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In impoverished nations, the COVID-19 pandemic has led to a widespread occurrence of deadly fungal diseases like mucormycosis. The limited availability of effective antifungal treatments and the emergence of drug-resistant fungal strains further exacerbate the situation. Factors such as systemic steroid use, intravenous drug misuse, and overutilization of broad-spectrum antimicrobials contribute to the prevalence of hospital-acquired infections caused by drug-resistant fungi. Fungal infections exploit compromised immune status and employ intricate mechanisms to evade immune surveillance. The immune response involves the innate and adaptive immune systems, leading to phagocytic and complement-mediated elimination of fungi. However, resistance to antifungals poses a challenge, highlighting the importance of antifungal prophylaxis and therapeutic vaccination. Understanding the host-fungal immunological interactions and developing vaccines are vital in combating fungal infections. Further research is needed to address the high mortality and morbidity associated with multidrug-resistant fungal pathogens and to develop innovative treatment drugs and vaccines. This review focuses on the global epidemiological burden of fungal infections, host-fungal immunological interactions, recent advancements in vaccine development and the road ahead.

Antimicrobial resistance (AMR) poses a significant global health threat, rendering standard antibiotics ineffective against multi-drug resistant bacteria. To tackle this urgent issue, innovative approaches are essential. Liposomes, small spherical vesicles made of a phospholipid bilayer, present a promising solution. These vesicles can encapsulate various medicines and are both biocompatible and biodegradable. Their ability to be modified for targeted tissue or cell uptake makes them an ideal drug delivery system. By delivering antibiotics directly to infection sites, liposomes minimize side effects and reduce the development of resistance. However, challenges such as poor stability and rapid drug leakage limit their biological application. Chitosan, a biocompatible polymer, enhances liposome interaction with specific tissues or cells, enabling selective drug release at infection sites. Incorporating chitosan into liposome formulations alters and diversifies their surface characteristics through electrostatic interactions, resulting in improved stability and pH-sensitive drug release. These interactions are crucial for enhancing drug retention and targeted delivery, especially in varying pH environments like tumor sites or infection areas, thereby improving therapeutic outcomes and reducing systemic side effects. This review discusses recent advancements, challenges, and the need for further research to optimize liposome formulations and enhance targeted drug delivery for effective AMR treatment. Chitosan-modified liposomes offer a promising strategy to overcome AMR and improve antimicrobial therapies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Pyocyanin is considered a maker of Pseudomonas aeruginosa ( P. aeruginosa ) infection. Pyocyanin is among the toxins released by the P. aeruginosa bacteria. Therefore, the development of a direct detection of PYO is crucial due to its importance. Among the different optical techniques, the Raman technique showed unique advantages because of its fingerprint data, no sample preparation, and high sensitivity besides its ease of use. Noble metal nanostructures were used to improve the Raman response based on the surface-enhanced Raman scattering (SERS) technique. Anodic metal oxide attracts much interest due to its unique morphology and applications. The porous metal structure provides a large surface area that could be used as a hard template for periodic nanostructure array fabrication. Porous shapes and sizes could be controlled by controlling the anodization parameters, including the anodization voltage, current, temperature, and time, besides the metal purity and the electrolyte type/concentration. The anodization of aluminum foil results in anodic aluminum oxide (AAO) formation with different roughness. Here, we will use the roughness as hotspot centers to enhance the Raman signals. Firstly, a thin film of gold was deposited to develop gold/alumina (Au/AAO) platforms and then applied as SERS-active surfaces. The morphology and roughness of the developed substrates were investigated using scanning electron microscopy (SEM) and atomic force microscopy (AFM) techniques. The Au/AAO substrates were used for monitoring pyocyanin secreted from Pseudomonas aeruginosa microorganisms based on the SERS technique. The results showed that the roughness degree affects the enhancement efficiency of this sensor. The high enhancement was obtained in the case of depositing a 30 nm layer of gold onto the second anodized substrates. The developed sensor showed high sensitivity toward pyocyanin with a limit of detection of 96 nM with a linear response over a dynamic range from 1 µM to 9 µM.

Heteroleptic metal complexes containing Cu II , Co II , and Zn II , incorporating curcumin and a Schiff base ligand (L), were synthesized and characterized, and their antifungal activity was evaluated. Their antifungal activities were investigated individually and in combination with fluconazole. Utilizing various analytical techniques such as UV-Vis, FT-IR, NMR, ESI-MS, TGA-DTG, elemental analyses, conductance, and magnetic susceptibility measurements, complex C1 ([Cu(Cur)LCl(H 2 O)]) was assigned a distorted octahedral geometry, while complexes C2 ([Co(Cur)LCl(H 2 O)]) and C3 ([Zn(Cur)LCl(H 2 O)]) were assigned octahedral geometries. Among these complexes, C2 exhibited the highest inhibitory activity against both FLC-susceptible and resistant strains of Candida albicans . Furthermore, C2 demonstrated candidicidal activity and synergistic interactions with fluconazole, effectively inhibiting the growth and survival of both FLC-resistant and FLC-sensitive C. albicans strains. The complex displayed a dose-dependent inhibition of drug efflux pumps in FLC-resistant C. albicans strains, indicating its potential to disrupt the cell membrane of these strains. The significant role of membrane efflux transporters in the development of antifungal drug resistance within Candida species has been extensively documented and our findings indicate that complex C2 specifically targets this crucial factor, thereby playing a pivotal role in mitigating drug resistance in C. albicans .

Candida auris , a recent addition to the Candida species, poses a significant threat with its association to numerous hospital outbreaks globally, particularly affecting immunocompromised individuals. Given its resistance to existing antifungal therapies, there is a pressing need for innovative treatments. In this study, novel triazole bridged quinoline derivatives were synthesized and evaluated for their antifungal activity against C. auris . The most promising compound, QT7, demonstrated exceptional efficacy with a minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of 0.12 μg mL -1 and 0.24 μg mL -1 , respectively. Additionally, QT7 effectively disrupted mature biofilms, inhibiting them by 81.98% ± 8.51 and 89.57 ± 5.47 at MFC and 2× MFC values, respectively. Furthermore, QT7 induced cellular apoptosis in a dose-dependent manner, supported by various apoptotic markers such as phosphatidylserine externalization, mitochondrial depolarization, and reduced cytochrome c and oxidase activity. Importantly, QT7 exhibited low hemolytic activity, highlighting its potential for further investigation. Additionally, the physicochemical properties of this compound suggest its potential as a lead drug candidate, warranting further exploration in drug discovery efforts against Candida auris infections., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (This journal is © The Royal Society of Chemistry.)

Natural products have a long history of success in treating bacterial infections, making them a promising source for novel antibacterial medications. Curcumin, an essential component of turmeric, has shown potential in treating bacterial infections and in this study, we covalently immobilized curcumin (Cur) onto chitosan (CS) using glutaraldehyde and tannic acid (TA), resulting in the fabrication of novel biocomposites with varying CS/Cur/TA ratios. Comprehensive characterization of these ternary biocomposites was conducted using FTIR, SEM, XPS, and XRD to assess their morphology, functional groups, and chemical structures. The inhibitory efficacy of these novel biocomposites (n = 4) against the growth and viability of Pseudomonas aeruginosa (ATCC27853) and Chromobacterium violaceum (ATCC12472) was evaluated and the most promising composite (C3) was investigated for its impact on quorum sensing (QS) and biofilm formation in these bacteria. Remarkably, this biocomposite significantly disrupted QS circuits and effectively curtailed biofilm formation in the tested pathogens without inducing appreciable toxicity. These findings underscore its potential for future in vivo studies, positioning it as a promising candidate for the development of biofilm disrupting antibacterial agents., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

The COVID-19 pandemic has become a significant global issue in terms of public health. While it is largely associated with respiratory complications, recent reports indicate that patients also experience neurological symptoms and other health issues. The objective of this study is to examine the network of protein-protein interactions (PPI) between SARS-CoV-2 proteins and human host proteins, pinpoint the central genes within this network implicated in disease pathology, and assess their viability as targets for drug development. The study adopts a network-based approach to construct a network of 29 SARS-CoV-2 proteins interacting with 2896 host proteins, with 176 host genes being identified as interacting genes with all the viral proteins. Gene ontology and pathway analysis of these host proteins revealed their role in biological processes such as translation, mRNA splicing, and ribosomal pathways. We further identified EEF2, RPS3, RPL9, RPS16, and RPL11 as the top 5 most connected hub genes in the disease-causing network, with significant interactions among each other. These hub genes were found to be involved in ribosomal pathways and cytoplasmic translation. Further a disease-gene interaction was also prepared to investigate the role of hub genes in other disorders and to understand the condition of comorbidity in COVID-19 patients. We also identified 13 drug molecules having interactions with all the hub genes, and estradiol emerged as the top potential drug target for the COVID-19 patients. Our study provides valuable insights using the protein-protein interaction network of SARS-CoV-2 proteins with host proteins and highlights the molecular basis of manifestation of COVID-19 and proposes drug for repurposing. As the pandemic continues to evolve, it is anticipated that investigating SARS-CoV-2 proteins will remain a critical area of focus for researchers globally, particularly in addressing potential challenges posed by specific SARS-CoV-2 variants in the future., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

A series of novel phenothiazine-containing imidazo[1,2- a ]pyridine derivatives were designed and synthesized under metal-free conditions in excellent yield. These derivatives were effectively transformed further into N -alkyl, sulfoxide, and sulfone derivatives. Derivatives were deployed against human microtubule affinity regulating kinase (MARK4), some molecules play crucial roles in cell-cycle progression such as G1/S transition and regulator of microtubule dynamics. Hence, molecules have shown excellent MARK4 inhibitory potential. Molecules with excellent IC 50 values were selected for further studies such as ligand interactions using fluorescence quenching experiments for the binding constant. The highest binding constant was calculated as K = 0.79 × 10 5 and K = 0.1 × 10 7 for compounds 6a and 6h, respectively. Molecular docking, cell cytotoxicity, mitochondrial reactive oxygen species measurement and oxidative DNA damage were also studied to understand the mechanism of action of the molecules on cancer cells. It was found that the designed and synthesized compounds played anti-cancer roles by binding and inhibiting MARK4 protein., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Over the past two decades, metal-organic frameworks (MOFs) have garnered substantial scientific interest across diverse fields, spanning gas storage, catalysis, biotechnology, and more. Zirconium, abundant in nature and biologically relevant, offers an appealing combination of high content and low toxicity. Consequently, Zr-based MOFs have emerged as promising materials with significant potential in biomedical applications. These MOFs serve as effective nanocarriers for controlled drug delivery, particularly for challenging antitumor and retroviral drugs in cancer and AIDS treatment. Additionally, they exhibit prowess in bio-imaging applications. Beyond drug delivery, Zr-MOFs are notable for their mechanical, thermal, and chemical stability, making them increasingly relevant in engineering. The rising demand for stable, non-toxic Zr-MOFs facilitating facile nanoparticle formation, especially in drug delivery and imaging, is noteworthy. This review focuses on biocompatible zirconium-based metal-organic frameworks (Zr-MOFs) for controlled delivery in treating diseases like cancer and AIDS. These MOFs play a key role in theranostic approaches, integrating diagnostics and therapy. Additionally, their utility in bio-imaging underscores their versatility in advancing medical applications.

Cancer poses a formidable challenge, necessitating improved treatment strategies. Metal-based drugs and nanotechnology offer new hope in this battle. Versatile gold complexes and functionalized gold nanoparticles exhibit unique properties like biologically inert behaviour, outstanding light absorption, and heat-conversion abilities. These nanoparticles can be finely tuned for drug delivery, enabling precise and targeted cancer therapy. Their exceptional drug-loading capacity and low toxicity, stemming from excellent stability, biocompatibility, and customizable shapes, make them a promising option for enhancing cancer treatment outcomes and improving diagnostic imaging. Leveraging these attributes, researchers can design more effective and targeted cancer therapeutics. The potential of functionalized gold nanoparticles to advance cancer treatment and diagnostics holds a promising avenue for further exploration and development in the fight against cancer. This review article delves into the finely tuned attributes of functionalized gold nanoparticles, unveiling their potential for application in drug delivery for precise and targeted cancer therapy.

Coumarins are compounds with scientifically proven antibacterial properties, and modifications to the chemical structure are known to improve their effects. This information is even more relevant with the unbridled advances of antibiotic resistance, where Staphylococcus aureus and its efflux pumps play a prominent role. The study's objective was to evaluate the potential of synthetic coumarins with different substitutions in the C-3 position as possible inhibitors of the NorA and MepA efflux pumps of S. aureus . For this evaluation, the following steps took place: (i) the determination of the minimum inhibitory concentration (MIC); (ii) the association of coumarins with fluoroquinolones and ethidium bromide (EtBr); (iii) the assessment of the effect on EtBr fluorescence emission; (iv) molecular docking; and (v) an analysis of the effect on membrane permeability. Coumarins reduced the MICs of fluoroquinolones and EtBr between 50% and 87.5%. Coumarin C1 increased EtBr fluorescence emission between 20 and 40% by reinforcing the evidence of efflux inhibition. The molecular docking results demonstrated that coumarins have an affinity with efflux pumps and establish mainly hydrogen bonds and hydrophobic interactions. Furthermore, C1 did not change the permeability of the membrane. Therefore, we conclude that these 3-substituted coumarins act as inhibitors of the NorA and MepA efflux pumps of S. aureus .

Growing antimicrobial resistance (AMR) is a threat to human and animal populations citing the limited available options. Alternative antimicrobial options or functional enhancement of currently available antimicrobials remains only options. One of the potential options seems stem cells especially the mesenchymal stem cells (MSCs) that show antimicrobial properties. These cells additionally have pro-healing effects that may plausibly improve healing outcomes. MSCs antimicrobial actions are mediated either through direct cell-cell contact or their secretome that enhances innate immune mediated antimicrobial activities. These cells synergistically enhance efficacy of currently available antimicrobials especially against the biofilms. Reciprocal action from antimicrobials on the MSCs functionality remains poorly understood. Currently, the main limitation with MSCs based therapy is their limited efficacy. This demands further understanding and can be enhanced through biotechnological interventions. One of the interventional options is the 'priming' to enhance MSCs resistance and specific expression potential. The available literature shows potential antimicrobial actions of MSCs both ex vivo as well as in vivo. The studies on veterinary species are very promising although limited by number and extensiveness in details for their utility as standard therapeutic agents. The current review aims to discuss the role of animals in AMR and the potential antimicrobial actions of MSCs in veterinary medicine. The review also discusses the limitations in their utilization as standard therapeutics., Competing Interests: Declaration of competing interest Authors declare there is no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Candida auris, the youngest Candida species, is known to cause candidiasis and candidemia in humans and has been related to several hospital outbreaks. Moreover, Candida auris infections are largely resistant to the antifungal drugs currently in clinical use, necessitating the development of novel medications and approaches to treat such infections. Following up on our previous studies that demonstrated eugenol tosylate congeners (ETCs) to have antifungal activity, several ETCs (C1-C6) were synthesized to find a lead molecule with the requisite antifungal activity against C. auris. Preliminary tests, including broth microdilution and the MUSE cell viability assay, identified C5 as the most active derivative, with a MIC value of 0.98 g/mL against all strains tested. Cell count and viability assays further validated the fungicidal activity of C5. Apoptotic indicators, such as phosphatidylserine externalization, DNA fragmentation, mitochondrial depolarization, decreased cytochrome c and oxidase activity and cell death confirmed that C5 caused apoptosis in C. auris isolates. The low cytotoxicity of C5 further confirmed the safety of using this derivative in future studies. To support the conclusions drawn in this investigation, additional in vivo experiments demonstrating the antifungal activity of this lead compound in animal models will be needed., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Alam et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

It is commonly known that agricultural pest and disease management is achieved through the use of agricultural chemicals and other synthetic compounds, which can contaminate water, soil, and food. Using agrochemicals indiscriminately has negative effects on the environment and poor food quality. In contrast, the world's population is increasing rapidly, and arable land is diminishing daily. Traditional agricultural methods must be replaced by nanotechnology-based treatments that efficiently address both the demands of the present and the needs of the future. As a promising contributor to sustainable agriculture and food production worldwide, nanotechnology has been applied through innovative and resourceful tools. Recent advances in nanomaterial engineering have increased agricultural and food sector production and protected crops using nanoparticles (1000 nm). Agrochemicals, nutrients, and genes can now be distributed to plants in a precise and tailored manner through nanoencapsulation (nanofertilizers, nanopesticides, and genes). Despite the advancement of technology in agriculture, some areas remain unexplored. The various agricultural domains must therefore be updated in priority order. The development of long-lasting and efficient nanoparticle materials will be key to the development of future eco-friendly and nanoparticle-based technologies. We thoroughly covered the many types of nanoscale agro-materials and gave an overview of biological techniques in nano-enabled tactics that can effectively reduce plant biotic and abiotic challenges while potentially boosting plant nutritional values., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Obesity presents a major health challenge that increases the risk of several non-communicable illnesses, such as but not limited to diabetes, hypertension, cardiovascular diseases, musculoskeletal and neurological disorders, sleep disorders, and cancers. Accounting for nearly 8% of global deaths (4.7 million) in 2017, obesity leads to diminishing quality of life and a higher premature mortality rate among affected individuals. Although essentially dubbed as a modifiable and preventable health concern, prevention, and treatment strategies against obesity, such as calorie intake restriction and increasing calorie burning, have gained little long-term success. In this manuscript, we detail the pathophysiology of obesity as a multifactorial, oxidative stress-dependent inflammatory disease. Current anti-obesity treatment strategies, and the effect of flavonoid-based therapeutic interventions on digestion and absorption, macronutrient metabolism, inflammation and oxidative stress and gut microbiota has been evaluated. The use of several naturally occurring flavonoids to prevent and treat obesity with a long-term efficacy, is also described., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Mahboob, Samuel, Mohamed, Wani, Ghorbel, Miled, Büsselberg and Chaari.)

Candida albicans and Staphylococcus aureus , representing two different kingdoms, are the most frequently isolated pathogens from invasive infections. Their pathogenic attributes, combined with drug resistance, make them a major threat and a challenge to successful treatments, mainly when involved in polymicrobial biofilm-associated infections. In the present study, we investigated the antimicrobial potential of Lactobacillus metabolite extracts (LMEs) purified from cell-free supernatant of four Lactobacillus strains (KAU007, KAU0010, KAU0021, and Pro-65). Furthermore, LME obtained from the strain KAU0021 (LME KAU0021 ), being the most effective, was analyzed for its anti-biofilm property against mono- and polymicrobial biofilms formed by C. albicans and S. aureus . The impact of LME KAU0021 on membrane integrity in single and mixed culture conditions was also evaluated using propidium iodide. The MIC values recorded for LME KAU0021 was 406 µg/mL, 203 µg/mL, and 406 µg/mL against planktonic cells of C. albicans SC5314, S. aureus and polymicrobial culture, respectively. The LME KAU0021 at sub-MIC values potentially abrogates both biofilm formation as well as 24 h mature mono- and polymicrobial biofilms. These results were further validated using different microscopy and viability assays. For insight mechanism, LME KAU0021 displayed a strong impact on cell membrane integrity of both pathogens in single and mixed conditions. A hemolytic assay using horse blood cells at different concentrations of LME KAU0021 confirmed the safety of this extract. The results from this study correlate the antimicrobial and anti-biofilm properties of lactobacilli against bacterial and fungal pathogens in different conditions. Further in vitro and in vivo studies determining these effects will support the aim of discovering an alternative strategy for combating serious polymicrobial infections caused by C. albicans and S. aureus .

In Asia, mulberry has long been used to treat various infectious and internal ailments as a traditional medication. The compounds found in it have the potential to improve human health. Because there is no approved and defined evaluation procedure, it has not been formally or scientifically recognized. As a result of these investigations, a new frontier in traditional Chinese medicine has opened up, with the possibility of modernization, for the interaction between active components of mulberry and their biological activities. These studies have used current biotechnological technologies. For ages, mulberry has been used as an herbal remedy in Asia to cure various diseases and internal disorders. It has a high concentration of bioactive chemicals that benefit human health. The most abundant phenolic components extracted from white mulberry leaves are flavonoids (Kuwanons, Moracinflavans, Moragrols, and Morkotins), phenolic acids, alkaloids, and so forth. Flavonoids, benzofurans, chalcones, and alkaloids have been discovered to have cytotoxic effects on human cancer cell lines. There is growing evidence that mulberry fruits can potentially prevent cancer and other aging-related disorders due to their high concentration of bioactive polyphenolic-rich compounds and macro and micronutrients. Anthocyanins are rapidly absorbed after eating, arriving in the plasmalemma within 15-50 min and entirely removed after 6-8 hr. Due to a lack of an approved and consistent technique for its examination, it has yet to be formally or scientifically recognized. The mulberry plant is commercially grown for silkworm rearing, and less attention is paid to its bioactive molecules, which have a lot of applications in human health. This review paper discusses the phenolic compounds of white mulberry and black mulberry in detail concerning their role in cancer prevention., (© 2023 John Wiley & Sons Ltd.)

Over the last few years, the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) unleashed a global public health catastrophe that had a substantial influence on human physical and mental health, the global economy, and socio-political dynamics. SARS-CoV-2 is a respiratory pathogen and the cause of ongoing COVID-19 pandemic, which testified how unprepared humans are for pandemics. Scientists and policymakers continue to face challenges in developing ideal therapeutic agents and vaccines, while at the same time deciphering the pathology and immunology of SARS-CoV-2. Challenges in the early part of the pandemic included the rapid development of diagnostic assays, vaccines, and therapeutic agents. The ongoing transmission of COVID-19 is coupled with the emergence of viral variants that differ in their transmission efficiency, virulence, and vaccine susceptibility, thus complicating the spread of the pandemic. Our understanding of how the human immune system responds to these viruses as well as the patient groups (such as the elderly and immunocompromised individuals) who are often more susceptible to serious illness have both been aided by this epidemic. COVID-19 causes different symptoms to occur at different stages of infection, making it difficult to determine distinct treatment regimens employed for the various clinical phases of the disease. Unsurprisingly, determining the efficacy of currently available medications and developing novel therapeutic strategies have been a process of trial and error. The global scientific community collaborated to research and develop vaccines at a neck-breaking speed. This review summarises the overall picture of the COVID-19 pandemic, different mutations in SARS-CoV-2, immune response, and the treatment modalities against SARS-CoV-2., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Streptococcus pyogenes is one of the most common bacteria causing sinusitis in children and adult patients. Probiotics are known to cause antagonistic effects on S. pyogenes growth and biofilm formation. In the present study, we demonstrated the anti-biofilm and anti-virulence properties of Lactiplantibacillus plantarum KAU007 against S. pyogenes ATCC 8668. The antibacterial potential of L. plantarum KAU007 metabolite extract (LME) purified from the cell-free supernatant of L. plantarum KAU007 was evaluated in terms of minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC). LME was further analyzed for its anti-biofilm potential using crystal violet assay and microscopic examination. Furthermore, the effect of LME was tested on the important virulence attributes of S. pyogenes , such as secreted protease production, hemolysis, extracellular polymeric substance production, and cell surface hydrophobicity. Additionally, the impact of LME on the expression of genes associated with biofilm formation and virulence attributes was analyzed using qPCR. The results revealed that LME significantly inhibited the growth and survival of S. pyogenes at a low concentration (MIC, 9.76 µg/mL; MBC, 39.06 µg/mL). Furthermore, LME inhibited biofilm formation and mitigated the production of extracellular polymeric substance at a concentration of 4.88 μg/mL in S. pyogenes . The results obtained from qPCR and biochemical assays advocated that LME suppresses the expression of various critical virulence-associated genes, which correspondingly affect various pathogenicity markers and were responsible for the impairment of virulence and biofilm formation in S. pyogenes . The non-hemolytic nature of LME and its anti-biofilm and anti-virulence properties against S. pyogenes invoke further investigation to study the role of LME as an antibacterial agent to combat streptococcal infections.

Although Candida auris was only identified in the year 2009, it has rapidly spread in more than a dozen countries and is proving more deadly and notorious. In our previous studies, we reported on the tremendous antifungal potential of a series of cinnamaldehyde based azole derivatives against fluconazole susceptible and resistant clinical isolates of Candida albicans and identified a promising lead molecule (6f). In this study, the effect of this compound on the viability and physiology of cell death in C. auris was assessed. The impact of compound 6f on cell cycle, oxidative stress enzymes and transcriptional profile of genes encoding these oxidative stress enzymes was also analysed. The results confirmed that compound 6f possessed the minimum inhibitory concentration of 0.98 µg/mL and prevented the growth and caused death in yeast cells. Furthermore, the compound at subinhibitory and inhibitory concentrations blocked the cell cycle in C. auris at S phase and G2/M phase and inhibited expression as well as activity of antioxidant enzymes that resulted in production of reactive oxygen species. Altogether, compound 6f showed potential antifungal activity against a virulent strain of C. auris and was able to induce oxidative stress and arrested cell cycle in C. auris and therefore, it can be considered as a strong candidate for antifungal drug development against C. auris., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Candida albicans is the most dominant and prevalent cause of fungal infections in humans. Azoles are considered as first-line drugs for the treatment of these infections. However, their prolonged and insistent use has led to multidrug resistance and treatment failures. To overcome this, modification or derivatization of the azole ring has led to the development of new and effective antifungal molecules. In a previous study, we reported on the development of new triazole-based molecules as potential antifungal agents against Candida auris. In this study, the most potent molecules from the previous study were docked and simulated with lanosterol 14-alpha demethylase enzyme. These compounds were further evaluated for in vitro susceptibility testing against C. albicans. In silico results revealed favorable structural dynamics of the compounds, implying that the compounds would be able to effectively bind to the target enzyme, which was further manifested by the strong interaction of the test compounds with the amino acid residues of the target enzyme. In vitro studies targeting quantification of ergosterol content revealed that pta1 was the most active compound and inhibited ergosterol production by >90% in both drug-susceptible and resistant C. albicans isolates. Furthermore, RT-qPCR results revealed downregulation of ERG11 gene when C. albicans cells were treated with the test compound, which aligns with the decreased ergosterol content. In addition, the active triazole derivatives were also found to be potent inhibitors of biofilm formation. Both in silico and in vitro results indicate that these triazole derivatives have the potential to be taken to the next level of antifungal drug development.

Population of drug-resistant bacteria have increased at an alarming rate in the past few decades. The major reason for increasing drug resistance is the lack of new antibiotics and limited drug targets. It has therefore been a vital task to develop new antibiotics with different drug targets. Two such targets are biofilm formation and quorum sensing. Quorum sensing is cell to cell communication used by bacteria that initiates many important survival processes and aids in establishing pathogenesis. Both biofilm and quorum sensing are inter-related processes and play a major role in physiological and pathogenesis processes. In this study, five novel imidazole derivatives (IMA-1-IMA-5) were synthesised and tested for their antibacterial and anti-quorum sensing activities against Chromobacterium violaceum using different in silico and in vitro techniques following the standard protocols. In silico results revealed that all compounds were able to effectively bind to and interact sufficiently with the target protein CviR. CviR is a protein to which autoinducers bind to initiate the quorum sensing process. In silico results also revealed that the compounds generated favourable structural dynamics implying that the compounds would be able to effectively bind to CviR and inhibit quorum sensing. Susceptibility results revealed that IMA-1 is the most active of all the derivatives against both planktonic cells and biofilms. Qualitative and quantitative evaluation of anti-quorum sensing activity at sub-inhibitory concentrations of these compounds also revealed high activity for IMA-1. Down-regulation of most of the quorum sensing genes when cells were treated with the test compounds affirmed the high anti-quorum sensing activities of these compounds. The results from this study are promising and urges on the use of anti-quorum sensing and biofilm disrupting molecules to combat multi-drug resistance problem., (© 2022. The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia.)

Coordination compounds from simple transition metals are robust substitutes for platinum-based complexes due to their remarkable anticancer properties. In a quest to find new metal complexes that could substitute or augment the platinum based chemotherapy we synthesized three transition metal complexes C1-C3 with Cu(ii), Ni(ii), and Co(ii) as the central metal ions, respectively, and evaluated them for their anticancer activity against the human keratinocyte (HaCaT) cell line and human cervical cancer (HeLa) cell lines. These complexes showed different activity profiles with the square planar copper complex C1 being the most active with IC 50 values lower than those of the widely used anticancer drug cisplatin. Assessment of the morphological changes by DAPI staining and ROS generation by DCFH-DA assay exposed that the cell death occurred by caspase-3 mediated apoptosis. C1 displayed interesting interactions with Ct-DNA, evidenced by absorption spectroscopy and validated by docking studies. Together, our results suggest that binding of the ligand to the DNA-binding domain of the p53 tumor suppressor (p53DBD) protein and the induction of the apoptotic hallmark protein, caspase-3, upon treatment with the metal complex could be positively attributed to a higher level of ROS and the subsequent DNA damage (oxidation), generated by the complex C1, that could well explain the interesting anticancer activity observed for this complex., Competing Interests: The authors declare no competing interests., (This journal is © The Royal Society of Chemistry.)

For combating life-threatening infections caused by Candida albicans there is an urgent requirement of new antifungal agents with a targeted activity and low host cytotoxicity. Manipulating the mechanistic basis of cell death decision in yeast may provide an alternative approach for future antifungal therapeutics. Herein, the effect of an active citral derivative (Cd1) over the physiology of cell death in C. albicans was assessed. The viability of C. albicans SC5314 cells was determined by broth microdilution assay. The crucial morphological changes and apoptotic markers in Cd1-exposed yeast cells were analyzed. Subsequently the results confirmed that Cd1 arrested growth and caused death in yeast cells. Furthermore, this molecule inhibited antioxidant enzymes that resulted in production of reactive oxygen species. DNA fragmentation and condensation, phosphatidylserine exposure at the outer leaflet of cell membrane, mitochondrial disintegration as well as accumulation of cells at G2/M phase of the cell cycle were recorded. Altogether, this derivative induced apoptotic-type cell death in C. albicans SC5314., (Copyright © 2021 Elsevier Inc. All rights reserved.)

With an upsurge in multidrug resistant bacteria backed by biofilm defence armours, there is a desperate need of new antibiotics with a non-traditional mechanism of action. Targeting bacteria by misguiding them or halting their communication is a new approach that could offer a new way to combat the multidrug resistance problem. Quorum sensing is considered to be the achilles heel of bacteria that has a lot to offer. Since, both quorum sensing and biofilm formation have been related to drug resistance and pathogenicity, in this study we synthesised new derivatives of citral with antiquorum sensing and biofilm disrupting properties. We previously reported antimicrobial and antiquorum sensing activity of citral and herein we report the synthesis and evaluation of citral and its derivatives (CD1-CD3) for antibacterial, antibiofilm and antiquorum sensing potential against Chromobacterium violaceum using standard methods. Preliminary results revealed that CD1 is the most active of all the derivatives. Qualitative and quantitative evaluation of antiquorum sensing activity at sub-inhibitory concentrations of these compounds also revealed high activity for CD1 followed by CD2, CD3 and citral. These compounds also inhibit biofilm formation at subinhibitory concentrations without causing any bacterial growth inhibition. These results were replicated by RT-qPCR with down regulation of the quorum sensing genes when C. violaceum was treated with these test compounds. Overall, the results are quite encouraging, revealing that biofilm and quorum sensing are interrelated processes and also indicating the potential of these derivatives to impede bacterial communication and biofilm formation.

The outbreak of coronavirus disease 2019 (COVID-19) as a pandemic has shaken the global health system and economy by their roots. This epidemic is still spreading and showing no signs of decreasing trend. Vaccination could be the only effective and economical means to control this pandemic. A number of research institutions and pharmaceutical companies have plunged into the race of vaccine development against COVID-19 which are in various stages of development. An intriguing fact of coronavirus infections is that in every decade of the 21st century there is a new major coronavirus epidemic, namely, severe acute respiratory syndrome (SARS) in 2002, Middle East respiratory syndrome (MERS) in 2012, and now COVID-19; and such epidemics are expected in future too. Since most of the biological characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are still obscure, the scientists are relying on the information available on SARS-CoV and to some extent on MERS-CoV for designing and developing COVID-19 vaccines. But there is a need of vigorous testing for immunogenicity, safety, efficacy, and level of protection conferred in the hosts. This review focuses on the challenges and prospects of vaccine development against COVID-19. It highlights seriousness, bottlenecks in vaccine development, possible vaccine candidates, different vaccine strategies, safety evaluation issues, and vaccine production processes pertaining to COVID-19 based on the knowledge acquired on SARS and MERS vaccine development in the past., (© 2020 Wiley-VCH GmbH.)

Quorum sensing is defined as a cell to cell communication between micro-organisms, which enables micro-organisms to behave as multicellular organisms. Quorum sensing enables many collaborative benefits such as synchronisation of virulence factors and biofilm formation. Both quorum sensing, as well as biofilm formation, encourage the development of drug resistance in micro-organisms. Biofilm formation and quorum sensing are causally linked to each other, playing a role in the pathogenesis of the micro-organisms. With the increasing drug resistance against the available antibiotics and antifungal medications, scientists are combining different options to develop new strategies. Such strategies rely on the inhibition of the communication and virulence factors rather than on killing or inhibiting the growth of the micro-organisms. This review encompasses the communication technique used by micro-organisms, how micro-organism resistance is linked to quorum sensing, and various chemical strategies to combat quorum sensing, thereby, drug resistance. Several compounds have been identified as quorum sensing inhibitors and are known to be effective in reducing resistance as they do not kill the pathogens but rather disrupt their communication. Natural compounds have been identified as anti-quorum sensing agents. However, natural compounds have several disadvantages. Therefore, the need for the development of synthetic or semi-synthetic compounds has arisen. This review argues that antiquorum sensing compounds are effective in disrupting quorum sensing and could, therefore be effective in reducing micro-organism drug resistance., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: The fungal pathogen Candida auris , is a serious threat to public health and is associated with bloodstream infections causing high mortality particularly in patients with serious medical problems. As this pathogen is generally resistant to all the available classes of antifungals, there is a constant demand for novel antifungal drugs with new mechanisms of antifungal action. Objective: Therefore, in this study we synthesised six novel piperidine based 1,2,3-triazolylacetamide derivatives (pta1-pta6) and tested their antifungal activity and mechanism of action against clinical C. auris isolates. Methods: Antifungal susceptibility testing was done to estimate MIC values of piperidine derivatives following CLSI recommended guidelines. MUSE Cell Analyzer was used to check cell viability and cell cycle arrest in C. auris after exposure to piperidine derivatives using different kits. Additionally, fluorescence microscopy was done to check the effect of test compound on C. auris membrane integrity and related apoptotic assays were performed to confirm cellular apoptosis using different apoptosis markers. Results: Out of the six derivatives; pta1, pta2 and pta3 showed highest active with MIC values from 0.24 to 0.97 μg/mL and MFC ranging from 0.97 to 3.9 μg/mL. Fungicidal behaviour of these compounds was confirmed by cell count and viability assay. Exposure to test compounds at sub-inhibitory and inhibitory concentrations resulted in disruption of C. auris plasma membrane. Further in-depth studies showed that these derivatives were able to induce apoptosis and cell cycle arrest in S-phase. Furthermore, the compounds demonstrated lower toxicity profile. Conclusion: Present study suggests that the novel derivatives (pta1-pta3) induce apoptotic cell death and cell cycle arrest in C. auris and could be potential candidates against C. auris infections., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors. Published by Elsevier B.V. on behalf of Cairo University.)

Development of new chemotherapeutic agents and strategies are urgently needed to curb and halt the growing menace caused by hard-to-treat microbes. Coordination of metals to bioactive organic ligands is now considered to be an efficient strategy for delivering bioactive compounds inside the microbial cell membranes. Metal complexes have been effectively used to treat many dreadful diseases were other treatment modalities had failed. Use of metal complexes to treat microbial infections is now conceived to be an alternative and efficient strategy. Towards this, some new homoleptic transition metal complexes, obtained by coordination of metal ions to bioactive S-benzyldithiocarbazate Schiff-base ligands were evaluated for their anti-Candida activity and their potential to disrupt the membrane architecture. The complexes displayed remarkable antifungal activity against a wide spectrum of fluconazole susceptible and resistant Candida albicans isolates, with Ni complex (dtc3) being highly active with minimum inhibitory concentration (MIC) values ranging from 1 to 32 µg/mL. Cell viability assay confirmed the fungicidal activity of these metal complexes, especially the complex dtc3. These metal complexes kill Candida albicans by inducing cellular apoptosis and necrosis thereby causing phosphatidylserine externalization as revealed by Annexin V-FITC and propidium iodide staining assays., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Opportunistic fungal pathogens including Candida albicans are responsible for the alarming rise in hospital acquired infections and millions of deaths worldwide. The current treatment modalities are not enough to handle this situation, and therefore, new treatment modalities and strategies are desperately needed. In this direction, we synthesized a series of azole based acetohydrazide derivatives of cinnamaldehyde and subjected it to antifungal activity evaluation. Preliminary antifungal activity evaluation revealed tremendous antifungal potential of some of the derivatives against fluconazole susceptible and resistant clinical isolates of Candida albicans . Although all the compounds in the series are structurally similar except for the presence of different substituents on the phenyl ring of the acetohydrazide pendent, they sharply differed in their activity profile. Further mechanism of action studies revealed that these compounds have an apoptotic effect on C. albicans confirmed via Annexin V-FITC staining and TUNEL assay., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

Despite the rise of new Candida species, Candida albicans tops the list with high morbidity and mortality rates. To tackle this problem there is a need to explore new antifungals that could replace or augment the current treatment options. We previously reported that tosylation of eugenol on hydroxyl group resulted in molecules with enhanced antifungal potency. In line with that work, we synthesized new eugenol tosylate congeners (ETC-1-ETC-7) with different substituents on pendent sulfonyl group and tested their susceptibility against different fluconazole susceptible and resistant C. albicans strains. We evaluated physiology and mode of cell death in response to the most active derivatives by analyzing major apoptotic markers in yeast such as phosphatidylserine externalization, DNA fragmentation, mitochondrial depolarization and decrease in cytochrome c oxidase activity. The results demonstrated that all C. albicans strains were variably susceptible to the test compounds with MIC ranging from 0.125-512 µg/ml, and the most active compounds (ETC-5, ETC-6 and ETC-7) actuate apoptosis and necrosis in Candida cells in a dose-dependent manner via metacaspase-dependent pathway. Furthermore haemolytic assay showed low cytotoxicity effect of these ETCs. Overall the results indicated that ETCs exhibit potential antifungal activity against C. albicans by activating apoptotic and necrotic pathways.

Metal based drugs are important class of chemotherapeutic agents that have the potential to circumvent drug resistance. Increasing drug resistance, treatment failures and limited treatment options necessitates the development of new therapeutic drugs with different mechanisms of action. Towards this direction, we synthesized a series of isatin based mixed ligand complexes of [Cu(dbm)LClH 2 O] (mlc1) , [Co(dbm)LCl 2 ] ‒ (mlc2) and [Ni(dbm)LClH 2 O] (mlc3) and evaluated their antifungal activity alone and in combination with fluconazole (FLC) against seven different Candida albicans isolates. The insight mechanism of antifungal action was revealed by studying apoptosis via terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. The study revealed that all these compounds showed antifungal activity at varying concentrations with mlc3 as the most potent compound with minimum inhibitory concentration ranging from 0.5-8 μg/mL and minimum fungicidal concentration ranging from 4-16 μg/mL. Upon combination with FLC, most of the interactions were either synergistic (54 %) or additive (32 %) with no antagonistic combination against any of the tested isolate. The study on their mechanism of action revealed that these compounds show apoptotic effect on C. albicans at sub-inhibitory concentrations, suggesting that strategies to target this process may augment the current antifungal treatment modalities.

New quinoline-3-carbonitrile derivatives were synthesized and evaluated for their potential antibacterial behavior. Compounds were obtained by a one-pot multicomponent reaction of appropriate aldehyde, ethyl cyanoacetate, 6-methoxy-1,2,3,4-tetrahydro-naphthalin-1-one and ammonium acetate. Structures were established by different physical and spectroscopic techniques. The molecular geometry, vibration frequencies, HOMO-LUMO energy gap, molecular hardness (g), ionization energy (IE), electron affinity (EA), and total energy of these compounds was assessed by DFT studies, employing DFT/RB3LYP method. Preliminary antibacterial studies using both Gram-positive and Gram-negative bacterial strains and cytotoxicity studies on mammalian cells revealed their promising antibacterial activity, without causing any severe host toxicity. All the compounds (QD1-QD5) in this study obeyed the 'Lipinski's Rule of Five' with logP values <5 and HBA <10, hydrogen bond donor's <5. The most active compound QD4 showed good interaction with the target DNA gyrase; target enzyme for quinoline class of antibiotics, which reveals its probable mechanism of action. Results of all these studies establish these compounds as important scaffolds with broad-spectrum antibacterial activity with no off-target toxicity. Having lower band gap energy of 3.40 eV and a low lying LUMO for compound QD4, this compound may be a valuable starting point for the development of quinoline-3-carbonitrile based broad-spectrum antibacterial agents., (Copyright © 2019. Published by Elsevier Inc.)

Development of new chemotherapeutic agents to treat microbial infections and recurrent cancers is of pivotal importance. Metal based drugs particularly ruthenium complexes have the uniqueness and desired properties that make them suitable candidates for the search of potential chemotherapeutic agents. In this study, two mixed ligand Ru(III) complexes [Ru(Cl) 2 (SB)(Phen] (RC-1) and [Ru(Cl) 2 (SB)(Bipy)] (RC-2) were synthesised and characterized by elemental analysis, IR, UV-Vis, 1 H, 13 C NMR spectroscopic techniques and their molecular structure was confirmed by X-ray crystallography. Antibacterial activity evaluation against two Gram-positive (S. pneumonia and E. faecalis) and four Gram-negative strains (P. aurogenosa, K. pneumoniae, S. enterica, and E. coli) revealed their moderate antibacterial activity with MIC value of ≥250 μg/mL. Anticancer activity evaluation against a non-small lung cancer cell line (H1299) revealed the tremendous anticancer activity of these complexes which was further validated by DNA binding and docking results. DNA binding profile of the complexes studied by UV-Visible and fluorescence spectroscopy showed an intercalative binding mode with CT-DNA and an intrinsic binding constant in the range of 3.481-1.015× 10 5  M -1 . Both the complexes were also found to exert weak toxicity to human erythrocytes by haemolytic assay compared to cisplatin. Potential of these complexes as anticancer agents will be further delineated by in vivo studies., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Development of new chemotherapeutic agents to treat multidrug-resistant fungal infections to augment the current treatment options is a must. In this direction, a series of mixed ligand complexes was synthesized from a Schiff base (L) obtained by the condensation of 2-hydroxynapthaldehyde and tryptamine, and 1,10-phenanthroline (1,10-phen) as a secondary ligand. Based on spectral characterization and physical measurements an octahedral geometry was assigned to [Co(phen)LClH 2 O] (C2), [Ni(phen)LClH 2 O](C3), and [Zn(phen)LClH 2 O](C4) complexes while a distorted octahedral geometry was assigned to the [Cu(phen)LClH 2 O](C1) complex. All the synthesized compounds were tested for antifungal activity against 11 Candida albicans isolates, including fluconazole (FLC) resistant isolates, by determining minimum inhibitory concentrations and studying growth curves. MIC results suggest that all the newly synthesized compounds have potent antifungal activity at varying levels. The rapid action of these compounds on fungal cells suggested a membrane-located target for their action., Competing Interests: The authors declare that they have no competing interests., (This journal is © The Royal Society of Chemistry.)

Background: The increasing incidence of fungal infections, especially caused by Candida albicans, and their increasing drug resistance has drastically increased in recent years. Therefore, not only new drugs but also alternative treatment strategies are promptly required., Methods: We previously reported on the synergistic interaction of some azole and non-azole compounds with fluconazole for combination antifungal therapy. In this study, we synthesized some non-azole Schiff-base derivatives and evaluated their antifungal activity profile alone and in combination with the most commonly used antifungal drugs- fluconazole (FLC) and amphotericin B (AmB) against four drug susceptible, three FLC resistant and three AmB resistant clinically isolated Candida albicans strains. To further analyze the mechanism of antifungal action of these compounds, we quantified total sterol contents in FLC-susceptible and resistant C. albicans isolates., Results: A pyrimidine ring-containing derivative SB5 showed the most potent antifungal activity against all the tested strains. After combining these compounds with FLC and AmB, 76% combinations were either synergistic or additive while as the rest of the combinations were indifferent. Interestingly, none of the combinations was antagonistic, either with FLC or AmB. Results interpreted from fractional inhibitory concentration index (FICI) and isobolograms revealed 4-10-fold reduction in MIC values for synergistic combinations. These compounds also inhibit ergosterol biosynthesis in a concentration-dependent manner, supported by the results from docking studies., Conclusion: The results of the studies conducted advocate the potential of these compounds as new antifungal drugs. However, further studies are required to understand the other mechanisms and in vivo efficacy and toxicity of these compounds., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

One of today's major challenges is to provide green materials for a cleaner environment. We have conducted studies on carbon dioxide (CO 2 ) adsorption and conversion to valuable products by an ecofriendly approach based in chitosan/graphene oxide (CSGO) nanocomposite film. Rheological behavior indicates that the CSGO has a better solvation property than the pure chitosan. An adsorption capacity of 1.0152mmolCO 2 /g of CSGO nanocomposite at 4.6bar was observed. The catalytic behavior of the CSGO nanocomposite in the presence of tetra-n-butylammonium iodide (n-Bu 4 NI) as co-catalyst was evaluated for the cycloaddition of CO 2 to epoxides, to give cyclic carbonates, in the absence of any solvent. These results strongly suggest that the CSGO nanocomposite may open new vistas towards the development of ecofriendly material for catalytic conversion and adsorption of CO 2 on industrial scale., (Copyright © 2017. Published by Elsevier B.V.)

Competing Interests: There are no conflicts of interest

Fluorescent materials are important for low-cost opto-electronic and biomedical sensor devices. In this study we present the synthesis and characterization of graphene modified with bis-thiosemicarbazone (BTS). This new material was characterized using Fourier transform infrared spectroscopy (FT-IR), Ultraviolet-visible (UV-Vis) and Raman spectroscopy techniques. Further evaluation by X-ray diffraction (XRD), thermo-gravimetric analysis (TGA), differential scanning calorimetry (DSC), scanning electron microscopy (SEM) and atomic-force microscopy (AFM) allowed us to fully characterize the morphology of the fabricated material. The average height of the BTSGO sheet is around 10nm. Optical properties of BTSGO evaluated by photoluminescence (PL) spectroscopy showed red shift at different excitation wavelength compared to graphene oxide or bisthiosemicarbazide alone. These results strongly suggest that BTSGO material could find potential applications in graphene based optoelectronic devices., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: The researchers working in the field of medical, veterinary and other biological sciences have uniformly described unique characteristic features of stem cells including selfrenewal, prolonged multiplication, immuno-modulation and multi-lineage differentiation. These characteristics of stem cells have opened new horizons in cellular therapy for the management of numerous incurable diseases in human and veterinary patients. Though the mechanisms involved in reparative processes may be similar, the indication for the stem cell therapy may be disparate in human and veterinary subjects., Objective: Among various stem cell types, currently mesenchymal stem cells (MSCs) are extensively studied in regenerative medicine owing to their readily available sources, easy harvesting and ability to differentiate both into mesodermal as well as non-mesodermal tissues under specific culture conditions with little associated ethical issues. The objective of the study was to analyze and summarize the studies and their results pertaining to the basic biology of stem cells, preclinical trials and their potential therapeutic application in veterinary medicine., Results: MSCs have been variably isolated, cultured and characterized from almost all the body tissues and fetal membranes in domestic and pet animals. The cells have been studied in numerous pre-clinical and clinical studies, in addition, to lab animal models. The results although are promising but need further extensive research studies before the cellular application becomes a clinical reality in veterinary medicine., Conclusion: The current review throws some light on different aspects of mesenchymal stem cells like sources, isolation, characterization and their potential therapeutic applications in farm and pet animals., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

In recent years, the number of people suffering from cancer and multidrug-resistant infections has sharply increased, leaving humanity without any choice but to search for new treatment options and strategies. Although cancer is considered the leading cause of death worldwide, it also paves the way many microbial infections and thus increases this burden manifold. Development of small molecules as anticancer and anti-microbial agents has great potential and a plethora of drugs are already available to combat these diseases. However, the wide occurrence of multidrug resistance in both cancer and microbial infections necessitates the development of new and potential molecules with desired properties that could circumvent the multidrug resistance problem. A successful strategy in anticancer chemotherapy has been the use of metallo-drugs and this strategy has the potential to be used for treating multidrug-resistant infections more efficiently. As a class of molecules, Schiff bases have been the topic of considerable interest, owing to their versatile metal chelating properties, inherent biological activities and flexibility to modify the structure to fine-tune it for a particular biological application. Schiff base-based metallo-drugs are being researched to develop new anticancer and anti-microbial chemotherapies and because both anticancer and anti-microbial targets are different, heterocyclic Schiff bases can be structurally modified to achieve the desired molecule, targeting a particular disease. In this review, we collect the most recent and relevant literature concerning the synthesis of heterocyclic Schiff base metal complexes as anticancer and anti-microbial agents and discuss the potential and future of this class of metallo-drugs as either anticancer or anti-microbial agents.

We have demonstrated the facile, environmentally friendly and sustainable preparation of chitosan based meso-tetrakis(4-sulfonatophenyl)porphyrin (CS-TPPS) for adsorption and catalytic conversion of carbon-dioxide (CO 2 ). The ionic complexation between chitosan (CS) and meso-tetrakis(4-sulfonatophenyl)porphyrin (TPPS) is confirmed by ultraviolet-visible (UV-vis) and Fourier transform infrared spectroscopy (FTIR). Physical properties, such as crystallinity, thermal stability, surface morphology and porosity were analyzed by X-ray diffraction, thermal analysis, scanning electron microscopy and BET isotherm analysis. CS-TPPS shows adsorption capacity of 0.9mmol CO 2 /g compared to the adsorption capacity of 0.05mmol CO 2 /g of pure chitosan and an adsorption capacity of 0.2mmol CO 2 /g of pure TPPS. It also exhibits higher conversion of CO 2 and propylene oxide into cyclic carbonate (66%), compared to pure chitosan (31%). The results are encouraging, and may open new perspectives for the use of biopolymers involving porphyrin based material in environmental and industrial applications., (Copyright © 2017. Published by Elsevier Ltd.)

The occurrence of invasive fungal diseases, particularly in immunocompromised patients, is life-threatening and increases the economic burden. The rising problem of multi-drug resistance is becoming a major concern for clinicians. In addition, a repertoire of antifungal agents is far less in number than antibacterial drugs. To combat these problems, combination therapy has gained a lot of interest. We previously reported the synergistic interaction of some mono- and bis-dihydropyrimidinone and thione derivatives with fluconazole and amphotericin B for combination antifungal therapy. In this study we used the same approach and synthesized different azole and non-azole derivatives of mono-( M ) and bis-( B ) chalcones and evaluated their antifungal activity profile alone and in combination with the most commonly used antifungal drug - fluconazole (FLC) - against seven FLC susceptible and three FLC resistant clinically isolated Candida albicans strains. Based on the minimum inhibitory concentration results, the bis-derivatives showed lower MIC values compared to their mono-analogues. Both fractional inhibitory concentration index and isobologram results revealed mostly synergistic, additive or indifferent interactions between the tested compounds and FLC against different Candida isolates. None of the tested compounds showed any effect on energy dependent R6G efflux, revealing that they do not reverse the mechanism of drug efflux. However, surprisingly, these compounds profoundly decreased ergosterol biosynthesis and showed down regulation of ERG11 gene expression, which is the possible mechanism of reversal of azole drug resistance by these compounds. These results provide a platform for further research to develop pyrimidinone/thione ring containing compounds as promising new antifungal agents, which could be used in antifungal combination therapy.

Invasive fungal infection is a problem that continues to challenge the healthcare sector. New antifungals and new therapeutic strategies are needed to address this challenge. We previously reported that the combination of a synthetic compound with a drug with known mechanism of action is a good strategy to treat aggressive and resistant fungi. Here we revisited our approach and synthesized structural analogues of flucytosine, which is a synthetic antifungal and is being studied for its use in combination therapy with other antifungal drugs. Pyrimidin-one and -thione (often known as DHPM's) as flucytosine analogues were obtained through a Biginelli reaction of corresponding aldehydes, ethylacetoacetate and urea/thiourea. Structure was confirmed by FTIR, 1 HNMR, 13 CNMR, COSY and MS (ESI + ) analysis. All the newly synthesized derivatives were evaluated for the antifungal activity alone and in combination of two most commonly used antifungal drugs, amphotericin B and fluconazole against different clinically isolated Candida albicans strains. Minimum inhibitory concentration results confirmed that BG4 possess high antifungal activity against all the tested strains (MIC = 1-32 μg/ml). For all the combinations with amphotericin B and fluconazole, 37% were synergistic followed by 30% additive and 24% indifferent interactions. Interestingly, 9% antagonistic interaction was observed when BG1 and BG3 were combined with fluconazole, however, no antagonistic interaction was observed with amphotericin B. In-depth studies of all the synergies were done by constructing isobolograms with nine different ratio combinations. These results warrant the use of DHPM derivatives as chemosensitising agents which could lower down the dosages of the antifungal drugs to treat invasive fungal diseases., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Chicken infectious anaemia virus (CIAV) is an economically important and a highly immunosuppressive virus affecting poultry industry worldwide. In this study we assessed the immunomodulatory effects of four herbal preparations namely Withania somnifera, Tinospora cordifolia, Azadirachta indica and E Care Se Herbal in resisting the viral multiplication and immunosuppression inflicted by CIAV in chicks. Day-old chicks ( n  = 90) were randomly and equally divided into six groups (Groups A-F). Groups A-D were administered with purified extracts of W. somnifera , T. cordifolia , A. indica and E Care Se Herbal, respectively followed by the evaluation of viral load in lymphoid organs by quantitative real-time PCR and cell mediated immune response by flow cytometric analysis of CD4 + and CD8 + T cells. Groups A-D were found to resist CIAV multiplication and pathogenesis with significant reduction of viral load compared with the infected control ( P  < 0.05). Group A-C chicks showed significantly higher ( P  < 0.05) CD4 + and CD8 + T cell counts compared to control birds while of E Care Se Herb had minimal effect on T cell count. The findings suggested that the herbal preparations used during the study were effective as both prophylactic and immunomodulatory agents and thus have potential of being used against CIAV induced immunosuppression in poultry.

Marek's disease (MD), is an economically important virus disease of poultry throughout the world. In this study, we for the first time reports development of a novel dot enzyme-linked immunosorbent assay (dot-ELISA) for the confirmatory diagnosis of lymphoma caused by Marek's Disease Virus (MDV). Suspected lymphoma tissue extracts from the diseased birds were used for the Meq oncoprotein antigen detection, which is expressed specifically in MDV lymphomas. Recombinant Meq oncoprotein was expressed using Expresso™ Rhamnose Sumo Cloning and Expression system and the hyperimmune serum was raised against it, which was used later while developing dot-ELISA. The dot-ELISA exhibited higher specificity (92%) in diagnosing MD lymphomas as compared to conventional PCR (40%), where later assay is unable to differentiate disease development (lymphoma) and/or infection. The developed dot-ELISA proved to be a specific, rapid and inexpensive technique detecting MDV lymphomas in poultry. Of the note, this new assay could be opted as a valuable diagnostic tool in the resource poor countries andcould further be used to differentiate from other tumor causing viruses in poultry., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Chicken anemia virus (CAV) is one the important pathogen affecting commercial poultry sector globally by causing mortality, production losses, immunosuppression, aggravating co-infections and vaccination failures. Here, we describe the effects of CAV load on hematological, histopathological and immunocytochemical alterations in 1-day old infected chicks. The effects of CAV on cytokine expression profiles and generation of virus specific antibody titer were also studied and compared with viral clearance in various tissues. The results clearly confirmed that peak viral load was achieved mainly in lymphoid tissues between 10 and 20 days post infection (dpi), being highest in the blood (log1010.63 ±0.87/ml) and thymus (log1010.29 ±0.94/g) followed by spleen, liver, bone marrow and bursa. The histopathology and immunoflowcytometric analysis indicated specific degeneration of T lymphoid cells in the thymus, spleen and blood at 15 dpi. While the transcript levels of interleukin (IL)-1, IL-2, IL-12 decreased at all dpi, interferon (IFN)-γ increased (3-15 fold) during early stages of infection and the appearance of virus specific antibodies were found to be strongly associated with virus clearance in all the tissues. Our findings support the immunosuppressive nature of CAV and provide the relation between the virus load in the various body tissues and the immunopathological changes during clinical CAV infections., (Copyright © 2016 Elsevier Ltd. All rights reserved.)