Mitigation of Hepatotoxicity via Boosting Antioxidants and Reducing Oxidative Stress and Inflammation in Carbendazim-Treated Rats Using Adiantum Capillus-Veneris L. Extract.

Exposure to food contaminants continues to be a substantial source of human health risks all over the world, particularly in developing countries. Carbendazim (CBZ) is a chemical fungicide used to control the spread of various fungi and other pathogens in the agriculture and veterinary sectors. The hazardous effects of CBZ on human health occur due to the accumulation of its residues in agricultural food products. In this study, the possible hepatoprotective effects of Adiantum capillus-veneris L. (ACVL) extract were evaluated in CBZ-treated rats. A GC-MS analysis revealed that ACVL extract contained several bioactive hydrocarbon components and fatty acids, and that the components exerted hepatic protection by mitigating oxidative stress via upregulating antioxidant agents and neutralizing nitrogen and oxygen free radicals. Moreover, ACVL extracts relieved hepatic inflammation via decreasing NO, NF-κB, and pro-inflammatory cytokines (TNF-a, IL-6) in the liver of CBZ-treated rats, both at protein and mRNA levels. In addition, the protective effect of ACVL has appeared in the histopathological figures and function markers in the livers of CBZ-treated rats. According to the present results, ACVL extract can protect the hepatic tissue and restore its functions to a control level in CBZ-treated rats; this effect may be attributed to its antioxidant and anti-inflammatory activities.

Chemical compositions of Commiphora opobalsamum stem bark to alleviate liver complications in streptozotocin-induced diabetes in rats: Role of oxidative stress and DNA damage.

CONTEXT: Hyperglycaemia plays an important role in the development of non-alcoholic fatty liver disease, which is a common complication in diabetics. OBJECTIVE: The present study aimed to investigate the chemical composition and the efficacy of Commiphora opobalsamum stem bark butanol fraction in ameliorating liver injury associated with diabetes induced by streptozotocin (STZ) in rats. MATERIALS AND METHODS: The butanol fraction was applied to high-performance liquid chromatography-mass spectrometry (HPLC/MSn) to identify the most bioactive metabolites. Diabetes was induced by a single intraperitoneal injection of STZ (60 mg/kg body weight), while treatment with the plant extract was performed (100 mg/kg body weight) for three weeks after diabetic induction for one month. RESULTS: Thirty eight metabolites were tentatively identified from the butanol fraction of C. opobalsamum stem bark. Insulin, glutathione, superoxide dismutase, and high density lipoprotein levels in diabetic rats were significantly low (p < 0.05), while glucose, α-amylase, malondialdehyde, aspartate and alanine aminotransferases, cholesterol, triglycerides, low density lipoprotein, tumour necrosis factor-α, interleukin-6, and DNA fragmentation levels were significantly high. Treatment with the plant extract showed improvements in the seleced parameters by variable degrees. Conclusion: The plant extract is considered as a promising natural therapeutic agent against liver injury, hyperglycemia, oxidative stress, inflammation, hyperlipidaemia, and DNA damage.

Mucuna pruriens seeds extract boosts growth, immunity, testicular histology, and expression of immune-related genes of mono-sex Nile tilapia (Oreochromisniloticus).

Nutraceuticals have received increased attention in sustainable aquaculture. Consequently, the present study aimed to evaluate the dietary effects of Mucuna pruriens (MP) seed extract on growth performance, immune status, hepatic function, biochemical profiles, gonadal histology, and expression of immune-related genes in mono-sex Nile tilapia (Oreochromis niloticus). Fish were allocated into four groups and received MP at rates of 0 (control), 2, 4, and 6 g/kg diet, respectively, for 90 days. The results revealed that MP significantly (P<0.05) modulated growth performance (specific growth rate, final length, and length gain rate, body mass gain, and feed conversion ratio), lysozyme activity, and liver enzymes (AST, ALT). However, a non-significant effect on nitric oxide (NO) or immunoglobulin M (IgM) levels was detected, whereas the dietary inclusion of MP had a hypoglycemic effect. In terms of plasma globulin, albumin, globulin/albumin ratio, and cortisol, the MP receiving groups showed insignificant difference (P<0.05) when compared to controls, except for the 2 g MP-supplemented group. The lower inclusion concentration of MP (2 g/kg diet) demonstrated the best result (P < 0.05) for gonadosomatic index (GSI) and plasma testosterone level that was consistent with the histological findings reflecting an improvement in the testicular development compared with the control group. Expressions of complement component (C5) and interleukin 1-ß (IL-1ß) genes were significantly up-regulated in MP receiving groups. In conclusion, M. pruriens can be used as a safe natural economic feed additive and a low inclusion level of 2 g/kg diet is recommended to improve growth, enhance immunity, maintain liver functioning, improve testicular development, and to modulate immune-related genes in the mono-sex O. niloticus.

Chemical Composition of Tagetes patula Flowers Essential Oil and Hepato-Therapeutic Effect against Carbon Tetrachloride-Induced Toxicity (In-Vivo).

The liver is a crucial organ among body organs due to its wide functions, in particular, detoxification and metabolism. Exposure to detrimental chemicals or viral infections may provoke liver dysfunction and ultimately induce liver tissue damage. Finding natural substances for liver disease treatment to overcome the conventional treatments' side effects has attracted the attention of researchers worldwide. Our current work was conducted to investigate the hepato-therapeutic activities of essential oil (EO) isolated from Tagetes patula flowers. EO was extracted using the hydro-distillation (HD) technique and its chemical composition was identified by GC/MS. Then, the hepatic treatment potential of extracted EO was evaluated in vivo against CCL4 in rats. HD of T. patula flowers yielded highly chemical constituents of EO along with significant antioxidant potential. A coherent molecular network was fashioned via the Global Natural Products Social Molecular Networking (GNPS) to visualize the essential components and revealed that the sesquiterpene (E)-ß-caryophyllene was the most predominant volatile constituent which accounted for 24.1%. The treatment of CCL4 led to significant induced oxidative stress markers malonaldehyde, total protein, and non-protein sulfhydryl, as well as elevated serum aminotransferase, gamma-glutamyl transferase, alkaline phosphatase, and bilirubin. In addition, it disrupted the level of lipid profile. The post-treatment using T. patula EO succeeded in relieving all toxic effects of CCl4 and recuperating the histopathological signs induced by CCL4. Silymarin was used as a standard hepatoprotective agent. The obtained results demonstrated that the extracted EO exerted high protective activities against the toxicity of CCL4. Moreover, the T. patula flowers EO can be used as a natural remedy to relieve many contemporary liver diseases related to oxidative stress.

Cefepime and diclofenac sodium combined treatment-potentiated multiple organ injury: Role of oxidative damage and disrupted lipid metabolism.

Concurrent exposure to antimicrobial and nonsteroidal anti-inflammatory drugs (NSAIDs) is usually inevitable in most infections and postsurgery. Consequently, the present study was designed to assess the intertwining impact of coadministration of cefepime (CP, a wide spectrum antibiotic) and diclofenac sodium (DF, an NSAID) on rat's liver, kidney, and testes. Rats received saline, CP (180 mg/kg/day, IM), DF (10 mg/kg/day, IM), or a combination of CP and DF. After 14 days, CP or DF induced tissue damage expressed by marked biochemical alterations in hepatic and renal function tests. Besides this, disrupted lipid metabolism and testosterone levels along with significant histological changes in hepatic, renal, and testicular tissues were noticed. A significant increase in malondialdehyde and decreases in superoxide dismutase and catalase activities alongside significant upregulated caspase 3 expression in tissues following CP or DF treatment suggested a bearable influence of oxidative stress, lipid peroxidation, and cell death. Accordingly, the simultaneous therapy of CP and DF evoked more obvious tissue damage than their individual treatment. Overall, data concluded that concurrent use of CP and DF in medical practice is a worrisome matter, so it should be done cautiously to avoid synergistic deleterious outcomes.

Cross-cultural Validation of the Full Range Test of Visual Motor Integration Used with Children in Four Arab Countries.

SIGNIFICANCE: Arab countries have a shortage of culturally sensitive psychoeducational assessments. Tests of visual-motor integration are low in their linguistic demands, yet they are not culture-free. PURPOSE: The aim of this study was to explore the psychometric properties and the validation of the Full Range Test of Visual Motor Integration (FRTVMI) across four Arabic speaking countries, namely, Sultanate of Oman, Kuwait, Qatar, and the Kingdom of Saudi Arabia (n = 2318). METHODS: The FRTVMI was administered to 2318 children from four Gulf countries. Criterion measures included the Reading Observation Scale and the achievement scores in reading. All raw data obtained for the FRTVMI were analyzed using the Statistical Package for Social Sciences and R package (version 3.5.1, 2018). Construct validity was examined using confirmatory factor analysis. The internal consistency, test-retest reliability, and interrater reliability of FRTVMI were also examined. RESULTS: The means for Cronbach α, intraclass correlation, and test-retest reliability across the four countries were 0.87, 0.87, and 0.90, respectively. Spearman ρ correlation between FRTVMI scores and Reading Observation Scale scores ranged between 0.16 and 0.51 across the four countries and were 0.57, 0.43, and 0.45 for male and female participants and the entire sample, respectively. The Spearman ρ correlations between FRTVMI scores and reading achievement scores ranged between 0.15 and 0.20 across the four countries and were 0.27, 0.29, and 0.26 for male and female participants and the entire sample, respectively. The modified model indices showed that the FRTVMI was adequate for use in the four countries and for both male and female participants. The reliability estimates for the test were high, whereas the concurrent validity estimates were moderate. CONCLUSIONS: The unidimensionality of the test should be taken with caution, as we found some indication for the multidimensionality of the test factor structure. Implications for cross-cultural assessment are discussed.

Phytochemical Profiling of Lavandula coronopifolia Poir. Aerial Parts Extract and Its Larvicidal, Antibacterial, and Antibiofilm Activity Against Pseudomonas aeruginosa.

Infections associated with the emergence of multidrug resistance and mosquito-borne diseases have resulted in serious crises associated with high mortality and left behind a huge socioeconomic burden. The chemical investigation of Lavandulacoronopifolia aerial parts extract using HPLC-MS/MS led to the tentative identification of 46 compounds belonging to phenolic acids, flavonoids and their glycosides, and biflavonoids. The extract displayed larvicidal activity against Culex pipiens larvae (LC50 = 29.08 µg/mL at 72 h). It significantly inhibited cytochrome P-450 monooxygenase (CYP450), acetylcholinesterase (AChE), and carboxylesterase (CarE) enzymes with the comparable pattern to the control group, which could explain the mode of larvae toxification. The extract also inhibited the biofilm formation of Pseudomonas aeruginosa by 17-38% at different Minimum Inhibitory Concentrations (MICs) (0.5-0.125 mg/mL) while the activity was doubled when combined with ciprofloxacin (ratio = 1:1 v:v). In conclusion, the wild plant, L.coronopifolia, can be considered a promising natural source against resistant bacteria and infectious carriers.

Cinnamic acid derivatives: inhibitory activity against Escherichia coli ß-glucuronidase and structure-activity relationships.

Gut microbial ß-glucuronidase (GUS) is a potential therapeutic target to reduce gastrointestinal toxicity caused by irinotecan. In this study, the inhibitory effects of 17 natural cinnamic acid derivatives on Escherichia coli GUS (EcGUS) were characterised. Seven compounds, including caffeic acid ethyl ester (CAEE), had a stronger inhibitory effect (IC50 = 3.2-22.2 µM) on EcGUS than the positive control, D-glucaric acid-1,4-lactone. Inhibition kinetic analysis revealed that CAEE acted as a competitive inhibitor. The results of molecular docking analysis suggested that CAEE bound to the active site of EcGUS through interactions with Asp163, Tyr468, and Glu504. In addition, structure-activity relationship analysis revealed that the presence of a hydrogen atom at R1 and bulky groups at R9 in cinnamic acid derivatives was essential for EcGUS inhibition. These data are useful to design more potent cinnamic acid-type inhibitors of EcGUS.

The Structural Diversity of Marine Microbial Secondary Metabolites Based on Co-Culture Strategy: 2009-2019.

Marine microorganisms have drawn great attention as novel bioactive natural product sources, particularly in the drug discovery area. Using different strategies, marine microbes have the ability to produce a wide variety of molecules. One of these strategies is the co-culturing of marine microbes; if two or more microorganisms are aseptically cultured together in a solid or liquid medium in a certain environment, their competition or synergetic relationship can activate the silent biosynthetic genes to produce cryptic natural products which do not exist in monocultures of the partner microbes. In recent years, the co-cultivation strategy of marine microbes has made more novel natural products with various biological activities. This review focuses on the significant and excellent examples covering sources, types, structures and bioactivities of secondary metabolites based on co-cultures of marine-derived microorganisms from 2009 to 2019. A detailed discussion on future prospects and current challenges in the field of co-culture is also provided on behalf of the authors' own views of development tendencies.

Temperament Styles of Children from Egypt and the United States: A Cross-Cultural Examination.

Age, gender, and cross-national differences of children ages 9 through 15 in Egypt (N = 800) and the United States (U.S., N = 800) are examined on four bipolar temperament styles: extroversion-introversion, practical-imaginative, thinking-feeling, and organized-flexible using the Student Styles Questionnaire (SSQ). Egyptian children generally prefer extroverted over introverted, practical over imaginative, and organized over flexible styles. Their general preference for feeling over thinking styles is gender related; although both males and females generally prefer feeling styles, males are less likely than females to prefer this style. Age differences are found on extroverted-introverted and practical-imaginative styles. Cross-national differences are found on four temperament styles. In contrast to children in the U.S., children in Egypt are more likely to prefer extroverted, practical, feeling, and organized styles.

A Polyphenols-Rich Extract from Moricandia sinaica Boiss. Exhibits Analgesic, Anti-Inflammatory and Antipyretic Activities In Vivo.

In this study, the aerial parts of Moricandia sinaica were evaluated for their in vivo analgesic, anti-inflammatory and antipyretic activities. The analgesic activities were examined using acetic acid-induced writhing, the hot plate test and the tail flick method. The anti-inflammatory and the antipyretic activities were evaluated using carrageenan-induced paw edema in rats and brewer's yeast-induced pyrexia in mice, respectively. The aqueous fraction of the methanol extract (MS-3) showed to be the most bioactive among the other investigated fractions. At the dose of 500 mg/kg, the fraction (MS-3) showed a significant percentage inhibition of the carrageenan-induced edema by 52.4% (p < 0.05). In addition, MS-3 exhibited a significant inhibition of acetic acid-induced writhes by 44.4% and 61.5% (p < 0.001) at 250-mg/kg and 500-mg/kg doses, respectively. At 120 min post-treatment, the rat groups treated with MS-3 displayed statistically significant reduction in rectal temperature (p < 0.001) by 1.7 °C and 2.2 °C at 250- and 500-mg/kg doses, respectively. The phytochemical composition of the fraction (MS-3) was characterized by high-performance liquid chromatography-mass spectrometry (HPLC-PDA-MS/MS). Molecular docking studies demonstrated that the polyphenols identified in MS-3 revealed good binding energy upon docking to some target proteins involved in pain response and inflammation, such as the cannabinoid receptors CB1 and CB2, the fatty acid amide hydrolase (FAAH) and the cyclooxygenase COX-1 and COX-2 enzymes. Based on the findings from the present work, it could be concluded that the aerial parts extract of M. sinaica exerts potential analgesic, anti-inflammatory and antipyretic effects in rats.

A New Polyoxygenated Flavonol Gossypetin-3-O-ß-d-Robinobioside from Caesalpinia gilliesii (Hook.) D. Dietr. and In Vivo Hepatoprotective, Anti-Inflammatory, and Anti-Ulcer Activities of the Leaf Methanol Extract.

A hitherto unknown polyoxygenated flavonol robinobioside (gossypetin-3-O-ß-d-robinobioside) was isolated from the leaves of Caesalpinia gilliesii along with thirteen known phenolic secondary metabolites. The isolated compounds were characterized using spectroscopic analysis, including 1D and 2D NMR and mass spectrometry (MS) analyses. The extract reduced the level of liver damage in CCl4-induced liver injury in rats. A decrease of the liver biomarkers-aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and an increase of total antioxidant capacity (TAC) levels-were observed similar to the liver protecting drug silymarin. In addition, the extract showed promising activity against carrageenan-induced paw edema in rats and protected their stomachs against ethanol-induced gastric ulcers in a concentration dependent fashion. The observed activities could be attributed to the high content of antioxidant polyphenols. Our results suggest that the C. gilliesii has the capacity to scavenge free radicals and can protect against oxidative stress, and liver and stomach injury.

Differential expression of epithelial and smooth muscle lineage-specific markers of metanephros in one-humped camel foetuses.

The development of the metanephros in one-humped camels involves a complex series of interactions between epithelial and mesenchymal cells. As a result, there is a synchronized differentiation process of stromal, vascular and epithelial cell types during glomerulogenesis, angiogenesis and tubulogenesis. In the current work, the metanephros of camel foetuses were divided into four stages where kidneys from each stage were processed and immunoassayed, followed by quantitative analysis to determine target protein intensities throughout metanephrogenesis in the camel. This study demonstrated robust expression of α-smooth muscle actin (α-SMA) in the glomerular mesangium, as well as in interlobular and glomerular arterioles during the earlier stages of development. However, in the late stages, α-SMA expression became more localized around the blood capillaries in both the cortex and medulla. Strong expression of CD34 was observed in the immature glomerular and peritubular endothelial cells within the subcapsular zone, as well as in the glomerular, proximal tubular and distal tubular epithelium of stage one foetuses, although its expression gradually diminished with foetal maturation. The expression pattern of osteopontin was prominently observed in the distal convoluted tubules throughout all stages, however, no expression was detected in the proximal tubules, glomeruli and arterioles. E-cadherin was detected in the developing renal tubular epithelial cells but not in the glomeruli. In conclusion, this study reveals the spatiotemporal distribution of key proteins, including α-SMA, CD34, Osteopontin and E-cadherin, which play a crucial role in metanephrogenesis in camel foetuses.

Sero epidemiological study on bovine babesiosis in cattle and buffaloes in Sharkia Governorate, Egypt.

Background: Bovine babesiosis represents a serious challenge for animal health, herd production, and profitability. Understanding the epidemiology and risk factors associated with babesiosis is critical to reduce their negative impacts. Aim: Investigation of the seroprevalence and risk factors associated with Babesia bigemina (B. bigemina) and Babesia bovis (B. bovis) in five districts in Sharkia governorate using ELISA. Methods: Across-sectional research was conducted to determine the seropositivity of babesiosis by collecting a total of 352 blood samples from 250 cattle and 102 buffaloes. A multivariate logistic regression model was implemented to evaluate the strength of the risk factors associated with both Babesia species infection. Results: The seroprevalence of B. bigemina and B. bovis was 42.6% and 17.0 %, respectively. The prevalence of babesiosis in cattle was found to be 48.8% for B. bigemina and 16.8% for B. bovis. Inclusive, in buffaloes, the prevalence was 27.5% for B. bigemina and 17.6% for B. bovis. Adult animals were more vulnerable to infection with babesia than young animals by 3-5 times, respectively. Males were more susceptible to B. bigemina and B. bovis than females by 3.7 and 3.5 times. Similarly, the odds of infection in infested animals with ticks were 2-4 times higher than in animals without ticks. Conclusion: The obtained results revealed that age, sex of the animal, and tick infestation were major risk factors for the seropositivity of both Babesia species. Inclusive, there was no evidence to support the premise that seroprevalence of babesiosis is correlated with the season and species.

Anti-Alzheimer's Potency of Rich Phenylethanoid Glycosides Extract from Marrubium vulgare L.: In Vitro and In Silico Studies.

BACKGROUND/OBJECTIVES: Marrubium vulgare L. (M. vulgare), the white horehound, is well known for treating inflammation-related diseases. METHODS: In this context, we investigated the efficacy of M. vulgare ingredients in treating Alzheimer's disease using various in vitro and in silico antioxidant, anti-inflammatory, anti-cholinesterase, and anti-tyrosinase mechanisms. RESULTS: In our results, sixty-one components were tentatively identified using gas and liquid chromatography (GC-MS and LC-MSn) and categorized as hydrocarbons, fatty acids, and polyphenolics. The extract inhibited linoleic oxidation with an IC50 value of 114.72 µg/mL, captured iron (Fe2+) ions with an IC50 value of 164.19 µg/mL, and displayed reducing power. In addition, the extract showed radical-scavenging ability towards DPPH•, NO•, ABTS•+, and H2O2 assays compared to L-ascorbic acid and butylated hydroxytoluene. The DPPH• was scavenged by 77.62% at 100 µg/mL, and NO•, ABTS•+, and H2O2 were scavenged with IC50 values of 531.66, 117.51, and 143.10 µg/mL, respectively. M. vulgare also exhibited discriminating anti-inflammatory potency against cyclooxygenase (COX-2) with IC50 values of 619.15 µg/mL compared to celecoxib (p > 0.05). Notably, three Alzheimer's biomarkers, acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and tyrosinase were significantly inhibited. The molecular docking study supposed that the phenylethanoid glycosides of samioside and forsythoside B inhibited AChE and tyrosinase enzymes with low binding affinities of -9.969 and -8.804 kcal/mol, respectively. Marruboside was a proper inhibitor of COX and BChE enzymes with a binding score of -10.218 and -10.306 kcal/mol, respectively. CONCLUSIONS: M. vulgare extract showed significant inhibitory actions, which suggest that it could have a promising potential as an anti-Alzheimer agent.

Exploring the therapeutic potential of Saudi Kleinia anteuphorbium (L.) DC. Essential oil: Insights into antioxidant, analgesic, and hepatorenal protective effects.

Lately, the herb's essential oils have received the intense attention of researchers and pharmaceutical agencies. The chemical composition, antioxidant, analgesic activity, anti-hyperpyrexia, and hepatorenal protective effects of the Kleinia anteuphorbium (L.) DC. Essential oil (KAEO) were evaluated. The KAEO was yanked by steam distillation and subjected to a GC/MS system. The antioxidant powers of KAEO were evaluated by DPPH, NO, and FRAP tests. Besides the anti-hyperpyrexia, the analgesic effects were assessed. Moreover, the hepatorenal curative effects were evaluated in a carbon tetrachloride-rat model. Sixty-eight active components were identified by GC/MS. α-pinene was the most dominant monoterpene in KAEO. KAEO showed anti-hyperpyrexia, anti-captive, and great antioxidant powers through DPPH, NO, and FRAP. The oral LD50 of KAEO was 187.5 mg/kg in rats. Furthermore, KAEO treatment succeeded in reliving the adverse effects of CCL4 in rats as a standard toxic model through reliving the hepatic pathological and oxidative stress and restoring the hepatic and renal functions. Overall, the obtained results demonstrated that KAEO might be used as a potential natural medicine to relieve a variety of modern symptoms and hepatorenal disorders associated with oxidative stress.

Mitigative Effects of l-Arginine and N-Acetyl Cysteine against Cisplatin-Induced Testicular Dysfunction and Toxicity through the Regulation of Antioxidant, Anti-inflammatory, and Antiapoptotic Markers: Role of miR-155 and miR-34c Expression.

Testicular dysfunction is a common adverse effect of cisplatin (CIS) administration as a chemotherapeutic drug. The current study has outlined the role of micro-RNAs (miR-155 and 34c) in CIS-induced testicular dysfunction and evaluated the protective effect of N-acetyl cysteine (NAC) and/or l-arginine (LA). Seven groups of Albino rats were used for this study. The control (C) group received physiological saline; the CIS group was injected CIS (7 mg/kg IP, once) on day 21 of the experiment; the NAC group was administered NAC (150 mg/kg intragastric, for 28 days); and the LA group was injected LA (50 mg/kg IP, for 28 days). NAC+CIS, LA+CIS, and NAC+LA+CIS groups received the above regime. CIS significantly reduced serum testosterone, LH, and FSH concentrations with decline of testicular enzyme activities. CIS caused significant elevation in testicular oxidative-stress biomarkers, inflammation-associated cytokines, and apoptosis markers, along with overexpression of miR-155 and low miR-34c expression. Additionally, marked testicular degenerative changes were observed in the examined histological section; a significant decrease in the expression of PCNA with significant increase in expressions of F4/80 and BAX was confirmed. The administration of NAC or LA upregulated testicular functions and improved histopathological and immunohistochemical changes as well as miRNA expression compared with the CIS-administered group. Rats receiving both NAC and LA showed a more significant ameliorative effect compared with groups receiving NAC or LA alone. In conclusion, NAC or LA showed an ameliorative effect against CIS-induced testicular toxicity and dysfunction through the regulation of antioxidant, anti-inflammatory, and antiapoptotic markers and via modulating miR-155 and miR-34c expression.

Nephthea sp. inhibits biofilm, DNA gyrase, HSP90, and DHFR: in vitro, in silico, and pharmacokinetics studies.

This study attempts to identify and assess a novel marine-derived antibiofilm agent. The antibacterial activity of n-hexane, dichloromethane, ethyl acetate, and butanol fractions from the crude extract of soft coral Nephthea sp. was evaluated against six microorganisms.Ethyl acetate fraction considered the most effective one against Bacillus subtilis, Escherichia coli, and Candida, investigated potential biofilm inhibition against the tested strains. Seventeen secondary metabolites were identified using (UPLC-Q/TOF-MS) responsible for these biological activities of the active fraction. Additionally, a molecular docking study showed free binding energy of -7.5 kcal/mol; Azamial A had the highest binding affinity for the DNA gyrase enzyme, while Sinularectin had -8.3 and -7.6 kcal/mol for the DHFR and HSP90 enzymes, respectively. Moreover, pharmacokinetics and (ADME) studies for Azamial A and Sinularectin were performed. Finally, results were confirmed by the in vitro enzymatic inhibitory effect of ethyl acetate fraction suggested in the in-silico study.

The Association between Prepartum Rumination Time, Activity and Dry Matter Intake and Subclinical Hypocalcemia and Hypomagnesemia in the First 3 Days Postpartum in Holstein Dairy Cows.

Changes in prepartum behaviors such as total daily rumination (TDR), total daily activity (TDA) and dry matter intake (DMI) have the potential to be used as early indicators for cows at risk for subclinical hypocalcemia (SCH) or hypomagnesemia (HYM) after calving. Our objective was to investigate associations between average daily rate of change in total daily rumination (ΔTDR), total daily activity (ΔTDA) and dry matter intake (ΔDMI) from -3 days prepartum to calving with SCH and HYM at D0 or D3 relative to calving. Prepartum TDR, TDA and DMI were measured in 64 Holstein dairy cows. Blood samples were taken at D0 and D3 post-calving for the measurement of total plasma Ca and Mg concentration. Linear regression models were used to analyze the association between ΔTDR, ΔTDA and ΔDMI and SCH and HYM at D0 and D3 relative to calving. Potential confounding variables were offered to the models and backwards selection was used to determine which covariates to retain. No significant differences in prepartum ΔTDR, ΔTDA or ΔDMI were found between cows with or without SCH and HYM at D0 and D3. Our results suggest that the change in TDR, TDA and DMI in the last 3 days prepartum are not effective predictors for cows that will have SCH or HYM in the first 3 days postpartum.

Pectin Nanoparticle-Loaded Soft Coral Nephthea sp. Extract as In Situ Gel Enhances Chronic Wound Healing: In Vitro, In Vivo, and In Silico Studies.

This study shed light for the first time on the in vivo diabetic wound healing potential activity of natural marine soft coral polymeric nanoparticle in situ gel using an excision wound model. A Nephthea sp. methanol-methylene chloride extract loaded with pectin nanoparticles (LPNs) was created. For the preparation of in situ gel, ion-gelation techniques, the entrapment efficiency, the particle size, the polydispersity index, the zeta potential, the in-vitro drug release, and a transmission electron microscope were used and the best formula was selected. Using (UPLC-Q/TOF-MS), 27 secondary metabolites responsible for extract biological activity were identified. Isolation and identification of arachidic acid, oleic acid, nervonic acid, and bis-(2-ethylhexyl)-phthalate (DEHP) of Nephthea sp. was firstly reported here using NMR and mass spectral analyses. Moreover, LPN in situ gel has the best effects on regulating the proinflammatory cytokines (NF-κB, TNF-α, IL-6, and IL-1ß) that were detected on days 7 and 15. The results were confirmed with an in vitro enzymatic inhibitory effect of the extract against glycogen synthase kinase (GSK-3) and matrix metalloproteinase-1 (MMP-1), with IC50 values of 0.178 ± 0.009 and 0.258 ± 0.011 µg/mL, respectively. The molecular docking study showed a free binding energy of -9.6 kcal/mol for chabrolosteroid E, with the highest binding affinity for the enzyme (GSK-3), while isogosterone B had -7.8 kcal/mol for the enzyme (MMP-1). A pharmacokinetics study for chabrolohydroxybenzoquinone F and isogosterone B was performed, and it predicted the mode of action of wound healing activity.