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Khan MK, Khan BA, Uzair B, et al. Int J Nanomedicine. 2021;16:8203–8219. The Editor and Publisher of International Journal of Nanomedicine are retracting the published article. An investigation by the Publisher found duplication in images from another article from a different author group. Specifically, From the published article above, Figure 4, F2 and F3, have been duplicated with the same images for Figure 4D from Yujuan Mao, Xiaolan Chen, Bohui Xu, Yan Shen, Zixuan Ye, Birendra Chaurasiya, Li Liu, Yi Li, Xiaoling Xing & Daquan Chen. Eprinomectin nanoemulgel for transdermal delivery against endoparasites and ectoparasites: preparation, in vitro and in vivo evaluation. Drug Delivery. 2019;26(1):1104–1114. DOI: 10.1080/10717544.2019.1682720. The authors cooperated with the investigation and provided data associated with the reported study. However, despite the authors’ assistance, a satisfactory explanation for how the images came to be duplicated could not be provided, and the validity of the published work could not be verified. Therefore, the Editor and Publisher are retracting the article and the authors do not agree with this decision. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Natural bioactive compounds with anti-carcinogenic activity are gaining tremendous interest in the field of oncology. Cinnamon, an aromatic condiment commonly used in tropical regions, appeared incredibly promising as adjuvant for cancer therapy. Indeed, its whole or active parts (e.g., bark, leaf) exhibited significant anti-carcinogenic activity, which is mainly due to two cinnamaldehyde derivatives, namely 2-hydroxycinnaldehyde (HCA) and 2-benzoyloxycinnamaldehyde (BCA). In addition to their anti-cancer activity, HCA and BCA exert immunomodulatory, anti-platelets, and anti-inflammatory activities. Highly reactive α,ß-unsaturated carbonyl pharmacophore, called Michael acceptor, contribute to their therapeutic effects. The molecular mechanisms, underlying their anti-tumoral and anti-metastatic effects are miscellaneous, strongly suggesting that these compounds are multi-targeting compounds. Nevertheless, unravelling the exact molecular mechanisms of HCA and BCA remain a challenging matter which is necessary for optimal controlled-drug targeting delivery, safety, and efficiency. Eventually, their poor pharmacological properties (e.g., systemic bioavailability and solubility) represent a limitation, and depend both on their administration route (e.g., per os, intravenously) and the nature of the formulation (e.g., free, smart nano-). This concise review focused on the potential of HCA and BCA as adjuvants in Cancer. We described their medicinal effects as well as provide an update about their molecular mechanisms reported either in-vitro, ex-vivo, or in animal models.

Muhammad Khalid Khan,1 Barkat Ali Khan,1 Bushra Uzair,2 Shah Iram Niaz,3 Haroon Khan,4 Khaled Mohamed Hosny,5 Farid Menaa6 1Drug Delivery and Cosmetics Laboratory (DDCL), Faculty of Pharmacy, Gomal University, Dera Ismail Khan, 29050, Pakistan; 2Department of Biotechnology and Bioinformatics, International Islamic University, Islamabad, 40000, Pakistan; 3Department of Chemistry, Institute of Chemical Sciences, Gomal University, Dera Ismail Khan, 29050, Pakistan; 4Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Gomal University, Dera Ismail Khan, 29050, Pakistan; 5Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, 21589, Saudi Arabia; 6Department of Nanomedicine, California Innovations Corporation, San Diego, CA, 92037, USACorrespondence: Muhammad Khalid Khan Email khalid.gomalian@gmail.comPurpose: Microbial resistance to antibiotics is one of the most important public health concerns of the 21st century. We isolated, purified, and structurally elucidated antifungal secondary metabolites from red soil microbes and encapsulated them into chitosan (CS)-based nanoemulsion (NE) gel (NEG).Methods: Three compounds were isolated and purified of which only one compound (Pure 2) showed potent antifungal activity (MFC: 8– 132 μg/mL), which was also significantly (P< 0.05) more efficient than fluconazole (MFC: 32– 132 μg/mL). Pure 2 was structurally elucidated using 1D- and 2D-NMR before its incorporation into NEG. The formulations were prepared by high-speed homogenization technique. Physicochemical and pharmacological characterizations of formulations (ie, droplet size, PDI, zeta potential, drug content, viscosity, SEM, FTIR, spreadability, in vitro drug release, ex vivo permeation, in vitro antifungal and in vivo antifungal activities) were assessed.Results: NMR analyses identified the compound as a derivative of phthalic acid ester (PAE). The optimized formulations displayed a droplet size < 100 nm, -ve zeta potential, and PDI < 0.45. The drug content was within the official limit of pharmacopeia (ie, 100± 10%). Insignificant changes (P> 0.05) in the viscosity of the formulations stored were observed. The morphology of the formulations indicated mesh-like structure. The FTIR study indicated that there were no interactions between the drug and other ingredients of the formulations. Optimum spreadability was observed in all formulations. NEG released 75.3± 1.12% of Pure 2 after 12 hrs while NE released 85.33± 1.88% of the compound. The skin permeation of F2 (71.15± 1.28%) was significantly different (P< 0.05) from F3 (81.80± 1.91%) in rabbits. Complete and apparently safe recovery from the fungal infection was achieved in rabbits treated topically with Pure 2-loaded NEGs.Conclusion: Hence, the NEG-loaded PAE isolated from Pseudomonas fluorescens represents a possible alternative for the treatment of fungal infections as compared to available therapies.Keywords: fungal resistance, red soil, Pseudomonas fluorescens, microbial secondary metabolites, phthalic acid ester derivative, nanoemulsion gel

Sadia Abid,1 Bushra Uzair,1 Muhammad Bilal Khan Niazi,2 Fehmida Fasim,3 Syeda Asma Bano,4 Nazia Jamil,5 Rida Batool,5 Shamaila Sajjad6 1Department of Biological Sciences, International Islamic University, Islamabad, Pakistan; 2School of Chemical & Materials Engineering, National University of Sciences and Technology, Islamabad, Pakistan; 3Discipline of Biomedical Science, Sydney Medical School, The University of Sydney, Sydney, NSW, Australia; 4Department of Microbiology, University of Haripur, Haripur, Pakistan; 5Department of Microbiology & Molecular Genetics, Punjab University, Lahore, Pakistan; 6Department of Physics, International Islamic University, Islamabad, PakistanCorrespondence: Bushra UzairDepartment of Biological Sciences, International Islamic University, New Campus, Female Block, Room No. 007, Islamabad, H-10, PakistanTel +92 33 1538 3988Fax +92 901 9815Email bushra.uzair@iiu.edu.pkIntroduction: Candida albicans is a major opportunistic pathogen that causes a wide range of human infections. Currently available therapeutic agents are limited for treating these fungal infections due to multidrug resistance as well as their nonbiodegradability, poor biocompatibility and toxicity. In order to battle these limitations, we have synthesized a polymeric system as microcarriers to deliver the antifungal drug. The objective of the present study was to immobilize MgO/CuO nanocomposite and nystatin-loaded MgO/CuO nanocomposites in nontoxic, nonimmunogenic, biodegradable and biocompatible sodium alginate microspheres for the first time.Materials and Methods: Nanoparticle-loaded sodium alginate microspheres were prepared by ionotropic gelation technique using calcium chloride as a cross-linker. Synthesized microspheres were characterized using standard characterization techniques and were evaluated for biological activity against MDR strain of C. albicans.Results: Characterization of microspheres by Fourier-transform infrared spectroscopy confirmed loading of Nys-MgO/CuO NPs, scanning electron microscopy (SEM) revealed rough spherical beads with a highly porous surface having an average size in the range of 8– 10 μm. X-ray diffraction (XRD) analyzed its semicrystalline structure. Entrapment efficiency of Nys-MgO/CuO NPs was 80% and release kinetic study revealed sustained and prolonged release of drug in pH 5.5. Flow cytometry analysis showed yeast cell death caused by Nys-MgO/CuO MS exhibits late apoptotic features. In cytotoxicity assay 5– 14 mg of microspheres did not cause hemolysis. Microspheres reduced virulence traits of C. albicans such as germ tube and biofilm formation were compromised at concentration of 5 mg/mL. Antimicrobial assessment results revealed a pronounced inhibitory effect against C. albicans.Conclusion: The in vitro experiments have shown promising results based on good stability, Nys-MgO/CuO NP-encapsulated microspheres can be used as a prolonged controlled release system against MDR pathogenic C. albicans.Keywords: microspheres, antimicrobial activity, nystatin, Candida, metal oxides

Transdermal application of analgesics allows efficient and painless delivery of medication with minimum side effect. This study was designed with the aim to formulate and characterize dexibuprofen-capsaicin emulgel for transdermal drug delivery with improved anti-inflammatory and analgesic effects. The emulgel was prepared and evaluated for physical examination, stability, spreadability, rheological behavior, viscosity, drug content determination, FTIR analysis, and ex vivo studies. Anti-inflammatory (carrageenan-induced paw edema) and analgesic (hot plate latency test) effects were determined in Sprague-Dawley rats. The dexibuprofen-capsaicin emulgel showed good physical appearance and stability having average pH 5.5 to 6.0, conductivity 73–76 s/m, spreadability (12–)17 g cm/s, drug content 102.84% ± 0.53 (for capsaicin) and 94.09% ± 0.41 (for dexibuprofen), and FTIR compatibility. It was noted that 86.956% ± 1.46 (with 100 mg menthol), 76.687% ± 1.21 (75 mg menthol), and 65.543% ± 1.71 (without menthol) of capsaicin were released. Similarly 81.342% ± 1.21 (with 100 mg menthol), 72.321% ± 1.31 (75 mg menthol), and 52.462% ± 1.23 (without menthol) of dexibuprofen were released. The cumulative amount of capsaicin permeated through rabbit skin was 9.83 ± 0.037 μg/cm2 with 100 mg menthol (as permeation enhancer), 7.23 ± 0.037 μg/cm2 with 75 mg menthol, and 2.23 ± 0.061 μg/cm2 without menthol after 6.5 h. The permeation of dexibuprofen was 19.53 ± 0.054 μg/cm2, 13.87 ± 0.032 μg/cm2, and 3.83 ± 0.074 μg/cm2. Carrageenan-induced paw edema of rat was effectively inhibited by the optimized emulgel. Similarly it was observed that DCE5 shows higher analgesic activity compared with marketed diclofenac sodium emulgel (Dicloran®). The conclusion of this research study evidently indicated a promising synergistic potential of dexibuprofen-capsaicin emulgel as an alternative to the conventional topical dosage form.

Crude ginger has been used to treat wounds since ancient times till nowadays. The present study aimed at designing and characterizing topical hydrogel films loaded with ginger extract for wound healing in animal model. The hydrogel films were prepared using PVA and gelatin. The prepared films were evaluated for FTIR analysis, surface morphology, pH, swelling behavior, in vitro release, and % drug content. The wound-healing activity of the extract-loaded hydrogel films was compared with commercially available Silver Sulfadiazine® cream. The drug was compatible with the selected polymers and indicated the suitability of the selected polymers for preparation of topical hydrogel films. The SEM images clearly indicated porous structure of the prepared hydrogel films. Slight changes were observed in pH, ranging from 4.98 ± 0.079 in the beginning of the study to 4.9 ± 0.58 in the end. The swelling percentage after 8 h was 257.7%. The films released 78.7 ± 1.7% of the drug in 250 min. The percent drug content was 97.78 ± 5% which did not change significantly during the storage period. The hydrogel films showed similar wound-healing activity as compared to the commercial product (p > 0.05; ANOVA), while greater wound-healing activity as compared to the control group (p

Background Cancer is considered one of the most predominant causes of morbidity and mortality all over the world and colorectal cancer is the most common fatal cancers, triggering the second cancer related death. Despite progress in understanding carcinogenesis and development in chemotherapeutics, there is an essential need to search for improved treatment. More than the half a century, cytotoxic and cytostatic agents have been examined as a potential treatment of cancer, among these agents; remarkable progresses have been reported by the use of the snake venom. Snake venoms are secreting materials of lethal snakes are store in venomous glands. Venoms are composite combinations of various protein, peptides, enzymes, toxins and non proteinaceous secretions. Conclusion Snake venom possesses immense valuable mixtures of proteins and enzymes. Venoms have potential to combat with the cancerous cells and produce positive effect. Besides the toxicological effects of venoms, several proteins of snake venom e.g. disintegrins, phospholipases A2, metalloproteinases, and L-amino acid oxidases and peptides e.g. bradykinin potentiators, natriuretic, and analgesic peptides have shown potential as pharmaceutical agents, including areas of diagnosis and cancer treatment. In this review we have discussed recent remarkable research that has involved the dynamic snake venoms compounds, having anticancer bustle especially in case of colorectal cancer.

Background Snake venom, a highly poisonous and active venomous snake's secretion, is a complex mixture of inorganic cations, carbohydrates, lipids, proteins, peptides, toxins and hydrolytic enzymes of importance including Phosphodiesterases (PDEs). These snake venom hydrolytic enzymes interfere in different physiological processes. Snake venom PDEs have several roles to metabolize extracellular nucleotides and to regulate nucleotide based intercellular signalling mechanisms including platelet aggregation, which can lead to death and debilitation in cardiac arrest and strokes in patients having cerebro-vascular and cardiovascular diseases, hypertension and atherosclerosis which is the primary cause of life-threatening diseases such as, stroke and myocardial- infarction. Conclusion PDEs are used to synthesize modified oligonucleotides, which are useful in potential therapeutic applications. Characterization of PDEs from different snake venoms has potential in identifying new anticoagulants that target specific active sites, which leads to the treatment of haemostatic disorders. Here, we review the snake venom PDEs potential therapeutic activity against platelet aggregation which could provide ideal platforms to design drugs for treatment or to fight against unwanted clots formation.

Hydrogel is the most emblematic soft material which possesses significantly tunable and programmable characteristics. Polymer hydrogels possess significant advantages including, biocompatible, simple, reliable and low cost. Therefore, research on the development of hydrogel for biomedical applications has been grown intensely. However, hydrogel development is challenging and required significant effort before the application at an industrial scale. Therefore, the current work focused on evaluating recent trends and issues with hydrogel development for biomedical applications. In addition, the hydrogel's development methodology, physicochemical properties, and biomedical applications are evaluated and benchmarked against the reported literature. Later, biomedical applications of the nano-cellulose-based hydrogel are considered and critically discussed. Based on a detailed review, it has been found that the surface energy, intermolecular interactions, and interactions of hydrogel adhesion forces are major challenges that contribute to the development of hydrogel. In addition, compared to other hydrogels, nanocellulose hydrogels demonstrated higher potential for drug delivery, 3D cell culture, diagnostics, tissue engineering, tissue therapies and gene therapies. Overall, nanocellulose hydrogel has the potential for commercialization for different biomedical applications.

The use of microbial technologies in agriculture is currently expanding quite rapidly with the identification of new bacterial strains, which are more effective in promoting plant growth. In the present study 18 strains of Pseudomonas were isolated from soil sample of Balochistan coastline. Among isolated Pseudomonas strains four designated as SP19, SP22, PS24, and SP25 exhibited biocontrol activities against phytopathogenic fungi, that is, Rhizopus microsporus, Fusarium oxysporum, Aspergillus niger, Alternaria alternata, and Penicillium digitatum; PS24 identified as Pseudomonas aeruginosa by 16srRNA gene bank accession number EU081518 was selected on the basis of its antifungal activity to explore its potential as plant growth promotion. PS24 showed multiple plant growth promoting attributes such as phosphate solubilization activity, indole acetic acid (IAA), siderophore, and HCN production. In order to determine the basis for antifungal properties, antibiotics were extracted from King B broth of PS24 and analyzed by TLC. Pyrrolnitrin antibiotic was detected in the culture of strain PS24. PS24 exhibited antifungal activities found to be positive for hydrogen cyanide synthase Hcn BC gene. Sequencing of gene of Hcn BC gene of strain PS24 revealed 99% homology with the Pseudomonas aeruginosa strain PA01. The sequence of PS24 had been submitted in gene bank accession number KR605499. Ps. aeruginosa PS24 with its multifunctional biocontrol possessions can be used to bioprotect the crop plants from phytopathogens.

Sickle cell retinopathy (SCR) is the most representative ophthalmologic complication of sickle cell disease (SCD), a hemoglobinopathy affecting both adults and children. SCR presents a wide spectrum of manifestations and may even lead to irreversible vision loss if not properly diagnosed and treated at the earliest. Over the past decade, multidisciplinary research developments have focused upon systemic, genetic, and ocular risk factors of SCR, enabling the clinician to better diagnose and manage these patients. In addition, newer imaging and testing modalities, such as spectral domain-optical coherence tomography angiography, have resulted in the detection of subclinical retinopathy related to SCD. Innovative therapy includes intravitreal injection of an anti-vascular endothelial growth factor (eg, Lucentis® [ranibizumab] or Eylea® [aflibercept]) which appears comparatively safe and efficient, and may be combined with laser photocoagulation (LPC) for proliferative SCR. The effect of LPC alone does not significantly lead to the regression of advanced SCR, although it helps in avoiding hemorrhage and sight loss. This comprehensive article is based on 10-years retrospective (2007–2017) studies. It aims to present advances and recommendations in SCR theranostics while pointing out the requirement of combinatorial approaches for better management of SCR patients. To reach this goal, we identified and analyzed randomized original and review articles, clinical trials, non-randomized intervention studies, and observational studies using specified keywords in various databases (eg, Medline, Embase, Cochrane, ClinicalTrials.gov).

Background Scorpion venom is the most expensive and deadly venom with exciting medical prospects and having a potential as a source of drug candidates. A number of scorpion venom peptides have shown promising site specificity and are involved in the regulation of biological mechanisms. Due to the structural and functional specificity, the scorpion peptides are widely used for the development of specific drugs especially for the cardiovascular and other immune diseases. In this review, we summarize scorpion venom's biological activities such as antimicrobial, antiviral, anti-cancerous and in immune diseases. Evolutionary perspective of peptides derived from different scorpion venoms are also described in this review. The most significant venom peptides are; Ctriporin, Chlorotoxins (cltx), Neopladine I and II, Meucin 24, Meucin 25 and Hp 1090. The most recognized scorpion species with pharmaceutical activities are; Pandinus imperator, Chaerilustricostatus, Buthus martensii, Mesobuthus eupeus, Leiurus quinnquestriatus, Tityus discrepans and Heterometrus bengalensis. Conclusion The role of peptides in cardiovascular events and in treating osteoporosis signifies their importance. The role of peptides against pathogens, skin infections, pain-relieving effects, anti-malarial and anti-viral effects are discussed in detail. We further, summarized the classification of scorpion peptides among different toxins, their evolutionary process and the pattern of scorpion venom resource analysis.

Background For about 30 years Human Immunodeficiency Virus (HIV) has been a significant social and health issue. It has been a perilous opponent in the human contest against HIV. At the end of 2015 there were 26.7 million people worldwide who were affected by the Human Immunodeficiency Virus (HIV) and this number is expected to increase. Unfortunately, currently there are no vaccines available for prevention and control of HIV. The global burden of HIV articulates the need for anti-HIV therapeutic factors. Venom toxins are commonly prescribed for treatment of various medical disorders. Honey Bee venom has recently been proven to be safe and maybe therapeutic in a specified dose. This therapeutic effect is due to the uptake of melittin by HIV infected cells which leads to decreased HIV gene expression and replication. Similarly, Scorpion venom acts as a therapeutic agent against HIV. Snake venoms have antiviral activity against defense mechanisms of viruses. Conclusion Antiretroviral therapy is promising in the fight against HIV because it limits viral replication. It has the potential to reduce the passage of HIV-1 and to limit the viral load in infected people. This review aims to shed light on an infectious potential of active constituents of bee, scorpion and snake venom articulated in many recent studies.

The Ocean, which is called the “mother of origin of life,” is also the source of structurally unique natural products that are mainly accumulated in living organisms. Cyanobacteria are photosynthetic prokaryotes used as food by humans. They are excellent source of vitamins and proteins vital for life. Several of these compounds show pharmacological activities and are helpful for the invention and discovery of bioactive compounds, primarily for deadly diseases like cancer, acquired immunodeficiency syndrome (AIDS), arthritis, and so forth, while other compounds have been developed as analgesics or to treat inflammation, and so forth. They produce a large variety of bioactive compounds, including substances with anticancer and antiviral activity, UV protectants, specific inhibitors of enzymes, and potent hepatotoxins and neurotoxins. Many cyanobacteria produce compounds with potent biological activities. This paper aims to showcase the structural diversity of marine cyanobacterial secondary metabolites with a comprehensive coverage of alkaloids and other applications of cyanobacteria.