synthesis of apoptotic related proteins and downregulated antiapoptotic protein expression. Notably, LUT pretreatment of PbAc-treated rats provided significant nephroprotection and reversed the alterations in the abovementioned parameters. In conclusion, LUT provided significant protection against PbAc intoxication via antioxidant, anti-inflammatory, and anti-apoptotic activities by activating the Nrf2/ARE signaling pathway.

Neuromodulatory effects of green coffee bean extract against brain damage in male albino rats with experimentally induced diabetes.

Diabetes mellitus is an increasing metabolic disease worldwide associated with central nervous system disorders. Coffee is a widely consumed beverage that enriched with antioxidants with numerous medicinal applications. Accordingly, the present study aimed to investigate the therapeutic potential of orally administered green coffee bean water extract (GCBWE) against cortical damage induced by high fat diet (HFD) followed by a single injection of streptozotocin (STZ) in rats. Metformin (Met) was used as standard antidiabetic drug. Animals were allocated into six groups: control, GCBWE (100 mg/kg), HFD/STZ (40 mg/kg), HFD/STZ + GCBWE (50 mg/kg), HFD/STZ + GCBWE (100 mg/kg) and HFD/STZ + Met (200 mg/kg) which were treated daily for 28 days. Compared to control rats, HFD/STZ-treated rats showed decreased levels of cortical dopamine, norepinephrine and serotonin with marked increases in their metabolites. Further, HFD/STZ treatment resulted in notable elevations in malondialdehyde, protein carbonyl and total nitrite levels paralleled with declines in antioxidant markers (SOD, CAT, GPx, GR and GSH) and down-regulations of Sod2, Cat, GPx1 and Gsr gene expression. Neuroinflammation was evident in diabetic animals by marked elevations in TNF-α, IL-1ß and up-regulation of inducible nitric oxide synthase. Significant rises incaspase-3 and Bax with decline in Bcl-2 level were noticed in diabetic rats together with similar results in their gene expressions. Cortical histopathological examination supported the biochemical and molecular findings. GCBWE administration achieved noteworthy neuroprotection in diabetic animals in most assessed parameters. The overall results suggested that antioxidant, anti-inflammatory; anti-apoptotic activities of GCBWE restored the cortical neurochemistry in diabetic rats.

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 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.

Synthesis and Characterization of Acrylamide/Acrylic Acid Co-Polymers and Glutaraldehyde Crosslinked pH-Sensitive Hydrogels.

This project aims to synthesize and characterize the pH-sensitive controlled release of 5-fluorouracil (5-FU) loaded hydrogels (5-FULH) by polymerization of acrylamide (AM) and acrylic acid (AA) in the presence of glutaraldehyde (GA) as a crosslinker with ammonium persulphate as an initiator. The formulation's code is named according to acrylamide (A1, A2, A3), acrylic acid (B1, B2, B3) and glutaraldehyde (C1, C2, C3). The optimized formulations were exposed to various physicochemical tests, namely swelling, diffusion, porosity, sol gel analysis, and attenuated total reflection-Fourier transform infrared (ATR-FTIR). These 5-FULH were subjected to kinetic models for drug release data. The 5-FU were shown to be soluble in distilled water and phosphate buffer media at pH 7.4, and sparingly soluble in an acidic media at pH 1.2. The ATR-FTIR data confirmed that the 5-FU have no interaction with other ingredients. The lowest dynamic (0.98 ± 0.04% to 1.90 ± 0.03%; 1.65 ± 0.01% to 6.88 ± 0.03%) and equilibrium swelling (1.85 ± 0.01% to 6.68 ± 0.03%; 10.12 ± 0.02% to 27.89 ± 0.03%) of formulations was observed at pH 1.2, whereas the higher dynamic (4.33 ± 0.04% to 10.21 ± 0.01%) and equilibrium swelling (22.25 ± 0.03% to 55.48 ± 0.04%) was recorded at pH 7.4. These findings clearly indicated that the synthesized 5-FULH have potential swelling characteristics in pH 6.8 that will enhance the drug's release in the same pH medium. The porosity values of formulated 5-FULH range from 34% to 62% with different weight ratios of AM, AA, and GA. The gel fractions data showed variations ranging from 74 ± 0.4% (A1) to 94 ± 0.2% (B3). However, formulation A1 reported the highest 24 ± 0.1% and B3 the lowest 09 ± 0.3% sol fractions rate among the formulations. Around 20% drug release from the 5-FULH was found at 1 h in an acidic media (pH1.2), whereas >65% of drug release (pH7.4) was observed at around 25 h. These findings concluded that GA crosslinked 5-FU loaded AM and AA based hydrogels would be a potential pH-sensitive oral controlled colon drug delivery carrier.

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.

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.

Phenolic Characterization Using cLC-DAD Analysis and Evaluation of In Vitro and In Vivo Pharmacological Activities of Ruta tuberculata Forssk.

The perennial aromatic plant Ruta tuberculata Forssk (Rutaceae) has been traditionally used by Mediterranean peoples as folk medicine against several types of disease to treat diverse illness. The objective of this work is to evaluate the in vitro and in vivo pharmacological activities of the aqueous (RAE) and methanolic (MeOH) 80% (RME) extracts of Algerian R. tuberculata aerial parts. Antioxidant potential, neuro-protective and anti-arthritic activities were investigated in vitro using six antioxidant approaches and by determining acetyl-cholinesterase and bovine albumin denaturation inhibitory capacities, respectively. Furthermore, in vivo anti-ulcer and anti-inflammatory activities were evaluated on EtOH-induced gastric mucosal damage and carrageenan-induced paw edema models in mice. Moreover, bio-compounds' contents were also quantified using spectrophotometric and cLC-DAD methods. Both in vivo and in vitro investigations showed remarkable antioxidant activity of Ruta tuberculata Forssk, while methanolic extract (RME) of Ruta tuberculata Forssk exhibited more significant neuro-protective and anti-inflammatory effects. However, the antiulcer activity was more pronounced with RAE of R. tuberculata, which suggests that this plant can be considered as a natural resource of potent bioactive compounds that may act as antioxidant and anti-inflammatory agents, which underlines the importance of incorporating them in therapies in order to treat various diseases linked to oxidative stress, and they may also provide crucial data for the development of new anticholinesterase drugs to improve neurodegenerative diseases, such as Alzheimer's.

The impact of betaine supplementation in quail diet on growth performance, blood chemistry, and carcass traits.

The study aimed to investigate the effect of various doses of betaine supplemented dietary on Japanese quail performance, carcass characteristics, and blood chemistry. Therefore, 400 seven days old Japanese quails were classified randomly into four equal groups. Each group was subdivided into five replicates of 20 birds each. Four rations were formulated using four different betaine levels (0, 0.75, 1.5 and 2.25 g/kg, respectively) for five successive weeks. All groups received feed and clean water ad-libitum. The results of this trial indicated that the feed intake was lowered in groups fed with betaine (p ≤ 0.05) when compared with the control one. The highest weight gain (p ≤ 0.05) was noticed in groups fed diets BS4 (betaine supplementation at the rate of 2.25 g/kg). No difference among groups was observed in body length, shank length, shank diameter, and keel bone length or breast width. Also, the carcass weight and breast yield were highest (p ≤ 0.05) in the group reared on the BS4 diet. In addition, intestinal length and weight were significantly higher (p ≤ 0.05) in groups fed betaine with a concentration of 2.25 g/kg. Fat weight was lower in the group fed BS4 than in the untreated group. Significantly higher values of high-density lipoprotein (p ≤ 0.05) were observed in the group fed BS4. All groups fed a ration containing betaine showed lower levels of liver enzymes such as alanine amino transferase, alkaline phosphatase, and aspartate amino transferase (p ≤ 0.05) and lowered low-density lipoprotein level. The quails fed BS4 had the greatest growth hormones and insulin (p ≤ 0.05) and the lowest thyroxin level. We concluded that dietary betaine supplementation positively impacts Japanese quail growth performance, carcass traits, and blood chemistry.

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.

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.

Synthesis of Ribose-Coated Copper-Based Metal-Organic Framework for Enhanced Antibacterial Potential of Chloramphenicol against Multi-Drug Resistant Bacteria.

The rise in bacterial resistance to currently used antibiotics is the main focus of medical researchers. Bacterial multidrug resistance (MDR) is a major threat to humans, as it is linked to greater rates of chronic disease and mortality. Hence, there is an urgent need for developing effective strategies to overcome the bacterial MDR. Metal-organic frameworks (MOFs) are a new class of porous crystalline materials made up of metal ions and organic ligands that can vary their pore size and structure to better encapsulate drug candidates. This study reports the synthesis of ribose-coated Cu-MOFs for enhanced bactericidal activity of chloramphenicol (CHL) against Escherichia coli (resistant and sensitive) and MDR Pseudomonas aeruginosa. The synthesized Cu-MOFs were characterized with DLS, FT-IR, powder X-ray diffraction, scanning electron microscope, and atomic force microscope. They were further investigated for their efficacy against selected bacterial strains. The synthesized ribose-coated Cu-MOFs were observed as spherical shape structure with the particle size of 562.84 ± 13.42 nm. CHL caused the increased inhibition of E. coli and MDR P. aeruginosa with significantly reduced MIC and MBIC values after being encapsulated in ribose-coated Cu-MOFs. The morphological analysis of the bacterial strains treated with ribose-coated CHL-Cu-MOFs showed the complete morphological distortion of both E. coli and MDR P. aeruginosa. Based on the results of the study, it can be suggested that ribose-coated Cu-MOFs may be an effective alternate candidate to overcome the MDR and provide new perspective for the treatment of MDR bacterial 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.