Insights into enterovirus a-71 antiviral development: from natural sources to synthetic nanoparticles.

Enteroviruses are pathogens responsible for several diseases, being enterovirus A71 (EVA71) the second leading cause of hand, foot, and mouth disease (HFMD), especially in Asia-Pacific countries. HFMD is mostly common in infants and children, with mild symptoms. However, the disease can result in severe nervous system disorders in children as well as in immunosuppressed adults. The virus is highly contagious, and its transmission occurs via fecal-oral, oropharyngeal secretions, and fomites. The EVA71 burdens the healthy systems and economies around the world, however, up to date, there is no antiviral approved to treat infected individuals and the existent vaccines are not available or approved to be used worldwide. In this context, an extensive literature research was conducted to describe and summarize the recent advances in natural and/or synthetic compounds with antiviral activity against EVA71. The summarized data presented here might simply encourage the future studies in EVA71 antiviral development, by encouraging further research encompassing these compounds or even the application of the techniques and technologies to improve or produce new antiviral molecules.

An update on the development of antiviral against Mayaro virus: from molecules to potential viral targets.

Mayaro virus (MAYV), first isolated in 1954 in Trinidad and Tobago islands, is the causative agent of Mayaro fever, a disease characterized by fever, rashes, headaches, myalgia, and arthralgia. The infection can progress to a chronic condition in over 50% of cases, with persistent arthralgia, which can lead to the disability of the infected individuals. MAYV is mainly transmitted through the bite of the female Haemagogus spp. mosquito genus. However, studies demonstrate that Aedes aegypti is also a vector, contributing to the spread of MAYV beyond endemic areas, given the vast geographical distribution of the mosquito. Besides, the similarity of antigenic sites with other Alphavirus complicates the diagnoses of MAYV, contributing to underreporting of the disease. Nowadays, there are no antiviral drugs available to treat infected patients, being the clinical management based on analgesics and non-steroidal anti-inflammatory drugs. In this context, this review aims to summarize compounds that have demonstrated antiviral activity against MAYV in vitro, as well as discuss the potentiality of viral proteins as targets for the development of antiviral drugs against MAYV. Finally, through rationalization of the data presented herein, we wish to encourage further research encompassing these compounds as potential anti-MAYV drug candidates.

Innovative Functional Biomaterials as Therapeutic Wound Dressings for Chronic Diabetic Foot Ulcers.

The imbalance of local and systemic factors in individuals with diabetes mellitus (DM) delays, or even interrupts, the highly complex and dynamic process of wound healing, leading to diabetic foot ulceration (DFU) in 15 to 25% of cases. DFU is the leading cause of non-traumatic amputations worldwide, posing a huge threat to the well-being of individuals with DM and the healthcare system. Moreover, despite all the latest efforts, the efficient management of DFUs still remains a clinical challenge, with limited success rates in treating severe infections. Biomaterial-based wound dressings have emerged as a therapeutic strategy with rising potential to handle the tricky macro and micro wound environments of individuals with DM. Indeed, biomaterials have long been related to unique versatility, biocompatibility, biodegradability, hydrophilicity, and wound healing properties, features that make them ideal candidates for therapeutic applications. Furthermore, biomaterials may be used as a local depot of biomolecules with anti-inflammatory, pro-angiogenic, and antimicrobial properties, further promoting adequate wound healing. Accordingly, this review aims to unravel the multiple functional properties of biomaterials as promising wound dressings for chronic wound healing, and to examine how these are currently being evaluated in research and clinical settings as cutting-edge wound dressings for DFU management.

Approach to anaerobic bio-degradation of natural and synthetic fabrics: Physico-chemical study of the alteration processes.

In this paper, the mesophilic Biochemical Methane Potential of several fabrics was assessed at different Total Solid concentrations (1-4%TS). Physico-chemical techniques were applied to explore the arising structural changes on fibers during the anaerobic digestion process. Additionally, the modified Gompertz model was used to assess and compare the AD performance of the fabrics. In cellulose-based fibers the production of biogas was enhanced thanks to the easy solubilization of acetate, which is generated upon partial breakage of cellulose bonds. The crystallinity of vegetal fibers decreased significantly from day 19. The highest methane yields were attained for silk and wool fabrics at the lowest TS concentrations. Conformational changes in fibroin and keratin were detected. The highest degrees of degradation were observed in solid samples with lower solid concentrations. Accordingly, the maximum methane yields were reported in the reactors operating with lower TS.

Surface-active natural saponins. Properties, safety, and efficacy.

In the future, cleaning products must fulfil the principles of green chemistry while maintaining efficacy against bacteria. This study aims to evaluate the detergent properties, ecotoxicity, and anti-biofilm potential of natural saponins compared to synthetic surfactants. We tested sodium dodecyl sulphate, quillaja saponin, escin, and sapogenin for emulsifying capacity, critical micelle concentration, ecotoxicity to yeast, and antibacterial and anti-biofilm potential against bacteria. The results show that the emulsifying capacities of quillaja saponin and sodium dodecyl sulphate are similar, while the critical micelle concentration for quillaja saponin is much lower . Furthermore, the antibacterial and antibiofilm potentials are much higher for quillaja saponin than for synthetic sodium dodecyl sulphate . Moreover, we have shown that natural saponins are less toxic to the S. cerevisiae than synthetic saponin is. All these facts indicate that quillaja is a suitable candidate to replace synthetic products as it meets the requirements of efficacy and safety.

Effects of malic acid and EDTA on oxidative stress and antioxidant enzymes of okra (Abelmoschus esculentus L.) exposed to cadmium stress.

Environmental stresses, including heavy metal pollution, are increasing at a growing rate and influencing arable lands. Chelators play an essential role in several biochemical pathways in the cells of plants treated with heavy metals. This research evaluated the modifying effect of malic acid (MA) and ethylenediaminetetraacetic acid (EDTA) on the physiological and biochemical parameters of okra plants exposed to Cd stress in which the okra plants were cultivated in hydroponic conditions. At the 4-leaf stage, they were applied with the treatments of cadmium nitrate at three levels (0, 50, and 100 mg/L), EDTA and MA at two levels (0.5 and 1 mM), and Cd + EDTA + MA at different rates for one month. The harvested plants were subjected to the measurement of the physico-biochemical factors. The results revealed that the application of Cd alone reduced leaf area (up to 21.57 %), and dissolved sugars (up to 40.51 % in the shoot and 45.19 % in the root) and increased MDA (up to 66.37 % and 76.43 % in the shoot and root, respectively), H2O2 (up to 67.14 % and 53.28 % in the shoot and root, respectively), proline (up to 52.04 % and 40.93 % in the shoot and root, respectively), and dissolved proteins (up to 14.59 % and 21.90 % in the shoot and root, respectively) contents in both shoots and roots whereas the application of MA and EDTA to the Cd-treated plants increased their leaf area and dissolved sugars and reduced MDA, H2O2, proline, and dissolved proteins content. The antioxidant enzymes, e.g., superoxide dismutase (SOD), catalase (CAT), and ascorbate peroxidase (APX), were significantly higher in the plants treated with MA, EDTA, and Cd, but the application of MA and EDTA to the Cd-treated plants reduced the activity of all these antioxidant enzymes versus the plants only treated with Cd. MA and EDTA are likely to prevent the accumulation of Cd in the cytosol by binding to it and transferring it into vacuoles, thereby mitigating Cd toxicity in the okra plants.

Cellular and Molecular Signatures of Oxidative Stress in Bronchial Epithelial Cell Models Injured by Cigarette Smoke Extract.

Exposure of the airways epithelium to environmental insults, including cigarette smoke, results in increased oxidative stress due to unbalance between oxidants and antioxidants in favor of oxidants. Oxidative stress is a feature of inflammation and promotes the progression of chronic lung diseases, including Chronic Obstructive Pulmonary Disease (COPD). Increased oxidative stress leads to exhaustion of antioxidant defenses, alterations in autophagy/mitophagy and cell survival regulatory mechanisms, thus promoting cell senescence. All these events are amplified by the increase of inflammation driven by oxidative stress. Several models of bronchial epithelial cells are used to study the molecular mechanisms and the cellular functions altered by cigarette smoke extract (CSE) exposure, and to test the efficacy of molecules with antioxidant properties. This review offers a comprehensive synthesis of human in-vitro and ex-vivo studies published from 2011 to 2021 describing the molecular and cellular mechanisms evoked by CSE exposure in bronchial epithelial cells, the most used experimental models and the mechanisms of action of cellular antioxidants systems as well as natural and synthetic antioxidant compounds.

Pharmaceutical, biomedical and ophthalmic applications of biodegradable polymers (BDPs): literature and patent review.

In the last few decades, the interest in biodegradable materials for biomedical applications has increased significantly. Both natural and synthetic biodegradable polymers (BDPs) have been broadly explored for various biomedical applications. These include sutures and wound dressings, screws for bone fracture, scaffolds in tissue engineering, implants, and other carriers for targeted and sustained release drug delivery. Owing to their unique characteristics, including their surface charge variable copolymer block and composition and film-forming properties, BDPs have been widely used as favourable materials for ophthalmic drug delivery. Mucoadhesive BDPs have been used in ophthalmic formulations to prolong drug retention time and improve bioavailability, allowing ophthalmic controlled release systems to design. Furthermore, BDPs-based implants, microneedles, and injectable nano- and micro-particles enabled ocular posterior segment targeting and, most importantly, circumvented the need for removing the delivery systems after application. This review outlines the major advances of BDPs and highlights the latest progress of employing natural and synthetic BDPs for various biomedical applications, emphasising the treatment and management of ophthalmic conditions.

Combining Biocompatible and Biodegradable Scaffolds and Cold Atmospheric Plasma for Chronic Wound Regeneration.

Skin regeneration is a quite complex process. Epidermal differentiation alone takes about 30 days and is highly regulated. Wounds, especially chronic wounds, affect 2% to 3% of the elderly population and comprise a heterogeneous group of diseases. The prevailing reasons to develop skin wounds include venous and/or arterial circulatory disorders, diabetes, or constant pressure to the skin (decubitus). The hallmarks of modern wound treatment include debridement of dead tissue, disinfection, wound dressings that keep the wound moist but still allow air exchange, and compression bandages. Despite all these efforts there is still a huge treatment resistance and wounds will not heal. This calls for new and more efficient treatment options in combination with novel biocompatible skin scaffolds. Cold atmospheric pressure plasma (CAP) is such an innovative addition to the treatment armamentarium. In one CAP application, antimicrobial effects, wound acidification, enhanced microcirculations and cell stimulation can be achieved. It is evident that CAP treatment, in combination with novel bioengineered, biocompatible and biodegradable electrospun scaffolds, has the potential of fostering wound healing by promoting remodeling and epithelialization along such temporarily applied skin replacement scaffolds.

Polymer Scaffolds for Biomedical Applications in Peripheral Nerve Reconstruction.

The nervous system is a significant part of the human body, and peripheral nerve injury caused by trauma can cause various functional disorders. When the broken end defect is large and cannot be repaired by direct suture, small gap sutures of nerve conduits can effectively replace nerve transplantation and avoid the side effect of donor area disorders. There are many choices for nerve conduits, and natural materials and synthetic polymers have their advantages. Among them, the nerve scaffold should meet the requirements of good degradability, biocompatibility, promoting axon growth, supporting axon expansion and regeneration, and higher cell adhesion. Polymer biological scaffolds can change some shortcomings of raw materials by using electrospinning filling technology and surface modification technology to make them more suitable for nerve regeneration. Therefore, polymer scaffolds have a substantial prospect in the field of biomedicine in future. This paper reviews the application of nerve conduits in the field of repairing peripheral nerve injury, and we discuss the latest progress of materials and fabrication techniques of these polymer scaffolds.

Bone Grafts and Substitutes in Dentistry: A Review of Current Trends and Developments.

After tooth loss, bone resorption is irreversible, leaving the area without adequate bone volume for successful implant treatment. Bone grafting is the only solution to reverse dental bone loss and is a well-accepted procedure required in one in every four dental implants. Research and development in materials, design and fabrication technologies have expanded over the years to achieve successful and long-lasting dental implants for tooth substitution. This review will critically present the various dental bone graft and substitute materials that have been used to achieve a successful dental implant. The article also reviews the properties of dental bone grafts and various dental bone substitutes that have been studied or are currently available commercially. The various classifications of bone grafts and substitutes, including natural and synthetic materials, are critically presented, and available commercial products in each category are discussed. Different bone substitute materials, including metals, ceramics, polymers, or their combinations, and their chemical, physical, and biocompatibility properties are explored. Limitations of the available materials are presented, and areas which require further research and development are highlighted. Tissue engineering hybrid constructions with enhanced bone regeneration ability, such as cell-based or growth factor-based bone substitutes, are discussed as an emerging area of development.

Antifungals discovery: an insight into new strategies to combat antifungal resistance.

Undeniably, new antifungal treatments are necessary against pathogenic fungi. Fungal infections have significantly increased in recent decades, being highlighted as important causes of morbidity and mortality, particularly in immunocompromised patients. Five main antifungal classes are used: (i) azoles, (ii) echinocandins, (iii) polyenes, (iv) allylamines and (v) pyrimidine analogues. Moreover, the treatment of mycoses has several limitations, such as undesirable side effects, narrow activity spectrum, a small number of targets and fungal resistance, which are still of major concern in clinical practice. The discovery of new antifungals is mostly achieved by the screening of natural or synthetic/semisynthetic chemical compounds. The most recent discoveries in drug resistance mechanism and their avoidance were explored in a review, focusing on different antifungal targets, as well as new agents or strategies, such as combination therapy, that could improve antifungal therapy. SIGNIFICANCE AND IMPACT OF THE STUDY: The failure to respond to antifungal therapy is complex and is associated with microbiological resistance and increased expression of virulence in fungal pathogens. Thus, this review offers an overview of current challenges in the treatment of fungal infections associated with increased antifungal drug resistance and the formation of biofilms in these opportunistic pathogens. Furthermore, the most recent and potential strategies to combat fungal pathogens are explored here, focusing on new agents as well as innovative approaches, such as combination therapy between antifungal drugs or with natural compounds.

Bioceramics for Osteochondral Tissue Engineering and Regeneration.

Considerable advances in tissue engineering and regeneration have been accomplished over the last decade. Bioceramics have been developed to repair, reconstruct, and substitute diseased parts of the body and to promote tissue healing as an alternative to metallic implants. Applications embrace hip, knee, and ligament repair and replacement, maxillofacial reconstruction and augmentation, spinal fusion, bone filler, and repair of periodontal diseases. Bioceramics are well-known for their superior wear resistance, high stiffness, resistance to oxidation, and low coefficient of friction. These specially designed biomaterials are grouped in natural bioceramics (e.g., coral-derived apatites), and synthetic bioceramics, namely bioinert ceramics (e.g., alumina and zirconia), bioactive glasses and glass ceramics, and bioresorbable calcium phosphates-based materials. Physicochemical, mechanical, and biological properties, as well as bioceramics applications in diverse fields of tissue engineering are presented herein. Ongoing clinical trials using bioceramics in osteochondral tissue are also considered. Based on the stringent requirements for clinical applications, prospects for the development of advanced functional bioceramics for tissue engineering are highlighted for the future.

Theoretical and Kinetic Tools for Selecting Effective Antioxidants: Application to the Protection of Omega-3 Oils with Natural and Synthetic Phenols.

Radical-scavenging antioxidants play crucial roles in the protection of unsaturated oils against autoxidation and, especially, edible oils rich in omega-3 because of their high sensitivity to oxygen. Two complementary tools are employed to select, among a large set of natural and synthetic phenols, the most promising antioxidants. On the one hand, density functional theory (DFT) calculations provide bond dissociation enthalpies (BDEs) of 70 natural (i.e., tocopherols, hydroxybenzoic and cinnamic acids, flavonoids, stilbenes, lignans, and coumarins) and synthetic (i.e., 2,6-di-tert-butyl-4-methylphenol (BHT), 3-tert-butyl-4-hydroxyanisol (BHA), and tert-butylhydroquinone (TBHQ)) phenols. These BDEs are discussed on the basis of structure-activity relationships with regard to their potential antioxidant activities. On the other hand, the kinetic rate constants and number of hydrogen atoms released per phenol molecule are measured by monitoring the reaction of phenols with 2,2-diphenyl-1-picrylhydrazyl (DPPH(•)) radical. The comparison of the results obtained with these two complementary methods allows highlighting the most promising antioxidants. Finally, the antioxidant effectiveness of the best candidates is assessed by following the absorption of oxygen by methyl esters of linseed oil containing 0.5 mmol L(-1) of antioxidant and warmed at 90 °C under oxygen atmosphere. Under these conditions, some natural phenols namely epigallocatechin gallate, myricetin, rosmarinic and carnosic acids were found to be more effective antioxidants than α-tocopherol.

Are pleural plaques an appropriate endpoint for risk analyses?

This review summarizes the literature on the relation between the development of pleural plaques and non-malignant and malignant disease in cohorts exposed to asbestos and other fibers. The available evidence indicates that, absent any other pleural disease, the presence of pleural plaques does not result in respiratory symptoms or clinically significant impacts on lung function. For certain types of asbestos, the development of pleural plaques is statistically correlated with malignant disease, but the evidence is consistent with the hypothesis that pleural plaques without other pleural disease are a marker of exposure, rather than an independent risk factor. Pleural plaques have also developed in cohorts exposed to other fibers that have not proven to be carcinogenic. Risk analyses should be based on the avoidance of known adverse conditions, rather than pleural plaques per se.

Incorporation of natural and synthetic polymers into honey hydrogel for wound healing: A review.

Background and Aims: The difficulty in treating chronic wounds due to the prolonged inflammation stage has affected a staggering 6.5 million people, accompanied by 25 billion USD annually in the United States alone. A 1.9% rise in chronic wound prevalence among Medicare beneficiaries was reported from 2014 to 2019. Besides, the global wound care market values were anticipated to increase from USD 20.18 billion in 2022 to USD 30.52 billion in 2030, suggesting an expected rise in chronic wounds financial burdens. The lack of feasibility in using traditional dry wound dressings sparks hydrogel development as an alternative approach to tackling chronic wounds. Since ancient times, honey has been used to treat wounds, including burns, and ongoing studies have also demonstrated its wound-healing capabilities on cellular and animal models. However, the fluidity and low mechanical strength in honey hydrogel necessitate the incorporation of other polymers. Therefore, this review aims to unravel the characteristics and feasibility of natural (chitosan and gelatin) and synthetic (polyvinyl alcohol and polyethylene glycol) polymers to be incorporated in the honey hydrogel. Methods: Relevant articles were identified from databases (PubMed, Google Scholar, and Science Direct) using keywords related to honey, hydrogel, and polymers. Relevant data from selected studies were synthesized narratively and reported following a structured narrative format. Results: The importance of honey's roles and mechanisms of action in wound dressings were discussed. Notable studies concerning honey hydrogels with diverse polymers were also included in this article to provide a better perspective on fabricating customized hydrogel wound dressings for various types of wounds in the future. Conclusion: Honey's incapability to stand alone in hydrogel requires the incorporation of natural and synthetic polymers into the hydrogel. With this review, it is hoped that the fabrication and commercialization of the desired honey composite hydrogel for wound treatment could be brought forth.

Efficacy of zeolites in radon adsorption: state of the art and development of an optimized approach.

Radon is a radioactive noble gas omnipresent in the environment, being part of the 238U and 232Th decay chains present in the Earth's crust. The gas can easily leak through the ground but also be present in natural construction materials and migrate into indoor places where it can be a carcinogen when inhaled. Studying the content and removal of indoor radon is crucial for the evaluation and mitigation of its radiological risks to public health. For more than 100 years, the removal by adsorption of the radon has been performed on activated charcoal. There is little progress in the field of radon adsorption at ambient conditions; the main progress is in the use of zeolite materials, having well-defined three-dimensional porous structures and radiation resistance. This study concerns a report on the state of the art of the application of zeolites in radon adsorption. Furthermore, an optimized approach for measuring the radon content in indoor environments and, consequently, its removal has been proposed. Adsorption systems based on zeolites have the potential to replace activated charcoal as a material of choice, allowing to facilitate the development of simple and compact radon adsorption systems.

Potential Chemopreventive Effects of Dietary Combination of Phytochemicals against Cancer Development.

Cancer remains a major cause of cancer-related death worldwide. Over 70% of epithelial malignancies are sporadic and are related to lifestyle. Epidemiological studies suggest an inverse correlation between cancer incidence and fruit and vegetable intake. Numerous preclinical studies using in vitro (cell lines) and in vivo animal models of oncogenesis have reported the chemopreventive effects of dietary phytochemical agents through alterations in different biomarkers and signaling pathways. However, there is contrasting evidence from preclinical studies and clinical trials. To date, the most studied compounds include curcumin, resveratrol, isoflavones, green tea extract (epigallocatechin gallate), black raspberry powder (anthocyanins and ellagitannins), bilberry extract (anthocyanins), ginger extract (gingerol derivatives), and pomegranate extract (ellagitannins and ellagic acid). Overall, the clinical evidence of the preventive effects of dietary phytochemicals against cancer development is still weak, and the amount of these phytochemicals needed to exert chemopreventive effects largely exceeds the common dietary doses. Therefore, we propose a combination treatment of natural compounds that are used clinically for another purpose in order to obtain excess inhibitory efficacy via low-dose administration and discuss the possible reasons behind the gap between preclinical research and clinical trials.

Are Natural Compounds a Promising Alternative to Synthetic Cross-Linking Agents in the Preparation of Hydrogels?

The main aim of this review is to assess the potential use of natural cross-linking agents, such as genipin, citric acid, tannic acid, epigallocatechin gallate, and vanillin in preparing chemically cross-linked hydrogels for the biomedical, pharmaceutical, and cosmetic industries. Chemical cross-linking is one of the most important methods that is commonly used to form mechanically strong hydrogels based on biopolymers, such as alginates, chitosan, hyaluronic acid, collagen, gelatin, and fibroin. Moreover, the properties of natural cross-linking agents and their advantages and disadvantages are compared relative to their commonly known synthetic cross-linking counterparts. Nowadays, advanced technologies can facilitate the acquisition of high-purity biomaterials from unreacted components with no additional purification steps. However, while planning and designing a chemical process, energy and water consumption should be limited in order to reduce the risks associated with global warming. However, many synthetic cross-linking agents, such as N,N'-methylenebisacrylamide, ethylene glycol dimethacrylate, poly (ethylene glycol) diacrylates, epichlorohydrin, and glutaraldehyde, are harmful to both humans and the environment. One solution to this problem could be the use of bio-cross-linking agents obtained from natural resources, which would eliminate their toxic effects and ensure the safety for humans and the environment.

Bile Acid Sequestrants Based on Natural and Synthetic Gels.

Bile acid sequestrants (BASs) are non-systemic therapeutic agents used for the management of hypercholesterolemia. They are generally safe and not associated with serious systemic adverse effects. Usually, BASs are cationic polymeric gels that have the ability to bind bile salts in the small intestine and eliminate them by excretion of the non-absorbable polymer-bile salt complex. This review gives a general presentation of bile acids and the characteristics and mechanisms of action of BASs. The chemical structures and methods of synthesis are shown for commercial BASs of first- (cholestyramine, colextran, and colestipol) and second-generation (colesevelam and colestilan) and potential BASs. The latter are based on either synthetic polymers such as poly((meth)acrylates/acrylamides), poly(alkylamines), poly(allylamines) and vinyl benzyl amino polymers or biopolymers, such as cellulose, dextran, pullulan, methylan, and poly(cyclodextrins). A separate section is dedicated to molecular imprinting polymers (MIPs) because of their great selectivity and affinity for the template molecules used in the imprinting technique. Focus is given to the understanding of the relationships between the chemical structure of these cross-linked polymers and their potential to bind bile salts. The synthetic pathways used in obtaining BASs and their in vitro and in vivo hypolipidemic activities are also introduced.