Hepatoprotective activity of Lactéol® forte and quercetin dihydrate against thioacetamide-induced hepatic cirrhosis in male albino rats.

Liver cirrhosis is a silent disease in humans and is experimentally induced by many drugs and toxins as thioacetamide (TAA) in particular, which is the typical model for experimental induction of hepatic fibrosis. Thus, the objective of the present study was to elucidate the possible protective effects of lactéol® forte (LF) and quercetin dihydrate (QD) against TAA-induced hepatic damage in male albino rats. Induction of hepatotoxicity was performed by TAA injection (200 mg/kg I/P, twice/ week) in rats. LF (1 × 109 CFU/rat 5 times/week) and QD (50 mg/kg 5 times/week) treated groups were administered concurrently with TAA injection (200 mg/kg I/P, twice/ week). The experimental treatments were conducted for 12 weeks. Hepatotoxicity was evaluated biochemically by measuring alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transferase (GGT) in the serum and histopathologically with the scoring of histopathological changes besides histochemical assessment of collagen by Masson's trichrome and immunohistochemical analysis for α-smooth muscle actin (α-SMA), Ki67 and caspase-3 expression in liver sections. Our results indicated that LF and QD attenuated some biochemical changes and histochemical markers in TAA-mediated hepatotoxicity in rats by amelioration of biochemical markers and collagen, α-SMA, Ki67 and caspase3 Immunoexpression. Additionally, LF and QD supplementation downregulated the proliferative, necrotic, fibroblastic changes, eosinophilic intranuclear inclusions, hyaline globules and Mallory-like bodies that were detected histopathologically in the TAA group. In conclusion, LF showed better hepatic protection than QD against TAA-induced hepatotoxicity in rats by inhibiting inflammatory reactions with the improvement of some serum hepatic transaminases, histopathological picture and immunohistochemical markers.

Genetic Components Derived Parameters and Heterosis in Okra under Saudi Arabia Conditions.

Four parental genotypes of okra were crossed in complete diallel design to study the direction and extent of relative heterosis and heterobeltiosis for yield and its associated traits for utilization of existing genetic diversity to develop heterotic F1 hybrids in okra. The additive genetic component (D) was significant in all studied traits except average pod weight. Nonadditive (H1 and H2) components were found to be significant in all studied traits. However, the values of the dominant effect (H1) were smaller than the D components for no. of nodes/plant, no. of pods/plant, weight of medium pods, weight of large pods, and total fresh pod yield. The maximum significant MP heterosis in the desirable direction (149.9%) was recorded for the weight of large pods/plot. The maximum significant heterobeltiosis in the desirable direction (120.1%) was recorded for the weight of small pods/plot followed by total fresh pod yield (107.4%), the weight of large pods/plot (104.9%), weight of medium pods/plot (92.1%), average pod weight (51.8%), number of pods/plant (38.4%), and plant height (34.3%). It could be concluded that plant height, average pod weight, and the number of branches could be considered for the development of elite hybrids (heterosis breeding) or inbred lines (pure line selection) in succeeding generations. Therefore, these parameters can be considered for selecting genotypes to improve the pod yield of okra. The superior crosses identified through heterosis analysis were Egyptian Balady × Line 4.1.18 (30.8 ton/ha), Line 4.1.18 × Egyptian Balady (29.8 ton/ha), Dwarf Green Long Pod × Line 4.1.18 (28.3 ton/ha), and Egyptian Balady × Dwarf Green Long Pod (27.6 ton/ha) as these crosses had high performance as well as significant and higher estimates of heterobeltiosis for fruit yield per plant and yield attributing other characters.

Escherichia coli isolates from meat and abattoirs environment in Egypt: molecular characterization and control by nanosilver particles.

Three hundred samples, including meat from the slaughtered carcass and water, air samples, and swabs from the floor, wall, and employees' hands, were collected from five municipal abattoirs spread across several Egyptian provinces. The Escherichia coli was isolated from floor swabs, meat, air, wall, hand, and water samples. Serotyping of the recovered isolates clarified the presence of various serotypes, including enterohemorrhagic serotypes (O111: H4, O128: H2, and O127: H6) and enterotoxigenic serotypes (O44: H18 and O125: H21). The isolates were resistant to cefotaxime (100%), amoxiclav (80%), then rifampin (66.7%). The stx1 gene, stx2 gene, eaeA gene, blaCMY2 gene and iss gene were detected in 10-80 % of the isolates. Nanosilver (AgNPs) showed that 12.5 ppm was the lowest concentration that prevented bacterial growth. It was observed that 12% of workers wore a clean white coat, only 24% washed their hands between activities during work, only 14% used soap for hand washing, and 42% utilized the same knife for meat and its offal.

Diacerein modulates TLR4/ NF-κB/IL-1ß and TRPC1/CHOP signalling pathways in gentamicin-induced parotid toxicity in rats.

The present study aimed to identify the possible protective effect of diacerein (DIA) on gentamicin (GNT)-induced parotid toxicity in rats. DIA was administered in the presence and absence of GNT. Thirty-two Wistar adult male rats were randomly arranged into four groups: control, DIA (50 mg/kg/day), GNT (100 mg/kg) and GNT+DIA groups for 8 days. Parotid oxidative stress parameters, besides inflammatory and apoptotic biomarkers, were evaluated. Salivary flow rate, transient receptor potential canonical 1 (TRCP1), and C/EBP homologous protein (CHOP) in parotid tissue were measured. A parotid histopathological examination and an interleukin-1 beta (IL-1ß) immunohistochemical study were also performed. GNT significantly increased parotid oxidative stress, inflammatory, apoptotic and CHOP biomarkers with decreased salivary flow rate and TRCP1 level. A histopathological picture of parotid damage and high IL-1ß immunoexpression were detected. DIA significantly normalized the distributed oxidative, inflammatory and apoptotic indicators, CHOP and TRCP1, with a prompt improvement in the histopathological picture and a decrease in IL-1ß immunoexpression. These results reported that DIA protects against GNT-induced parotid toxicity via modulation of TLR4/NF-κB/IL-1ß and TRPC1/CHOP signalling pathways.

Antioxidant, Diabetic and Inflammatory Activities of Alpinia calcarata Roscoe Extract.

BACKGROUND: Alpinia calcarata (AC) Roscoe of Zingiberaceae popularly known as lesser galangal has a widespread occurrence in China, India, Sri-Lanka, Bangladesh, Malaysia, Indonesia and Thailand. Essential oil (Eoil) was obtained from leaves/rhizomes of AC via hydro-distillation process. METHODS: To identify chemical ingredients in oil from leaves/rhizomes of AC through GC/MS technique for volatile components and their anti-oxidant, inflammatory/diabetic activities. RESULTS: The 38 and 65 components were found to make up 99.9 and 99.6 %, respectively in total of Eoil composition of AC leaves/rhizomes. Key chemical constituents were eucalyptol (28.7 % in leaves; 25.4 % in rhizomes), camphor (12.8 % in leaves; 4.2 % in rhizomes), and carotol (9.8 % in leaves; 5.6 % in rhizomes) found in oil of AC leaves/rhizomes. Colorimetric assay showed anti-oxidant activities in leaves and rhizomes are IC50 =71.01±0.71 µg/mL and IC50 =73.83±0.49 µg/mL, respectively in the Eoils. Eoils had high anti-oxidant capabilities in IC50 -values of AC-L-Eoil=43.09±0.82&AC-Rh-Eoil=68.11±0.87 in reducing power in µg/mL was found. Albumin test of rhizome oil had IC50 -values of 15.19±0.25 µg/mL. Concentrations range of 7.81 µg/mL and 250 µg/mL in the Eoils of AC leaves and rhizome, respectively by α-glucosidase inhibition assay. CONCLUSION: Our findings demonstrated that leaf oil was slightly more promising results than rhizome oil of AC extract, which was ultimately showed medicinal potential of secondary metabolites with anti-oxidant, diabetic/inflammatory activities. Further, Eoils of AC have a wide range of pharmacological potential and promising anti-diabetic effects.

Papaverinol-N-Oxide: A Microbial Biotransformation Product of Papaverine with Potential Antidiabetic and Antiobesity Activity Unveiled with In Silico Screening.

Bioconversion of biosynthetic heterocyclic compounds has been utilized to produce new semisynthetic pharmaceuticals and study the metabolites of bioactive drugs used systemically. In this investigation, the biotransformation of natural heterocyclic alkaloid papaverine via filamentous fungi was explored. Molecular docking simulations, using protein tyrosine phosphatase 1B (PTP1B), α-glucosidase and pancreatic lipase (PL) as target enzymes, were performed to investigate the antidiabetic potential of papaverine and its metabolites in silico. The metabolites were isolated from biotransformation of papaverine with Cunninghamella elegans NRRL 2310, Rhodotorula rubra NRRL y1592, Penicillium chrysogeneum ATCC 10002 and Cunninghamella blackesleeana NRRL 1369 via reduction, demethylation, N-oxidation, oxidation and hydroxylation reactions. Seven metabolites were isolated: namely, 3,4-dihydropapaverine (metabolite 1), papaveroline (metabolite 2), 7-demethyl papaverine (metabolite 3), 6,4'-didemethyl papaverine (metabolite 4), papaverine-3-ol (metabolite 5), papaverinol (metabolite 6) and papaverinol N-oxide (metabolite 7). The structural elucidation of the metabolites was investigated with 1D and 2D NMR and mass spectroscopy (EI and ESI). The molecular docking studies showed that metabolite 7 exhibited better binding interactions with the target enzymes PTP1B, α-glucosidase and PL than did papaverine. Furthermore, papaverinol-N-oxide (7) also displayed inhibition of α-glucosidase and lipase enzymes comparable to that of their ligands (acarbose and orlistat, respectively), as unveiled with an in silico ADMET profile, molecular docking and molecular dynamics studies. In conclusion, this study provides evidence for enhanced inhibition of PTP1B, α-glucosidase and PL via some papaverine fungal transformation products and, therefore, potentially better antidiabetic and antiobesity effects than those of papaverine and other known therapeutic agents.

The Effect of Combining Post-Harvest Calcium Nanoparticles with a Salicylic Acid Treatment on Cucumber Tissue Breakdown via Enzyme Activity during Shelf Life.

In the present study, an experiment was carried out on the postharvest of cucumber fruit during a 14-day shelf life. The aim was to assess the impact of calcium nanoparticles (CaNPs) blended with different concentrations of salicylic acid (SA) on the shelf life of cucumbers during the seasons of 2018 and 2019. The investigation further monitored the influences of CaNPs-SA on some physical properties of cucumber, including the percentage weight loss, color, and fruit firmness. In addition, chemical properties, such as total soluble solids (SSC%), total acidity (TA%), total soluble sugars, and chlorophyll pigmentation of the fruit skin, were assessed during a 14-day shelf lifeCell wall degradation enzymes (CWEAs) such as polygalacturonase (PG), cel-lulase (CEL), xylanase (XYL), and pectinase (PT) were also researched. In addition, the generation rates of H2O2 and O2•- were calculated, as well as the reduction of DPPH. The lipid peroxidation (malondialdehyde, MDA) and cell membrane permeability (IL%) of cell wall composites were also determined. CaNPs-SA at 2 mM suppressed CWEAs, preserved fruit quality, reduced weight loss throughout the shelf-life period, and reduced the percent leakage value. At this concentration, we also found the lowest levels of MDA and the highest levels of DPPH.

The role of the angle of progression in the prediction of the outcome of occiput posterior position in the second stage of labor.

BACKGROUND: Occiput posterior position is the most frequent cephalic malposition, and its persistence at delivery is associated with a higher risk of maternal and perinatal morbidity. Diagnosis and management of occiput posterior position remain a clinical challenge. This is partly caused by our inability to predict fetuses who will spontaneously rotate into occiput anterior from those who will have persistent occiput posterior position. The angle of progression, measured with transperineal ultrasound, represents a reliable tool for the evaluation of fetal head station during labor. The relationship between the persistence of occiput posterior position and fetal head station in the second stage of labor has not been previously assessed. OBJECTIVE: This study aimed to evaluate the role of fetal head station, as measured by the angle of progression, in the prediction of persistent occiput posterior position and the mode of delivery in the second stage of labor. STUDY DESIGN: We recruited a nonconsecutive series of women with posterior occiput position diagnosed by transabdominal ultrasound in the second stage of labor. For each woman, a transperineal ultrasound was performed to measure the angle of progression at rest. We compared the angle of progression between women who delivered fetuses in occiput anterior position and those with persistent occiput posterior position at delivery. Receiver operating characteristics curves were performed to evaluate the accuracy of the angle of progression in the prediction of persistent occiput posterior position. Finally, we performed a multivariate logistic regression to determine independent predictors of persistent occiput posterior position. RESULTS: Overall, 63 women were included in the analysis. Among these, 39 women (62%) delivered in occiput anterior position, whereas 24 (38%) delivered in occiput posterior position (persistent occiput posterior position). The angle of progression was significantly narrower in the persistent occiput posterior position group than in women who delivered fetuses in occiput anterior position (118.3°±12.2° vs 127.5°±10.5°; P=.003). The area under the receiver operating characteristics curve was 0.731 (95% confidence interval, 0.594-0.869) with an estimated best cutoff range of 121.5° (sensitivity of 72% and specificity of 67%). On logistic regression analysis, the angle of progression was found to be independently associated with persistence of occiput posterior position (odds ratio, 0.942; 95% confidence interval, 0.889-0.998; P=.04). Finally, women who underwent cesarean delivery had significantly narrower angle of progression than women who had a vaginal delivery (113.5°±8.1 vs 128.0°±10.7; P<.001). The area under the receiver operating characteristics curve for the prediction of cesarean delivery was 0.866 (95% confidence interval, 0.761-0.972). At multivariable logistic regression analysis including the angle of progression, parity, and gestational age at delivery, the angle of progression was found to be the only independent predictor associated with cesarean delivery (odds ratio, 0.849; 95% confidence interval, 0.775-0.0930; P<.001). CONCLUSION: In fetuses with occiput posterior at the beginning of the second stage of labor, narrower values of the angle of progression are associated with higher rates of persistent occiput posterior position at delivery and a higher risk of cesarean delivery.

The Therapeutic Mechanisms of Propolis Against CCl4 -Mediated Liver Injury by Mediating Apoptosis of Activated Hepatic Stellate Cells and Improving the Hepatic Architecture through PI3K/AKT/mTOR, TGF-ß/Smad2, Bcl2/BAX/P53 and iNOS Signaling Pathways.

BACKGROUND/AIMS: Propolis is one of the most promising natural products, exhibiting not only therapeutic but also prophylactic actions. Propolis has several biological and pharmacological properties, including hepatoprotective activities. The present study aimed to investigate the underlying molecular mechanisms of propolis against CCl4-mediated liver fibrosis. METHODS: Three groups of male BALB/c mice (n=15/ group) were used: group 1 comprised control mice; groups 2 and 3 were injected with CCl4 for the induction of liver fibrosis. Group 3 was then orally supplemented with propolis (100 mg/kg body weight) for four weeks. Different techniques were used to monitor the antifibrotic effects of propolis, including histopathological investigations using H&E, Masson's trichrome and Sirius red staining; Western blotting; flow cytometry; and ELISA. RESULTS: We found that the induction of liver fibrosis by CCl4 was associated with a significant increase in hepatic collagen and α-smooth muscle actin (α-SMA) expression. Moreover, CCl4-treated mice also exhibited histopathological alterations in the liver architecture. Additionally, the liver of CCl4-treated mice exhibited a marked increase in proinflammatory signals, such as increased expression of HSP70 and increased levels of proinflammatory cytokines and ROS. Mechanistically, the liver of CCl4-treated mice exhibited a significant increase in the phosphorylation of AKT and mTOR; upregulation of the expression of BAX and cytochrome C; downregulation of the expression of Bcl2; a significant elevation in the levels of TGF-ß followed by increased phosphorylation of SMAD2; and a marked increase in the expression of P53 and iNOS. Interestingly, oral supplementation of CCl4-treated mice with propolis significantly abolished hepatic collagen deposition, abrogated inflammatory signals and oxidative stress, restored CCl4-mediated alterations in the signaling cascades, and hence repaired the hepatic architecture nearly to the normal architecture observed in the control mice. CONCLUSION: Our findings revealed the therapeutic potential and the underlying mechanisms of propolis against liver fibrosis.

Camel Whey Protein Disrupts the Cross-Talk Between PI3K and BCL-2 Signals and Mediates Apoptosis in Primary Acute Myeloid Leukemia Cells.

In the present study, we investigated the impact of camel whey protein (CWP) on the survival of primary acute myeloid leukemia (AML) cells that were isolated from 20 patients diagnosed with AML. We found that CWP induced apoptosis in the primary AML cells without affecting the normal PBMCs that were isolated from healthy individuals, as determined by PI/annexin V double staining followed by flow-cytometry analysis. Furthermore, we demonstrated that these primary AML cells exhibited aberrant phosphorylation of AKT, mTOR and STAT3. Treatment of AML cells with CWP mediated significant reduction in the phosphorylation of AKT, mTOR and STAT3. Additionally, we demonstrated that blockade of PI3K/AKT signaling pathway by wortmannin (WM) impaired the expression of Bcl-2 and BclXL in the primary AML cells, suggesting an essential cross-talk between PI3K and Bcl-2 that maintains the survival of AML cells. In this context, treatment of AML cells with CWP disrupted the PI3K/Bcl-2 cross-talk; significantly downregulated the expression of anti-apoptotic Bcl-2 family members Bcl-2 and BclXL; markedly upregulated the expression of the pro-apoptotic Bcl-2 family members Bak and Bax; and subsequently sensitized tumor cells to growth arrest. Our data revealed the therapeutic potential of CWP and the underlying mechanisms against leukemia.

Camel whey protein protects lymphocytes from apoptosis via the PI3K-AKT, NF-κB, ATF-3, and HSP-70 signaling pathways in heat-stressed male mice.

Heat stress (HS) is an environmental factor that depresses the immune systems that mediate dysfunctional immune cells. Camel whey protein (CWP) can scavenge free radicals and enhance immunity. This study investigated the impact of dietary supplementation with CWP on immune dysfunction induced by exposure to HS. Male mice (n = 45) were distributed among 3 groups: control group; HS group; and HS mice that were orally administered CWP (HS + CWP group). The HS group exhibited elevated levels of reactive oxygen species (ROS) and pro-inflammatory cytokines (interleukin (IL)-1ß, IL-6, tumor necrosis factor-α) as well as a significant reduction in the IL-2 and IL-4 levels. Exposure to HS resulted in impaired phosphorylation of AKT and IκB-α (nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha); increased expression of activating transcription factor 3 (ATF-3) and 70 kDa heat shock proteins (HSP70); and aberrant distribution of CD3+ T cells and CD20+ B cells in the thymus and spleen. Interestingly, HS mice treated with CWP presented significantly restored levels of reactive oxygen species and pro-inflammatory cytokines near the levels observed in the control mice. Furthermore, supplementation of HS mice with CWP enhanced the phosphorylation of AKT and IκB-α; attenuated the expression of ATF-3, HSP70, and HSP90; and improved T and B cell distributions in the thymus and spleen. Our findings reveal a potential immunomodulatory effect of CWP in attenuating immune dysfunction induced by exposure to thermal stress.

Protective effects of camel whey protein against scrotal heat-mediated damage and infertility in the mouse testis through YAP/Nrf2 and PPAR-gamma signaling pathways.

Elevation of scrotal temperature is one of the most important causes of impaired spermatogenesis and male infertility, but the exact mechanism remains controversial. The present study investigated the impact of camel whey protein (CWP) on the mechanisms of heat stress (HS)-mediated testicular damage in male mice. Exposure to HS was associated with significant increase in the testicular tissues' oxidative stress. Mechanistically, exposure to HS resulted in upregulation of P53 and Nrf2 expressions; downregulation of Bcl2 and PPAR-γ expressions; and induction of testicular Leydig cell hyperplasia. Because Leydig cells produce testosterone up on stimulation with Luteinizing hormone (LH), HS mice also exhibited significant reduction in the serum testosterone levels followed by significant reduction in the percentages of progressively motile sperm and higher percentages of immotile sperm, when compared with those of control mice. Interestingly, treatment of HS mice with CWP significantly restored the levels of ROS and the activities of antioxidant enzymes in the testicular tissues nearly to those observed in control mice. Furthermore, CWP supplemented HS mice exhibited complete restoration of Bcl2, P53, Nrf2, and PPAR-γ expressions; testicular Leydig cell distribution; significant higher levels of testosterone levels; and hence higher percentages of progressively motile sperm and lower percentages of immotile sperm as compared to HS mice. Our findings reveal the protective effects of CWP against testis injury and infertility induced by exposure to HS by rescuing functional Leydig cells. Additionally, the present study has shed light on the molecular mechanisms underlying improved testicular damage following CWP treatment.

Camel Whey Protein Protects B and T Cells from Apoptosis by Suppressing Activating Transcription Factor-3 (ATF-3)-Mediated Oxidative Stress and Enhancing Phosphorylation of AKT and IκB-α in Type I Diabetic Mice.

BACKGROUND: Diabetes mellitus (DM) is associated with severe immune system complications. Camel whey protein (CWP) decreases free radicals (ROS) and modulates immune functions, but its effect on DM-impaired immune systems has not been studied. We investigated the impact of CWP on the immune system in a Type 1 diabetes mouse model. METHODS: Three experimental groups were used: (1) non-diabetic control; (2) diabetic; and (3) CWP-treated diabetic mice. RESULTS: Induction of diabetes by streptozotocin was associated with reduction of body weight and insulin level, increase in glucose level and pro-inflammatory cytokines (IL-1ß, IL-6, and TNF-α), and reduction in IL-2 and IL-4 levels. Upregulated ATF-3 expression was followed by a marked elevation in ROS levels. Lymphocytes from diabetic mice exhibited increased apoptosis through decreased phosphorylation of AKT and IκB-α, increased infiltration of T cells in the spleen and thymus, and decreased B cell numbers in the spleen. Supplementation with CWP decreased the levels of proinflammatory cytokines, ROS, and ATF-3 expression, and increased the levels of IL-4. Treatment with CWP decreased apoptosis by enhancing the phosphorylation of AKT and IκB-α as well as T-cell and B-cell distribution in the spleen and thymus. CONCLUSIONS: Our findings suggest the beneficial effects of CWP supplementation during diabetes on decreasing and orchestrating the redox status and subsequently rescuing the immune cells from exhaustion.

Increased levels of type 1 interferon in a type 1 diabetic mouse model induce the elimination of B cells from the periphery by apoptosis and increase their retention in the spleen.

BACKGROUND: The autoimmune disease type 1 diabetes mellitus (T1D) is associated with a defect in the immune response, which increases susceptibility to infection. We recently demonstrated that prolonged elevated levels of type 1 interferon (IFN) induce lymphocyte exhaustion during T1D. AIMS: In the present study, we further investigated the effect of blocking the type I IFN receptor signaling pathway on diabetic dyslipidemia, in which an abnormal lipid profile leads to the exhaustion of B cells and alteration of their distribution and functions. METHODS: T1D was induced in a mouse model by an intraperitoneal injection of a single dose (60 mg/kg) of streptozotocin (STZ). Three groups of mice were examined: a non-diabetic control group, a diabetic group and a diabetic group treated with an anti-IFN (alpha, beta and omega) receptor 1 (IFNAR1) blocking antibody to block type I IFN signaling. RESULTS: We observed that induction of T1D was accompanied by a marked destruction of ß cells and a reduction in the insulin levels in the diabetic group. Diabetic mice exhibited many changes, including alterations in their lipid profiles, expansion of splenic B cells, increased caspase-3, -8 and -9 activity, and apoptosis in peripheral B cells. Blocking type 1 IFN signaling in diabetic mice significantly returned the insulin and lipid profiles to normal levels, subsequently restored the B cell distribution, and rescued the peripheral B cells from apoptosis. CONCLUSION: Our data suggest the potential role of type I IFN in mediating diabetic dyslipidemia and an exhausted state of B cells during T1D.

Effect of a high fat, high sucrose diet on the promotion of non-alcoholic fatty liver disease in male rats: the ameliorative role of three natural compounds.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a multifactorial disease with a complex pathophysiology. The clinical features of NAFLD include obesity, insulin resistance (IR) and dyslipidemia. Consumption of a diet high in saturated fats and sucrose is an important factor in the increasing occurrence of these metabolic disorders, primarily NAFLD and IR. We sought to assess the role of a high-fat, high-sucrose (HFS) diet in the promotion of NAFLD and to evaluate the effects of quercetin (Q), berberine (BB) and o-coumaric acid (CA) on modulation of these disorders. METHODS: Fifty male rats were divided into 2 main groups as follows: group 1 comprised 10 rats fed a standard diet (SD), and group 2 comprised 40 rats fed an HFS diet for 6 weeks and then subdivided equally into 4 groups; one of these groups served as the HFS diet and each of the other three groups received daily supplementation with either Q, CA or BB for 6 weeks. RESULTS: In the present study, several metabolic disorders were induced in our laboratory animal model, as evidenced by histological and biochemical changes. These alterations included serum and hepatic dyslipidemia (i.e., increased triglyceride, total cholesterol and low-density lipoprotein levels and decreased high-density lipoprotein levels), alterations in metabolic enzyme activities (lipase, glycerol-3-phosphate dehydrogenase, and glucose-6-phosphate dehydrogenase), histological changes in the liver (micro- and macrovesicular steatosis) and the downregulation of peroxisome proliferator-activated receptor γ (PPARγ) in adipose tissue and the liver. Daily oral supplementation with Q, CA or BB for 6 weeks after NAFLD induction had a hypolipidemic action and modulated metabolic markers. CONCLUSION: We showed that an HFS diet is able to promote NAFLD, and our results suggest that CA and BB are promising complementary supplements that can ameliorate the metabolic disorders associated with an HFS diet; however, Q requires further investigation.

Modulation of the rat intestinal microbiota in the course of Anisakis pegreffii infection.

Background: Anisakis are globally distributed, marine parasitic nematodes that can cause human health problems, including symptoms such as vomiting, acute diarrhea, and allergic reactions. As parasitic nematodes that primarily affect the patient's digestive tract, intestinal helminths can interact directly with the host microbiota through physical contact, chemicals, or nutrient competition. It is widely accepted that the host microbiota plays a crucial role in the regulation of immunity. Materials and methods: Nematodes collected from the abdominal cavity of marine fish were identified by molecular biology and live worms were artificially infected in rats. Infection was determined by indirect ELISA based on rat serum and worm extraction. Feces were collected for 16S rDNA-based analysis of microbiota diversity. Results: Molecular biology identification based on ITS sequences identified the collected nematodes as A. pegreffii. The success of the artificial infection was determined by indirect ELISA based on serum and worm extraction from artificially infected rats. Microbiota diversity analysis showed that a total of 773 ASVs were generated, and PCoA showed that the infected group was differentiated from the control group. The control group contained five characterized genera (Prevotellaceae NK3B31 group, Turicibacter, Clostridium sensu stricto 1, Candidatus Stoquefichus, Lachnospira) and the infected group contained nine characterized genera (Rodentibacter, Christensenella, Dubosiella, Streptococcus, Anaeroplasma, Lactococcus, Papillibacter, Desulfovibrio, Roseburia). Based on the Wilcoxon test, four processes were found to be significant: bacterial secretion system, bacterial invasion of epithelial cells, bacterial chemotaxis, and ABC transporters. Conclusion: This study is the first to analyze the diversity of the intestinal microbiota of rats infected with A. pegreffii and to determine the damage and regulation of metabolism and immunity caused by the infection in the rat gut. The findings provide a basis for further research on host-helminth-microbe correlationships.

Correction: Nutritional analysis and characterization of carbapenemase producing-Klebsiella pneumoniae resistant genes associated with bovine mastitis infected cow's milk.

[This corrects the article DOI: 10.1371/journal.pone.0293477.].

Optimization of Pramipexole-Loaded In Situ Thermosensitive Intranasal Gel for Parkinson's Disease.

The objective of the present work was to develop and optimize an intranasal in situ gel of Pramipexole dihydrochloride for enhanced drug delivery, better patient acceptability, and possible proper treatment of Parkinson's disease. Preliminary studies were performed to select formulation components and identify key variables affecting the formulation. The optimization of the in situ gelling system of Pramipexole dihydrochloride was achieved by applying 32 full factorial design using Design-Expert® software (Stat-Ease 9.0.6 version) and taking concentrations of Poloxamer 407 (X1) and HPMC K4M (X2) as independent variables. The gelling temperature, gel strength, and percentage of drug diffused after 8 h were taken as dependent variables. The software provided an optimized formulation, with 16.50% of X1 and 0.2% of X2 with the highest desirability. An in vivo drug retention time study was performed for the optimized formulation in Wistar rats. The results of the optimization process demonstrated that the selected gel formulation exhibited desirable characteristics, including gelation near body temperature, good gel strength, suitable viscosity, and sustained drug release. The optimized formulation displayed significantly higher drug retention, lasting about 5 h, versus the plain poloxamer gel formulation. Hence, it was concluded that the optimized formulation will remain affixed at the site of application for a significant time after intranasal administration and consequently sustain the release of the drug. The optimized formulation was found to be stable during the stability studies. The developed dosage form may improve patient compliance, enhance nasal drug residence, and offer sustained drug release. However, further clinical studies are necessary to validate these findings.

Uncovering the antimicrobial activity of G-type lysozyme 2 derived from Cyprinus carpio mucus against bacterial and fungal pathogens.

This study aimed to explore the antimicrobic potential of mucus samples collected from Cyprinus carpio and identify the specific antimicrobial peptides responsible for its activity. The crude extract was tested against various bacterial and fungal pathogens, and its protein content and profile were analyzed. Purification steps, including gel filtration chromatography, were employed to isolate the most active fraction (peak IV), which was further identified via liquid chromatography and mass spectroscopy. The results revealed varying degrees of antimicrobial activity of the crude extract against different bacterial and fungal strains, with Leclercia adecarboxylata, Candida glabrata, and Candida parapsilosis showing the highest susceptibility. SDS-PAGE analysis demonstrated the existence of multiple low molecular weight protein bands in the crude extract, while fraction IV obtained from gel filtration chromatography exhibited the strongest antimicrobial activity. Peak IV displayed a range of minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and minimum fungicidal concentration (MFC) values against the tested pathogens, spanning from 0.038 to 4.960 mg/mL. Further investigation identified the purified peptide derived from peak IV as G-type lysozyme 2, characterized by a molecular weight of 21 kDa. These findings shed light on the existence of a highly effective antimicrobial peptide, G-type lysozyme 2, within the mucus of Cyprinus carpio. This peptide demonstrates notable activity against diverse bacterial and fungal pathogens. The insights from this study enhance our understanding of the fish's antimicrobial defense mechanisms and hold promise for developing novel antimicrobial agents.

An investigation of the prevalence and diversity of Anisakis in China: marine food safety implications.

Anisakis can cause Anisakiasis in humans if raw or undercooked fish is consumed. Symptoms of infection may include vomiting, acute abdominal symptoms, or allergies. In this study, we collected 187 commercially available marine fish from the Yellow Sea, East China Sea, and South China Sea. Among them, 79 were found positive containing 520 Anisakis worms. The average prevalence rate was found 42% in this investigation. Ninety-two worms from different sea areas were selected and analyzed for identification, revealing the presence of five different species, which are Anisakis pegreffii, Hysterothylacium aduncum, Hysterothylacium zhoushanense, Hysterothylacium amoyense, and Hysterothylacium sp. In the meta-analysis, three databases: PubMed, CNKI, and BaiduXueshu were searched for surveys on the prevalence of Anisakis in Chinese waters from January 2000 to December 2023. A total of 26 studies were included in this analysis of which 25 publications were retrieved from different databases and one being the present study. The pooled prevalence of Anisakis was 45% among commercially available marine fish. Variances in the prevalence of Anisakis were noted among the four seas, with the highest rates in the East China Sea and the Bohai Sea, reaching 53% [0.38; 0.68] and 49% [0.36; 0.62], respectively. The Prevalence of Anisakis infection was significantly higher in astern parts such as Liaoning, Shanghai, and Zhejiang. Analysis of the host fish subgroups revealed that the orders of Anguilliformes, Scombriformes, and Gadiformes had high rates of infection. These findings suggest a significant prevalence of Anisakis, posing an increasing risk of infection for individuals. This study provides impactful information for implementing preventative measures against Anisakis.