Assessment of some toxic elements (Co, Cr, Mn, Se, and As) in muscle, offal, hair, and blood of camels (Camelus dromedaries) and their risk assessment.

Background: Camel meat tainted with heavy metals or trace elements may pose a health risk to consumers. Heavy metal contamination poses a severe danger due to both their toxicity and bioaccumulation in the food chain. Aim: To estimate the residual levels of heavy metals (Co, Cr, Mn, Se, and As) in muscle, liver, kidney, hair, and serum of three camel breeds (Magaheem, Maghateer, and Wadha) collected from Al-Omran abattoir, Al-Ahsa, Saudi Arabia. Methods: A total of 225 tissue samples (muscles, liver, kidney, serum, and hair) were taken and analyzed using an Atomic Absorption Spectrophotometer. Health risk assessment was assessed using the guidelines set by the US Environmental Protection Agency. Results: Camel breed significantly (p < 0.05) influences Co, Cr, Mn, and Se accumulation and distribution in organs and muscle; however, arsenic accumulation was not significantly affected (p < 0.05) by camel breeds. The highest values of Co, Cr, Se, and Mn in all examined samples were detected in the liver samples of Maghateer and Magaheem breeds. Furthermore, significant strong positive correlation between serum and liver cobalt, chromium, manganese, and arsenic. The estimated daily intake owing to camel meat consumption was less than the tolerated daily intake. Conclusion: Heavy metals were distributed among different breeds of camel. Trace elements (Pb and Cd) in meat and offal were below the international maximum permissible limit. The correlation between samples reflects the role of hair as a good tool for the identification of heavy metal pollution.

Development and characterization of a novel flavored functional fermented whey-based sports beverage fortified with Spirulina platensis.

Spirulina platensis, a microalga known for its exceptional nutritional value, especially its bioactive compounds and protein content, holds promise for incorporation into functional food products. Ricotta cheese whey is a byproduct of the production of ricotta cheese that is difficult to use in industries due to its low pH and less favorable processing qualities. This research aimed to create a unique fermented ricotta cheese whey-based beverage supplemented with various Spirulina powder concentrations (0.25 %, 0.5 %, and 0.75 % w/w) cooperated with a mixture of lemon and peppermint juice 10 % and fermented by probiotic (ABT) culture. The physicochemical, rheological, bioactive compounds, microbiological, and sensory properties were evaluated over a storage period of 21 days at cold storage. Spirulina-fermented whey-based beverages with a mixture of lemon and peppermint juice increased the concentration of vitamins, minerals, antioxidants, and total phenolic compounds in the final product. The count of probiotic bacteria in all fermented beverage samples exceeded 7 log CFU/mL throughout storage, indicating that the fermented beverage kept its probiotic properties. The addition of 0.5 % Spirulina significantly improved the final product's structural qualities and sensory acceptance.

Future scope of plant-derived bioactive compounds in the management of methicillin-resistant Staphylococcus aureus: In vitro antimicrobial and antivirulence prospects to combat MRSA.

Methicillin-resistant Staphylococcus aureus (MRSA) is a foremost human and animal pathogen with public health and veterinary significance causing hospital and community infections and contagious bovine mastitis. Due to its ability to develop multidrug resistance (MDR) and its pathogenicity, MRSA infection control is becoming a global concern. Natural antibacterial options are needed to combat MDR development and infectious dissemination. This study investigated the antimicrobial resistance and virulence genes profiling of MRSA isolates and explored the antivirulence efficacy of trans-cinnamaldehyde, thymol, and carvacrol essential oils (EOs) against multivirulent and MDR-MRSA isolates. Thirty six S. aureus isolates (25%) were retrieved, of which 34 (94.4%) were MRSA. A high prevalence of MDR (66.7%) was monitored and all 53 molecularly verified isolates possessed icaA and cna virulence genes. Moreover, 94.1% of these isolates were multivirulent with 23.5% of them carrying icaA, cna, eta, tst, and sea virulence genes. Our data proved superior in vitro antimicrobial and antivirulence activities of trans-cinnamaldehyde, thymol, and carvacrol. They inhibited the growth of multi-virulent and MDR-MRSA isolates and downregulated the transcription of examined virulence genes. Our study suggests using EOs as prospective antimicrobials with excellent antivirulence activities against MRSA isolates. We provided data regarding the eventual role of phytogenics in prevention and control of MRSA infection.

Genetic Factors Associated with Morphine Consumption in Women Undergoing Laparoscopic Cholecystectomy: A Prospective Cohort Study.

Introduction: Morphine has been a crucial analgesic agent used perioperatively in various surgical procedures. Genetic factors can lead to morphine dose requirement interpatient variability. Our objective was to determine the contribution of genetic polymorphisms in human µ-opioid receptor gene (OPRM1), ATP binding cassette gene (ABCB1) and rs2952768 to the variation of the perioperative morphine consumption in women undergoing laparoscopic cholecystectomy. Methods: This is a prospective cohort study that included 102 adult Arab females undergoing laparoscopic cholecystectomy. The exposures were carrying the genetic variants of OPRM1, ABCB1 and rs2952768. Our primary outcome was total morphine or morphine equivalent dose required perioperatively. The secondary outcomes were pain score during the first 24 hours and adverse drug reactions. A standardized, general anaesthesia was used for all subjects. In addition to the genetic factors, we also investigated non-genetic factors influencing post-operative pain sensitivity and morphine consumption. Results: Both (rs1799971, A>G) in OPRM1 and (rs2952768, T>C) showed statistically significant association with intra-operative total morphine dose requirements. Patients carrying the "G" allele in OPRM1 had a significantly higher total morphine mean rank dose compared to the AA genotype [62.9 vs 47.1, p=0.008]. Furthermore, patients homozygous for the rs2952768 (T>C) minor allele "CC" had a higher mean rank compared to the other genotypes [72.7 vs 50.1, p=0.046]. Conclusion: OPRM1 (rs1799971) and rs2952768 are associated with variation of intra-operative morphine consumption in laparoscopic cholecystectomy. Clinical Trial Identifier: This study was registered at ClinicalTrials.gov, NCT04621864. https://clinicaltrials.gov/ct2/show/NCT04621864.

Curcumin loaded liposome formulation: Enhanced efficacy on performance, flesh quality, immune response with defense against Streptococcus agalactiae in Nile tilapia (Orechromis niloticus).

Application of novel trend comprising antioxidant phytogenics is aiming to minimize the stress related factors and associated diseases in intensive fish culturing. Today, the concept of exploiting and protecting natural antioxidants represents a paradigm shift for the aqua feed industry. Therefore, our principal goal targeting liposome as a novel nanocarrier for curcumin is directed to attain superior performance, fillet antioxidant stability and bacterial resistance in Nile tilapia. A total of 500 Nile tilapia fingerlings (average body weight, 10.27 ± 0.10 g) assigned into five experimental groups in 25 glass aquaria of 120 L capacity at the density 20 fish/aquaria. The experimental groups were supplemented with varying doses of liposomal curcumin-NPs, LipoCur-NPs (0, 5, 15, 25 and 35 mg/kg diet) were reared for 12 weeks and later Streptococcus agalactiae (S. agalactiae) challenged model was performed. Inclusion of LipoCur-NPs (25 and 35 mg/kg diet) had the most prominent impact on Nile tilapia growth rate and feed conversion ratio. The immune boosting outcomes post supplementing 35 mg/kg diet of LipoCur-NPs were evidenced by higher myeloperoxidase, lysozyme and total immunoglobulin levels. Even after 4 weeks frozen storage, LipoCur-NPs at the dose of 35 mg/kg diet prominently increased (P < 0.05) the fillet scavenging capability for free radicals (1,1-diphenyl-2-picrylhydrazyl and 2,2'-Azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) with an inverse reduction in lipid peroxidation biomarker (malondialdehyde). Notably, upregulation of GSH-Px, CAT, and SOD genes in fillet of 35 mg/kg LipoCur-NPs fed fish coordinated with higher T-AOC and lower oxidative markers (ROS and H2O2). Post S. agalactiae challenge, higher supplementation levels of LipoCur-NPs (35 mg/kg diet) greatly attenuated the expression of its vital virulence genes (cfb, fbsA and cpsA) with higher expression of Igm, CXC-chemokine and MHC genes. Concordantly, downregulation of inflammatory markers (IL-1ß, TNF-α and IL-8) and upregulation of anti-inflammatory ones (IL-10 and TGF-ß) were remarkably documented. Based on these findings, the innovative curcumin loaded liposome was considered a novel multitargeting alternative not only playing an imperative role in Nile tilapia growth promotion and fillet stability upon storage, but also protecting efficiently against S. agalactiae.

Novel Antioxidant Insights of Myricetin on the Performance of Broiler Chickens and Alleviating Experimental Infection with Eimeria spp.: Crosstalk between Oxidative Stress and Inflammation.

In the modern poultry industry, the application of novel phytogenic bioactive compounds with antioxidant potential aims to enhance productivity and quality and to minimize the stress of associated diseases. Herein, myricetin, a natural flavonoid, was evaluated for the first time on broiler chickens' performance, antioxidants and immune modulating functions, and tackling avian coccidiosis. A total of 500 one-day-old chicks were divided into five groups. The negative (NC) and infected control (IC) groups were fed a control diet without additives, and the latter was infected with Eimeria spp. Groups supplemented with myricetin (Myc) were fed a control diet of Myc (200, 400 and 600 mg/kg diet each). On d 14, all chicks except those in NC were challenged with oocysts of mixed Eimeria spp. Significant improvements in the overall growth rate and feed conversion ratio were detected in the group that was fed 600 mg/kg, unlike the IC group. Notably, groups that were fed 400 and 600 mg/kg showed higher total meat antioxidant capacity with an inverse reduction in oxidative and lipid peroxidation biomarkers (hydrogen peroxide: H2O2; reactive oxygen species: ROS; Malondialdehyde: MDA). Of note, the upregulation of glutathione peroxidase; GSH-Px, catalase; CAT, superoxide dismutase; SOD, heme oxygenase-1; HO-1 and NAD(P)H dehydrogenase quinone 1 NQO1 genes in jejunum and muscle were prominently observed with increasing levels of supplemental Myc. At 21 dpi, the severity of coccoidal lesions (p < 0.05) induced by mixed Eimeria spp. and oocyst excretion were greatly reduced in the group that was fed 600 mg/kg of Myc. In the IC group, higher serum levels of C-reactive protein; CRP and nitric oxide; and NO and the upregulated expression of inflammatory biomarkers (interleukin-1ß; IL-1ß, interleukin-6; IL-6, tumor necrosis factor-α; TNF-α, chemotactic cytokines; CCL20, stromal cell-derived factor-1; CXCL13, and avian defensins; AvBD612) were subsided in higher levels in the Myc-fed groups. Taken together, these findings indicate the promising antioxidant role of Myc in modulating immune responses and reducing growth depression associated with coccidia challenges.

Liposomal encapsulated oregano, cinnamon, and clove oils enhanced the performance, bacterial metabolites antioxidant potential, and intestinal microbiota of broiler chickens.

Encapsulated phytochemicals with augmented therapeutic and nutritional characteristics have become promising alternatives to antimicrobials in the poultry industry. Hence, our key target was to explore the efficacy of liposomal encapsulation, as a novel carrier, for essential oils (LEOs) on growth, digestibility, intestinal microbiota, and bacterial metabolites of broiler chickens. Moreover, the impact of encapsulated EOs on transcription mechanisms targeting the genes encoding digestive enzymes, gut barrier functions and antioxidant potential of broiler chickens was evidenced. Four equal broiler groups were fed 4 basal diets fortified with LEOs (oregano, cinnamon, and clove) at the levels of 0, 200, 300, and 400 mg/kg diet. Our findings revealed significant improvement in body weight gain and feed conversion ratio of birds fed higher levels of LEOs. These results came concurrently with increasing the activities of digestive enzymes at both serum and molecular levels and consequently nutrient digestibility (dry matter, ether extract, crude protein, and crude fiber) in these groups. Remarkably, the abundance of beneficial bacteria as well as the bacterial metabolites (valeric acid, butyric acid, propionic acid, acetic acid, and total short-chain fatty acids) was increased, while that of pathogenic ones was reduced following dietary inclusion of LEOs. Of note, the mRNA expression of genes encoding antioxidant stability [catalase (CAT), superoxide dismutase 1 (SOD-1), glutathione peroxidase 1 (GPX-1), nuclear factor erythroid 2-related factor 2 (NRF2), NAD(P)H dehydrogenase quinone 1 (NQO1), and heme oxygenase-1 (HO-1)] as well as barrier functions [mucin-2 (MUC-2)] and tight junction proteins, TJP [junctional adhesion molecule-2 (JAM-2) and occludin] were noticeably upregulated in broilers fortified with 400 mg/kg diet of LEOs. Overall, the present work recommended dietary inclusion of LEOs as beneficial additives for attaining targeted performance, gut health and antioxidant stability in poultry farming.

Double-Fermented Soybean Meal Totally Replaces Soybean Meal in Broiler Rations with Favorable Impact on Performance, Digestibility, Amino Acids Transporters and Meat Nutritional Value.

Inclusion of microbial fermented soybean meal in broiler feed has induced advantageous outcomes for their performance and gastrointestinal health via exhibiting probiotic effects. In this study, soybean meal (SBM) was subjected to double-stage microbial fermentation utilizing functional metabolites of fungi and bacteria. In broiler diet, DFSBM replaced SBM by 0, 25, 50 and 100%. DFSBM was reported to have higher protein content and total essential, nonessential and free amino acids (increased by 3.67%, 12.81%, 10.10% and 5.88-fold, respectively, compared to SBM). Notably, phytase activity and lactic acid bacteria increased, while fiber, lipid and trypsin inhibitor contents were decreased by 14.05%, 38.24% and 72.80%, respectively, in a diet containing 100% DFSBM, compared to SBM. Improved growth performance and apparent nutrient digestibility, including phosphorus and calcium, and pancreatic digestive enzyme activities were observed in groups fed higher DFSBM levels. In addition, higher inclusion levels of DFSBM increased blood immune response (IgG, IgM, nitric oxide and lysozyme levels) and liver antioxidant status. Jejunal amino acids- and peptide transporter-encoding genes (LAT1, CAT-1, CAT-2, PepT-1 and PepT-2) were upregulated with increasing levels of DFSBM in the ration. Breast muscle crude protein, calcium and phosphorus retention were increased, especially at higher inclusion levels of DFSBM. Coliform bacteria load was significantly reduced, while lactic acid bacteria count in broiler intestines was increased with higher dietary levels of DFSBM. In conclusion, replacement of SBM with DFSBM positively impacted broiler chicken feed utilization and boosted chickens' amino acid transportation, in addition to improving the nutritional value of their breast meat.

Prospective Application of Nanoencapsulated Bacillus amyloliquefaciens on Broiler Chickens' Performance and Gut Health with Efficacy against Campylobacter jejuni Colonization.

Probiotics as novel antibiotics' substitutes are verified to provide barriers for hindering the colonization of enteric bacterial pathogens with nutritional benefits. For enhancement of the probiotics' effectiveness, their integration within nanomaterials is a paramount tool to support the progress of new compounds with functional features. Therefore, we addressed the impact of effective delivery of probiotics (Bacillus amyloliquefaciens) loaded nanoparticles (BNPs) on performance and Campylobacter jejuni (C. jejuni) shedding and colonization in poultry. Two hundred Ross broiler chickens were divided into four groups fed various BNP levels: BNPs I, BNPs II, BNPs III, and BNPs-free diets for 35 days. Nanoparticles delivery of probiotics within broiler diets improved growth performance as reflected by higher body weight gain and superior feed conversion ratio, especially in BNPs II- and BNPs III-fed groups. In parallel, the mRNA expression levels of digestive enzymes encoding genes (AMY2a, PNLIP, CELA1, and CCK) achieved their peaks in BNPs III-fed group (1.69, 1.49, 1.33, and 1.29-fold change, respectively) versus the control one. Notably, with increasing the levels of BNPs, the abundance of beneficial microbiota, such as Bifidobacterium and Lactobacillus species, was favored over harmful ones, including Clostridium species and Enterobacteriaceae. Birds fed higher levels of BNPs displayed significant improvement in the expression of barrier functions-linked genes including DEFB1, FABP-2, and MUC-2 alongside substantial reduction in cecal colonization and fecal shedding of C. jejuni. From the aforementioned positive effects of BNPs, we concluded their potential roles as growth promoters and effective preventive aids for C. jejuni infection in poultry.

Overview of Tissue Engineering and Drug Delivery Applications of Reactive Electrospinning and Crosslinking Techniques of Polymeric Nanofibers with Highlights on Their Biocompatibility Testing and Regulatory Aspects.

Traditional electrospinning is a promising technique for fabricating nanofibers for tissue engineering and drug delivery applications. The method is highly efficient in producing nanofibers with morphology and porosity similar to the extracellular matrix. Nonetheless, and in many instances, the process has faced several limitations, including weak mechanical strength, large diameter distributions, and scaling-up difficulties of its fabricated electrospun nanofibers. The constraints of the polymer solution's intrinsic properties are primarily responsible for these limitations. Reactive electrospinning constitutes a novel and modified electrospinning techniques developed to overcome those challenges and improve the properties of the fabricated fibers intended for various biomedical applications. This review mainly addresses reactive electrospinning techniques, a relatively new approach for making in situ or post-crosslinked nanofibers. It provides an overview of and discusses the recent literature about chemical and photoreactive electrospinning, their various techniques, their biomedical applications, and FDA regulatory aspects related to their approval and marketing. Another aspect highlighted in this review is the use of crosslinking and reactive electrospinning techniques to enhance the fabricated nanofibers' physicochemical and mechanical properties and make them more biocompatible and tailored for advanced intelligent drug delivery and tissue engineering applications.

Physicochemical, functional and sensory properties of probiotic yoghurt flavored with white sapote fruit (Casimiroa edulis).

Yoghurt is one of the health-functional foods and its nutritive value can be enhanced by adding native fruit. This study aimed to produce novel functional probiotic yoghurt using Bifidobacterium longum (B. longum) strain and White sapote fruits pulp (WSP) at levels of 5, 10, and 15%. WSP contains 19.87% carbohydrates, 0.90% protein, 0.35% fat, 0.78% fiber, 0.6% ash, 48.70 (mg GAE/100 g) total phenolic, 28.25 (mg/100 g) ascorbic acid and 153.53 (IC50 (mg/mL)) for antioxidant activity. Physicochemical, microbiological and sensory evaluation of flavored yoghurt samples were investigated during storage at 5 ± 1 °C for 21 days. The results revealed that increases in total solids, protein, ash, and carbohydrates content were observed in the flavored probiotic yoghurt compared to the control sample. Syneresis and WHC values of flavored yoghurt were influenced by supplementation with WSP whether in fresh or stored samples. Furthermore, significant (P< 0.05) increases in ascorbic acid, antioxidant activity, total phenols, vitamins, and minerals were observed in flavored probiotic yoghurt. Molds & yeast were not detected in all samples except in both control and probiotic yoghurt samples that appeared after 14 and 21 days. Similarly, coliforms were not found in all fresh and stored yoghurt samples. Sensory evaluation results showed that probiotic yoghurt flavored with 10% WSP had the highest acceptance scores compared to other treatments. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-022-05393-5.

Direct Oral Anticoagulants vs. Warfarin in Hemodialysis Patients With Atrial Fibrillation: A Systematic Review and Meta-Analysis.

Background: The use of Direct Oral Anticoagulants (DOACs) in patients who have both atrial fibrillation (AF) and end-stage renal disease (ESRD) requiring hemodialysis remains controversial, with warfarin remaining the mainstay of the treatment. As hemodialysis patients were excluded from most clinical DOACs trials, the evidence of their efficacy and safety is lacking in this cohort of patients. Aim: To review the current evidence investigating safety profile and the efficacy of DOACs in comparison with warfarin in patients with AF and end-stage renal disease (ESRD) requiring hemodialysis. Methods and Results: We included five studies with a total of 34,516 patients in our meta-analysis. The outcomes were major bleeding, ischemic stroke, systemic embolization, hemorrhagic stroke, gastrointestinal bleeding, minor bleeding, and death. Of these patients, 31,472 (92.14%) received warfarin and 3,044 patients received DOACs (8.91%). No significant differences in the incidence of hemorrhagic stroke, major bleeding, hemodialysis access site bleeding, ischemic stroke, and GI bleeding were found between DOACs and warfarin. However, there were higher rates of systemic embolization, minor bleeding, and death events in patients who received DOACs than in the warfarin group (3.39% vs. 1.97%, P-value = 0.02), (6.78% vs. 2.2%, P-value 0.02), and (11.38% vs. 5.12%, P-value < 0.006) respectively. Conclusion: In patients on dialysis who require anticoagulation for AF, warfarin could be associated with a significant reduction in minor bleeding, systemic embolization, and death compared to DOACs. These findings need to be validated by further prospective studies to address the best strategy to deal with the increased thrombotic and bleeding risks in such patients.

Preparation and evaluation of Quinoa-Kishk as a novel functional fermented dairy product.

Quinoa is gaining more attention throughout the world because of its high nutritional, antioxidant and antimicrobial impacts. This study aimed to develop a novel functional Kishk prepared from wheat burghul replacement with quinoa seeds at 0, 25, 50, 75, and 100% levels. Changes in chemical, microbial, and sensory properties were followed during storage at room temperature for 3 months. The obtained results revealed that Kishk samples fortified with quinoa seeds had higher protein (17.18-18.37%), fat (3.00-5.99%), ash (6.64-8.01%) and fiber (1.32-2.05%) compared to control sample (16.52, 2.82, 6.00 and 1.18%), respectively for fresh samples. Furthermore, incorporation of quinoa into Kishk formulations improved amino acid profile, mineral contents, antioxidant activity and total phenols. However, addition of quinoa affected the color attributes and significant decreases in L* and b* values were noticed compared to control sample. During the storage period, overall bacterial and lactic acid bacteria counts for all samples were reduced. Coliform, mould and yeast counts of all fresh samples were less than 10 CFU/g and not detected throughout the storage. Sensory evaluation results revealed that Kishk fortified with 50% quinoa seeds exhibited good sensory properties. Therefore, fortification with quinoa could improve nutritional and functional properties of fermented dairy products. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13197-021-05110-8.

Efficacy of Oil Pulling in the Management of Oral Submucous Fibrosis: A Preliminary Study

ABSTRACT Objective: To evaluate the effectiveness of oil pulling in the management of oral submucous fibrosis (OSMF). Material and Methods: A total of 62 patients clinically and histopathologically diagnosed as OSMF were incorporated in the present study. The subjects are randomly divided equally into two groups, Group A (oil pulling group) and Group B (placebo group). Subjects in Group A were asked to perform OP with sesame oil on an empty stomach in the morning for 3 months and Group B was given placebo capsules for 3 months. Assessment of various clinical parameters was done regularly, and data were analyzed using the Chi-square test. Results: Eighty-two percent had a habit of betel nut chewing, while 18% of the patients had tobacco chewing habits, which were among the main causative factors for OSMF. Clinical improvements in mouth opening, tongue protrusion, difficulty in speech and deglutition, and burning sensation were significant in the Group A. None of the patients reported any discomfort or side effects. The symptoms were not severe in nature and resolved in few days without stopping the therapy. Conclusion: Oil pulling can bring about significant clinical improvements in the symptoms like a mouth opening and tongue protrusion.

Cognitive enhancing effect of diapocynin in D-galactose-ovariectomy-induced Alzheimer's-like disease in rats: Role of ERK, GSK-3ß, and JNK signaling.

NADPH oxidase (NOX) has been identified as a crucial contender of oxidative damage in Alzheimer's disease (AD). However, the capability of diapocynin, a NOX inhibitor, to offer neuroprotection in AD models is still a matter of debate. Hence, the current work is dedicated to investigate the influence of diapocynin on cognitive impairment prompted by ovariectomy combined with D-galactose injection in rats (an AD animal model), and to elucidate the signaling mechanisms regulating diapocynin-induced effects. Female rats were exposed to ovariectomy or sham operation. Ovariectomized rats were injected intraperitoneally with D-galactose (150 mg/kg/day) for 70 days and, on day 43, they were orally treated with diapocynin (10 mg/kg/day) for 28 days. Diapocynin amended cognitive functions as confirmed using novel object recognition and Morris water maze tests along with histopathological improvement. It caused a prominent decrement in ß-secretase, p-tau, and amyloid ß, contrary to α-secretase elevation in hippocampus and hampered neuroinflammation and oxidative stress, manifested by declined levels of NOX1, tumor necrosis factor-α, and nuclear factor-kappa B p65. In addition, diapocynin augmented synaptophysin, brain-derived neurotrophic factor, and phospho-cAMP response element binding protein and enhanced protein expression of phosphorylated forms of phosphoinositide 3-kinase (PI3K), glycogen synthase kinase-3ß (GSK-3ß), protein kinase B (Akt), extracellular signal-regulated kinase (ERK) 1/2, ERK kinase kinase (Raf-1), and ERK kinase (MEK) 1/2, while inhibiting those of c-Jun and c-Jun N-terminal kinase (JNK). In conclusion, diapocynin attenuated memory impairment and AD-like anomalies via activating Raf-1/MEK/ERK and PI3K/Akt/GSK-3ß, while inhibiting JNK/c-Jun signaling cascades.

Accuracy of Cone Beam Computed Tomography in the Assessment of Mandibular Molar Furcation Defects

Abstract Objective: To evaluate the accuracy of cone-beam computed tomography (CBCT) in the assessment of mandibular molar furcation defects. Material and Methods: Thirty patients with furcation defects were selected, oral hygiene instructions, scaling, and root planing with ultrasonic devices and hand instruments and occlusal adjustments were performed. Pre-surgical clinical measurements were carried out at the buccal aspect of the selected mandibular molars. The horizontal furcation measurements were measured with a Nabers Probe starting at the furcation entrance to the greatest horizontal depth. The degree of furcation involvement was graded from 0 to III. Bone loss in the horizontal and vertical direction and the width of the furcation entrance were measured on CBCT and after reflecting the full-thickness flap and debridement of the defects. The data were analyzed using t-test and Pearson's correlation coefficient. Results: The width of furcation entrance in clinical method was 3.27 ± 0.77, while in CBCT method was 3.35 ± 0.71, clinically the vertical bone loss was 3.61±1.09, while in CBCT was 3.57 ± 1.15, horizontal bone loss in clinical method was 5.08 ± 2.21, while in CBCT was 5.11 ± 2.23. No significant difference between the two methods was noted, and a high correlation between the two methods was observed. With regards to the agreement between the two methods of assessment, the width of furcation entrance revealed a difference between the two methods by 0.08 ± 0.21, while vertical bone loss showed difference between the two methods by -0.04 ± 0.19, the horizontal bone loss showed a mean difference between the two methods by 0.03 ± 0.21. Conclusion: CBCT provided high accuracy for the furcation involvement detection and anatomy of surrounding periodontal tissues.

Escitalopram Ameliorates Cognitive Impairment in D-Galactose-Injected Ovariectomized Rats: Modulation of JNK, GSK-3ß, and ERK Signalling Pathways.

Though selective serotonin reuptake inhibitors (SSRIs) have been found to increase cognitive performance in some studies on patients and animal models of Alzheimer's disease (AD), other studies have reported contradictory results, and the mechanism of action has not been fully described. This study aimed to examine the effect of escitalopram, an SSRI, in an experimental model of AD and to determine the involved intracellular signalling pathways. Ovariectomized rats were administered D-galactose (150 mg/kg/day, i.p) over ten weeks to induce AD. Treatment with escitalopram (10 mg/kg/day, p.o) for four weeks, starting from the 7th week of D-galactose injection, enhanced memory performance and attenuated associated histopathological changes. Escitalopram reduced hippocampal amyloid ß 42, ß-secretase, and p-tau, while increasing α-secretase levels. Furthermore, it decreased tumor necrosis factor-α, nuclear factor-kappa B p65, and NADPH oxidase, while enhancing brain-derived neurotrophic factor, phospho-cAMP response element binding protein, and synaptophysin levels. Moreover, escitalopram diminished the protein expression of the phosphorylated forms of c-Jun N-terminal kinase (JNK)/c-Jun, while increasing those of phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), glycogen synthase kinase-3ß (GSK-3ß), extracellular signal-regulated kinase (ERK) and its upstream kinases MEK and Raf-1. In conclusion, escitalopram ameliorated D-galactose/ovariectomy-induced AD-like features through modulation of PI3K/Akt/GSK-3ß, Raf-1/MEK/ERK, and JNK/c-Jun pathways.

In silico and in vivo models for Qatari-specific classical homocystinuria as basis for development of novel therapies.

Homocystinuria is a rare inborn error of methionine metabolism caused by cystathionine ß-synthase (CBS) deficiency. The prevalence of homocystinuria in Qatar is 1:1,800 births, mainly due to a founder Qatari missense mutation, c.1006C>T; p.R336C (p.Arg336Cys). We characterized the structure-function relationship of the p.R336C-mutant protein and investigated the effect of different chemical chaperones to restore p.R336C-CBS activity using three models: in silico, ΔCBS yeast, and CRISPR/Cas9 p.R336C knock-in HEK293T and HepG2 cell lines. Protein modeling suggested that the p.R336C induces severe conformational and structural changes, perhaps influencing CBS activity. Wild-type CBS, but not the p.R336C mutant, was able to restore the yeast growth in ΔCBS-deficient yeast in a complementation assay. The p.R336C knock-in HEK293T and HepG2 cells decreased the level of CBS expression and reduced its structural stability; however, treatment of the p.R336C knock-in HEK293T cells with betaine, a chemical chaperone, restored the stability and tetrameric conformation of CBS, but not its activity. Collectively, these results indicate that the p.R336C mutation has a deleterious effect on CBS structure, stability, and activity, and using the chemical chaperones approach for treatment could be ineffective in restoring p.R336C CBS activity.

OCRL deficiency impairs endolysosomal function in a humanized mouse model for Lowe syndrome and Dent disease.

Mutations in OCRL encoding the inositol polyphosphate 5-phosphatase OCRL (Lowe oculocerebrorenal syndrome protein) disrupt phosphoinositide homeostasis along the endolysosomal pathway causing dysfunction of the cells lining the kidney proximal tubule (PT). The dysfunction can be isolated (Dent disease 2) or associated with congenital cataracts, central hypotonia and intellectual disability (Lowe syndrome). The mechanistic understanding of Dent disease 2/Lowe syndrome remains scarce due to limitations of animal models of OCRL deficiency. Here, we investigate the role of OCRL in Dent disease 2/Lowe syndrome by using OcrlY/- mice, where the lethal deletion of the paralogue Inpp5b was rescued by human INPP5B insertion, and primary culture of proximal tubule cells (mPTCs) derived from OcrlY/- kidneys. The OcrlY/- mice show muscular defects with dysfunctional locomotricity and present massive urinary losses of low-molecular-weight proteins and albumin, caused by selective impairment of receptor-mediated endocytosis in PT cells. The latter was due to accumulation of phosphatidylinositol 4,5-bisphosphate PI(4,5)P2 in endolysosomes, driving local hyper-polymerization of F-actin and impairing trafficking of the endocytic LRP2 receptor, as evidenced in OcrlY/- mPTCs. The OCRL deficiency was also associated with a disruption of the lysosomal dynamic and proteolytic activity. Partial convergence of disease-pathways and renal phenotypes observed in OcrlY/- and Clcn5Y/- mice suggest shared mechanisms in Dent diseases 1 and 2. These studies substantiate the first mouse model of Lowe syndrome and give insights into the role of OCRL in cellular trafficking of multiligand receptors. These insights open new avenues for therapeutic interventions in Lowe syndrome and Dent disease.