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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 The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.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.

The multidrug resistance (MDR) Escherichia coli having Extended-Spectrum Beta-Lactamase (ESBL) genes and the capacity to create a biofilm acts as a major reduction in the therapeutic effectiveness ...

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

In this paper, MgO and CuO/MgO nanomaterials were green-synthesized by Opuntia monacantha plant extract. Phytochemical analysis of methanolic extract of the plant showed the presence of terpenoids and flavonoids which are responsible for the synthesis of nanoparticles. XRD revealed the crystalline nature of cubical MgO and CuO/MgO nanocomposite that exhibited additional peaks related to CuO nanomaterial. FESEM images confirmed 2D flower-like nanosheets of MgO and defective crumpled structure of CuO/MgO nanocomposites. CuO adsorbed on interfaces of MgO nanosheets by making Cu–O–Mg linkage is studied in FTIR spectrum. Improved optical features of CuO/MgO composite and reduced bandgap were confirmed in UV–Vis analysis. Prepared samples were employed in antimicrobial and photocatalysis applications. The prepared MgO, CuO/MgO nanocomposite and their synergism with standard antibiotics showed significant antimicrobial activity against Candida albicans and Bacillus subtilis. CuO/MgO composite showed a higher degradation of methyl orange (MO) (88%) than MgO. These results are expected to develop a new eco-friendly and cheap MgO and CuO/MgO nanocomposite with potent antimicrobial and photocatalytic applications.

An economical, accessible and facile method was implemented for the synthesis of silica (SiO2) and SiO2-based hierarchical structures to improve the sorption efficiency via providing surface roughness, porous structure and increased active sites for adsorption process, aiming to attract petrol, diesel and mustard oil from aqueous solution. As synthesized materials were characterized by powder X-ray diffractometer (XRD), scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX). The results showed that the composites were amorphous with the expected elemental composition and surface roughness. Absence of hydroxyl groups in FTIR spectra confirms the hydrophobic nature of composites. SiO2-based di and tri-composite were firmly anchored onto the skeleton of polyurethane (PU) sponges for adsorption application. PU sponges decorated with ternary composite (AC/GO-SiO2) exhibited marvelous sorption capacity for removal of adsorbates from oil–water mixture. This can be attributed towards the surface roughness and morphological defects which provides high surface area and active sites to reside maximum oil contents. These modified PU sponges could be recycled up to five cycles to reuse without losing the sorption capacity. Using this simple and in-expensive approach, this work could be extended to design novel SiO2-based sorbent materials with other variant functionalities over large-scale oily water treatment.

The pace at which nanotheranostic technology for human disease is evolving has accelerated exponentially over the past five years. Nanotechnology is committed to utilizing the intrinsic properties of materials and structures at submicroscopic-scale measures. Indeed, there is generally a profound influence of reducing physical dimensions of particulates and devices on their physico-chemical characteristics, biological properties, and performance. The exploration of nature’s components to work effectively as nanoscaffolds or nanodevices represents a tremendous and growing interest in medicine for various applications (e.g., biosensing, tunable control and targeted drug release, tissue engineering). Several nanotheranostic approaches (i.e., diagnostic plus therapeutic using nanoscale) conferring unique features are constantly progressing and overcoming all the limitations of conventional medicines including specificity, efficacy, solubility, sensitivity, biodegradability, biocompatibility, stability, interactions at subcellular levels. : This review introduces two major aspects of nanotechnology as an innovative and challenging theranostic strategy or solution: (i) the most intriguing (bare and functionalized) nanomaterials with their respective advantages and drawbacks; (ii) the current and promising multifunctional “smart” nanodevices.

Many soil microorganisms’ i.e., bacteria and fungi produce secondary metabolites called antibiotics. These are used for the treatment of some of the bacterial, fungal and protozoal diseases of humans. There is a need for isolation of a broad spectrum of antibiotics from microorganisms due to the emergence of antibiotic resistance. In the present study two antibiotic producing bacteria Klebsiella pneumoniae and Bacillus cereus were isolated from pharmaceutical and poultry feed industry of Hattar, Haripur Pakistan. Total 10 waste samples were collected from different industries (Marble, Ghee, Soap, Mineral, Steel, Poultry Feed, Pharmaceutical, Qarshi, Cosmetic and Glass). Thirty-three bacterial strains were isolated from industrial wastes of these ten different industries. Fourteen out of thirty-three bacterial strains exhibited antimicrobial activities against at least one of the test microbes considered in this study including Escherchia coli, Staphylococcus aureus and Salmonella typhi. The bacteria were isolated by standard serial dilution spread plate technique. Morphological characterization of the isolates was done by Gram staining. Nine bacterial isolates out of fourteen were initially identified as B. cereus and five as K. pneumoniae through biochemical characterization. The antibacterial activities were tested by well diffusion method. Maximum number of antibiotic producing bacteria were isolated from pharmaceutical and poultry feed industry based on the results of primary screening, the most potential isolates S9, S19, S20, S22 and S23 were selected for secondary screening. The maximum activity against E. coli and S. aureus was recorded by bacterial isolate S19 i.e zones of inhibition of 6.5mm and 9mm while S20 showed 7.5mm and 6mm zones respectively. Molecular identification was carried out on the basis of 16S rRNA sequence analysis. Finally, the isolates were identified as B. cereus accession number LC538271and K. pneumoniae accession number MT078679. Analysis of bacterial extract S20 through GC-MS indicated the presence of 8 compounds of diverse nature and structure. Present study suggests that wastes of pharmaceutical and poultry feed industry may have antibiotic producing bacteria. These bacteria could be utilized for the production of antibiotics. B. cereus and K. pneumoniae isolated from wastes of poultry feed and pharmaceutical industries have the potential to produce antibiotics and could be used to control the microbial growth. Resumo Muitos microrganismos do solo, ou seja, bactérias e fungos produzem metabólitos secundários chamados antibióticos. Eles são usados para tratamento de algumas doenças bacterianas, fúngicas e protozoárias em humanos. Há necessidade de isolamento de um amplo espectro de antibióticos de microrganismos devido ao surgimento de resistência aos antibióticos. No presente estudo, duas bactérias produtoras de antibióticos, Klebsiella pneumoniae e Bacillus cereus, foram isoladas da indústria farmacêutica e de ração avícola de Hattar, Haripur, Paquistão. Um total de 10 amostras de resíduos foi coletado de diferentes indústrias (mármore, ghee, sabão, mineral, aço, ração para aves, farmacêutica, Qarshi, cosmética e vidro). Trinta e três cepas bacterianas foram isoladas de resíduos industriais dessas dez diferentes indústrias. Quatorze das 33 cepas bacterianas exibiram atividades antimicrobianas contra pelo menos um dos micróbios de teste considerados neste estudo, incluindo Escherchia coli, Staphylococcus aureus e Salmonella typhi. As bactérias foram isoladas pela técnica de placa de diluição em série padrão. A caracterização morfológica dos isolados foi feita por coloração de gram. Nove isolados bacterianos de 14 foram inicialmente identificados como B. cereus e cinco como K. pneumoniae por meio de caracterização bioquímica. As atividades antibacterianas foram testadas pelo método de difusão em poço. O número máximo de bactérias produtoras de antibióticos foi isolado da indústria farmacêutica e de ração avícola com base nos resultados da triagem primária, os isolados mais potenciais S9, S19, S20, S22 e S23 foram selecionados para a triagem secundária. A atividade máxima contra E. coli e S. aureus foi registrada pelo isolado bacteriano S19, ou seja, zonas de inibição de 6,5 mm e 9 mm, enquanto S20 mostrou zonas de 7,5 mm e 6 mm, respectivamente. A identificação molecular foi realizada com base na análise da sequência 16S rRNA. Finalmente, os isolados foram identificados como B. cereus número de acesso LC538271 e K. pneumoniae número de acesso MT078679. A análise do extrato bacteriano S20 por meio de GC-MS indicou a presença de oito compostos de natureza e estrutura diversas. O presente estudo sugere que resíduos da indústria farmacêutica e de ração para aves podem conter bactérias produtoras de antibióticos. Essas bactérias podem ser utilizadas para a produção de antibióticos B. cereus e K. pneumoniae isolados de resíduos de rações de aves e indústrias farmacêuticas têm potencial para produzir antibióticos e podem ser usados para controlar o crescimento microbiano.

The multidrug resistance (MDR)

Food-borne diseases are the main public health problem throughout the world. Milk is important component of human diet including fats, proteins, vitamins and minerals. It is a best source of calcium and phosphorus. Different types of pathogenic bacteria like S. aureus and Salmonella enter in milk and then multiply, after multiplication they become active in causing diseases. These bacteria create serious problems for human health. This study aimed to isolate and identify pathogenic bacteria Staphylococcus aureus and Salmonella from raw milk samples of different cities of Pakistan. Primary screening of raw milk samples was done on the basis of morphological, cultural and biochemical techniques. The final identification was made using 16SrRNA sequence analysis. A total of 200 raw milk samples were collected from different cities of Pakistan. Selective medium xylose lysine deoxycholate agar (XLD) and Mannitol salt agar were used for the identification of Salmonella sp. and S. aureus. Staphylococcus aureus produced yellow colonies with yellow zones on Mannitol salt agar. Staphylococcus aureus exhibited gram-positive character with purple coloration and it was detected as cocci-shaped. Biochemically 91 (45%) samples enhibited Catalase, Coagulase, DNase, Urease, Citrate, fermentation tests positive and indole, oxidase and H2S tests negative with nonmotile character, indicating the presence of Staphylococcus aureus. Salmonella sp. was detected as gram negative rods with pink coloration on gram staining. Biochemically 87 (43%) samples revealed catalase, citrate, H2S and fermentation tests positive while oxidase, DNase, Indole and urease tests negative, indicating the presence of Salmonella sp. in these samples. Of the 200 samples tested, 43% were positive for Salmonella, while 45% samples were contaminated with S. aureus. The 16SrRNA sequence analysis confirmed the results of biochemical and cultural characterization by depicting 99% identity of samples with S. aureus and 98% identity with Salmonella spp. The occurrence of high percentage of these pathogenic bacteria in raw milk may be linked to its contamination at the time of collection, processing, strorage and distribution. This quantitative data could be utilized to better establish the appropriate levels of protection for raw milk, dairy products and processing technologies.

Pseudomonas includes ubiquitous, opportunistic, pathogenic bacteria known to produce a variety of bioactive compounds. Objective of present study was to evaluate bioactive secondary metabolites produced by novel Pseudomonas aeruginosa BS25 strain. The bacterium isolated from patient’s wound was identified via 16S rRNA sequencing. To prepare extracts, nonpolar to polar solvents, i.e., hexane [H], ethyl acetate [E], acetone–ethyl acetate [AE] and water [W], were used. Cytotoxicity screening was performed against three cancer cell lines: HeLa, HepG2 and SHSY5Y. The effect on cell proliferation and mitochondrial activity was measured in HepG2 and Leishmania major. Furthermore, induction of apoptosis, necrosis, singlet oxygen release, lipid peroxidation and DNA binding were evaluated. For chemical composition colorimetric methods, TLC, HPLC and GC–MS analysis were performed. Extract [H] was effective against all cancer cell lines (relative viability: HeLa = 42.97 ± 3.46%, HepG2 = 41.54 ± 4.26%, SHSY5Y = 49.18 ± 2.98%). It strongly inhibited cell proliferation and mitochondrial activity (HepG2 IC50: 168.93 µg/ml), inducing apoptosis (apoptotic cells: 150 µg/ml = 24.89 ± 1.7%, 200 µg/ml = 43.83 ± 2.92%). Furthermore, [H] induced oxidative stress (ΦΔ = 0.5 ± 0.17) and generated TBARs (150 µg/ml = 1.81 ± 0.02 and 200 µg/ml = 2.1 ± 0.2) and DNA degradation. On the other hand, IC50 for L. major was 94.2 µg/ml. Chemical composition analysis indicated the presence of flavonoids, whereas TLC and HPLC revealed two major fractions, and GC–MS showed similarity with l-(+)-ascorbic acid 2,6-dihexadecanoate and 7,9-di-tertbutyl-1-oxaspiro (4,5) deca-6,9-diene-8-one. [H] of BS25 strain exhibits strong biological activity including ROS production, DNA damage and induction of apoptosis. Further investigations on normal cells and in vivo effects are required to fully understand its therapeutic potential.

The design of actively efficient and low-toxicity formulations against virulent bacterial strains causing skin infections remains a challenging task. The aim of the present study was to develop and evaluate in vitro a hydrogel impregnated with a known plant extract for topical applications against major skin bacteria. A poly(vinyl alcohol) (PVA)/gelatin hydrogel, namely HG, was prepared by esterification following the solution casting method. The gelling process was realized by cross-linking the synthetic polymer PVA and the biopolymer gelatin in the presence of hydrochloric acid (HCl). A crude extract of Nigella sativa seeds was then encapsulated in HG, and the resulting HGE was characterized morphologically (by Scanning Electron Microscopy (SEM)), structurally (by X-ray powder diffraction (XRD) and Fourier Transform Infrared (FTIR) spectroscopy), behaviorally (by swelling behavior), and biologically (by the agar well diffusion method). The results of HGE were compared to HG and HG impregnated with 10% acetic acid (HGAA). SEM sections of HGE revealed a dense and porous surface, suggesting a good hydrophilicity. X-ray diffractograms indicated that HGE and HG had a similar degree of crystallinity. FTIR spectra confirmed that esterification occurred between PVA and gelatin suggesting that the amine group is involved in the intercalation of the plant extract components in HG. Further, HGE was found to be as wettable and swellable as HG, suggesting a good biocompatibility. Eventually, HGE exerted a pronounced inhibitory effect against two major skin pathogens, the Gram-negative Pseudomonas aeruginosa and the Gram-positive Staphylococcus aureus, suggesting a good extract release. Taken together, the experimental data indicated that HGE might be a promising wound dressing.

Cancer remains a global health burden prompting affordable, target-oriented, and safe chemotherapeutic agents to reduce its incidence rate worldwide. In this study, a rapid, cost-effective, and green synthesis of titanium dioxide (TiO2) nanoparticles (NPs) has been carried out, Ex vivo and in vivo evaluation of their safety and anti-tumor efficacy compared to doxorubicin (DOX), a highly efficient breast anti-cancer agent but limited by severe cardiotoxicity in many patients. Thereby, TiO2 NPs were eco-friendly synthetized using aqueous leaf extract of the tropical medicinal shrub Zanthoxylum armatum as a reducing agent. Butanol was used as a unique template. TiO2 NPs were physically characterized by ultraviolet-visible (UV–Vis) spectroscopy, dynamic light scattering (DLS), transmission electron microscopy (TEM), scanning electron microscope (SEM), X-ray powder diffraction (XRD), and Fourier-transform infrared spectroscopy (FTIR) as routine state-of-the art techniques. The synthesized TiO2 NPs were then evaluated for their cytotoxicity (by MTT, FACS, and oxidative stress assays) in 4T1 breast tumor cells, and their hemocompatibility (by hemolysis assay). In vivo anti-tumor efficacy and safety of the TiO2 NPs were further assessed using subcutaneous 4T1 breast BALB/c mouse tumor model. The greenly prepared TiO2 NPs were small, spherical, and crystalline in nature. Interestingly, they were hemocompatible and elicited a strong DOX-like concentration-dependent cytotoxicity-induced apoptosis both ex vivo and in vivo (with a noticeable tumor volume reduction). The underlying molecular mechanism was, at least partially, mediated through reactive oxygen species (ROS) generation (lipid peroxidation). Unlike DOX (P &lt, 0.05), it is important to mention that no cardiotoxicity or altered body weight were observed in both the TiO2 NPs-treated tumor-bearing mouse group and the PBS-treated mouse group (P &gt, 0.05). Taken together, Z. armatum-derived TiO2 NPs are cost-effective, more efficient, and safer than DOX. The present findings shall prompt clinical trials using green TiO2 NPs, at least as a possible alternative modality to DOX for effective breast cancer therapy.

To improve the efficacy of existing classes of antibiotics (ciprofloxacin), allow dose reduction, and minimize related toxicity, this study was executed becausenew target-oriented livestock antimicrobials are greatly needed to battle infections caused by multidrug-resistant (MDR) strains. The present study aims to green synthesize a biocompatible nanohybrid of ciprofloxacin (CIP)-Ag/TiO2/chitosan (CS). Silver and titanium nanoparticles were green synthesized using Moringa concanensis leaves extract. The incorporation of silver (Ag) nanoparticles onto the surface of titanium oxidenanoparticles (TiO2NPs) was done by the wet chemical impregnation method, while the encapsulation of chitosan (CS) around Ag/TiO2 conjugated with ciprofloxacin (CIP) was done by the ionic gelation method. The synthesized nanohybrid (CIP-Ag/TiO2/CS) was characterized using standard techniques. The antibacterial potential, killing kinetics, cytotoxicity, drug release profile, andminimum inhibitory concentration (MIC) were determined. Field emission scanning electron microscopy (FESEM) and transmission electron microscopy (TEM) revealed spherical agglomerated nanoparticles (NPs) of Ag/TiO2 with particle sizes of 47–75 nm, and those of the CIP-Ag/TiO2/CS nanohybrid were in range of 20–80 nm. X-ray diffractometer(XRD)patterns of the hetero system transmitted diffraction peaks of anatase phase of TiO2 and centered cubic metallic Ag crystals. Fourier Transform Infrared spectroscopy (FTIR) confirmed the Ti-O-Ag linkage in the nanohybrid. The zeta potential of CIP-Ag/TiO2/CS nanohybrid was found (67.45 ± 1.8 mV), suggesting stable nanodispersion. The MIC of CIP-Ag/TiO2/CS was 0.0512 μg/mL, which is much lower than the reference value recorded by the global CLSI system (Clinical Laboratory Standards Institute). The CIP-Ag/TiO2/CS nanohybrid was found to be effective against mastitis causing MDR E. coli, killing kinetics showed an excellent reduction of E. coli cells at 6 h of treatment. Flow cytometry further confirmed antibacterial potential by computing 67.87% late apoptosis feature at 6 h of treatment, antibiotic release kinetic revealed a sustained release of CIP. FESEM and TEM confirmed the structural damages in MDR E. coli (multidrug-resistant Escherichia coli). The CIP-Ag/TiO2/CS nanohybrid was found to be biocompatible, as more than 93.08% of bovine mammary gland epithelial cells remained viable. The results provide the biological backing for the development of nanohybrid antibiotics at a lower MIC value to treat infectious diseases of cattle and improve the efficacy of existing classes of antibiotics by conjugation with nanoparticles.

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

Methicillin-resistant Staphylococcus aureus (MRSA)-induced mastitis is one of the biggest animal welfare issues and economic burdens worldwide. As a possible effective treatment, ciprofloxacin (CIP)-loaded cerium oxide (CeO2)/chitosan (CS) nanocomposite was synthesized using an eco-friendly approach, characterized, and evaluated. From 350 mastitis-positive milk samples, 35 mecA-positive MRSA strains were confirmed by antibiotic sensitivity testing and PCR. CeO2 nanoparticles (NPs) were synthetized using the seeds' extract of Amomum subulatum (aka black cardamom/BC) as a reducing and capping agent, which was conjugated with CS by ionic gelation before CIP was nanoencapsulated. The resulting NPs were characterized physically (by using FESEM, TEM, EDS, XRD, FTIR, ZP, and UV-Vis spectrophotometry), biologically and pharmacologically (through in-vitro/ex-vivo antibacterial, cytotoxic, and drug release behavior assays). The CIP-nanocomposite was represented by pure, stable, small, pseudospherical NPs of crystalline nature. FTIR confirmed the surface linkage of CS and CIP in CeO2 NPs. CIP-CeO2/CS nanocarrier exerted enhanced antibacterial activity at lower MIC (8 μg/mL) compared to that of free CIP drug alone. Also, they were hemocompatible and not hepatotoxic. CIP release from the nanocarrier was better sustained in physiological-like conditions. Taken together, the phytogenic CIP-CeO2/CS nanocarrier could be considered as a potent and safe therapeutic solution for MRSA-induced mastitis.

Seaweeds are broadly distributed and represent an important source of secondary metabolites (e.g., halogenated compounds, polyphenols) eliciting various pharmacological activities and playing a relevant ecological role in the anti-epibiosis. Importantly, host (as known as basibiont such as algae)–microbe (as known as epibiont such as bacteria) interaction (as known as halobiont) is a driving force for coevolution in the marine environment. Nevertheless, halobionts may be fundamental (harmless) or detrimental (harmful) to the functioning of the host. In addition to biotic factors, abiotic factors (e.g., pH, salinity, temperature, nutrients) regulate halobionts. Spatiotemporal and functional exploration of such dynamic interactions appear crucial. Indeed, environmental stress in a constantly changing ocean may disturb complex mutualistic relations, through mechanisms involving host chemical defense strategies (e.g., secretion of secondary metabolites and antifouling chemicals by quorum sensing). It is worth mentioning that many of bioactive compounds, such as terpenoids, previously attributed to macroalgae are in fact produced or metabolized by their associated microorganisms (e.g., bacteria, fungi, viruses, parasites). Eventually, recent metagenomics analyses suggest that microbes may have acquired seaweed associated genes because of increased seaweed in diets. This article retrospectively reviews pertinent studies on the spatiotemporal and functional seaweed-associated microbiota interactions which can lead to the production of bioactive compounds with high antifouling, theranostic, and biotechnological potential.

Metal nanoparticles (NPs) have received much attention for potential applications in medicine (mainly in oncology, radiology and infectiology), due to their intriguing chemical, electronical, catalytical, and optical properties such as surface plasmon resonance (SPR) effect. They also offer ease in controlled synthesis and surface modification (e.g., tailored properties conferred by capping/protecting agents including N-, P-, COOH-, SH-containing molecules and polymers such as thiol, disulfide, ammonium, amine, and multidentate carboxylate), which allows (i) tuning their size and shape (e.g., star-shaped and/or branched) (ii) improving their stability, monodispersity, chemical miscibility, and activity, (iii) avoiding their aggregation and oxidation over time, (iv) increasing their yield and purity. The bottom-up approach, where the metal ions are reduced in the NPs grown in the presence of capping ligands, has been widely used compared to the top-down approach. Besides the physical and chemical synthesis methods, the biological method is gaining much consideration. Indeed, several drawbacks have been reported for the synthesis of NPs via physical (e.g., irradiation, ultrasonication) and chemical (e.g., electrochemisty, reduction by chemicals such as trisodium citrate or ascorbic acid) methods (e.g., cost, and/ortoxicity due to use of hazardous solvents, low production rate, use of huge amount of energy). However, (organic or inorganic) eco-friendly NPs synthesis exhibits a sustainable, safe, and economical solution. Thereby, a relatively new trend for fast and valuable NPs synthesis from (live or dead) algae (i.e., microalgae, macroalgae and cyanobacteria) has been observed, especially because of its massive presence on the Earth’s crust and their unique properties (e.g., capacity to accumulate and reduce metallic ions, fast propagation). This article discusses the algal-mediated synthesis methods (either intracellularly or extracellularly) of inorganic NPs with special emphasis on the noblest metals, i.e., silver (Ag)- and gold (Au)-derived NPs. The key factors (e.g., pH, temperature, reaction time) that affect their biosynthesis process, stability, size, and shape are highlighted. Eventually, underlying molecular mechanisms, nanotoxicity and examples of major biomedical applications of these algal-derived NPs are presented.

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

This study is planned to synthesise new biocompatible, nano antimicrobial formulation against biofilm producing strains. Aqueous root extract of Arctium lappa l. was used to synthesise ceria nanoparticles (CeO(2) ‐NPs). The synthesised nanoparticles were encapsulated with nano‐chitosan by sol–gel method and characterised using standard techniques. Gas chromatography‐mass spectrometer of Arctium lappa l. revealed the presence of ethanol, acetone, 1‐ propanol, 2‐methylethane, 1,1‐di‐ethoxy, 1‐Butanol, and oleic acid acted as reducing and surface stabilising agents for tailoring morphology of CeO(2) ‐NPs. Erythrocyte integrity after treatment with synthesised nanomaterials was evaluated by spectrophotometer measurement of haemoglobin release having biocompatibility. Scanning electron microscopy revealed the formation of mono dispersed beads shaped particles with mean particle size of 26.2 nm. X‐ray diffractometry revealed cubic crystalline structure having size of 28.0 nm. After encapsulation by nano‐chitosan, the size of CeO(2) ‐NPs enhances to 48.8 nm making average coverage of about 22.6 nm. The synthesised nanomaterials were found effective to disrupt biofilm of S. aureus and P. aeruginosa. Interestingly, encapsulated CeO(2) ‐NPs revealed powerful antibacterial and biofilm disruption activity examined by fluorescent live/dead staining using confocal laser scanning microscopy. The superior antibacterial activities exposed by encapsulated CeO(2) ‐NPs lead to the conclusion that they could be useful for controlling biofilm producing multidrug resistance pathogens.

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.

Background and Objective: Synergistic combinations of various antimicrobial agents have been introduced as extra successful strategies to combat multidrug resistant (MDR) infections. This study was undertaken to evaluate MDR profiling of Staphylococcus aureus strains isolated from clinical specimens of two public hospitals of twin Pakistani cities as well as to explore in vitro antibacterial potential of Nigella sativa L. (black cumin or black seeds) extract against Mec A gene positive Staphylococcus aureus strains. Materials and Methods: The MDR strains were then screened for positive Mec A gene by PCR and sequencing. A total of 500 bacterial strains were subjected to antimicrobial and Nigella sativa seeds susceptibility and minimal inhibitory concentration assays. The data were evaluated as Mean±Standard deviation of five independent experiments. The results were analyzed using t-test with SPSS version 16.0. Results: Methanolic extracts of Nigella sativa seeds showed maximum activity against Mec A gene positive Staphylococcus aureus alone and in combination with the penicillin antibiotic Augmentin® plus the second-generation Cephamycin, Cephalosporins, Mefoxin® (Cefoxitin). The anti-MRSA activity was reduced when methanolic extracts of Nigella sativa seeds were used in combination with the pain reliever and the fever reducer paracetamol (acetaminophen). Eventually, it has been observed that the anti-staphylococcal activity of Nigella sativa led to changes in bacterial cell morphology indicating that the cell wall of Gram-positive bacteria as likely a target of action. Conclusion: This study provides new insights about synergistic antimicrobial and Nigella sativa crude extract activities against MDR Staphylococcus aureus strains. Scopus

Background and Objective: Various parts of medicinal plants have been used to treat specific disorder from ancient times. Swertia chirayita (Roxb. ex Fleming) is a customary folklore medicine, used in the treatment of liver disorders, fevers, dysentery, diarrhea, stomach problems and other disorders. The present study was carried out in order to assess the antioxidant activity, to evaluate the antifungal properties of the plant’s root and to observe anticancer potential of methanolic extract of Swertia chirayita root. Materials and Methods: Phytochemical analysis and different chemical tests for the screening and identification of bioactive chemical constituents in Swertia chirayita methanolic root extract (SCME) were carried out using the standard procedures. The plants were purchased from local herbal market. In vitro determination of antioxidant properties of SCME were conducted using 1,1-diphenyl-2-picrylhydrazyl (DPPH)radical scavenging activity, H2O2 scavenging activity, Beta-carotene bleaching assay, total antioxidant activity by phosphomolybdenum method, azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical cation scavenging activity and hydroxyl radical scavenging activity. Anticancer activity of SCME was determined according to the protocol of brine shrimp lethality test. Antifungal potential was determined by measuring zone of inhibition on Potato Dextrose Agar (PDA) plates. The different concentrations of SCME used were 3.0, 1.5, 0.75 and 0.37 mg mL–1. The data were evaluated as Mean±Standard Deviations of 5 independent experimental responses. The results were analyzed using t-test for independent samples with SPSS version 16.0. Results: Phytochemical analysis of SCME showed that phlobatannins, tannins, saponins and terpenoids were present. The SCME exhibited strong antioxidant activity in a concentration dependent manner for in all six models. The SCME at dose of 3 mg mL–1 caused 100% death rate of brine shrimp after 72 h. The SCME showed potent activity against Aspergillus flavus (87%) followed by Aspergillus niger (88%) while the highest activity was shown against Aspergillus fumigatus (92%). Conclusion: The SCME exhibited strong antioxidant, antifungal and cytotoxic potential. Purification of different bioactive compounds should be carried out and in vivo studies are required for further verification. Scopus