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 The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

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

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.

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.

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.

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.

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.

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

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).

The silver oxide nanoparticles (AgO(2) ‐NPs) were synthesised using silver foil as a new precursor in wet chemical method. X‐ray diffraction analysis shows crystallographic structures of AgO(2) ‐NPs with crystallite size of 35.54 nm well‐matched with standard cubic structure. Scanning electron microscopy analysis clearly shows the random distribution of spherical‐shaped nanoparticles. Energy dispersive X‐ray analysis confirmed the purity of the samples as it shows no impurity element. Fourier transforms infra‐red analysis confirmed the formation of AgO(2) ‐NPs with the presence of Ag‐O‐Ag stretching bond. All the techniques also confirmed the loading of ceftriaxone drug on the surface of AgO(2) ‐NPs. This study also described the effect of AgO(2) ‐NPs having synergistic activity with β lactam antibiotic i.e. ceftriaxone against ESBL generating Escherichia coli (E. coli). Among isolated strains of E. coli, 60.0% were found to be ESBL producer. The synergistic activities of AgO(2) ‐NPs with ceftriaxone suggest that these combinations are effective against MDR‐ESBL E. coli strains as evident by increase in zone sizes. The present study observed rise in MDR‐ESBL E. coli with polymorphism of blaCTXM and blaSHV causing UTI infections in Pakistani population. The antibiotic and AgO(2) ‐NPs synergistic effect can be used as an efficient approach to combat uro‐pathogenic infections.

One of the most severe health threats to both humans and animals is Antimicrobial resistance development in microorganisms AMR is a significant and growing challenge and to combat this issue new antimicrobials are urgently needed Fifteen microbial strains isolated from Arabian Sea were screened for their capacity to produce antimicrobial metabolites of pharmaceutical interest. These strains were associated to the brown seaweed Pelvetia canaliculata (Linnaeus) attached to the rocks of Sonmiani Beach (Karachi, Pakistan). Bacterial strains were isolated from sea weeds attached to rocks of Baluchistan coast line using marine agar 2216 and screened for antibacterial activity by agar well diffusion method and crude extract was made and antimicrobial metabolites were purified using silica gel column and structure of pure compound was elucidated using spectroscopic techniques. Crude extract filtrates from CMG 2180 strain, grew on ZMA medium, showed the most remarkable antimicrobial activity, and thus was chosen for further examination. The identification of CMG 2180 as a probable new type strain of the Actinobacterium Kocuria marina was based on phenotypic aspects and biochemical characteristics (e.g. halotolerant Gram-positive micrococcoid) as well as on the nucleotide sequence analysis of its full-length 16S rRNA gene showing the highest similarity with the type strain KMM 3905 (GenBank accession number EU073966). Interestingly, a unique UV-bioactive compound, for which the name of kocumarin was proposed, was isolated and purified from CMG 2180 strain’s crude extracts by flash silica gel column chromatography and TLC/HPTLC. Using routine methods, kocumarin demonstrated prominent and rapid activities against all tested fungi and pathogenic bacteria including MRSA. Its chemical structure was unraveled by 1D and 2D-NMR spectroscopy as 4-[(Z)−2 phenyl ethenyl] benzoic acid.

Two dimensional (2D) heterostructures in combination with other 2D materials play a vital role to boost photocatalytic efficiency owing to increase in interfacial charge separation/transferring rate. Graphene modified NiO 2D-2D nanocomposites were prepared via wet impregnation method and confirmed by various spectroscopic and analytical techniques. XRD patterns of pure and composites confirmed the characteristic peaks of NiO and graphene. NiO nanosheets are uniformly dispersed on graphene sheets which facilitate interfacial coupling between them as observed in SEM images. UV–Vis spectra of composite showed band gap reduction from 3.3 to 2.3 ​eV owing to incorporation of graphene sheets. Further, suppression of charge carriers was confirmed by photoluminescence spectra. Consequently, 10.0% graphene/NiO composite exhibits increased photocatalytic activity towards MO degradation under visible light due to strong interfacial coupling and 2D-2D surface morphologies of photocatalysts which are beneficial to suppress the charge recombination and provide massive reactive sites.

The Gram-positive microorganism Staphylococcus aureus is the major infective agent responsible for life-threatening infections. Staphylococcus aureus have developed resistance against last resort therapeutics. Nonetheless, there is a great urge to synthesize novel antimicrobial agents with proficient activity and great biocompatibility for clinical administrations. Advanced technologies emphasize more on detecting and identifying diseases for successful therapy combined with the diagnostic agents itself. Theranostics is a novel approach in which the exact treatment is conjugated with specific diagnostic tests. With a key spotlight on patient-focused consideration, theranostics alter traditional prescription to a contemporary personalized and accurate medicine approach. The research has been supported toward the development of enhanced imaging agents as carbon quantum dots, nanoparticles, and other new theranostic drugs. Better diagnosis helps in prescreening the profile of target particles to create biomarkers dependent on disease-specific therapy, thus making it less expensive with less off-target toxicity and high efficiency and specificity with continuous analysis for detailed observation and guidance and examining impacts and side effects to develop further alternatives. In this chapter, numerous theranostics methods are discussed to cure ailments caused by Staphylococcus aureus.

Worldwide the infectious diseases are a major threat to the human population. However, the most important parameter is the prompt and sensitive diagnosis of pathogens. Therefore, tremendous efforts have been made for the development of rapid and portable detection techniques. The identification and treatment of infectious diseases at the nano and molecular levels is a hard task to achieve because of the scarcity of effective probes for characterization and recognition of biomarkers of these pathogens. Nonetheless, if it made possible simultaneous diagnosis and treatment at the specific spot, i.e., theranostics can be beneficial for treating the disease at a cellular level and can be helpful to understand the disease system. However, for theranostics a sensing system should be able to detect and measure biomarkers quickly. In this regard, aptamers (oligonucleotide polymers consist of single-stranded DNA (ssDNA) or RNA) have displayed the ability to be used as probes for the recognition of various targets at molecular level. DNA and RNA have the capacity of doing much lot than just keeping genetic information and therefore are also known as functional nucleic acids. Aptamer-based biosensors would be an attractive format because they can be developed for various molecules using the same sensing format. Therefore, the aptasensors utilizing aptamers for various bacterial infections have stimulating theranostic potential as well. In this chapter, the potential of aptamers as theranostic agent for bacterial infections has been discussed. The advantages and limitations of aptamer-based theranostics for the development of personalized medicine are also discussed.

An antifungal compound 9, 10-dihydrophenanthrene - 2 - carboxylic acid was isolated from a marine derived bacterium Pseudomonas putida isolated from surface water samples of Karachi fish harbor coast line. The structure was explored using extensive 1D- and 2D-NMR spectroscopic techniques. The compound was found to be active against fungal strains obtained from clinical samples whereas strong activity was noted against Candida albicans with a MIC value of 20μg/ml, as the purified compound showed promising anticandidal activity a multidisciplinary approach is needed to explore further this compound as potential pharmacological lead compound against Candida spp and will add in the global hunt for clinically functional antifungal agents.

Bacterial resistance is spreading globally due to excessive use of antibiotics, making it one of our times biggest challenges. To address this issue present study was conducted to evaluate the antibacterial activity of copper oxide nanoparticles against methicillin-resistant S. aureus (MRSA). Copper oxide nanoparticles were synthesized by chemical precipitation method and were characterized by UV-Visible, FT-IR spectroscopy, X-ray diffraction (XRD) and Scanning Electron Microscopy. These nanoparticles of 27nm were assessed for antibacterial activity using disc diffusion method. Our results showed superb inhibitory effects of CuO nanoparticles with increase in concentration and complete inhibition was recorded against tested strains of S. aureus at 100μl/ml and 125μl/ml concentration. The study concludes that the drugs which do not show any inhibitory effects against resistant bugs could be augmented with CuO nanoparticles to achieve the treatment goal.

This study was carried out to formulate and evaluate controlled release (CR) matrix tablets of Acyclovir using combination of hydrophilic and hydrophobic polymers. Acyclovir is a guanine derivative and is its half-life is short hence administered five times a day using immediate release tablets. Six formulations (F1-F6) were developed using Ethocel and Carbopol in equal combinations at drug-polymer (D:P) ratio of 10:5, 10:6, 10:7, 10:8, 10:9 and 10:10. Solubility study was performed using six different solvents. The compatibility studies were carried out using FTIR and DSC. According to USP, Quality Control and dimensional tests (hardness, friability, disintegration and thickness) were executed. In-vitro drug release studies of Acyclovir was carried out in dissolution apparatus using using 0.1 N HCl medium at constant temperature of 37 ± 0.5 ºC. In order to analyze the drug release kinetics, five different mathematical models were applied to the release data. The results showed that there was no incompatibility between drug and polymers. Physical QC tests were found within limits of USP. The release was retarded upto 24 hrs and non-fickian in-vitro drug release mechanism was found. A formulation developed using blend of polymers, showed excellent retention and desired release profiles thus providing absolute control for 24 hrs.

This study was planned in order to investigate effective essential oils to inhibit in-vitro growth of Methicillin resistant Staphylococcus aureus (MRSA). In this study using disc diffusion method anti MRSA activity of ten diverse essential oils extracted from traditional plants namely Thymus vulgaris L, Mentha pulegium, Ocimum sanctum, Mentha piperita, Cymbopogon citratus, Rosmarinus officinalis L., Cortex cinnamom, Citrus nobilis x Citrus deliciosa, Origanum vulgare and Mentha sp. was examined. All the essential oils inhibited growth of S. aureus to different extent, by exhibiting moderate to elevated zones of inhibitions. Essential oils of cinnamon (Cortex cinnamomi) and thyme (Thymus vulgaris L) were observed to be the most powerful against MRSA strains used in this study. At lowest concentration of 25μl/ml essential oils comprehensible zone of inhibition was found 9±0.085mm and 8±0.051mm respectively, and at elevated concentrations there was a total decline in growth of MRSA and a very clear zone of inhibition was observed. A synergistic effect of essential oils in amalgamation with amoxicillin a Penicillin group of antibiotic was also examined. Interestingly a strong synergism was observed with oregano (Origanum vulgare) and pennyroyal mint (Mentha pulegium) essential oils, which were not so effective alone driven out to be important synergistic candidate. Our results demonstrated that essential oils of cinnamon and thyme can be used as potential antimicrobial agent against the Methicillin-resistant Staphylococcus aureus infections and Amoxicillin antibacterial activity can be enhanced using active constituents present in oregano and pennyroyal mint essential oils.

Aims Screening of seaweed-associated bacteria capable of producing antimicrobials. Methods and results Fifteen microbial strains, associated to the brown seaweed Pelvetia canaliculata (Linnaeus) attached to the rocks of Sonmiani Beach (Karachi, Pakistan), were screened. Crude extract filtrates of CMG S2 strain grew on Zobell marine agar (ZMA) had the most remarkable antimicrobial activity. Based on its phenotypic aspects (e.g. Gram-positive, microccoid form), biochemical characteristics (e.g. halotolerance) and genetic analyses, CMG S2 is identified as a putatively new Kocuria marina type strain belonging to the actinobacteria’s class and micrococcaceae family. Thereby, the nucleotide sequence analysis of its full-length 16S ribosomal ribonucleic acid (rRNA) gene (GenBank accession number EU073966.1 ) displayed highest identity (i.e. 99%) and score (2630) with K. marina KMM 3905. Phylogenic trees analysis using the neighbor-joining method showed closest evolutionary distance of CMG S2 with KMM 3905 strain and K. carniphila (DC2201) specie. Interestingly, a unique ultraviolet (UV)-bioactive compound was purified from CMG S2 crude extracts by flash silica gel column and thin-layer chromatography (TLC) techniques. Its chemical structure was unraveled as 4-[(Z)-2 phenyl ethenyl] benzoic acid (PEBA, later named kocumarin) by nuclear magnetic resonance (NMR) spectroscopy techniques. Importantly, kocumarin demonstrated prominent and rapid growth inhibition against all tested fungi and pathogenic bacteria including methicillin-resistant Staphylococcus aureus (MRSA), with a minimal fungal inhibitory concentration (MFC) of 15–25 μg/mL and a minimal (bacterial) inhibitory concentration (MIC) of 10–15 μg/mL. Significance and impact of the study Kocumarin represents a new promising natural antibiotic for in vivo and environmental applications.

A novel compound designated zafrin [4beta-methyl-5, 6, 7, 8 tetrahydro-1 (4beta-H)-phenanthrenone] was isolated from a crude extract of a marine bacterium identified as Pseudomonas stutzeri. Zafrin showed strong antibacterial activity against both Gram-positive and Gram-negative bacteria. The compound was purified and its structure was elucidated by spectroscopic methods including 1H-nuclear magnetic resonance (NMR), 13C-NMR, 1D-NMR and 2D-NMR spectroscopy. It could be demonstrated that a purified solution of zafrin was active against several human pathogens, including Staphylococcus aureus, and Salmonella typhi. By contrast, zafrin did not inhibit the growth of eukaryotic organisms Candida albicans and Schizosaccharomyces pombe. The minimal inhibitory concentration for Gram-positive bacteria ranged from 50 to 75 microg mL(-1) and varied between 75 and 125 microg mL(-1) for Gram-negative bacteria. Zafrin lysed Bacillus subtilis cells grown in an osmotically protected medium, suggesting that it does not act upon the cell wall. Further investigation using B. subtilis indicated that the compound is bactericidal and is likely to target the cell membrane.

Purpose: To formulate stable water in oil (W/O) emulsion containing hydroalcoholic crude extract of Ziziphus mauritiana leaves for skin rejuvenation. Methods: Placebo (base) without any plant extract and formulation with 4 % Ziziphus mauritiana extract were prepared by mixing. Samples of the emulsions were subjected to varying storage conditions, i.e., 8, 25, 40 o C and 40 o C + 75 % relative humidity for a period of 4 weeks to predict their stability. During this period, stability parameters, including liquefaction, phase separation, color, electrical conductivity, centrifugation and pH were monitored at specified time intervals. Skin rejuvenation was evaluated using 13 healthy human volunteers over a period of 8 weeks. During this period, various skin parameters such as erythema, melanin level, moisture content, elasticity and sebum content of the skin were evaluated at specified intervals. Results: Both the active formulation and placebo were stable in terms of liquifaction, phase separation and color at all the storage conditions of temperature and humidity. Active formulation showed statistically significant ( p 0.05). Both active and placebo formulations changed skin elasticity and erythema significantly ( p < 0.05). Conclusion: It is evident from the findings that the leaf extract of Ziziphus mauritiana possesses antiaging properties as well as exert skin lightening, moisturizing and viscoelastic effects on human skin. Keywords: Ziziphus mauritiana , Melanin, Erythema, Sebum, Skin-tlightening, Moistirizing, Anti-aging

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.