Development of Biologically Active Phytosynthesized Silver Nanoparticles Using Marrubium vulgare L. Extracts: Applications and Cytotoxicity Studies.

Metal nanoparticle phytosynthesis has become, in recent decades, one of the most promising alternatives for the development of nanomaterials using "green chemistry" methods. The present work describes, for the first time in the literature, the phytosynthesis of silver nanoparticles (AgNPs) using extracts obtained by two methods using the aerial parts of Marrubium vulgare L. The extracts (obtained by classical temperature extraction and microwave-assisted extraction) were characterized in terms of total phenolics content and by HPLC analysis, while the phytosynthesis process was confirmed using X-ray diffraction and transmission electron microscopy, the results suggesting that the classical method led to the obtaining of smaller-dimension AgNPs (average diameter under 15 nm by TEM). In terms of biological properties, the study confirmed that AgNPs as well as the M. vulgare crude extracts reduced the viability of human gingival fibroblasts in a concentration- and time-dependent manner, with microwave-assisted extracts having the more pronounced effects. Additionally, the study unveiled that AgNPs transiently increased nitric oxide levels which then decreased over time, thus offering valuable insights into their potential therapeutic use and safety profile.

The Phenomenon of Antiretroviral Drug Resistance in the Context of Human Immunodeficiency Virus Treatment: Dynamic and Ever Evolving Subject Matter.

Human immunodeficiency virus (HIV) is a significant global health issue that affects a substantial number of individuals across the globe, with a total of 39 million individuals living with HIV/AIDS. ART has resulted in a reduction in HIV-related mortality. Nevertheless, the issue of medication resistance is a significant obstacle in the management of HIV/AIDS. The unique genetic composition of HIV enables it to undergo rapid mutations and adapt, leading to the emergence of drug-resistant forms. The development of drug resistance can be attributed to various circumstances, including noncompliance with treatment regimens, insufficient dosage, interactions between drugs, viral mutations, preexposure prophylactics, and transmission from mother to child. It is therefore essential to comprehend the molecular components of HIV and the mechanisms of antiretroviral medications to devise efficacious treatment options for HIV/AIDS.

Application of Common Culinary Herbs for the Development of Bioactive Materials.

Hyssop (Hyssopus officinalis L.) and oregano (Origanum vulgare L.), traditionally used for their antimicrobial properties, can be considered viable candidates for nanotechnology applications, in particular for the phytosynthesis of metal nanoparticles. The present work aims to evaluate the potential application of hyssop and oregano for the phytosynthesis of silver nanoparticles, as well as to evaluate the biological activities of their extracts and obtained nanoparticles (antioxidant potential, as well as cell viability, inflammation level and cytotoxicity in human fibroblasts HFIB-G cell line studies). In order to obtain natural extracts, two extraction methods were applied (classical temperature extraction and microwave-assisted extraction), with the extraction method having a major influence on their composition, as demonstrated by both the total phenolic compounds (significantly higher for the microwave-assisted extraction; the oregano extracts had consistently higher TPC values, compared with the hyssop extracts) and in terms of individual components identified via HPLC. The obtained nanoparticles ware characterized via X-ray diffraction (XRD) and transmission electron microscopy (TEM), with the lowest dimension nanoparticles being recorded for the nanoparticles obtained using the oregano microwave extract (crystallite size 2.94 nm through XRD, average diameter 10 nm via TEM). The extract composition and particle size also influenced the antioxidant properties (over 60% DPPH inhibition being recorded for the NPs obtained using the oregano microwave extract). Cell viability was not affected at the lowest tested concentrations, which can be correlated with the nitric oxide level. Cell membrane integrity was not affected after exposure to classic temperature hyssop extract-NPs, while the other samples led to a significant LDH increase.

Development and Characterization of New Miconazole-Based Microemulsions for Buccal Delivery by Implementing a Full Factorial Design Modeling.

This research aimed to develop miconazole-based microemulsions using oleic acid as a natural lipophilic phase and a stabilizer mixture comprising Tween 20 and PEG 400 to solubilize miconazole as an antifungal agent known for its activity in oral candidiasis and to improve its bioavailability. The formulation and preparation process was combined with a mathematical approach using a 23-full factorial plan. Fluid and gel-like microemulsions were obtained and analyzed considering pH, conductivity, and refractive index, followed by extensive analyses focused on droplet size, zeta potential, rheological behavior, and goniometry. In vitro release tests were performed to assess their biopharmaceutical characteristics. Independent variables coded X1-Oleic acid (%, w/w), X2-Tween 20 (%, w/w), and X3-PEG 400 (%, w/w) were analyzed in relationship with three main outputs like mean droplet size, work of adhesion, and diffusion coefficient by combining statistical tools with response surface methodology. The microemulsion containing miconazole base-2%, oleic acid-5%, Tween 20-40%, PEG 400-20%, and water-33% exhibited a mean droplet size of 119.6 nm, a work of adhesion of 71.98 mN/m, a diffusion coefficient of 2.11·10-5 cm2/s, and together with remarked attributes of two gel-like systems formulated with higher oil concentrations, modeled the final optimization step of microemulsions as potential systems for buccal delivery.

Pyrethrins and Pyrethroids: A Comprehensive Review of Natural Occurring Compounds and Their Synthetic Derivatives.

This comprehensive scientific review provides an in-depth analysis of both the natural compounds, pyrethrins, and their synthetic derivatives, pyrethroids, focusing on their classification, biosynthesis, mechanism of action, general and pharmaceutical uses, as well as their toxicity and environmental impact. Pyrethrins, derived from certain plant species, have long been recognized for their potent insecticidal properties. The review begins by examining the classification of pyrethrins and pyrethroids, elucidating their structural characteristics and unique features within the field of natural and synthetic compounds. The biosynthetic pathways responsible for producing pyrethrins in plants are discussed, highlighting the enzymatic reactions and genetic regulation involved. In addition, the synthesis of pyrethroid derivatives is explored, including both natural and synthetic sources and potential optimization strategies. Understanding the mechanisms of action by which pyrethrins and pyrethroids exert their insecticidal effects is a crucial aspect of this review. Complex interactions with the nervous systems of target organisms are examined, providing insights into their selective toxicity and modes of action. In addition, the various applications of these compounds are explored, from their use in agriculture for pest control to their incorporation into household insecticides and potential pharmaceutical applications. The review also critically evaluates the potential toxicity of pyrethrins and pyrethroids to human health. By consolidating current knowledge and research findings, this review provides a comprehensive understanding of the properties and applications of pyrethrins and pyrethroids, highlighting their benefits and risks, and the importance of responsible and sustainable use in various areas.

Chitosan Biomaterials: Advances and Challenges.

The purpose of this Special Issue was to review research focusing on the development of formulations based on chitosan or its derivatives together with other molecules, producing biomaterials with improved physicochemical properties and effects [...].

Molecular Mapping of Antifungal Mechanisms Accessing Biomaterials and New Agents to Target Oral Candidiasis.

Oral candidiasis has a high rate of development, especially in immunocompromised patients. Immunosuppressive and cytotoxic therapies in hospitalized HIV and cancer patients are known to induce the poor management of adverse reactions, where local and systemic candidiasis become highly resistant to conventional antifungal therapy. The development of oral candidiasis is triggered by several mechanisms that determine oral epithelium imbalances, resulting in poor local defense and a delayed immune system response. As a result, pathogenic fungi colonies disseminate and form resistant biofilms, promoting serious challenges in initiating a proper therapeutic protocol. Hence, this study of the literature aimed to discuss possibilities and new trends through antifungal therapy for buccal drug administration. A large number of studies explored the antifungal activity of new agents or synergic components that may enhance the effect of classic drugs. It was of significant interest to find connections between smart biomaterials and their activity, to find molecular responses and mechanisms that can conquer the multidrug resistance of fungi strains, and to transpose them into a molecular map. Overall, attention is focused on the nanocolloids domain, nanoparticles, nanocomposite synthesis, and the design of polymeric platforms to satisfy sustained antifungal activity and high biocompatibility with the oral mucosa.

Food Habits and Lifestyle of Romanians in the Context of the COVID-19 Pandemic.

The pandemic caused by the SARS-CoV-2 virus has produced significant changes in socio-cultural life, diet, and interpersonal relationships across the world's population. The present study aims to identify changes in lifestyle and diet among the Romanian population one year after the onset of the COVID-19 pandemic. An online questionnaire with 58 items (addressing the following aspects: socio-demographic and anthropometric data, current eating habits, and lifestyle changes) was distributed using institutional mailing lists and social media. A total number of 2040 respondents participated in the study, of whom 1464 were women, and 576 men. Among the respondents, 1598 came from urban areas and 442 from rural areas. The processing of the collected data showed significant changes in the behavior of the respondents caused by the pandemic situation with psycho-affective changes in some cases. The number of people who had anxiety, depression and nervousness increased by up to 20%. The majority of respondents (over 57%) were up to 30 years old, either students (43.50%) or employees going to workplaces (33.20%). Analyzing eating habits, we found that diet modification was needed to increase the daily consumption of fruits, vegetables, fish, and seafood. Regarding weight status during the pandemic, we noticed that 34.7% of normal-weight respondents said that they gained weight while 49.7% of overweight people and 52.5% of obese people said that they gained weight (p < 0.0001). Regarding psycho-emotional behavior, 11.81% of the surveyed women stated that they frequently had depressive states during the pandemic period and 11.63% of the men stated that they frequently presented depressive states during the pandemic (p = 0.005).

Bacterial Cellulose-A Remarkable Polymer as a Source for Biomaterials Tailoring.

Nowadays, the development of new eco-friendly and biocompatible materials using 'green' technologies represents a significant challenge for the biomedical and pharmaceutical fields to reduce the destructive actions of scientific research on the human body and the environment. Thus, bacterial cellulose (BC) has a central place among these novel tailored biomaterials. BC is a non-pathogenic bacteria-produced polysaccharide with a 3D nanofibrous structure, chemically identical to plant cellulose, but exhibiting greater purity and crystallinity. Bacterial cellulose possesses excellent physicochemical and mechanical properties, adequate capacity to absorb a large quantity of water, non-toxicity, chemical inertness, biocompatibility, biodegradability, proper capacity to form films and to stabilize emulsions, high porosity, and a large surface area. Due to its suitable characteristics, this ecological material can combine with multiple polymers and diverse bioactive agents to develop new materials and composites. Bacterial cellulose alone, and with its mixtures, exhibits numerous applications, including in the food and electronic industries and in the biotechnological and biomedical areas (such as in wound dressing, tissue engineering, dental implants, drug delivery systems, and cell culture). This review presents an overview of the main properties and uses of bacterial cellulose and the latest promising future applications, such as in biological diagnosis, biosensors, personalized regenerative medicine, and nerve and ocular tissue engineering.

Insights from a Box-Behnken Optimization Study of Microemulsions with Salicylic Acid for Acne Therapy.

The present study brings to attention a method to develop salicylic acid-based oil in water (O/W) microemulsions using a tensioactive system based on Tween 80, lecithin, and propylene glycol (PG), enriched with a vegetable oat oil phase and hyaluronic acid. The systems were physically characterized and the Quality by design approach was applied to optimize the attributes of microemulsions using Box-Behnken modeling, combined with response surface methodology. For this purpose, a 33 fractional factorial design was selected. The effect of independent variables namely X1: Tween 80/PG (%), X2: Lecithin (%), X3: Oil phase (%) was analyzed considering their impact upon the internal structure and evaluated parameters chosen as dependent factors: viscosity, mean droplet size, and work of adhesion. A high viscosity, a low droplet size, an adequate wettability-with a reduced mechanical work-and clarity were considered as desirable for the optimal systems. It was found that the optimal microemulsion which complied with the established conditions was based on: Tween 80/PG 40%, lecithin 0.3%, oat oil 2%, salicylic acid 0.5%, hyaluronic acid 1%, and water 56.2%. The response surface methodology was considered an appropriate tool to explain the impact of formulation factors on the physical properties of microemulsions, offering a complex pattern in the assessment of stability and quality attributes for the optimized formulation.

An Overview Regarding Microbial Aspects of Production and Applications of Bacterial Cellulose.

Cellulose is the most widely used biopolymer, accounting for about 1.5 trillion tons of annual production on Earth. Bacterial cellulose (BC) is a form produced by different species of bacteria, representing a purified form of cellulose. The structure of bacterial cellulose consists of glucose monomers that give it excellent properties for different medical applications (unique nanostructure, high water holding capacity, high degree of polymerization, high mechanical strength, and high crystallinity). These properties differ depending on the cellulose-producing bacteria. The most discussed topic is related to the use of bacterial cellulose as a versatile biopolymer for wound dressing applications. The aim of this review is to present the microbial aspects of BC production and potential applications in development of value-added products, especially for biomedical applications.

An Overview of Cellulose Derivatives-Based Dressings for Wound-Healing Management.

Presently, notwithstanding the progress regarding wound-healing management, the treatment of the majority of skin lesions still represents a serious challenge for biomedical and pharmaceutical industries. Thus, the attention of the researchers has turned to the development of novel materials based on cellulose derivatives. Cellulose derivatives are semi-synthetic biopolymers, which exhibit high solubility in water and represent an advantageous alternative to water-insoluble cellulose. These biopolymers possess excellent properties, such as biocompatibility, biodegradability, sustainability, non-toxicity, non-immunogenicity, thermo-gelling behavior, mechanical strength, abundance, low costs, antibacterial effect, and high hydrophilicity. They have an efficient ability to absorb and retain a large quantity of wound exudates in the interstitial sites of their networks and can maintain optimal local moisture. Cellulose derivatives also represent a proper scaffold to incorporate various bioactive agents with beneficial therapeutic effects on skin tissue restoration. Due to these suitable and versatile characteristics, cellulose derivatives are attractive and captivating materials for wound-healing applications. This review presents an extensive overview of recent research regarding promising cellulose derivatives-based materials for the development of multiple biomedical and pharmaceutical applications, such as wound dressings, drug delivery devices, and tissue engineering.

Foray into Concepts of Design and Evaluation of Microemulsions as a Modern Approach for Topical Applications in Acne Pathology.

With a fascinating complexity, governed by multiple physiological processes, the skin is considered a mantle with protective functions which during lifetime are frequently impaired, triggering dermatologic disorders. As one of the most prevalent dermatologic conditions worldwide, characterized by a complex pathogenesis and a high recurrence, acne can affect the patient's quality of life. Smart topical vehicles represent a good option in the treatment of a versatile skin condition. By surpassing the stratum corneum known for diffusional resistance, a superior topical bioavailability can be obtained at the affected place. In this direction, the literature study presents microemulsions as a part of a condensed group of modern formulations. Microemulsions are appreciated for their superior profile in matters of drug delivery, especially for challenging substances with hydrophilic or lipophilic structures. Formulated as transparent and thermodynamically stable systems, using simplified methods of preparation, microemulsions have a simple and clear appearance. Their unique structures can be explained as a function of the formulation parameters which were found to be the mainstay of a targeted therapy.

Heavy metal and pesticide levels in dairy products: Evaluation of human health risk.

Cattle milk's health benefits can be compromised by the presence of contaminants. The levels of cadmium, copper, lead and zinc, and residues of dichlorodiphenyldichloroethylene (DDE), dichlorodiphenyldichloroethane (DDD), dichlorodiphenyltrichloroethane (DDT) were determined in soil, milk and cheese samples collected from cow farms from 3 Romanian areas with industrial and agriculture tradition. A new methodology was applied for the determination of the corrected estimated daily intake (cEDI) corresponding to the aggregate dietary exposure. For the risk assessment, we calculated the source hazard quotient (HQs) for each contaminant and the adversity specific hazard index (HIA). Cadmium, copper, lead and zinc, and the sum of DDT levels in soil samples were below maximum residue levels (MRLs). The MRLs of lead and DDD were exceeded in milk and cheese samples from all the 3 areas. The MRLs of copper and zinc were exceeded in cheese samples from area 2 and 3. HQs >10 for lead indicates increased risk, while HQ > 1 for copper and sum of DDT indicates moderate risk for both milk and cheese. By calculating the HIA, we identified a moderate and increase risk for nephrotoxicity, hepatotoxicity, hematotoxicity, cardiotoxicity and reproduction toxicity after consumption of the dairy products from the 3 areas.

Ciprofloxacin-Collagen-Based Materials with Potential Oral Surgical Applications.

We report in this paper the synthesis and characterization of a new collagen-based material. This material was obtained in a spongy form and was functionalized with an antibiotic, ciprofloxacin. The targeted applications of these kind of materials concern the post-operative prophylaxis. The in vitro tests (antimicrobial, cytotoxic, drug release) showed that sponges with a concentration of 0.75 g of ciprofloxacin per gram of collagen could be beneficial for the desired applications.

New Opportunity to Formulate Intranasal Vaccines and Drug Delivery Systems Based on Chitosan.

In an attempt to develop drug delivery systems that bypass the blood-brain barrier (BBB) and prevent liver and intestinal degradation, it was concluded that nasal medication meets these criteria and can be used for drugs that have these drawbacks. The aim of this review is to present the influence of the properties of chitosan and its derivatives (mucoadhesion, permeability enhancement, surface tension, and zeta potential) on the development of suitable nasal drug delivery systems and on the nasal bioavailability of various active pharmaceutical ingredients. Interactions between chitosan and proteins, lipids, antigens, and other molecules lead to complexes that have their own applications or to changing characteristics of the substances involved in the bond (conformational changes, increased stability or solubility, etc.). Chitosan and its derivatives have their own actions (antibacterial, antifungal, immunostimulant, antioxidant, etc.) and can be used as such or in combination with other molecules from the same class to achieve a synergistic effect. The applicability of the properties is set out in the second part of the paper, where nasal formulations based on chitosan are described (vaccines, hydrogels, nanoparticles, nanostructured lipid carriers (NLC), powders, emulsions, etc.).

Selection of Optimal Operating Conditions for Extraction of Myrtus Communis L. Essential Oil by the Steam Distillation Method.

Myrtus communis L. is one of the important aromatic and medicinal species from the Mediterranean area. It is used in various fields such as culinary, cosmetic, pharmaceutical, therapeutic, and industrial applications. Thus, a Box-Wilson experimental plan was used in this study to select the optimal operating conditions in order to obtain high volumes of essential oils. The factorial design method was applied to evaluate at an industrial scale the effect of major process variables on the essential oil extraction from Myrtus communis L. herbs by the steam distillation method. The input variables considered as significant operating conditions were: X1-boiler occupancy rate (boilers were filled to 50%, 75%, and 100%), X2-distillation duration (distillation was continued 60, 75, and 90 min), and X3-particle size (herbs were cut in sizes of 10, 20, and 30 mm via guillotine). The dependent variable selected, coded as Y, was the essential oil volume obtained (mL). The steps of the classical statistical experimental design technique were complemented with the Taguchi method to improve the extraction efficacy of essential oil from Myrtus communis L., and the optimum parameter conditions were selected: boiler occupancy rate 100%, distillation duration 75 min, and particle size 20 mm. Following the optimum parameters, the GC-MS assay revealed for the Myrtus communis L. essential oil two predominant components, α-pinene-33.14% and eucalyptol-55.09%.

The application of essential oils as a next-generation of pesticides: recent developments and future perspectives.

The overuse of synthetic pesticide, a consequence of the rush to increase crop production, led to tremendous adverse effects, as they constitute a major pollutant for both soils and water, with a high toxicity towards humans and animals and, at the same time, led to development of pest resistance. In the last period, the researches were directed towards finding new solutions with a lower toxicity, less damaging behaviour towards the environment, and a better specificity of action. In this context, the use of essential oils, a complex and unique mixture of compounds, can be considered for the next-generation pesticides. This review aims to present the main applications of the essential oils as insecticides, herbicides, acaricides, and nematicides, as they emerged from the scientific literature published in the last 5 years (2015 to present). From the identified articles within the time period, only those dealing with essential oils obtained by the authors (not commercially available) were selected to be inserted in the review, characterized using established analytical techniques and employed for the envisaged applications. The review is concluded with a chapter containing the main conclusions of the literature study and the future perspectives, regarding the application of essential oils as next-generation pesticides.

Leonurus cardiaca L. as a Source of Bioactive Compounds: An Update of the European Medicines Agency Assessment Report (2010).

Leonurus cardiaca L. (motherwort) is a perennial herb, native to Asia and southeastern Europe, with widespread global occurrence in present days. The plant was historically used as cardiotonic and for treating gynaecological afflictions (such as amenorrhea, dysmenorrhea, menopausal anxiety, or postpartum depression). Although its use in oriental and occidental medicine is relatively well documented, the recent progress registered raises the need for an update of the Medicines Agency assessment report on Leonurus cardiaca L., herba (2010). The current study presents the progress made within the 2010-2018 timeframe regarding the potential applications and scientific evidences supporting the traditional use of motherwort, in the same time suggesting future research opportunities.

Predictive power of the Triticum root elongation test for the assessment of novel anti­proliferative therapies.

The use of alternative techniques to reduce the number of animals used in anticancer research is an issue of current interest. The aim of this study was to validate the use of a simple and efficient alternative tool for the assessment of the potential of novel anti­proliferative agents. A set of 20 compounds with various mechanisms were tested in the Triticum aestivum root elongation assay, using aminophylline as negative control. Hierarchical cluster analyses were performed using the furthest neighbor method based on Euclidean distance measure, and the compounds were statistically analyzed in reference to their anti­proliferative pattern registered in the NCI60 human tumor cell line anticancer drug screen. A correlation between the Triticum test results and the NCI60 anti­proliferative profile was made for a number of human cells that we defined as the Triticum cell panel. Linear equations were computed that can be used to transform the inhibitory effect measured in any future Triticum assay in order to predict the effect on particular human cells. Of the tested anti­proliferative agents, methotrexate, colchicine, cantharidin, cisplatin and verapamil produced a growth inhibition over 50%. On the whole, the findings of this study suggest that the Triticum test can be used to detect several types of anti­proliferative mechanisms, particularly those targeting tubulin, rendering it a useful tool with which to identify novel mitotic spindle inhibitors.