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Asmaa M Shehata,1 Fatma MS Salem,1 Eiman M El-Saied,1 Sahar S Abd El-Rahman,2 Mohamed Y Mahmoud,1 Peter A Noshy1 1Department of Toxicology and Forensic Medicine, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt; 2Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Giza, EgyptCorrespondence: Peter A Noshy Email vet_peter@cu.edu.egIntroduction: Silver nanoparticles (Ag-NPs) are among the most commonly used nanoparticles in different fields. Zinc nanoparticles (Zn-NPs) are known for their antioxidant effect. This study was designed to investigate the adverse effects of Ag-NPs (50 nm) on the male reproductive system and also the ameliorative effect of Zn-NPs (100 nm) against these harmful effects.Methods: Forty adult male rats were used in this study; they were randomly divided into four equal groups: control group, Ag-NPs group, Zn-NPs group, Ag-NPs + Zn-NPs group. Ag-NPs (50 mg/kg) and/or Zn-NPs (30 mg/kg) were administered orally for 90 days.Results: The results revealed that exposure to Ag-NPs adversely affected sperm motility, morphology, viability, and concentration. Ag-NPs also induced oxidative stress and lipid peroxidation in testicular tissue. The exposure to Ag-NPs decreased serum FSH, LH, and testosterone hormones. Additionally, comet assay revealed DNA degeneration in the testicular tissue of rats exposed to Ag-NPs. Histopathological examination showed various histological alterations in the testes of rats intoxicated with Ag-NPs. Furthermore, co-administration of Zn-NPs ameliorated most of the toxic effects of Ag-NPs via their antioxidative capacity.Keywords: antioxidants, DNA damage, endocrinology, oxidative stress, sperm evaluation, testes

Amit Alexander,1 Mukta Agrawal,1 Ajaz Uddin,1 Sabahuddin Siddique,2 Ahmed M Shehata,3,4 Mahmoud A Shaker,5,6 Syed Ata Ur Rahman,7 Mohi Iqbal M Abdul,3 Mohamed A Shaker6,71Department of Pharmaceutics, Rungta College of Pharmaceutical Sciences and Research, Bhilai, Chhattisgarh, India; 2Patel College of Pharmacy, Madhyanchal Professional University, Bhopal, Madhya Pradesh, India; 3Department of Pharmacology and Toxicology, College of Pharmacy, Taibah University, Al-Madinah Al-Munawarah, Kingdom of Saudi Arabia; 4Department of Pharmacology and Toxicology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt; 5Department of Pharmaceutics, College of Pharmacy, King Khalid University, Abha, Kingdom of Saudi Arabia; 6Pharmaceutics Department, Faculty of Pharmacy, Helwan University, Cairo, Egypt; 7Pharmaceutics and Pharmaceutical Technology Department, College of Pharmacy, Taibah University, Al-Madinah Al-Munawarah, Kingdom of Saudi ArabiaAbstract: The treatment of central nervous system (CNS) disorders always remains a challenge for the researchers. The presence of various physiological barriers, primarily the blood–brain barrier (BBB) limits the accessibility of the brain and hinders the efficacy of various drug therapies. Hence, drug targeting to the brain, particularly to the diseased cells by circumventing the physiological barriers is essential to develop a promising therapy for the treatment of brain disorders. Presently, the investigations emphasize the role of different nanocarrier systems or surface modified target specific novel carrier system to improve the efficiency and reduce the side effects of the brain therapeutics. Such approaches supposed to circumvent the BBB or have the ability to cross the barrier function and thus increases the drug concentration in the brain. Although the efficacy of novel carrier system depends upon various physiological factors like active efflux transport, protein corona of the brain, stability, and toxicity of the nanocarrier, physicochemical properties, patient-related factors and many more. Hence, to develop a promising carrier system, it is essential to understand the physiology of the brain and BBB and also the other associated factors. Along with this, some alternative route like direct nose-to-brain drug delivery can also offer a better means to access the brain without exposure of the BBB. In this review, we have discussed the role of various physiological barriers including the BBB and blood-cerebrospinal fluid barrier (BCSFB) on the drug therapy and the mechanism of drug transport across the BBB. Further, we discussed different novel strategies for brain targeting of drug including, polymeric nanoparticles, lipidic nanoparticles, inorganic nanoparticles, liposomes, nanogels, nanoemulsions, dendrimers, quantum dots, etc. along with the intranasal drug delivery to the brain. We have also illustrated various factors affecting the drug targeting efficiency of the developed novel carrier system.Keywords: brain, drug targeting, nanocarrier, BBB, liposome, intranasal drug delivery

Monitoring antipsychotic drugs in biological fluids, such as human serum and urine, is important for ensuring the safety and efficacy of psychiatric treatments. This process helps maintain therapeutic drug levels, minimize side effects, and optimize patient well-being. Chlorpromazine (CZ) is a widely prescribed antipsychotic drug used for conditions like schizophrenia, bipolar disorder, and acute psychosis. Almost all existing sensing techniques for CZ are either insensitive spectrophotometric methods or involve long and complex chromatographic procedures, limiting their routine use. In this work, we introduce a facile, green, and sensitive fluorimetric strategy with high reproducibility for detecting CZ in its pure form, tablet formulation, and spiked human plasma and urine without the need for derivatization reactions. The proposed method relies on the inhibition of the intramolecular photoinduced electron transfer (PET) effect by using 2.0 M acetic acid. This approach enables the linear detection of CZ from 3.0 to 600 ng/mL with remarkably low quantitation and detection limits of 1.51 and 0.49 ng/mL, respectively. Moreover, the developed method's greenness was evaluated., (© 2024 John Wiley & Sons Ltd.)

Heavy metal contamination threatens the aquatic environment and human health. Different physical and chemical procedures have been adopted in many regions; however, their adoption is usually limited since they take longer time, are more expensive, and are ineffective in polluted areas with high heavy metal contents. Thus, biological remediation is considered a suitable applicable method for treating contaminates due to its aquatic-friendly features. Bacteria possess an active metabolism that enables them to thrive and develop in highly contaminated water bodies with arsenic (As). They achieve this by utilizing their genetic structure to selectively target As and deactivate its toxic influences. Therefore, this review extensively inspects the bacterial reactions and interactions with As. In addition, this literature demonstrated the potential of certain genetically engineered bacterial strains to upregulate the expression and activity of specific genes associated with As detoxification. The As resistant mechanisms in bacteria exhibit significant variation depending on the genetics and type of the bacterium, which is strongly affected by the physical water criteria of their surrounding aquatic environment. Moreover, this literature has attempted to establish scientific connections between existing knowledge and suggested sustainable methods for removing As from aquatic bodies by utilizing genetically engineered bacterial strains. We shall outline the primary techniques employed by bacteria to bioremediate As from aquatic environments. Additionally, we will define the primary obstacles that face the wide application of genetically modified bacterial strains for As bioremediation in open water bodies. This review can serve as a target for future studies aiming to implement real-time bioremediation techniques. In addition, potential synergies between the bioremediation technology and other techniques are suggested, which can be employed for As bioremediation., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Sepsis-associated acute kidney injury (AKI) is a health complication, encompassing excessive inflammatory response, oxidative stress, and tubular necrosis; leading to kidney failure and death. Sepsis treatments are nonspecific and palliative. In this study, we evaluated the effect of morin, a flavonoid with known nephroprotective capabilities, on sepsis-induced AKI by dividing eighty male mice into: normal, morin-treated, septic, and septic mice treated with morin. Half of the groups were sacrified 3 days post sepsis induction, while the rest was sacrified on the 7th day. Treating septic mice with morin resulted in the amelioration of sepsis-associated pathophysiological renal alterations and the increase of the survival and recovery rates compared with those of septic control group. These findings indicate that morin has a therapeutic effect against sepsis-associated AKI via its anti-inflammatory, antioxidant and regenerative effects. Thus, it could be used as potential pharmacological intervention for preventing renal complications of sepsis., Competing Interests: Declaration of Competing Interest On behalf of all the authors of the submission, I declare no conflicts of interest, and disclose any financial and personal relationships with other people or organizations that could inappropriately influence this work., (Copyright © 2024. Published by Elsevier B.V.)

An experiment was conducted to assess the response of chicks to in-ovo injection of Bacillus subtilis (probiotic), raffinose (prebiotic), and their combinations. The study used 1,500 embryonated eggs allotted to 10 groups/ 6 replicates (150 eggs/group). The experimental treatments were: 1) un-injected control (NC); 2) sham (sterile distilled water) (PC); 3) probiotic 4 × 10 5 CFU/egg (LBS); 4) probiotic 4 × 10 6 CFU/egg (HBS); 5) prebiotic 2 mg/egg (LR); (6 prebiotic 3 mg/egg (HR); 7) probiotic 4 × 10 5 CFU + prebiotic 2 mg/egg (LBS+LR); 8) probiotic 4 × 10 5 CFU + prebiotic 3 mg/egg (LBS+HR); 9) probiotic 4 × 10 6 CFU + prebiotic 2 mg/egg (HBS+LR); and 10) probiotic 4 × 10 6 CFU + prebiotic 3 mg/egg (HBS+HR). Results showed that in-ovo inclusion of Bacillus subtilis, prebiotic, and their combinations improved hatchability, yolk-free chick weight, and chick weight compared to the control group. Moreover, the in-ovo treatment reduced residual yolk weight on the day of hatch compared to the control group. Different levels of in-ovo B. subtilis alone or combined with raffinose significantly (P ≤ 0.001) reduced total bacterial count and total yeast and mold count compared to the negative control group. Total coliform and E. coli decreased significantly (P ≤ 0.001) in groups treated with probiotics, prebiotics, and synbiotics with different doses during incubation compared to those in the control. Clostridium spp. was not detected in the groups injected with B. subtilis alone or combined with raffinose. In-ovo probiotics and synbiotics (LBS+LR & LBS+HR) significantly (P ≤ 0.001) increased ileal villus length compared to other groups. In-ovo treatment increased mRNA expression of JAM-2 compared to the control group. The fold change significantly increased in group LBS+HR for genes MUC-2, OCLN, VEGF, SGLT-1, and EAAT-3 compared to the negative control. In conclusion, in-ovo injection of a low dose of B. subtilis plus a high or low dose of raffinose can positively affect hatching traits, cecal microbial populations, intestinal histomorphometry, nutrient transport- and intestinal function-related genes, and chick quality of newly hatched broiler chicks., Competing Interests: DISCLOSURES The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Assessing medication adherence through the determination of antihypertensive drugs in biological matrices holds significant importance. Amlodipine (AP), a potent antihypertensive medication extensively prescribed for hypertensive patients, is particularly noteworthy in this context. This article aims to introduce a rapid, simple, improved sensitivity, and reproducibility in detecting AP in its pure form, tablet formulation, and spiked human plasma than the other reported methods. The proposed method utilizes a fluorescence approach, relying on the inhibition of the intramolecular photoinduced electron transfer (PET) effect of the lone pair of the N-atom in the primary amino moiety of AP. This inhibition is achieved by acidifying the surrounding medium using 0.2 M acetic acid. By blocking PET, the target AP drug is sensitively detected, at [Formula: see text] 423 nm over a concentration range 25-500 ng mL - 1 showcasing an exceptionally low quantitation limit of 1.41 ng mL - 1 . Notably, this innovative technique was successfully applied to detect AP in its solid dosage form and spiked human plasma. Remarkably, matrix interference was found to be insignificant, underscoring the robustness and applicability of the established approach. The combination of speed, sensitivity, and reproducibility makes this method particularly suitable for assessing medication adherence in patients prescribed AP for hypertension., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Sechium edule , commonly known as chayote is known for its low glycemic index, high fiber content, and rich nutritional profile, which suggests it may be beneficial for individuals with diabetes. While research specifically examining the impact of chayote on diabetes is limited, this study screened its biological impacts by using different biomarkers on streptozotocin-induced diabetic (STZ-ID) rats. The ethanolic extract of the Sechium edule fruits was assessed for different phytochemical, biochemical, and anti-diabetic properties. In the results, chayote extract had high phenolic and flavonoid contents respectively (39.25 ± 0.65 mg/mL and 12.16 ± 0.50 mg/mL). These high phenolic and flavonoid contents showed high implications on STZ-ID rats. Altogether 200 and 400 mg/kg of the extract considerably reduced the blood sugar level and enhanced the lipid profile of the STZ-ID rats. Additionally, they have decreased blood urea and serum creatinine levels. Besides, the levels of SGOT, SGPT, LDH, sodium, and potassium ions were significantly lowered after the administration period. More importantly, the electrocardiogram (ECG) parameters such as QT, RR, and QTc which were prolonged in the diabetic rats were downregulated after 35 days of administration of S. edule extract (400 mg/kg). And, the histological examination of the pancreas and kidney showed marked improvement in structural features of 200 and 400 mg/kg groups when compared to the diabetic control group. Where the increase in the glucose levels was positively correlated with QT, RR, and QTc (r 2  = 0.76, r 2  = 0.76, and r 2  = 0.43) which means that ECG could significantly reflect the diabetes glucose levels. In conclusion, our findings showed that the fruit extract exerts a high potential to reduce artifacts secondary to diabetes which can be strongly suggested for diabetic candidates. However, there is a need to study the molecular mechanisms of the extract in combating artifacts secondary to diabetes in experimental animals., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Antimicrobial resistance is one of the largest medical challenges because of the rising frequency of opportunistic human microbial infections across the globe. This study aimed to extract chitosan from the exoskeletons of dead bees and load it with bee venom (commercially available as Apitoxin [Api]). Then, the ionotropic gelation method would be used to form nanoparticles that could be a novel drug-delivery system that might eradicate eight common human pathogens (i.e., two fungal and six bacteria strains). It might also be used to treat the human colon cancer cell line (Caco2 ATCC ATP-37) and human liver cancer cell line (HepG2ATCC HB-8065) cancer cell lines. The x-ray diffraction (XRD), Fourier transform infrared (FTIR), and dynamic light scattering (DLS) properties, ζ-potentials, and surface appearances of the nanoparticles were evaluated by transmission electron microscopy (TEM). FTIR and XRD validated that the Api was successfully encapsulated in the chitosan nanoparticles (ChB NPs). According to the TEM, the ChB NPs and the ChB NPs loaded with Apitoxin (Api@ChB NPs) had a spherical shape and uniform size distribution, with non-aggregation, for an average size of approximately 182 and 274 ± 3.8 nm, respectively, and their Zeta potential values were 37.8 ± 1.2 mV and - 10.9 mV, respectively. The Api@ChB NPs had the greatest inhibitory effect against all tested strains compared with the ChB NPs and Api alone. The minimum inhibitory concentrations (MICs) of the Api, ChB NPs, and Api@ChB NPs were evaluated against the offer mentioned colony forming units (CFU/mL), and their lowest MIC values were 30, 25, and 12.5 μg mL -1 , respectively, against Enterococcus faecalis . Identifiable morphological features of apoptosis were observed by 3 T3 Phototox software after Api@ChB NPs had been used to treat the normal Vero ATCC CCL-81, Caco2 ATCC ATP-37, and HepG2 ATCC HB-8065 cancer cell lines for 24 h. The morphological changes were clear in a concentration-dependent manner, and the ability of the cells was 250 to 500 μg mL -1 . These results revealed that Api@ChB NPs may be a promising natural nanotreatment for common human pathogens., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer GMEE declared a shared affiliation with the authors MS, AZ, AM, and AS to the handling editor at the time of review., (Copyright © 2024 Sharaf, Zahra, Alharbi, Mekky, Shehata, Alkhudhayri, Ali, Al Suhaimi, Zakai, Al Harthi and Liu.)

The ability to determine antihistaminic drugs in biological matrices is critical for the medication adherence assessment. Among these antihistaminic medications, cyproheptadine (CPD); that is acting as a potent first-generation antihistaminic drug that has been extensively prescribed for allergic patients. Most of the established approaches for CPD detection are not appropriate for this purpose owing to their weak sensitivity, lack of rapidity, and complicated experimental procedures. Herein, we present a very fast, highly sensitive, and reproducible approach for the detection of CPD in its pure form, tablet formulation, and spiked human plasma. The photoluminescence approach depends on hindering the intramolecular photoinduced electron transfer (PET) effect of the lone pair of the N-atom present on the piperidine ring of CPD by making the surrounding medium acidic using 1.0 M acetic acid. Based on blocking PET, the target CPD drug has been sensitively detected from 5.0 to 500 ng mL -1 with a very low detection and quantitation limit of 7.01 and 21.25 ng mL -1 , respectively. Moreover, the established approach was used for checking the tablet content uniformity testing for each tablet and spiked human plasma, and noteworthy, the matrices interference was insignificant., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The Western Delta Deep Marine Concession (WDDM) in the Eastern Mediterranean Sea is one of northern Africa's most recent petroleum-potential regions for gas and condensate exploration. The present study aims to determine the characteristics of the 15 natural gases and 5 associated condensate samples, using molecular compositions and isotopes from the Miocene reservoir rocks in the various wells located in the WDDM. The results of this study are also used to determine the gas-condensate correlation for their probable source rocks as well as the methane-generating mechanisms (i.e., thermogenic or microbiological). Results highlighted in this research reveal that most of the natural gases in WDDM are mainly thermogenic methane gases, with small contributions of biogenic methane gases that were generated from mainly mixed sources, with a high sapropelic organic matter input for biogenic gases. The thermogenic methane gases were formed from secondary oil and oil/gas cracking at the high maturity stage of the gas window. The biogenic gases are also contributed to the Miocene reservoirs, which are formed from the primary cracking of kerogen at low maturity stage by the action of CO 2 bacterial reduction. In addition, the saturated and aromatic biomarker results show that the condensate samples were generated from clay-rich source rocks. This source unit of the Miocene condensates were deposited in a fluvial deltaic environmental setting, containing mixed kerogen type II/III and accumulated during the Jurassic-Cretaceous, as evidenced by the age dating indicators. The properties of the natural gases and associated condensates in the Miocene reservoir rocks suggest that most of the thermogenic methane gases, together with the condensate, are derived primarily from mature Jurassic-Cretaceous source rocks and formed by secondary oil and oil/gas cracking at the gas generation window, as demonstrated by the 1-D basin modelling results highlighted in the prior works. Therefore, most of the natural gases in WDDM are non-indigenous and migrated from more mature Jurassic-Cretaceous source rocks in the nearby Northern Sinai provinces or the deeper sequences in the offshore Nile Delta provinces., (© 2023. The Author(s).)

This study aims to address the issue of environmental pollution caused by non-biodegradable petroleum-based food packaging by exploring the application of biodegradable films. Film casting was employed to fabricate food packaging films from chitosan (CS) and polyvinyl alcohol (PVA) polymers blended with moringa extract (MoE) and various concentrations of magnesium oxide nanoparticles (MgO NPs). The films were characterized through multiple techniques, including UV spectroscopy, Thermogravimetric Analysis (TGA), Differential Scanning Calorimetry (DSC), Scanning Electron Microscopy (SEM), Energy-Dispersive X-ray Spectroscopy (EDX), X-ray Diffraction (XRD), and Fourier-transform Infrared Spectroscopy (FTIR). The study investigated the physicomechanical properties, water solubility, water vapor transmission rate, oxygen permeability, migration test, biodegradability, contact angle, anti-fogging, antibacterial and antifungal activity, and application of the films for food packaging. The results showed that blending CS/PVA films with MoE and MgO NPs significantly improved their mechanical properties. The highest tensile strength of 98 MPa was observed in the CPMMgO-0.5 film. The solubility of the films was low, with CPMMgO-0 and CPMMgO-0.25 demonstrating the lowest solubility as weight decreased by 3.41 % and 3.47 %, respectively. The water vapor transmission rate and oxygen permeability decreased with increasing MgO NP concentrations, with the CPMMgO-0.5 film exhibiting the lowest values. The films also demonstrated good biodegradability, anti-fogging ability, antibacterial and antifungal activity, and low water solubility, enabling bead encapsulation over 14 days in good condition. Moreover, the thermal stability of the films was improved, extending the shelf life of bread. Therefore, the fabricated films provide a promising alternative to non-degradable plastic packaging, which heavily contributes to environmental pollution., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

This study investigates the intricate relationship between exposure to information sources, trust in these sources, conspiracy and misinformation beliefs, and COVID-19 anxiety among 509 Omani citizens aged 11 to 50, representing 11 governorates. Employing structural equation modeling, we not only examine these associations but also explore how trust and COVID-19 anxiety act as moderating variables in this context. Additionally, we delve into demographic factors such as age group, educational level, gender, and place of residence (governorate) to discern potential variations.Our findings reveal that trust in health experts is inversely related to belief in conspiracy theories, while trust in health experts negatively correlates with exposure to conspiracy and misinformation. Intriguingly, trust in health experts exhibits divergent effects across governorates: it diminishes conspiracy and misinformation beliefs in some regions but not in others. Exposure to personal contacts and digital media, on the other hand, is associated with heightened beliefs in misinformation and conspiracy theories, respectively, in select governorates. These distinctions may be attributed to proximity to Muscat, the capital city of Oman, where various media outlets and policy-making institutions are situated. Furthermore, lower educational attainment is linked to greater belief in conspiracy and misinformation. Females reported higher levels of conspiracy theory beliefs and COVID-19 anxiety while no significant differences were detected in misinformation beliefs.This study sheds light on the intricate dynamics of misinformation and conspiracy theories in the context of COVID-19 in Oman, highlighting the pivotal roles of trust and COVID-19 anxiety as moderating factors. These findings offer valuable insights into understanding and addressing the spread of misinformation and conspiracy theories during a public health crisis., (© 2023. The Author(s).)

The independent detection and classification of brain malignancies using magnetic resonance imaging (MRI) can present challenges and the potential for error due to the intricate nature and time-consuming process involved. The complexity of the brain tumor identification process primarily stems from the need for a comprehensive evaluation spanning multiple modules. The advancement of deep learning (DL) has facilitated the emergence of automated medical image processing and diagnostics solutions, thereby offering a potential resolution to this issue. Convolutional neural networks (CNNs) represent a prominent methodology in visual learning and image categorization. The present study introduces a novel methodology integrating image enhancement techniques, specifically, Gaussian-blur-based sharpening and Adaptive Histogram Equalization using CLAHE, with the proposed model. This approach aims to effectively classify different categories of brain tumors, including glioma, meningioma, and pituitary tumor, as well as cases without tumors. The algorithm underwent comprehensive testing using benchmarked data from the published literature, and the results were compared with pre-trained models, including VGG16, ResNet50, VGG19, InceptionV3, and MobileNetV2. The experimental findings of the proposed method demonstrated a noteworthy classification accuracy of 97.84%, a precision success rate of 97.85%, a recall rate of 97.85%, and an F1-score of 97.90%. The results presented in this study showcase the exceptional accuracy of the proposed methodology in accurately classifying the most commonly occurring brain tumor types. The technique exhibited commendable generalization properties, rendering it a valuable asset in medicine for aiding physicians in making precise and proficient brain diagnoses.

Hybrid beamforming is a viable method for lowering the complexity and expense of massive multiple-input multiple-output systems while achieving high data rates on track with digital beamforming. To this end, the purpose of the research reported in this paper is to assess the effectiveness of the three architectural beamforming techniques (Analog, Digital, and Hybrid beamforming) in massive multiple-input multiple-output systems, especially hybrid beamforming. In hybrid beamforming, the antennas are connected to a single radio frequency chain, unlike digital beamforming, where each antenna has a separate radio frequency chain. The beam formation toward a particular angle depends on the channel state information. Further, massive multiple-input multiple-output is discussed in detail along with the performance parameters like bit error rate, signal-to-noise ratio, achievable sum rate, power consumption in massive multiple-input multiple-output, and energy efficiency. Finally, a comparison has been established between the three beamforming techniques.

Objectives: Breast cancer is the most diagnosed cancer in females worldwide. Phytochemicals are among the recent compelling approaches showing anticancer activity. Geraniol is a monoterpenoid showing anti-tumoral potential in cell lines. However, its exact mechanism in breast cancer has not been elucidated. In addition, the possible chemosenstizing effect of geraniol when combined with chemotherapeutic drugs in breast carcinoma has not been previously addressed., Methods: Therefore, the aim of the current work is to investigate the potential therapeutic as well as chemosensitizing effects of geraniol on breast carcinoma induced in mice through examination of tumour biomarkers and histopathology profile., Key Findings: Results showed a prominent suppression of tumour growth following geraniol treatment. This was accompanied with miR-21 downregulation that subsequently upregulated PTEN and suppressed mTOR levels. Geraniol was also able to activate apoptosis and inhibit autophagy. Histopathological examination revealed high necrosis areas separating malignant cells in the geraniol-treated group. Combined geraniol and 5-fluorouracil treatment induced more than 82% inhibition of tumour rate, surpassing the effect of each drug alone., Conclusions: It can be concluded that geraniol could represent a promising avenue for breast cancer treatment as well as a potential sensitizing agent when combined with chemotherapeutic drugs., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The current study was conducted to investigate the possible ameliorative role of zinc nanoparticles (Zn NPs) against silver nanoparticles (Ag NPs)-induced oxidative and apoptotic brain damage in adult male rats. Twenty-four mature Wistar rats were randomly and equally divided into four groups: control group, Ag NPs group, Zn NPs group, and Ag NPs + Zn NPs group. Rats were exposed to Ag NPs (50 mg/kg) and/or Zn NPs (30 mg/kg) daily by oral gavage for 12 weeks. The results revealed that exposure to Ag NPs significantly increased malondialdehyde (MDA) content, decreased catalase and reduced glutathione (GSH) activities, downregulated the relative mRNA expression of antioxidant-related genes (Nrf-2 and SOD), and upregulated the relative mRNA expression of apoptosis-related genes (Bax, caspase 3 and caspase 9) in the brain tissue. Furthermore, severe neuropathological lesions with a substantial increase in the caspase 3 and glial fibrillary acidic protein (GFAP) immunoreactivity were observed in the cerebrum and cerebellum of Ag NPs-exposed rats. Conversely, co-administration of Zn NPs with Ag NPs significantly ameliorated most of these neurotoxic effects. Collectively, Zn NPs can be used as a potent prophylactic agent against Ag NPs-induced oxidative and apoptotic neural damage., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Tadalafil (TAD) is a poorly soluble, phosphodiesterase inhibitor used to treat erectile dysfunction. The primary goal of this project was to prepare nano-emulsions using ultrasonic technology to address TAD bioavailability concerns. The Box−Behnken design was employed to find prominent correlations between factors impacting the sono-emulsification process. The emulsifier concentration, amplitude level, and ultrasonication time were the independent factors, whereas the average droplet size (ADS) and polydispersity index (PDI) were designated as the response variables. TAD-loaded nano-emulsions (93−289 nm) were generated and the emulsifier concentration showed a crucial role in directing emulsion droplet size. The model desirability function was utilized to optimize a nano-emulsion with a small ADS (99.67 ± 7.55 nm) and PDI (0.45 ± 0.04) by adjusting the emulsifiers concentration, amplitude level, and ultrasonication time at 9.85%, 33%, 49 s, respectively. The optimized nano-emulsions did not demonstrate any precipitation or phase separation after stability stress tests. TAD jellies were formulated based on the optimized nano-emulsion and subjected to in vitro evaluation for physical characteristics; TAD content, pH, spreadability, viscosity, syneresis, and taste-masking ability. An optimized nano-emulsion-based jelly (NEJ) formulation showed more than 96% drug dissolution in 30 min relative to 14% for the unprocessed TAD. In vivo assessment of NEJ in experimental rats demonstrated a significant enhancement (p < 0.05) of TAD bioavailability with an AUC0−24h of 2045 ± 70.2 vs. 259.9 ± 17.7 ng·h·mL−1 for the unprocessed TAD. Storage stability results revealed that NEJ remained stable with unremarkable changes in properties for 3 months. Overall, NEJ can be regarded as a successful therapeutic option for TAD administration with immediate-release properties and improved bioavailability.

Advances in animal husbandry and better performance of livestock results in growing demands for feed and its nutrients, bioactive compounds (bioactives), such as vitamins, minerals, proteins, and phenolics, along with drugs/vaccines. To protect the feed bioactives in unintended circumstances, they can be encapsulated to achieve desired efficacy in animal feeding and nanoencapsulation gives more potential for better protection, absorption and targeted delivery of bioactives. This study reviews structures, properties, and methods of nanoencapsulation for animal feedings and relevant drugs. Essential oil (EOs) and plant extracts are mostly encapsulated bioactives and phytochemicals for poultry diets and chitosan is found as most effective nanocarrier to load EOs and plant extracts. Nanoparticles (NPs) and nanocapsules are frequently studied nanocarriers, which are mostly processed by using the ionotropic/ionic gelation. Nanofibers, nanohydrogels and nanoemulsions are not found yet for their application in feed bioactives. These nanocarriers can have an improved protection, stability, and controlled release of feed bioactives which benefits to additional nutrition for the growth of livestock regardless of the low stability and water solubility of bioactives. For ruminants' feeds, nano-minerals, vitamins, phytochemicals, essential fatty acids, and drugs are encapsulated by NPs to facilitate the delivery to target organs through direct penetration, to improve their bioavailability, to generate more efficient absorption in cells and tissues, and protect them from rapid degradation. Furthermore, safety and regulatory issues, as well as advantages and disadvantages of nanoencapsulation application in animal feeds are also discussed. The review shows an accurate design of NPs can largely mask safety issues with straightforward approaches and awareness of safety concerns is fundamental for better designing of nanoencapsulation systems and commercialization. This review gives an insight of understanding and potential of nanoencapsulation in ruminants and poultry feedings to obtain a better bioavailability of the nutrients and bioactives with improved safety and awareness for better designing of nanoencapsulating systems., Competing Interests: Declaration of Competing Interest All authors declare that there is no conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Alpha-mangostin (α-MN) is a xanthone obtained from Garcinia mangostana that has diverse anti-oxidative and anti-inflammatory potentials. However, its pharmacological activity against autoimmune hepatitis (AIH) has not been investigated before. Concanavalin A (Con A) was injected into mice to induce AIH and two doses of α-MN were tested for their protective effects against Con A-induced AIH. The results demonstrated the potent hepatoprotective activity of α-MN evidenced by a remarkable decrease of serum indices of the hepatic injury and amendment of the histological lesions. α-MN significantly attenuated the level and immuno-expression of myeloperoxidase (MPO) indicating a decrease in the neutrophil infiltration into the liver. Additionally, the recruitment of the CD4+ T cell was suppressed in the α-MN pre-treated animals. α-MN showed a potent ability to repress the Con A-induced oxidative stress evident by the reduced levels of malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), and protein carbonyl (PC), as well as the enhanced levels of antioxidants as the reduced glutathione (GSH), superoxide dismutase (SOD), and total antioxidant capacity (TAC). The ELISA, RT-PCR, and IHC analyses revealed that α-MN enhanced the sirtuin1/nuclear factor erythroid 2 related factor-2 (SIRT1/Nrf2) signaling and its downstream cascade genes concurrently with the inhibition of the nuclear factor kappa B (NF-κB) and the inflammatory cytokines (tumor necrosis factor-alpha and interleukine-6) signaling. Taken together, these results inferred that the hepatoprotective activity of α-MN could prevent Con A-induced AIH through the modulation of the SIRT1/Nrf2/NF-κB signaling. Hence, α-MN may be considered as a promising candidate for AIH therapy.

Silver nanoparticles (AgNPs) interact with the microbes and host immune system to protect against diseases. Fertile broiler eggs ( n = 900) were allotted to six groups: un-injected control, sham (sterile water), AgNPs (50 μg), AgNPs+Amino acids (Methionine-10 mg + Arginine-25 mg), AgNPs+Vitamins (Vit B1-72μg + Vit B6-140μg), and AgNPs+Trace Elements (Zn-80 μg and Se-0.3 μg) and incubated for 18 days. On 18th embryonic day, 0.6 ml test solution was injected at the broad end of egg using 25 mm needle and transferred to hatcher. Post-hatch, half of the chicks from each group were vaccinated with Newcastle disease (ND) vaccine, and the other half were kept as unvaccinated unit and reared for 42 d with standard management practices. Hatchability, 1st and 42nd d body weight, feed intake, and feed conversion ratio were similar between treatment groups in both vaccinated and unvaccinated units. The relative weight of bursa Fabricius and thymus was similar, but spleen weight was higher ( P ≤ 0.05) in AgNPs, AgNPs+Vits, and AgNPs+TEs chicks than control group. Cellular immune response (against mitogen phytohemagglutinin-P) was higher ( P ≤ 0.05) in AgNPs+TEs chicks, whereas HA titer against sheep red blood cells antigen, serum IgG, IgM, and HI titer against ND vaccine was apparently higher in AgNPs+Vits group chicks than control. No clinical symptoms were observed in the vaccinated groups except for a few control birds 6 days postchallenge (PC). Three days PC, unvaccinated birds show depression, off feed, greenish diarrhea, and nasal discharge and the control group started dying. The highest cumulative infection (CI) was observed in sham (79.17%) and un-injected control (75%), but lowest in AgNPs+AAs birds (58.33%) on 3rd dpi. The CI reached 100% on 5th dpi in control groups and AgNPs, and 91.67% and 93.75% in AgNPs+TEs and AgNPs+AAs group, respectively. The AgNPs+TEs and AgNPs+AAs group birds lived for more than 90 h compared to 75 h in control groups and also had higher IL-6 and IL-2 gene expressions at 24 h PC. It was concluded that 50 μg/egg AgNPs with vitamins (B1 and B6) and trace elements (Zn and Se) improved performance, but AgNPs with trace elements and amino acids enhanced immune response and resistance against vND virus challenge in broilers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bhanja, Rath, Goel, Mehra, Dhara, Paswan, Attia, Alqhtani, Ali and Shehata.)

This research aimed to develop innovative self-nanoemulsifying chewable tablets (SNECT) to increase oral bioavailability of tadalafil (TDL), a nearly insoluble phosphodiesterase-5 inhibitor. Cinnamon essential oil, PEG 40 hydrogenated castor oil (Cremophor® RH 40), and polyethylene glycol 400 served as the oil, surfactant, and cosurfactant in the nanoemulsifying system, respectively. Primary liquid self-nanoemulsifying delivery systems (L-SNEDDS) were designed using phase diagrams and tested for dispersibility, droplet size, self-emulsifying capability, and thermodynamic stability. Adsorption on a carrier mix of silicon dioxide and microcrystalline cellulose was exploited to solidify the optimum L-SNEDDS formulation as self-nanoemulsifying granules (SNEG). Lack of crystalline TDL within the granules was verified by DSC and XRPD. SNEG were able to create a nanoemulsion instantaneously (165 nm), a little larger than the original nanoemulsion (159 nm). SNECT were fabricated by compressing SNEG with appropriate excipients. The obtained SNECT retained their quick dispersibility dissolving 84% of TDL within 30 min compared to only 18% dissolution from tablets of unprocessed TDL. A pharmacokinetic study in Sprague−Dawley rats showed a significant increase in Cmax (2.3-fold) and AUC0−24 h (5.33-fold) of SNECT relative to the unprocessed TDL-tablet (p < 0.05). The stability of TDL-SNECT was checked against dilutions with simulated GI fluids. In addition, accelerated stability tests were performed for three months at 40 ± 2 °C and 75% relative humidity. Results revealed the absence of obvious changes in size, PDI, or other tablet parameters before and after testing. In conclusion, current findings illustrated effectiveness of SNECT to enhance TDL dissolution and bioavailability in addition to facilitating dose administration.

The current study coupled fabric phase sorptive extraction (FPSE) with ultraperformance liquid chromatography method with electrospray ionization and tandem mass detection (UPLC-ESI-MS/MS) for fast and sensitive determination of tadalafil (TAD) in a bioequivalence study. Fabric phase sorptive extraction allowed direct extraction of TAD from the sample matrix with improved selectivity, repeatability, and recoveries. A sol-gel Carbowax 20 M (CX-20 M) coated FPSE membrane revealed the best extraction efficiency for TAD because of its strong affinity for analytes via intermolecular interactions, high mass transfer rate to FPSE membrane, and high permeability. An automated multiple reaction monitoring (MRM) optimizer was employed for the best selection of the precursor and product ions, ion breakdown profile, the fine adjustment of the fragmentor voltages for each precursor ions, and the collision energies for the product ions. The chromatographic separation was conducted using a mobile phase A: 5.0 mM ammonium acetate with 0.1 % formic acid in water and mobile phase B: formic acid (0.1%) in acetonitrile in ratio (55:45, v/v) through isocratic elution mode on an Agilent EclipsePlus C18 (50 × 2.1 mm, 1.8 μm) column and the flow rate was adjusted at 0.4 mL min -1 . The total run time per sample was 1.0 min. The method was validated by FDA standards for bioanalytical method validation over a concentration range of 0.1-100 ng mL -1 with a correlation coefficient of 0.9993 and the lower limit of quantitation (LLOQ) was 0.1 ng mL -1 in rat plasma. Intra- and inter-assay precision (%RSD) were lower than 4.1% and accuracy (%RE) was within 2.4%. The developed FPSE-UPLC-ESI-MS/MS method was effectively used in a randomized, two-way, single-dose, crossover study to compare the bioequivalence of two TAD formulations from different companies in male rats and verified to be bioequivalent., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Banning antibiotic growth promoters has negatively impacted poultry production and sustainability, which led to exploring efficient alternatives such as probiotics, probiotics, and synbiotics. Effect of in ovo injection of Bacillus subtilis , raffinose, and their synbiotics on growth performance, cecal microbial population and volatile fatty acid concentration, ileal histomorphology, and ileal gene expression was investigated in broilers ( Gallus gallus ) raised for 21 days. On 300 h of incubation, a total of 1,500 embryonated eggs were equally allotted into 10 groups. The first was non-injected (NC) and the remaining in ovo injected with sterile distilled water (PC), B. subtilis 4 × 10 5 and 4 × 10 6 CFU (BS1 and BS2), Raffinose 2 and 3 mg (R1 and R2), B. subtilis 4 × 10 5 CFU + raffinose 2 mg (BS1R1), B. subtilis 4 × 10 5 CFU + raffinose 3 mg (BS1R2), B. subtilis 4 × 10 6 CFU + raffinose 2 mg (BS2R1), and B. subtilis 4 × 10 6 CFU + raffinose 3 mg (BS2R2). At hatch, 60 chicks from each group were randomly chosen, divided into groups of 6 replicates (10 birds/replicate), and fed with a corn-soybean-based diet. In ovo inoculation of B. subtilis and raffinose alone or combinations significantly improved body weight, feed intake, and feed conversion ratio of 21-day-old broilers compared to NC. Cecal concentrations of butyric, pentanoic, propionic, and isobutyric acids were significantly elevated in R1, R2, BS2R1, and BS2R2, whereas isovaleric and acetic acids were significantly increased in R1 and BS2R1 compared to NC. Cecal microbial population was significantly altered in treated groups. Ileal villus height was increased ( p < 0.001) in BS1, R2, and BS2R2 compared to NC. The mRNA expression of mucin-2 was upregulated ( p < 0.05) in synbiotic groups except for BS1R1. Vascular endothelial growth factor (VEGF) expression was increased ( p < 0.05) in BS2, R1, BS1R1, and BS1R2 compared to NC. SGLT-1 expression was upregulated ( p < 0.05) in all treated birds except those of R1 group compared to NC. The mRNA expressions of interleukin (IL)-2 and toll-like receptor (TLR)-4 were downregulated ( p < 0.05) in BS2 and R1 for IL-2 and BS1R1 and BS2R2 for TLR-4. It was concluded that in ovo B. subtilis , raffinose, and synbiotics positively affected growth performance, cecal microbiota, gut health, immune responses, and thus the sustainability of production in 21-day-old broilers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shehata, Paswan, Attia, Abougabal, Khamis, Alqosaibi, Alnamshan, Elmazoudy, Abaza, Salama, El-Saadony, Saad and Abdel-Moneim.)

Purpose: To assess the effect of different concentrations of tacrolimus eye suspension on the epithelium and stromal keratocytes of human corneas and investigate whether it can be safely used for severe cases of vernal keratoconjunctivitis (VKC). Methods: Tacrolimus eye suspension was prepared in a range of concentrations of 0.005%, 0.01%, 0.05%, 0.1%, and 0.2%. Molecular analysis was performed ex vivo on human corneas ( n = 18), obtained from the eye bank. Transparency and thickness of each cornea were measured while live/dead staining was performed using a triple labeling assay. An incremental concentration approach was then tested on three severe cases of VKC. Results: All tested tacrolimus concentrations showed no significant changes in corneal thickness or transparency. In corneas treated with 0.1%, rare scattered dead cells were observed, while the folds of corneal surfaces were mostly viable, unlike concentrations higher than 0.1% and lower than 0.05%. Stromal cell densities were highest in the 0.1% tacrolimus treatment condition. Incremental concentrations of tacrolimus suspension were shown to significantly improve VKC cases, where the concentration used for each case depended on the severity of the case. Conclusions: Topical administration of tacrolimus was not toxic to human corneal cells at all tested concentrations, and the 0.1% concentration has shown the best viability of the corneal tissue. Tacrolimus eye suspension was shown to be safe and effective for use in severe VKC and is proposed as a topical ocular immunosuppressant drug enabling clinicians to incrementally increase the drug concentration according to the clinical severity of the disease to achieve the optimal therapeutic response., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Albarry, Parekh, Ferrari, Eltahir, Shehata, Shaker and Elbadawy.)

Silver nanoparticles (Ag-NPs) have various pharmaceutical and biomedical applications owing to their unique physicochemical properties. Zinc (Zn) is an essential trace element, a strong antioxidant, and has a primary role in gene expression, enzymatic reactions, and protein synthesis. The present study aims to explore the toxic effects of Ag-NPs (50 nm) on the liver and kidney of rats and also to evaluate the potential protective effect of Zn-NPs (100 nm) against these adverse effects. Forty adult Sprague-Dawley rats were randomly divided into four equal groups: control group, Ag-NPs group, Zn-NPs group, and Ag-NPs + Zn-NPs group. Ag-NPs (50 mg/kg) and/or Zn-NPs (30 mg/kg) were administered daily by gavage for 90 days. The results showed that exposure to Ag-NPs increased serum ALT, AST, urea, and creatinine. Ag-NPs also induced oxidative stress and lipid peroxidation and increased inflammatory cytokines in hepatic and renal tissues. Moreover, histopathological and immunohistochemical examinations revealed various histological alterations and positive caspase-3 expressions in the liver and kidney following exposure to Ag-NPs. On the other hand, most of these toxic effects were ameliorated by co-administration of Zn-NPs. It was concluded that Ag-NPs have hepatotoxic and nephrotoxic effects in rats via different mechanisms including oxidative stress, inflammation, and apoptosis and that Zn-NPs can be used to alleviate these harmful effects by their antioxidative, anti-inflammatory, and antiapoptotic properties., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This study was conducted to assess the impact of dietary incorporation of Spirulina platensis and selenium nanoparticles (SeNPs) individually or in combinations on growth performance, antioxidant status, humoral immune response, and microbial populations in diet and ileum of heat-stressed broilers. Ross-308 one-day chicks (n = 450) were fed one of 9 experimental diets with five replicate cages in 2 phases for 35 d. The experimental diets were a control basal diet without supplementation or with 0.1 mg SeNPs, 0.2 mg SeNPs, 5 g Spirulina, 10 g Spirulina, 0.1 mg SeNPs + 5 g Spirulina, 0.1 mg SeNPs + 10 g Spirulina, 0.2 mg SeNPs + 5 g Spirulina and 0.2 mg SeNPs + 10 g Spirulina per kg diet. Dietary supplementation with Spirulina and SeNPs significantly (P < 0.05) increased body weight gain and European production efficiency factor. Serum GPx and SOD were significantly (P < 0.05) increased with dietary Spirulina and SeNPs supplementation, while, TBARS was decreased (P < 0.05). Circulating immunoglobulin IgM, IgA and IgG were increased in treated birds compared to the control ones, while the antibody titers to IBD, AIV, and NDV were not significantly altered. The results showed that SeNPs and Spirulina exhibited dose-dependent antimicrobial activities against ileal counts of total bacterial, total molds and yeast, coliform, E. coli, Salmonella spp. and Enterococcus spp. However, ileal populations of Lactic acid bacteria were increased with dietary Spirulina and SeNPs in a dose-dependent manner. The microbial load in broilers' diets was reduced by dietary incorporation of S. platensis and SeNPs. These results indicate that Spirulina and SeNPs can be potentially used as growth promoters and antioxidant, immunostimulant, and antimicrobial agents in heat-stressed broilers., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

This study investigated the antimicrobial and antioxidant activity of three Spirulina extracts (methanol, acetone, and hexane) and the biological selenium nanoparticles (SeNPs) fabricated by Bacillus subtilis AL43. The results showed that Spirulina extracts exhibited antimicrobial activity against tested pathogens. Besides, Spirulina extracts significantly scavenged ABTS and DPPH radicals in a dose-dependent manner. The methanolic extract had higher total phenolic content, antimicrobial activity, and antioxidant activity than other extracts. The selenium nanoparticles were synthesized by Bacillus subtilis AL43 under aerobic conditions and were characterized as spherical, crystalline with a size of 65.23 nm and a net negative charge of -22.7. We evidenced that SeNPs possess considerable antimicrobial activity against three gram-positive, three gram-negative bacteria, and three strains from both Candida sp. and Aspergillus sp. Moreover, SeNPs were able to scavenge ABTS and DPPH radicals in a dose-dependent manner. An association was found between the total phenolic content of Spirulina and SeNPs and their biological activities. Our results indicate that Spirulina and SeNPs with significant antimicrobial and antioxidant activities seem to be successful candidates for safe and reliable medical applications., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors.)

This study examined the effects of dietary Spirulina platensis (SP) at levels of 0, 5, and 10 g.kg -1 and selenium nanoparticles (SeNPs) at 0, 0.1, and 0.2 mg.kg -1 , individually and in combination, on heat-stressed broiler chickens for 5 weeks. Four hundred fifty one-day-old Ross-308 chicks were allocated to 9 dietary groups with 5 replicates (10 chicks each). The control diet was consisted of corn-soybean-based basal diet. The obtained results displayed a significant increase in final body weight (p = 0.005) and weight gain during the periods from 22 to 35 days (p = 0.002) and 1 to 35 days (p = 0.005) in birds fed supplemented diets compared to those fed control diet, with the highest being in birds fed with both 10 g SP and 0.1 mg SeNPs. Feed conversion ratio was also improved in birds fed supplemented compared to control group. Dietary supplements significantly improved carcass dressing (p < 0.001), carcass yield (p = 0.001) percentages, and blood lipid profile. Blood triiodothyronine was higher (p = 0.005) with all treated diets except that contain 5 g SP compared to the control, with the highest being in birds fed diet contains 5 g SP + 0.2 mg SeNPs. Immunoglobulin subclasses IgG, IgM, and IgA were higher in birds fed supplemented diets compared to the control group. Antibody titers to Newcastle disease, avian influenza, and infectious bursal disease were numerically increased with dietary supplementation compared to the control group. Dietary treatments increased (p < 0.001) glutathione peroxidase and superoxide dismutase (SOD) levels, except diet contains 5 g SP for SOD level and decreased (p < 0.001) malondialdehyde level. It is concluded that dietary inclusion of SP and SeNPs, particularly their combination at levels 5 g SP plus 0.2 mg SeNPs kg -1 and 10 g SP plus 0.1 mg SeNPs kg -1 , improved growth performance, carcass yield, immunity, and antioxidant capacity of heat-stressed broilers., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The chicken gut is the habitat to trillions of microorganisms that affect physiological functions and immune status through metabolic activities and host interaction. Gut microbiota research previously focused on inflammation; however, it is now clear that these microbial communities play an essential role in maintaining normal homeostatic conditions by regulating the immune system. In addition, the microbiota helps reduce and prevent pathogen colonization of the gut via the mechanism of competitive exclusion and the synthesis of bactericidal molecules. Under commercial conditions, newly hatched chicks have access to feed after 36-72 h of hatching due to the hatch window and routine hatchery practices. This delay adversely affects the potential inoculation of the healthy microbiota and impairs the development and maturation of muscle, the immune system, and the gastrointestinal tract (GIT). Modulating the gut microbiota has been proposed as a potential strategy for improving host health and productivity and avoiding undesirable effects on gut health and the immune system. Using early-life programming via in ovo stimulation with probiotics and prebiotics, it may be possible to avoid selected metabolic disorders, poor immunity, and pathogen resistance, which the broiler industry now faces due to commercial hatching and selection pressures imposed by an increasingly demanding market.

Background: Hypercoagulability may be a key mechanism of death in patients with coronavirus disease 2019 (COVID-19)., Objective: To evaluate the incidence of venous thromboembolism (VTE) and major bleeding in critically ill patients with COVID-19 and examine the observational effect of early therapeutic anticoagulation on survival., Design: In a multicenter cohort study of 3239 critically ill adults with COVID-19, the incidence of VTE and major bleeding within 14 days after intensive care unit (ICU) admission was evaluated. A target trial emulation in which patients were categorized according to receipt or no receipt of therapeutic anticoagulation in the first 2 days of ICU admission was done to examine the observational effect of early therapeutic anticoagulation on survival. A Cox model with inverse probability weighting to adjust for confounding was used., Setting: 67 hospitals in the United States., Participants: Adults with COVID-19 admitted to a participating ICU., Measurements: Time to death, censored at hospital discharge, or date of last follow-up., Results: Among the 3239 patients included, the median age was 61 years (interquartile range, 53 to 71 years), and 2088 (64.5%) were men. A total of 204 patients (6.3%) developed VTE, and 90 patients (2.8%) developed a major bleeding event. Independent predictors of VTE were male sex and higher D-dimer level on ICU admission. Among the 2809 patients included in the target trial emulation, 384 (11.9%) received early therapeutic anticoagulation. In the primary analysis, during a median follow-up of 27 days, patients who received early therapeutic anticoagulation had a similar risk for death as those who did not (hazard ratio, 1.12 [95% CI, 0.92 to 1.35])., Limitation: Observational design., Conclusion: Among critically ill adults with COVID-19, early therapeutic anticoagulation did not affect survival in the target trial emulation., Primary Funding Source: None.

Global warming and climate change adversely affect livestock and poultry production sectors under tropical and subtropical conditions. Heat stress is amongst the most significant stressors influencing poultry productivity in hot climate regions, causing substantial economic losses in poultry industry. These economic losses are speculated to increase in the coming years with the rise of global temperature. Moreover, modern poultry strains are more susceptible to high ambient temperature. Heat stress has negative effects on physiological response, growth performance and laying performance, which appeared in the form of reducing feed consumption, body weight gain, egg production, feed efficiency, meat quality, egg quality and immune response. Numerous practical procedures were used to ameliorate the negative impacts of increased temperature; among them the dietary manipulation, which gains a great concern in different regions around the world. These nutritional manipulations are feed additives (natural antioxidants, minerals, electrolytes, phytobiotics, probiotics, fat, and protein), feed restriction, feed form, drinking cold water and others. However, in the large scale of poultry industry, only a few of these strategies are commonly used. The current review article deliberates the different practical applications of useful nutritional manipulations to mitigate the heat load in poultry. The documented information will be useful to poultry producers to improve the general health status and productivity of heat-stressed birds via enhancing stress tolerance, oxidative status and immune response, and thereby provide recommendations to minimize production losses due to heat stress in particular under the growing global warming crisis., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The liver is the main organ responsible for drug and xenobiotic metabolism and detoxification in the body. There are many antiepileptic drugs and nanoparticles that have been reported to cause serious untoward biological responses and hepatotoxicity. The aim of this study is to investigate the potential toxic effect of aspartic acid-coated magnesium oxide nanoparticles (Mg nano) and valproate (valp) using an in vitro three-dimensional (3D) human liver organoid model and an in vivo pentylenetetrazole (PTZ)-induced convulsion model in rats. Here, 3D human liver organoids were treated with valp or valp + Mg nano for 24 h and then incubated with PTZ for an extra 24 h. As the in vivo model, rats were treated with valp, Mg nano, or valp + Mg nano for 4 weeks and then they were treated with PTZ for 24 h. Toxicity in the liver organoids was demonstrated by reduced cell viability, decreased ATP, and increased reactive oxygen species. In the rat convulsion model, results revealed elevated serum alanine aminotransferase and aspartate aminotransferase levels. Both the in vitro and in vivo data demonstrated the potential toxic effects of valp + Mg nano on the liver tissues., (© 2020 Wiley Periodicals LLC.)

Campylobacter, Gram-negative bacteria, is the most common cause of acute bacterial enteritis in human beings, both in developing and developed countries. It is believed that poultry, in particular broiler chickens, is the main host of human infection with Campylobacter. Handling and consumption of contaminated chicken meat are the usual modes of transmission. Prevention and reduction of Campylobacter colonization in poultry farms will cut off the road of infection transmission to humans throughout the food chain. With the incidence of antibiotic resistance and with growing concern about superbugs, the search for natural and safe alternatives will considerably increase in the coming years. In this review, we will discuss the prevalence and risk factors of Campylobacter colonization in broiler chickens and sources of infection. This review also provides extensive and recent approaches to prevent and control Campylobacter colonization in broiler chickens, including biosecurity measures, natural feed/drinking water additives with antimicrobial properties, bacteriocins, bacteriophages, antimicrobial peptides, and vaccination strategies to prevent and control the incidence of human campylobacteriosis.

Heat stress, one of the critical obstacles to poultry sector in subtropical and tropical countries, reduces performance, immune response, and animal welfare. This study examined the effect of dietary inclusion of probiotic (PRO), citric acid (CIT), garlic powder (GAR) or their combinations on growth, blood constituents, ileal microflora and morphology and humoral immunity of broiler chickens subjected to cyclic heat stress. Four hundred ninety one-day-old Ross-308 broiler chicks were randomly allocated to 7 groups with 7 replicates of 10 birds each as follows: control (C) group received the basal diet without supplements, PRO, CIT and GAR groups supplemented with 0.5 g kg -1 multi-strain probiotic mixture (MPM), citric acid and garlic powder, respectively. PRO-CIT and PRO-GAR groups treated with 0.5 g kg -1 MPM, and 0.5 g kg -1 citric acid and garlic powder, while CIT-GAR group fed diet with 0.5 g kg -1 of citric acid and garlic powder. Results revealed that dietary supplements and their combinations improved (P < 0.001) growth performance and decreased abdominal fat of heat-stressed birds. Dietary supplements decreased (P < 0.01) serum concentrations of cholesterol, triglycerides and LDL, while HDL was elevated (P < 0.05). Feed additives reduced (P < 0.01) ileal enumeration of Escherichia coli and total coliform while Lactobacillus count was increased (P < 0.05) only in MPM-enriched groups. Supplementation of these natural products improved (P < 0.01) ileal architecture while humoral immune response was not significantly influenced except antibody titre against Newcastle disease virus which was increased (P < 0.05) in MPM-supplemented groups. Conclusively, addition of the dietary supplements and their combinations, particularly, probiotic and citric acid combination can improve productive performance, and intestinal flora and histomorphometry of broilers exposed to cyclic heat stress.

Background: AKI is a common sequela of coronavirus disease 2019 (COVID-19). However, few studies have focused on AKI treated with RRT (AKI-RRT)., Methods: We conducted a multicenter cohort study of 3099 critically ill adults with COVID-19 admitted to intensive care units (ICUs) at 67 hospitals across the United States. We used multivariable logistic regression to identify patient-and hospital-level risk factors for AKI-RRT and to examine risk factors for 28-day mortality among such patients., Results: A total of 637 of 3099 patients (20.6%) developed AKI-RRT within 14 days of ICU admission, 350 of whom (54.9%) died within 28 days of ICU admission. Patient-level risk factors for AKI-RRT included CKD, men, non-White race, hypertension, diabetes mellitus, higher body mass index, higher d-dimer, and greater severity of hypoxemia on ICU admission. Predictors of 28-day mortality in patients with AKI-RRT were older age, severe oliguria, and admission to a hospital with fewer ICU beds or one with greater regional density of COVID-19. At the end of a median follow-up of 17 days (range, 1-123 days), 403 of the 637 patients (63.3%) with AKI-RRT had died, 216 (33.9%) were discharged, and 18 (2.8%) remained hospitalized. Of the 216 patients discharged, 73 (33.8%) remained RRT dependent at discharge, and 39 (18.1%) remained RRT dependent 60 days after ICU admission., Conclusions: AKI-RRT is common among critically ill patients with COVID-19 and is associated with a hospital mortality rate of >60%. Among those who survive to discharge, one in three still depends on RRT at discharge, and one in six remains RRT dependent 60 days after ICU admission., (Copyright © 2021 by the American Society of Nephrology.)

Heat stress is one of the most challenging environmental stresses affecting domestic animal production, particularly commercial poultry, subsequently causing severe yearly economic losses. Heat stress, a major source of oxidative stress, stimulates mitochondrial oxidative stress and cell dysfunction, leading to cell damage and apoptosis. Cell survival under stress conditions needs urgent response mechanisms and the consequent effective reinitiation of cell functions following stress mitigation. Exposure of cells to heat-stress conditions induces molecules that are ready for mediating cell death and survival signals, and for supporting the cell's tolerance and/or recovery from damage. Heat-shock proteins (HSPs) confer cell protection against heat stress via different mechanisms, including developing thermotolerance, modulating apoptotic and antiapoptotic signaling pathways, and regulating cellular redox conditions. These functions mainly depend on the capacity of HSPs to work as molecular chaperones and to inhibit the aggregation of non-native and misfolded proteins. This review sheds light on the key factors in heat-shock responses for protection against cell damage induced by heat stress in chicken.

Importance: The US is currently an epicenter of the coronavirus disease 2019 (COVID-19) pandemic, yet few national data are available on patient characteristics, treatment, and outcomes of critical illness from COVID-19., Objectives: To assess factors associated with death and to examine interhospital variation in treatment and outcomes for patients with COVID-19., Design, Setting, and Participants: This multicenter cohort study assessed 2215 adults with laboratory-confirmed COVID-19 who were admitted to intensive care units (ICUs) at 65 hospitals across the US from March 4 to April 4, 2020., Exposures: Patient-level data, including demographics, comorbidities, and organ dysfunction, and hospital characteristics, including number of ICU beds., Main Outcomes and Measures: The primary outcome was 28-day in-hospital mortality. Multilevel logistic regression was used to evaluate factors associated with death and to examine interhospital variation in treatment and outcomes., Results: A total of 2215 patients (mean [SD] age, 60.5 [14.5] years; 1436 [64.8%] male; 1738 [78.5%] with at least 1 chronic comorbidity) were included in the study. At 28 days after ICU admission, 784 patients (35.4%) had died, 824 (37.2%) were discharged, and 607 (27.4%) remained hospitalized. At the end of study follow-up (median, 16 days; interquartile range, 8-28 days), 875 patients (39.5%) had died, 1203 (54.3%) were discharged, and 137 (6.2%) remained hospitalized. Factors independently associated with death included older age (≥80 vs <40 years of age: odds ratio [OR], 11.15; 95% CI, 6.19-20.06), male sex (OR, 1.50; 95% CI, 1.19-1.90), higher body mass index (≥40 vs <25: OR, 1.51; 95% CI, 1.01-2.25), coronary artery disease (OR, 1.47; 95% CI, 1.07-2.02), active cancer (OR, 2.15; 95% CI, 1.35-3.43), and the presence of hypoxemia (Pao2:Fio2<100 vs ≥300 mm Hg: OR, 2.94; 95% CI, 2.11-4.08), liver dysfunction (liver Sequential Organ Failure Assessment score of 2-4 vs 0: OR, 2.61; 95% CI, 1.30-5.25), and kidney dysfunction (renal Sequential Organ Failure Assessment score of 4 vs 0: OR, 2.43; 95% CI, 1.46-4.05) at ICU admission. Patients admitted to hospitals with fewer ICU beds had a higher risk of death (<50 vs ≥100 ICU beds: OR, 3.28; 95% CI, 2.16-4.99). Hospitals varied considerably in the risk-adjusted proportion of patients who died (range, 6.6%-80.8%) and in the percentage of patients who received hydroxychloroquine, tocilizumab, and other treatments and supportive therapies., Conclusions and Relevance: This study identified demographic, clinical, and hospital-level risk factors that may be associated with death in critically ill patients with COVID-19 and can facilitate the identification of medications and supportive therapies to improve outcomes.

In the last two decades, poultry and animal industries became increasingly interested in using plant-based feed supplements, herbs and their derivatives to retain or enhance their health and productivity. These health benefits for the host mainly attributed to the secondary plant metabolites, namely polyphenols. Polyphenols are renowned for their antioxidant, immunomodulatory, anti-mutagenic and anti-inflammatory properties. However, despite these advantages of polyphenols, they have been characterized by poor absorption in the gut and low concentration in target cells that compromise their role as effective antioxidants. The low bioavailability of polyphenols necessitates the need for further investigations to harness their full potential in poultry farms. This review is existing evidence about the bioavailability of polyphenols and their antioxidant, immunomodulatory, antimicrobial, detoxification properties and their impacts on poultry performance., (© 2020 Wiley-VCH GmbH.)

A series of benzothiazole/isatin linked to 1,2,3-triazole moiety and terminal sulpha drugs 5a-e and 6a-e were synthesized and evaluated for cytotoxic activity against a panel of cancer cell lines. The novel compounds showed variable IC 50 range of activity and some of them were potent compared to reference drug. The promising compounds were subjected as postulated the mimicry proposal for quinazoline-based EGFR inhibitors for their inhibitory profile against EGFR TK enzyme. That data obtained revealed that most of these compounds were potent EGFR TK inhibitors at nanomolar concentrations. Among these, compounds 5a and 5b showed more potent activity on EGFR compared to erlotinib (IC 50 103 and 104 versus 67.6 nM). Based upon the results, molecular docking analysis was performed on EGFR receptor and proved the strong contribution of fragments; benzothiazole, isatin, and triazole to the binding ATP pocket. When these selected compounds 5a and 5b were tested in an HepG2 model, they could effectively inhibited tumor growth, strongly induced cancer cell apoptosis, and suppressed cell cycle progression leading to DNA fragmentation. Well-DMET profile of the most active derivatives was presented and compared to the reference drugs. Taken together, we introduced novel triazole-sulpha drug hybrid for the first time as EGFR inhibitors and the results of our studies indicate that the newly discovered inhibitors have significant potential for anticancer treatment., Competing Interests: Declaration of Competing Interest The authors declared that there is no conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Despite the fact that levodopa has proven its effectiveness in treating the symptoms of Parkinson's disease (PD), increasing concerns have emerged about its possible long-term toxic effects on dopamine (DA) neurons. The study investigated the possible ameliorative effect of virgin coconut oil against l-dopa- induced neurotoxicity in adult rats. A total number of 40 rats were divided into four groups. Briefly, the first served as control, the second was orally administered virgin coconut oil (1.42 mL/kg), the third group was administered a single daily dose of l-dopa/carbidopa (100/10 mg/kg/day, p.o) and the fourth group pre-treated with virgin coconut oil then administered a single daily dose of l-dopa/carbidopa. The different treatments were extended for 30 days. l-dopa treated group exhibited aggressive behavior and behavioral abnormalities in open field test compared to control group. In addition, l-dopa treatment caused significant increase in the levels of striatal dopamine and norepinephrine and their metabolites with concomitant decrease of serotonin and its metabolite. Moreover, l-dopa treatment increased histamine and GABA levels. In addition, l-dopa treatment induced oxidative stress and energy crisis. The histological and immunohistochemical studies showed that l-dopa caused a remarkable neurodegeneration and increased glial fibrillary acidic protein (GFAP) immunoexpression in the striatal area. Virgin coconut oil co-treatment significantly minimized the harmful effects of l-dopa. In conclusion, the present study revealed that virgin coconut oil provided a notable protection against l-dopa's untoward effects., (Copyright © 2020 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Despite the introduction of directly acting antivirals (DAAs), for the treatment of hepatitis C virus (HCV) infection, their cost, patient compliance, and viral resistance are still important issues to be considered. Here, we describe the generation of a novel JFH1-based HCV subgenomic replicon double reporter cell line suitable for testing different antiviral drugs and therapeutic interventions. This cells line allowed a rapid and accurate quantification of cell growth/viability and HCV RNA replication, thus discriminating specific from unspecific antiviral effects caused by DAAs or cytotoxic compounds, respectively. By correlating cell number and virus replication, we could confirm the inhibitory effect on the latter of cell over confluency and characterize an array of lentiviral vectors expressing single, double, or triple cassettes containing different combinations of short hairpin (sh)RNAs, targeting both highly conserved viral genome sequences and cellular factors crucial for HCV replication. While all vectors were effective in reducing HCV replication, the ones targeting viral sequences displayed a stronger antiviral effect, without significant cytopathic effects. Such combinatorial platforms as well as the developed double reporter cell line might find application both in setting-up anti-HCV gene therapy approaches and in studies aimed at further dissecting the viral biology/pathogenesis of infection.

The incidence of adverse reactions in food is very low, however, some food products contain toxins formed naturally due to their handling, processing and storage conditions. 5-(Hydroxymethyl)-2-furfural (HMF) can be formed by hydrogenation of sugar substances in some of manufactured foodstuffs and honey under elevated temperatures and reduced pH conditions following Maillard reactions. In previous studies, it was found that HMF was responsible for harmful (mutagenic, genotoxic, cytotoxic and enzyme inhibitory) effects on human health. HMF occurs in a wide variety of food products like dried fruit, juice, caramel products, coffee, bakery, malt and vinegar. The formation of HMF is not only an indicator of food storage conditions and quality, but HMF could also be used as an indicator of the potential occurrence of contamination during heat-processing of some food products such as coffee, milk, honey and processed fruits. This review focuses on HMF formation and summarizes the adverse effects of HMF on human health.

The present study aims to investigate the potential antioxidant, anti-inflammatory and anti-fibrotic effects of Boswellia serrate (BS) gum resin against carbon tetrachloride (CCl 4 )-induced liver damage. Four groups consisting of eight rats each were designated: Group I, normal healthy control; group II, CCl 4 -induced liver fibrosis; group III, CCl 4 -induced liver fibrosis followed by BS treatment daily for two weeks; and group IV, CCl 4 -induced liver fibrosis followed by silymarin treatment daily for two weeks. Expression of tumor necrosis factor-α (TNF-α) and nuclear factor κB (NF-κB), interleukin-6 (IL-6), transforming growth factor-β (TGF-β) and cyclooxygenase-2 (COX-2) were assessed, in addition to histopathological and fibrotic changes in liver tissues isolated from the rats. BS significantly ameliorated CCl 4 -induced increases in serum aspartate (AST) and alanine transaminase (ALT) levels, reduced lactate dehydrogenase (LDH) activities in addition to restoring total bilirubin, triglyceride and albumin levels. BS treatment also alleviated oxidative stress and improved total antioxidant capacity in the liver, and reduced the expression of TNF-α, NF-κB, TGF-β, IL-6 and COX-2. On a histopathological level, BS treatment also exhibited antifibrotic activity. In conclusion, these findings suggest that BS contains potentially hepatoprotective effects against CCl4-induced liver injury via its antioxidant, anti-inflammatory and antifibrotic characteristics., (Copyright: © Eltahir et al.)

Aim: The aim of this study was to investigate the effect of three different hydrogen peroxide (H 2 O 2 ) levels on blood and liver oxidative status, energy metabolites, and gene expression in male albino rats at two time intervals (2 and 4 weeks)., Methods: A total of 32 rats were divided into four groups. The first group received tap water and served as control. The second group received low dose of hydrogen peroxide (H 2 O 2 ; 0.25%), The third group received medium dose of H 2 O 2 (0.5%) and the fourth group received high dose of H 2 O 2 (1%) in drinking water., Results: Present data showed that medium and high dose increased oxidative stress markers, decreased cell energy, and decreased antioxidant enzyme gene expression (GPx and Nrf2) and its downstream in contrast low dose did not show significant effects., Conclusion: This study might indicate that hydrogen peroxide medium level is the best dose for redox model status., (© 2018 Wiley Periodicals, Inc.)