Fungus-mediated synthesis of Se-BiO-CuO multimetallic nanoparticles as a potential alternative antimicrobial against ESBL-producing Escherichia coli of veterinary origin.

Bacterial infections emerge as a significant contributor to mortality and morbidity worldwide. Emerging extended-spectrum ß-lactamase (ESBL) Escherichia coli strains provide a greater risk of bacteremia and mortality, are increasingly resistant to antibiotics, and are a major producer of ESBLs. E. coli bacteremia-linked mastitis is one of the most common bacterial diseases in animals, which can affect the quality of the milk and damage organ functions. There is an elevated menace of treatment failure and recurrence of E. coli bacteremia necessitating the adoption of rigorous alternative treatment approaches. In this study, Se-Boil-CuO multimetallic nanoparticles (MMNPs) were synthesized as an alternate treatment from Talaromyces haitouensis extract, and their efficiency in treating ESBL E. coli was confirmed using standard antimicrobial assays. Scanning electron microscopy, UV-visible spectroscopy, and dynamic light scattering were used to validate and characterize the mycosynthesized Se-BiO-CuO MMNPs. UV-visible spectra of Se-BiO-CuO MMNPs showed absorption peak bands at 570, 376, and 290 nm, respectively. The average diameters of the amorphous-shaped Se-BiO-CuO MMNPs synthesized by T. haitouensis extract were approximately 66-80 nm, respectively. Se-BiO-CuO MMNPs (100 µg/mL) showed a maximal inhibition zone of 18.33 ± 0.57 mm against E. coli. Se-BiO-CuO MMNPs also exhibited a deleterious impact on E. coli killing kinetics, biofilm formation, swimming motility, efflux of cellular components, and membrane integrity. The hemolysis assay also confirms the biocompatibility of Se-BiO-CuO MMNPs at the minimum inhibitory concentration (MIC) range. Our findings suggest that Se-BiO-CuO MMNPs may serve as a potential substitute for ESBL E. coli bacteremia.

In vitro activity of novel apramycin-dextran nanoparticles and free apramycin against selected Dutch and Pakistani Klebsiella pneumonia isolates.

Klebsiella pneumoniae are bacteria associated with respiratory tract infections and are increasingly becoming resistant to antibiotics, including carbapenems. Apramycin is a veterinary antibiotic that may have the potential to be re-purposed for use in human health, for example, for the treatment of respiratory tract infections after coupling to inhalable nanoparticles. In the present study, the antibiotic apramycin was formulated with single chain polymeric nanoparticles and tested in free and formulated forms against a set of 13 Klebsiella pneumoniae isolates (from the Netherlands and Pakistan) expressing different aminoglycoside resistance phenotypes. Minimum Inhibitory Concentration, Time Kill Kinetics and biofilm experiments were performed providing evidence for the potential efficacy of apramycin and apramycin-based nanomedicines for the treatment of human Klebsiella pneumonia infections.

Untapped rich microbiota of mangroves of Pakistan: diversity and community compositions.

The mangrove ecosystem is the world's fourth most productive ecosystem in terms of service value and offering rich biological resources. Microorganisms play vital roles in these ecological processes, thus researching the mangroves-microbiota is crucial for a deeper comprehension of mangroves dynamics. Amplicon sequencing that targeted V4 region of 16S rRNA gene was employed to profile the microbial diversities and community compositions of 19 soil samples, which were collected from the rhizosphere of 3 plant species (i.e., Avicennia marina, Ceriops tagal, and Rhizophora mucronata) in the mangrove forests of Lasbela coast, Pakistan. A total of 67 bacterial phyla were observed from three mangroves species, and these taxa were classified into 188 classes, 453 orders, 759 families, and 1327 genera. We found that Proteobacteria (34.9-38.4%) and Desulfobacteria (7.6-10.0%) were the dominant phyla followed by Chloroflexi (6.6-7.3%), Gemmatimonadota (5.4-6.8%), Bacteroidota (4.3-5.5%), Planctomycetota (4.4-4.9%) and Acidobacteriota (2.7-3.4%), Actinobacteriota (2.5-3.3%), and Crenarchaeota (2.5-3.3%). After considering the distribution of taxonomic groups, we prescribe that the distinctions in bacterial community composition and diversity are ascribed to the changes in physicochemical attributes of the soil samples (i.e., electrical conductivity (ECe), pH, total organic matter (OM), total organic carbon (OC), available phosphorus (P), and extractable potassium (CaCO3). The findings of this study indicated a high-level species diversity in Pakistani mangroves. The outcomes may also aid in the development of effective conservation policies for mangrove ecosystems, which have been hotspots for anthropogenic impacts in Pakistan. To our knowledge, this is the first microbial research from a Pakistani mangrove forest.

Synthesis and characterization of nanobiochar from rice husk biochar for the removal of safranin and malachite green from water.

Xenobiotic pollution in environment is a potential risk to marine life, and human health. Nanobiotechnology is an advanced and emerging solution for the removal of environmental pollutants. Adsorption-based technologies are being used to alleviate the global prevalence of xenobiotics like dyes, due to their high efficacy and cost effectiveness. Current study explored the potential of nanobiochar syntehsized via ultrasonication and centrifugation from rice husk for dye removal from water. It involves the synthesis of nanobiochar from rice husk biochar for removal of Safranin, Malachite green, and a mixture of both from aqueous water. Biochar was synthesized through pyrolysis at 600 °C for 2 h. To convert it into nanobiochar, sonication and centrifugation techniques were applied. The yield obtained was 27.5% for biochar and 0.9% for nanobiochar. Nanobiochar analysis through Fourier-Transform Spectrometer (FTIR), X-ray Power Diffraction (XRD) and scanning electron microscopy (SEM) suggested its crystalline nature having minerals rich in silicon, with a cracked and disintegrated carbon structure due to high temperature and processing treatments. Removal of dyes by nanobiochar was evaluated by changing different physical parameters i.e., nanobiochar dose, pH, and temperature. Pseudo-first order model and pseudo-second order model were applied to studying the adsorption kinetics mechanism. Kinetics for adsorption of dyes followed the pseudo-second order model suggesting the removal of dyes by process of chemical sorption. High adsorption was found at a higher concentration of nanobiochar, high temperature, and neutral pH. Maximum elimination percentages of safranin, malachite green, and a mixture of dyes were obtained as 91.7%, 87.5%, and 85% respectively. We conclude that nanobiochar could be a solution for dye removal from aqueous media.

Synthesis and Characterization of Calcium Alginate-Based Microspheres Entrapped with TiO2 Nanoparticles and Cinnamon Essential Oil Targeting Clinical Staphylococcus aureus.

It is important to create new generations of materials that can destroy multidrug-resistant bacterial strains, which are a serious public health concern. This study focused on the biosynthesis of an essential oil entrapped in titanium dioxide (TiO2) calcium alginate-based microspheres. In this research, calcium alginate-based microspheres with entrapped TiO2 nanoparticles and cinnamon essential oil (CI-TiO2-MSs) were synthesized, using an aqueous extract of Nigella sativa seeds for TiO2 nanoparticle preparation, and the ionotropic gelation method for microsphere preparation. The microspheres obtained were spherical, uniformly sized, microporous, and rough surfaced, and they were fully loaded with cinnamon essential oil and TiO2 nanoparticles. The synthesized microspheres were analyzed for antibacterial activity against the clinical multidrug-resistant strain of Staphylococcus aureus. Disc diffusion and flow cytometry analysis revealed strong antibacterial activity by CI-TiO2-MSs. The synthesized CI-TiO2-MSs were characterized by the SEM/EDX, X-ray diffraction, and FTIR techniques. Results showed that the TiO2 nanoparticles were spherical and 99 to 150 nm in size, whereas the CI-TiO2-MSs were spherical and rough surfaced. Apoptosis analysis and SEM micrography revealed that the CI-TiO2-MSs had strong bactericidal activity against S. aureus. The in vitro antibacterial experiments proved that the encapsulated CI-TiO2-MSs had strong potential for use as a prolonged controlled release system against multidrug-resistant clinical S. aureus.

Moringa concanensis-Mediated Synthesis and Characterizations of Ciprofloxacin Encapsulated into Ag/TiO2/Fe2O3/CS Nanocomposite: A Therapeutic Solution against Multidrug Resistant E. coli Strains of Livestock Infectious Diseases.

Background: Multidrug resistant MDR bacterial strains are causing fatal infections, such as mastitis. Thus, there is a need for the development of new target-oriented antimicrobials. Nanomaterials have many advantages over traditional antibiotics, including improved stability, controlled antibiotic release, targeted administration, enhanced bioavailability, and the use of antibiotic-loaded nanomaterials, such as the one herein reported for the first time, appear to be a promising strategy to combat antibiotic-resistant bacteria. The use of rationally designed metallic nanocomposites, rather than the use of single metallic nanoparticles (NPs), should further minimize the bacterial resistance. Aim: Green synthesis of a multimetallic/ternary nanocomposite formed of silver (Ag), titanium dioxide (TiO2), and iron(III) oxide (Fe2O3), conjugated to chitosan (CS), in which the large spectrum fluoroquinolone antibiotic ciprofloxacin (CIP) has been encapsulated. Methods: The metallic nanoparticles (NPs) Ag NPs, TiO2 NPs, and Fe2O3 NPs were synthesized by reduction of Moringa concanensis leaf aqueous extract. The ternary junction was obtained by wet chemical impregnation technique. CIP was encapsulated into the ternary nanocomposite Ag/TiO2/Fe2O3, followed by chitosan (CS) conjugation using the ionic gelation method. The resulting CS-based nanoparticulate drug delivery system (NDDS), i.e., CIP-Ag/TiO2/Fe2O3/CS, was characterized in vitro by gold standard physical techniques such as X-ray diffractometry (XRD), field emission scanning electron microscopy (FESEM), Fourier-transform infrared (FTIR) spectroscopy. Pharmacological analyses (i.e., LC, EE, ex-vivo drug release behavior) were also assessed. Further, biological studies were carried out both ex vivo (i.e., by disk diffusion method (DDM), fluorescence-activated single cell sorting (FACS), MTT assay) and in vivo (i.e., antibacterial activity in a rabbit model, colony-forming unit (CFU) on blood agar, histopathological analysis using H&E staining). Results: The encapsulation efficiency (EE) and the loading capacity (LC) of the NDDS were as high as 94% ± 1.26 and 57% ± 3.5, respectively. XRD analysis confirmed the crystalline nature of the prepared formulation. FESEM revealed nanorods with an average diameter of 50−70 ± 12 nm. FTIR confirmed the Fe-O-Ti-CS linkages as well as the successful encapsulation of CIP into the NDDS. The zeta potential (ZP) of the NDDS was determined as 85.26 ± 0.12 mV. The antimicrobial potential of the NDDS was elicited by prominent ZIs against MDR E. coli (33 ± 1.40 mm) at the low MIC of 0.112 µg/mL. Morphological alterations (e.g., deformed shape and structural damages) of MDR pathogens were clearly visible overtime by FESEM after treatment with the NDDS at MIC value, which led to the cytolysis ultimately. FACS analysis confirmed late apoptotic of the MDR E. coli (80.85%) after 6 h incubation of the NDDS at MIC (p < 0.05 compared to untreated MDR E. coli used as negative control). The highest drug release (89% ± 0.57) was observed after 8 h using PBS medium at pH 7.4. The viability of bovine mammary gland epithelial cells (BMGE) treated with the NDDS remained superior to 90%, indicating a negligible cytotoxicity (p < 0.05). In the rabbit model, in which infection was caused by injecting MDR E. coli intraperitoneally (IP), no colonies were detected after 72 h of treatment. Importantly, the histopathological analysis showed no changes in the vital rabbit organs in the treated group compared to the untreated group. Conclusions: Taken together, the newly prepared CIP-Ag/TiO2/Fe2O3/CS nanoformulation appears safe, biocompatible, and therapeutically active to fight MDR E. coli strains-causing mastitis.

Challenges and recent trends with the development of hydrogel fiber for biomedical applications.

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.

Synthesis and Characterization of Carbon Dots Coated CaCO3 Nanocarrier for Levofloxacin Against Multidrug Resistance Extended-Spectrum Beta-Lactamase Escherichia coli of Urinary Tract Infection Origin.

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 of antimicrobials. In search of a novel nanocarrier (NC) for targeted delivery of antibiotics, carbon dots (CDs) coated calcium carbonate nanocarriers (CCNC) from organic chicken eggshells conjugated with levofloxacin (Lvx) were synthesized. Our main objectives were to explore the antimicrobial, antibiofilm, and NC potential of CDs coated CaCO3 Nanocarrier conjugated with levofloxacin (CD-CCNC-Lvx) to combat biofilm-producing MDR ESBL E. coli of urinary tract infection origin. The synthesized NC system was physiochemically characterized, validating the synthesis of CCNC and CD-CCNC-Lvx with a particle size of 56 and 14 nm, respectively. Scanning electron microscopy (SEM) showed rod shape morphology. X-ray diffraction results discovered crystalline and dispersed nanoparticles. In vitro release drug kinetics illustrated sustained release of Lvx. NC system exhibited strong antibacterial and antibiofilm potential against E. coli with a noticeable low minimal inhibitory concentration (MIC). MIC of CCNC was found to be 30 ± 0.1 µg/mL and CD-CCNC-Lvx was 20 ± 0.1 µg/mL for MDR ESBL-producing E. coli. The synergistic effect of NC upon conjugation with Lvx showed incredible activity with 30 mm zone of inhibition and 68% biofilm inhibition. Flow cytometry analysis revealed treated E. coli cells showed 58.69% reduction in cell viability. SEM images of treated bacterial cells showed morphological changes, which were also confirmed by our flow cytometry findings leading to cell membrane damage in E. coli. NC system also downregulated the blaCTX-M gene in E. coli. The hemolytic analysis proved biocompatibility with human red blood cells (RBCs). It is concluded that CCNC has the potential to be used as NC for target delivery of antibiotics and may combat toxicity of antibiotics as the inhibition of E. coli was noticed at low MIC concentration.

Two Promising Anti-Cancer Compounds, 2-Hydroxycinnaldehyde and 2- Benzoyloxycinnamaldehyde: Where do we stand?

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 an 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. The highly reactive α,ßunsaturated carbonyl pharmacophore, called Michael acceptor, contributes 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 remains 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 describe their medicinal effects as well as provide an update about their molecular mechanisms reported either in-vitro, ex-vivo, or in animal models.

Development of Chitosan-Based Nanoemulsion Gel Containing Microbial Secondary Metabolite with Effective Antifungal Activity: In vitro and in vivo Characterizations.

PURPOSE: 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.

Breast Cancer Inhibition by Biosynthesized Titanium Dioxide Nanoparticles Is Comparable to Free Doxorubicin but Appeared Safer in BALB/c Mice.

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 vivoevaluation 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 < 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 > 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.

Green Synthesis of Ciprofloxacin-Loaded Cerium Oxide/Chitosan Nanocarrier and its Activity Against MRSA-Induced Mastitis.

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.

Bursting the Virulence Traits of MDR Strain of Candida albicans Using Sodium Alginate-based Microspheres Containing Nystatin-loaded MgO/CuO Nanocomposites.

INTRODUCTION: 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.

Ecological and Industrial Implications of Dynamic Seaweed-Associated Microbiota Interactions.

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.

Fabrication, Physical Characterizations, and In Vitro, In Vivo Evaluation of Ginger Extract-Loaded Gelatin/Poly(Vinyl Alcohol) Hydrogel Films Against Burn Wound Healing in Animal Model.

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 < 0.05; ANOVA) evidenced by intensive collagen formation in histopathological analysis.

Green and Cost-Effective Synthesis of Metallic Nanoparticles by Algae: Safe Methods for Translational Medicine.

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.

Formulation Development, Characterization, and Evaluation of a Novel Dexibuprofen-Capsaicin Skin Emulgel with Improved In Vivo Anti-inflammatory and Analgesic Effects.

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.

Targeting microbial biofilms: by Arctium lappa l. synthesised biocompatible CeO2-NPs encapsulated in nano-chitosan.

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 (CeO2-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 CeO2-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 CeO2-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 CeO2-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 CeO2-NPs lead to the conclusion that they could be useful for controlling biofilm producing multidrug resistance pathogens.

Synergistic evaluation of AgO2 nanoparticles with ceftriaxone against CTXM and blaSHV genes positive ESBL producing clinical strains of Uro-pathogenic E. coli.

The silver oxide nanoparticles (AgO2-NPs) were synthesised using silver foil as a new precursor in wet chemical method. X-ray diffraction analysis shows crystallographic structures of AgO2-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 AgO2-NPs with the presence of Ag-O-Ag stretching bond. All the techniques also confirmed the loading of ceftriaxone drug on the surface of AgO2-NPs. This study also described the effect of AgO2-NPs having synergistic activity with ß 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 AgO2-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 AgO2-NPs synergistic effect can be used as an efficient approach to combat uro-pathogenic infections.

In vitro antifungal activity of 9, 10-dihydrophenanthrene-2-carboxylic acid isolated from a marine bacterium: Pseudomonas putida.

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.