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Ahmed AH Abdellatif,1,2,* Fatma Ahmed,3,* Ahmed M Mohammed,2 Mansour Alsharidah,4 Amal Al-Subaiyel,1 Waad A Samman,5 Aisha A Alhaddad,5 Samiah Hamad Al-Mijalli,6 Mohammed A Amin,1,2 Hassan Barakat,7,8 Shaaban K Osman2,* 1Department of Pharmaceutics, College of Pharmacy, Qassim University, Qassim, 51452, Saudi Arabia; 2Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Al-Azhar University, Assiut, 71524, Egypt; 3Department of Zoology, Faculty of Science, Sohag University, Sohag, 82524, Egypt; 4Department of Physiology, College of Medicine, Qassim University, Buraydah, 51452, Saudi Arabia; 5Department of Pharmacology and Toxicology, College of Pharmacy, Taibah University, Medina, 42353, Saudi Arabia; 6Department of Biology, College of Sciences, Princess Nourah Bint Abdulrahman University, Riyadh, 11671, Saudi Arabia; 7Department of Food Science and Human Nutrition, College of Agriculture and Veterinary Medicine, Qassim University, Buraydah, 51452, Saudi Arabia; 8Food Technology Department, Faculty of Agriculture, Benha University, Moshtohor, 13736, Egypt*These authors contributed equally to this workCorrespondence: Shaaban K Osman, Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Al-Azhar University, Assiut, 71524, Egypt, Tel +2 01129059936, Fax +2-088-312191, Email Shaabanosman@azhar.edu.eg Ahmed AH Abdellatif, Department of Pharmaceutics, College of Pharmacy, Qassim University, Qassim, 51452, Saudi Arabia, Email a.abdellatif@qu.edu.saAbstract: The real problem in pharmaceutical preparation is drugs’ poor aqueous solubility, low permeability through biological membranes, and short biological t1/2. Conventional drug delivery systems are not able to overcome these problems. However, cyclodextrins (CDs) and their derivatives can solve these challenges. This article aims to summarize and review the history, properties, and different applications of cyclodextrins, especially the ability of inclusion complex formation. It also refers to the effects of cyclodextrin on drug solubility, bioavailability, and stability. Moreover, it focuses on preparing and applying gold nanoparticles (AuNPs) as novel drug delivery systems. It also studies the uses and effects of cyclodextrins in this field as novel drug carriers and targeting devices. The system formulated from AuNPs linked with CD molecules combines the advantages of both CD and AuNPs. Cyclodextrins benefit in increasing aqueous drug solubility, loading capacity, stability, and size control of gold NPs. Also, AuNPs are applied as diagnostic and therapeutic agents because of their unique chemical properties. Plus, AuNPs possess several advantages such as ease of detection, targeted and selective drug delivery, greater surface area, high loading efficiency, and higher stability than microparticles. In the present article, we tried to present the potential pharmaceutical applications of CD-derived AuNPs in biomedical applications including antibacterial, anticancer, gene-drug delivery, and various targeted drug delivery applications. Also, the article highlighted the role of CDs in the preparation and improvement of catalytic enzymes, the formation of self-assembling molecular print boards, the fabrication of supramolecular functionalized electrodes, and biosensors formation.Keywords: AuNPs, nanotechnology, drug delivery, drug targeting, inclusion complexes, cancer management

Objective: There is a need to treat cancer cells with safe and natural nanoparticles to avoid the side effects of chemotherapeutic agents. Chamomile is considered a safe, natural plant with anticancer activity. We synthesize simple, inexpensive, and eco-friendly silver nanoparticles (SNs) using Chamomile (CHM) to tune their anticancer properties., Materials and Methods: SN-CHM was synthesized by reducing 1 mM silver nitrate aqueous solution in 100 mL with the aqueous ethanolic flower extract of CHM (18 mg/mL, w/v). The reaction proceeded overnight at 600 rpm and 28°C. SN-CHM was characterized for their % yield, average diameter, charge, morphology, and silver release. Moreover, SN-CHM was investigated for its antioxidant and anticancer activities at 200 µg/mL and 5 mg/ mL, respectively., Results: A 59.12% yield and a uniform SN-CHM size of 115 ± 3.1 nm with a ζ-potential of -27.67 ± (-3.92) mv were observed. The UV-visible absorption showed shifts from 379.5 to 383.5 nm for CHM and SN-CHM, respectively. Moreover, Ag+ was ultimately released from SN-CHM after 5 h. Fourier Transform Infrared Spectroscopy (FT-IR) showed characteristic absorption peaks of CHM and produced SN-CHM. Furthermore, SN-CHM showed moderate antioxidant activity. SN-CHM inhibited the % viability of SW620 and HT-29 cell lines at 20 μM. SN-CHM may also greatly upregulate the apoptotic gene BAX while considerably downregulating the anti-apoptotic genes BCL2 and BCL-Xl., Conclusions: CHM can be a safe soft drink, especially when conjugated with Ag ions as anticancer NPs. SN-CHM is considered potent anticancer activity against SW620, and HT-29 cell lines.

Background: Alzheimer's disease (AD) is a common neurodegenerative disorder without effective treatment. Thymoquinone (TQ) has demonstrated potential in exhibiting anti-inflammatory, anti-cancer, and antioxidant characteristics. Despite TQ's neuroprotection effect, there is a scarcity of information regarding its application in AD research, and its molecular trajectories remain ambiguous. Thus, the objective of the current investigation was to examine the potential beneficial effects and underlying mechanisms of TQ in scopolamine (SCOP)-induced neuronal injury to mimic AD in vivo model., Methods: Thirty mice were divided into normal, SCOP, and TQ groups. The Y-maze and pole climbing tests were performed to measure memory and motor performance. Afterwards, histopathological and immunohistochemical examinations were carried out. Furthermore, peroxisome proliferator-activated receptor gamma (PPAR-γ) signaling pathway-related proteins and genes were detected with an emphasis on the role of miR-9., Results: TQ has the potential to ameliorate cognitive deficits observed in SCOP-induced AD-like model, as evidenced by the improvement in behavioral outcomes, histopathological changes, modulation of the expression pattern of PPAR-γ downstream targets with a significant decrease in the deposition of amyloid beta (Aβ)., Conclusions: TQ provided meaningful multilevel neuroprotection through its anti-inflammatory and its PPAR-γ agonist activity. Consequently, TQ may possess a potential beneficial role against AD development.

The coronavirus has become the most interesting virus for scientists because of the recently emerging deadly SARS-CoV-2. This study aimed to understand the behavior of SARS-CoV-2 through the comparative genomic analysis with the closest one among the seven species of coronavirus that infect humans. The genomes of coronavirus species that infect humans were retrieved from NCBI, and then subjected to comparative genomic analysis using different bioinformatics tools. The study revealed that SARS-CoV-2 is the most similar to SARS-CoV among the coronavirus species. The core genes were shared by the two genomes, but there were some genes, found in one of them but not in both, such as ORF8, which is found in SARS-CoV-2. The ORF8 protein of SARS-CoV-2 could be considered as a good therapeutic target for stopping viral transmission, as it was predicted to be a transmembrane protein, which is responsible for interspecies transmission. This is supported by the molecular interaction of ORF8 with both the ORF7 protein, which contains a transmembrane domain that is essential to retaining the protein in the Golgi compartment, and the S protein, which facilitates the entry of the coronavirus into host cells. ORF1ab, ORF1a, ORF8, and S proteins of SARS-CoV-2 could be immunogenic and capable of evoking an immune response, which means that these four proteins could be considered a potential vaccine source. Overall, SARS-CoV-2 is most related to SARS-CoV. ORF8 could be considered a potential therapeutic target for stopping viral transmission, and ORF1ab, ORF1a, ORF8, and the S proteins of SARS-CoV-2 could be utilized as a potential vaccine source.

Background: Oral isotretinoin (Roaccutane) is one of the most effective treatments for severe acne. However, it displays significant side effects such as teratogenicity and psychological adverse events. Previous studies have reported inadequate awareness of community pharmacists and the general population regarding the medication's potential risks and adverse effects. The aim of this study is to assess pharmacy students' awareness and knowledge about the appropriate use of oral isotretinoin (known as Roaccutane) and its associated side effects in Saudi Arabia., Methods:  This is a cross-sectional study that uses a validated online questionnaire adopted from the literature distributed among pharmacy students between September 2021 and November 2021., Results: This study includes 1044 pharmacy students from multiple regions of Saudi Arabia. Among the total number of students included, 47.5% of the participants had used oral isotretinoin before or had a close family member who had used it previously. The most well-known side effect reported is skin dryness (87.7%), followed by teratogenicity (45.2%) and depression (37.9%). Most of the students (90.6%) know that isotretinoin's use is contraindicated in pregnancy. Despite this, only 39.6% of the participants state that married women of childbearing age using isotretinoin must utilize two types of contraception. There was a significant difference between genders in their knowledge about the side effects of the medication ( P =0.01), as well as the safety precautions that women of childbearing age should take while taking the medication, as females had better knowledge and understanding of the required measures., Conclusion: The total awareness level of pharmacy students about the most common side effects of isotretinoin is generally high. However, the students' knowledge about teratogenicity and depression is inadequate. We recommend paying attention to providing better education on the potential risks and precautionary measures related to the use of this medication, especially for women of childbearing age., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Malebari et al.)

Tropomyosin-receptor kinase A (TrkA) is the primary isoform among the tropomyosin-receptor kinases that have been associated with human cancer development, contributing to approximately 7.4% of all cancer cases. TrkA represents an attractive target for cancer treatment; however, currently available TrkA inhibitors face limitations in terms of resistance development and potential toxicity. Hence, the objective of this study was to identify new allosteric-approved inhibitors of TrkA that can overcome these challenges and be employed in cancer therapy. To achieve this goal, a screening of 9,923 drugs from the ChEMBL database was conducted to assess their repurposing potential using molecular docking. The top 49 drug candidates, exhibiting the highest docking scores (-11.569 to -7.962 kcal/mol), underwent MM-GBSA calculations to evaluate their binding energies. Delanzomib and tibalosin, the top two drugs with docking scores of -10.643 and -10.184 kcal/mol, respectively, along with MM-GBSA dG bind values of -67.96 and -50.54 kcal/mol, were subjected to 200 ns molecular dynamic simulations, confirming their stable interactions with TrkA. Based on these findings, we recommend further experimental evaluation of delanzomib and tibalosin to determine their potential as allosteric inhibitors of TrkA. These drugs have the potential to provide more effective and less toxic therapeutic alternatives. The approach employed in this study, which involves repurposing drugs through molecular docking and molecular dynamics, serves as a valuable tool for identifying novel drug candidates with distinct therapeutic uses. This methodology can contribute to reducing the attrition rate and expediting the process of drug discovery., 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 © 2023 Mukhtar, Abdelmoniem, Elrufaie, Edris, Ghaboosh, Mahgoub, Garelnabi, Osman, Sherif, Ashour, Ghazawi, Samman, Alhaddad, Bafail, Ibrahim, Mohamed and Alzain.)

Depsidones are a class of polyphenolic polyketides that have been proposed to be biosynthesized from oxidative coupling of esters of two polyketidic benzoic acid derivatives. They are principally encountered in fungi and lichens. In addition to their diversified structural features, they revealed varied bioactivities such as antimicrobial, antimalarial, cytotoxic, anti-inflammatory, anti- Helicobacter pylori , antimycobacterial, antihypertensive, anti-diarrheal, antidiabetic, phytotoxic, anti-HIV, anti-osteoclastogenic, and butyrylcholinesterase, tyrosinase, hyaluronidase, and acetylcholinesterase inhibition. The current work was targeted to provide an overview on the naturally reported depsidones from various sources in the period from 2018 to the end of 2022 including their structures, biosynthesis, sources, and bioactivities, as well as the reported structure-activity relationship and semisynthetic derivatives. A total of 172 metabolites with 87 references were reviewed. The reported findings unambiguously demonstrated that these derivatives could be promising leads for therapeutic agents. However, further in-vivo evaluation of their potential biological properties and mechanistic investigations are needed., Competing Interests: The authors declare that they have no competing interests., (© 2023 Khayat et al.)

CA (cyclosporine A) is a powerful immunosuppressing agent that is commonly utilized for treating various autoimmune illnesses and in transplantation surgery. However, its usage has been significantly restricted because of its unwanted effects, including nephrotoxicity. The pathophysiology of CA-induced kidney injury involves inflammation, apoptosis, tubular injury, oxidative stress, and vascular injury. Despite the fact that exact mechanism accountable for CA's effects is inadequately understood, ROS (reactive oxygen species) involvement has been widely proposed. At present, there are no efficient methods or drugs for treating CA-caused kidney damage. It is noteworthy that diverse natural products have been investigated both in vivo and in-vitro for their possible preventive potential in CA-produced nephrotoxicity. Various extracts and natural metabolites have been found to possess a remarkable potential for restoring CA-produced renal damage and oxidative stress alterations via their anti-apoptosis, anti-inflammatory, and antioxidative potentials. The present article reviews the reported studies that assess the protective capacity of natural products, as well as dietary regimens, in relation to CA-induced nephrotoxicity. Thus, the present study presents novel ideas for designing and developing more efficient prophylactic or remedial strategies versus CA passive influences.

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.

Background: Remineralization potential of dentifrices with novel compositions that can restore minerals back into incipient carious lesions has not been extensively studied so far., Objectives: The aim of this study was to assess the efficacy of a dentifrice based on novel fluoride incorporated bioactive glass in remineralizing artificial carious lesions in human enamel, and compare it with a standard fluoride-containing dentifrice., Material and Methods: Twenty-four human extracted teeth were sectioned at the cementoenamel junction to obtain enamel blocks. These blocks (n = 24) were randomly divided into 3 groups, with each group containing 8 specimens: group 1 (negative control group; distilled water), group 2 (positive control group; fluoride toothpaste) and group 3 (test group; BioMinTM F toothpaste). Artificial carious lesions were produced in the enamel surfaces by exposing them to a demineralization solution (6% citric acid, pH 2.2) for 96 h. After demineralization, the specimens were brushed with manual toothbrushes in a toothbrush simulation machine (each sample received 800 strokes). For brushing the specimens from group 1, 20 mL of distilled water was used, for group 2 - 20 mL of slurry of toothpaste mixed with artificial saliva, and for group 3 - 20 mL of slurry of toothpaste (BioMin F) mixed with artificial saliva. The micro-hardness data (VHN - Vickers hardness number) was collected at baseline (sound enamel), post-demineralization and post-remineralization., Results: The biggest difference between the post-remineralization and post-demineralization values was observed in group 3 (mean VHN = 118.73), followed by group 2 (mean VHN = 60.54) and group 1 (mean VHN = 47.44). All the groups revealed significant differences (p < 0.05) when the post-demineralization and post-remineralization values were compared to baseline values within each group., Conclusions: The BioMin F group outperformed the other 2 groups in terms of remineralizing the demineralized enamel structure.

Transanal Minimally Invasive Surgery (TAMIS) is a one of new platform used to help and achieve better outcome in using transanal approach for the treatment of rectal neoplasm. High definition camera and high tech equipment are used to perform this kind of surgery. The main benefit of using this approach is to provide the best outcome or the patient compared to the traditional transanal approach. This platform can be used for a variety of cases, benign and malignant tumor and for the benign condition. We report the first TAMIS perfo b rmed in the Kuwait and probably in the Middle East with 2 years of follow up. We had no complication and patient returned home and to normal activity in next day. More studies needed to validate this technique.