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Background: In livestock breeding, oocyte cryopreservation is crucial for preserving and transferring superior genetic traits. This study was conducted to examine the additional effect of melatonin to maturation and vitrification media on the in vitro developmental capacity, mitochondrial distribution, and intensity of buffalo oocytes. The study involved obtaining ovaries from a slaughterhouse and conducting two phases. In the first phase, high-quality oocytes were incubated in a maturation medium with or without 10−9M melatonin for 22 h (at 38.5°C in 5% CO2). Matured oocytes were fertilized in vitro and cultured in SOF media for seven days. In the second phase, vitrified in vitro matured oocytes were stored in vitrified media (basic media (BM) containing a combination of cryoprotectants (20% Ethyl Glycol and 20% Dimethyl sulfoxide), with or without melatonin, and then stored in liquid nitrogen. Normal vitrified/thawed oocytes were fertilized in vitro and cultured as described. Finally, the matured oocytes from the fresh and vitrified/thawed groups, both with and without melatonin, were stained using DAPI and Mitotracker red to detect their viability (nuclear maturation), mitochondrial intensity, and distribution using a confocal microscope. The study found that adding 10−9M melatonin to the maturation media significantly increased maturation (85.47%), fertilization rate (84.21%)cleavage (89.58%), and transferable embryo (48.83%) rates compared to the group without melatonin (69.85%,79.88%, 75.55%, and 37.25% respectively). Besides that, the addition of melatonin to the vitrification media improved the recovery rate of normal oocytes (83.75%), as well as the cleavage (61.80%) and transferable embryo (27.00%) rates when compared to the vitrified TCM group (67.46%, 51.40%, and 17.00%, respectively). The diffuse mitochondrial distribution was higher in fresh with melatonin (TCM + Mel) (80%) and vitrified with melatonin (VS2 + Mel groups) (76.70%), Furthermore, within the same group, while the mitochondrial intensity was higher in the TCM + Mel group (1698.60) than other group. In conclusion, Melatonin supplementation improves the developmental competence and mitochondrial distribution in buffalo oocytes in both cases(in vitro maturation and vitrification). [ABSTRACT FROM AUTHOR]

Background: Vibriosis is one of the most serious bacterial diseases and causes high morbidity and mortality among cultured sea breams. This study was undertaken to track the surveillance of Vibrio infection and its correlation to environmental factors. A total of 115 gilthead sea breams were collected seasonally from a private earthen pond fish farm in the Shatta area of Damietta, Egypt from September 2022 to July 2023. Physicochemical parameters of water were analyzed, and heavy metal levels were measured. The fish samples were subjected to clinical, bacteriological, Enterobacterial Repetitive Intergenic Consensus (ERIC) fingerprinting, and hematoxylin and Eosin histopathological staining. Results: The results revealed significant variations in the water quality parameters over different seasons, in addition to an increase in heavy metals. Naturally infected fish showed external signs and postmortem lesions that were relevant to bacterial infection. Two dominant Vibrio subspecies of bacteria were identified: V. alginolyticus (205 isolates) and V. fluvialis (87 isolates). PCR confirmed the presence of V. alginolyticus using the species-specific primer collagenase at 737 bp. The highest prevalence of V. alginolyticus was detected during the summer season (57.72%), and the lowest prevalence was observed in autumn (39.75%). The correlation analysis revealed a positive relationship between V. alginolyticus and water temperature (r = 0.69). On the other hand, V. fluvialis showed a high prevalence during the autumn season (25.30%) and the lowest prevalence during the summer season (10.56%), where it was negatively correlated with water temperatures (r =—0.03). ERIC fingerprinting showed genetic variation within the Vibrio isolates. Antimicrobial susceptibility testing revealed sensitivity to ciprofloxacin and doxycycline, and resistance to amoxicillin and erythromycin. The multiple antibiotic resistance (MAR) index values for V. alginolyticus and V. fluvialis ranged from 0.3 to 0.7, with a multi-drug resistance pattern to at least three antibiotics. Histopathological alterations in the affected tissues revealed marked hemorrhage, vascular congestion, and hemosiderosis infiltration. Conclusion: This study provides insights into the potential propagation of waterborne diseases and antibiotic resistance in the environment. Ensuring that the environment does not serve as a reservoir for virulent and contagious Vibrio species is a critical concern for regional aquaculture industries. Therefore, we recommend implementing environmental context-specific monitoring and surveillance tools for microbial resistance. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the effect of melatonin and melatonin-loaded chitosan nanoparticle (CMN) supplementation to maturation media on buffalo oocyte maturation rate and relative expression of genes: growth differentiation factor 9 (GDF9), bone morphogenetic protein 15 (BMP15), B Cell Lymphoma 2 (BCL2), Associated X protein (BAX) and superoxide dismutase 1 (SOD1). Buffalo ovaries were heaved from Al-Mounib slaughterhouse, cumulus-oocyte complexes (COCs) were in vitro matured in three different media, TCM-199 medium (control), TCM-199 with melatonin 10-9M, and TCM-199 with CMN 10-9M. The assessment of the nuclear maturation rate was carried out through the presence of the first polar body. In addition, the mature buffalo oocytes were stored on RNA later for genetic analysis of GDF9, BMP15, SOD1, BCL2, and BAX genes using quantitative real-time PCR (qRT-PCR). The results were reported that buffalo oocytes supplemented with melatonin-loaded chitosan nanoparticle (CMN) or melatonin have a significant effect on nuclear maturation rate 94.04±0.65 and 88.74±0.77 respectively when compared with buffalo oocytes matured with basic media (control) 79.67±1.35. Furthermore, buffalo oocytes supplemented with melatonin-loaded chitosan nanoparticle (CMN) or melatonin showed significant upregulation of GDF9, BMP15, SOD1, and BCL2 genes and significant downregulation of BAX gene when compared with oocyte matured with basic media (control). In conclusion, the results of nuclear maturation rate and relative expression pattern of GDF9, BMP15, SOD1, BCL2, and BAX reflect that melatonin-loaded chitosan nanoparticle (CMN) and melatonin' may play an important role in the buffalo oocytes developmental competence. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the impact of zinc sulfate and nano zinc oxide on the In-vitro maturation (IVM) of oocytes and on the In-vitro embryo developmental competence of buffaloes. Ovaries were obtained from the abattoir. Good quality oocytes (excellent & good) were matured in tissue culture medium -199 (TCM-199) vs. TCM-199 +10-6M zinc sulfate vs. TCM-199 +10-6 M nano zinc oxide enriched by fetal calf serum 10% (FCS) + 10 μg/ml follicle-stimulating hormone + 50 μg/ml gentamicin. The oocyte maturation was done in the incubator for 22 h in a humidified environment with CO2 5% and 38.5°C. Frozen-thawed semen was used to fertilize Mature oocytes, which were then incubated for 18 hours, before being cultured by synthetic oviduct fluid (SOF) for 7 days. The obtained results showed that supplementing maturation medium with 10-6 M zinc sulfate and 10-6 M nano zinc oxide resulted in a significant (P<0.05) rise in GIII cumulus cell expansion of buffalo oocytes by 52.93 %, and 59.75%, respectively, as compared to oocytes cultured in free medium (36.8%). G0 cumulus cell expansion showed a significant (P<0.05) decrease in zinc sulfate and nano zinc oxide groups (7.85, 3.29 %, respectively) when compared with oocytes cultured in free medium (14.73 %). The rate of maturation of oocytes with polar bodies was significantly greater in the zinc sulfate and nano zinc oxide groups (86.98, and 92.43%, respectively) when compared with those matured in free medium (80.11%). The hatching (cleavage) rate was significantly greater (P<0.05) in the zinc sulfate and nano zinc oxide groups (83.17, 87.66 respectively %) when compared with the TCM-199 (free medium) group (78.60%). The transferable embryos (blastocyst & morula) rates significantly raised (P<0.05) in the zinc sulfate (17.28 & 19.87 %, respectively) and nano zinc oxide groups (21.23 and 26.21%, respectively) when compared with TCM-199 group (11.19 &13.75 %, respectively). In conclusion, in vitro maturation rate and transferable embryo rates in buffaloes improve by adding zinc sulfate and nano zinc oxide to the medium of maturation. [ABSTRACT FROM AUTHOR]

Background: Patients on continuous flow ventricular assist devices (CF‐VADs) are at high risk for the development of Acquired von‐Willebrand Syndrome (AVWS) and non‐surgical bleeding. von Willebrand Factor (vWF) plays an essential role in maintaining hemostasis via platelet binding to the damaged endothelium to facilitate coagulation. In CF‐VAD patients, degradation of vWF into low MW multimers that are inefficient in facilitating coagulation occurs and has been primarily attributed to the supraphysiological shear stress associated with the CF‐VAD impeller. Methods: In this review, we evaluate information from the literature regarding the unraveling behavior of surface‐immobilized vWF under pulsatile and continuous flow pertaining to: (A) the process of arterial endothelial vWF production and release into circulation, (B) the critical shear stress required to unravel surface bound versus soluble vWF which leads to degradation, and (C) the role of pulsatility in on the production and degradation of vWF. Results and Conclusion: Taken together, these data suggests that the loss of pulsatility and its impact on arterial endothelial cells plays an important role in the production, release, unraveling, and proteolytic degradation of vWF into low MW multimers, contributing to the development of AVWS. Restoration of pulsatility can potentially mitigate this issue by preventing AVWS and minimizing the risk of non‐surgical bleeding. [ABSTRACT FROM AUTHOR]

Natural products are important in drug discovery because they provide structural clues for the creation of novel therapeutic treatments for a variety of ailments. The present study aims to focus on the in silico assessment of the therapeutic potential of phytochemical compounds isolated from Tarchonanthuscamphoratus L. The physicochemical and pharmacokinetic parameters of the three identified compounds were predicted using various integrated web-based tools. Following that, the PharmMapper web server was used to undertake structural-based virtual screening for the probable targets. Based on the findings, molecular docking was then used to investigate the binding interactions between the most promising lead and the targets indicated by the PharmMapper server. The obtained results revealed that the hydrogen bonds and total polar surface area for all compounds were within the limit range stated for Lipinski's rule of five and subsequently easily transported. However, only trifloculoside was found to be soluble (Log P = 2.3), permeable with no violation. Trifloculoside was suggested as potential antineoplastic agent based on its activity, safety, and binding energy to the target (− 6.8 kcal/mol). The obtained molecular dynamic simulation results were further supported the stability and flexibility of the complex. These findings suggest trifloculoside could be used as a starting point for future drug development initiatives in chemotherapy. [ABSTRACT FROM AUTHOR]

Background: Patients with continuous flow ventricular assist devices (CF‐VADs) are at high risk for non‐surgical bleeding, speculated to associate with the loss of pulsatility following CF‐VAD placement. It has been hypothesized that continuous shear stress causes elongation and increased enzymatic degradation of von Willebrand Factor (vWF), a key player in thrombus formation at sites of vascular damage. However, the role of loss of pulsatility on the unravelling behavior of vWF has not been widely explored. Methods: vWF molecules were immobilized on the surface of microfluidic devices and subjected to various pulsatile flow profiles, including continuous flow and pulsatile flow of different magnitudes, dQ/dt (i.e., first derivative of flow rate) of pulsatility and pulse frequencies to mimic in vivo shear flow environments with and without CF‐VAD support. VWF elongation was observed using total internal reflection fluorescence (TIRF) microscopy. Besides, the vWF level is measured from the patients' blood sample before and after CF‐VAD implantation from a clinical perspective. To our knowledge, this work is the first in providing direct, visual observation of single vWF molecule extension under controlled‐pulsatile shear flow. Results: Unravelling of vWF (total sample size n ~ 200 molecules) is significantly reduced under pulsatile flow (p < 0.01) compared to continuous flow. An increase in the magnitude of pulsatility further reduces unravelling lengths, while lower frequency of pulsatility (20 vs. 60 pulses per min) does not have a major effect on the maximum or minimum unravelling lengths. Evaluation of CF‐VAD patient blood samples (n = 13) demonstrates that vWF levels decreased by ~40% following CF‐VAD placement (p < 0.01), which correlates to single‐molecule observations from a clinical point of view. Conclusions: Pulsatile flow reduces unfolding of vWF compared to continuous flow and a lower pulse frequency of 20 pulses/minute yielded comparable vWF unfolding to 60 pulses/minute. These findings could shed light on non‐surgical bleeding associated with the loss of pulsatility following CF‐VAD placement. [ABSTRACT FROM AUTHOR]

Natural products play a pivotal role in innovative drug discovery by providing structural leads for the development of new therapeutic agents against various diseases.The present study aims to focus on the in silico assessment of the therapeutic potential of antidiabetic phytoconstituents which were identified and isolated from the extracts of Bauhinia rufescens Lam, a medicinal plant traditionally used for various pharmacotherapeutic purposes. The physicochemical and pharmacokinetic parameters of the previously isolated thirty eight compounds were predicted using SwissADME web tool whereas OSIRIS Property Explorer was used for toxicity risk assessment and drug- likeliness. Twelve compounds were selected for docking on human α-glucosidase and α-amylaseenzymes using Autodock 4.0 software. Furthermore, the active extract was in vivo tested for the antidiabetic activity and then identified usingTLC bioautographic method. Eriodictyol was found to have the highest potential as an inhibitor against α-amylase with binding energy of −9.92 kcal/mol. Rutin was the most potent against α-glucosidase with binding energy of-9.15 kcal/mol. A considerable number of hydrogen bonds and hydrophobic interactions were computed between the compounds and the enzymes thereby making them energetically favorable and suggesting inhibition of these two enzymes as a plausible molecular mechanism for their antidiabetic effect. These two flavonoids could therefore be used as potential leads for structure- based design of new effective hypoglycemic agents. [ABSTRACT FROM AUTHOR]

The recent outbreak of the highly contagious coronavirus disease 2019 (COVID-19) caused by the novel coronavirus SARS-CoV-2 has created a global health crisis with socioeconomic impacts. Although, recently, vaccines have been approved for the prevention of COVID-19, there is still an urgent need for the discovery of more efficacious and safer drugs especially from natural sources. In this study, a number of quinoline and quinazoline alkaloids with antiviral and/or antimalarial activity were virtually screened against three potential targets for the development of drugs against COVID-19. Among seventy-one tested compounds, twenty-three were selected for molecular docking based on their pharmacokinetic and toxicity profiles. The results identified a number of potential inhibitors. Three of them, namely, norquinadoline A, deoxytryptoquivaline, and deoxynortryptoquivaline, showed strong binding to the three targets, SARS-CoV-2 main protease, spike glycoprotein, and human angiotensin-converting enzyme 2. These alkaloids therefore have promise for being further investigated as possible multitarget drugs against COVID-19. [ABSTRACT FROM AUTHOR]

Background: Acute respiratory distress syndrome (ARDS) is a common and disabling disease with high rates of mortality and morbidity. The role of steroids in treating ARDS remains controversial. We aim to examine the evidence behind using glucocorticoids in the management of ARDS from the available studies. Methods: We performed a literature review of major electronic databases for randomized controlled trials (RCTs) comparing glucocorticoids versus placebo in treating patients with ARDS. Our primary outcome was hospital mortality. Other outcomes included ICU mortality, number of ventilator-free days at day 28, incidence of nosocomial infections, and hyperglycemia. We performed a meta-analysis using a random effects model to calculate risk ratios (RR) and mean difference (MD) with their corresponding 95% confidence intervals (CI). A subsequent trial sequential analysis was performed to examine the strength of evidence and to guard against statistical type I and type II errors for our results. Results: Eight RCTs were included in the final analysis totaling of 1091 patients, with a mean age of 57 ± 16, and 56.2% were male. In our pooled analysis, use of glucocorticoids was associated with a significant reduction in hospital mortality (RR 0.79; 95% CI 0.64–0.98; P = 0.03) and ICU mortality (RR 0.64; 95% CI 0.42–0.97; P = 0.04). Furthermore, glucocorticoid use was associated with an increased number of ventilator-free days at day 28 (MD 4.06 days; 95% CI 2.66–5.45; P < 0.01). Regarding adverse events, glucocorticoids use was not associated with an increased risk for nosocomial infections (RR 0.82; 95% CI 0.68–1.00; P = 0.05); however, it was associated with an increased risk of hyperglycemia (RR 1.11; 95% CI 1.01–1.24; P = 0.04). In our trial sequential analysis, the required diversity-adjusted information size (sample size = 2692 patients) was not reached, and the evidence was insufficient from the available RCTs. Conclusion: Among patients with ARDS, use of glucocorticoids is associated with a significant reduction in mortality and duration of mechanical ventilation, without increased risk of hospital-acquired infections. However, based on a trial sequential analysis, these findings may be secondary to a false-positive (type I) error. Further studies are needed for a firm conclusion with guarding against possible statistical errors. [ABSTRACT FROM AUTHOR]

Xanthones from natural and synthetic origins have shown interesting diverse pharmacological activities. This study aims to assess the in silico and in vitro activities of new synthetic xanthones as inhibitors of acetylcholinesterase enzyme (AChE). A series of eight new xanthones were designed and synthesised, using an in house strategy, from a readily available starting material. Their inhibitory activities against AChE were assessed in vitro and presented as IC50 values. The binding mode of these compounds inside AChE was investigated using Auto-Dock 4.2.2. Additionally, molecular dynamics simulation was performed, using GROMACS 5.0.2, to explore the dynamics of the inhibitory mechanism and stability of xanthone 5a within the active site of AChE enzyme. All xanthones showed promising activities when tested in vitro and in silico with xanthone 5a being the most potent in terms of both binding energy (−12.32 kcal/mol) and IC50 (0.20 ± 0.04 µM). Molecular dynamics simulation revealed several interesting features responsible for the potency of xanthone 5a as an AChE inhibitor. Furthermore, the calculated Log P of xanthone (5a) was found to be 6.56 suggesting it to be a potential drug candidate for the management of AChE associated diseases such as Alzheimer's disease and myasthenia gravis. [ABSTRACT FROM AUTHOR]

Summary: Background: Despite the wide therapeutic options available for the treatment of melasma, including many active topical medications, technologies with lights and peelings, clinical control of this disorder is extremely challenging. Objectives: To evaluate the effect of microneedling with topical vitamin C in the treatment of melasma. Methods: Thirty female patients with melasma received six sessions of microneedling with addition of topical vitamin C every two weeks. At each session, photos were taken and Melasma Area and Severity Index (MASI) score was calculated to assess the clinical improvement. Results: Mean age of the eligible patients was 33.2 ± 5.77 years. About 50% of cases were of Fitzpatrick skin type III. All patients showed improvement at the end of the sessions. Mean MASI score in the first session was 8.61 ± 4.45 and there was a gradual decline in its value till it reached a mean of 5.75 ± 4.16 in the last session (P < 0.0001). Conclusion: Microneedling with topical vitamin C is an effective and safe treatment option for epidermal melasma especially in Fitzpatrick skin phototypes I‐III. [ABSTRACT FROM AUTHOR]