The Challenging Triad: Microbiota, Immune System and Anticancer Drugs

Gut microbiota is essential for the development of the intestinal immune system, protecting the host against pathogens and harmful inflammatory processes. Germ‐free animals have smaller Peyer\u27s patches, fewer immune cells and impaired immunoglobulin A (IgA) secretion, fewer intraepithelial lymphocytes, as well as compromised production of antimicrobial peptides. Mucositis (mucosal barrier injury) is a major oncological problem caused by chemotherapeutic agents. Intestinal mucositis translates into a broad spectra of clinical symptoms (diarrhea, vomiting) and can be worsened by neutropenia and antibiotics. Since IECs do not regulate intestinal homeostasis by themselves, but require symbiotic coordination with commensal bacteria and local gut leukocytic cells, the role of intestinal microbiota in the development and severity of mucositis induced by chemotherapeutic products became an issue. The present chapter reviews the interplay between microbiota, immune system, and anticancer therapy. The published researches in this field showed that microbiota has immunomodulatory effect on the anticancer immune response, both in the presence and in the absence of chemotherapy. Animal and human studies evoked that the anticancer response depends on microbiota variability

Melatonin: A Silent Regulator of the Glucose Homeostasis

In the human organism, the circadian regulation of carbohydrates metabolism is essential for the glucose homeostasis and energy balance. Unbalances in glucose and insulin tissue and blood levels have been linked to a variety of metabolic disorders such as obesity, metabolic syndrome, cardiovascular diseases and type 2 diabetes. Melatonin, the pineal hormone, is the key mediator molecule for the integration between the cyclic environment and the circadian distribution of physiological and behavioral processes and for the optimization of energy balance and body weight regulation, events that are crucial for a healthy organism. This chapter reviews the interplay between melatonin modulatory physiological effects, glucose homeostasis and metabolic balance, from the endocrinology perspective. The tremendous effect of melatonin in the regulation of metabolic processes is observed from the chronobiology perspective, considering melatonin as a major synchronizer of the circadian internal order of the physiological processes involved in energy metabolism

Liquid Marbles: From Industrial to Medical Applications

Liquid marbles are versatile structures demonstrating a pseudo-Leidenfrost wetting regime formed by encapsulating microscale volumes of liquid in a particle shell. The liquid core is completely separated from the exterior through air pockets. The external phase consists of hydrophobic particles, in most cases, or hydrophilic ones distributed as aggregates. Their interesting features arise from the double solid-fluid character. Thus, these interesting formations, also known as “dry waters”, have gained attention in surface science. This review paper summarizes a series of proposed formulations, fabrication techniques and properties, in correlation with already discovered and emerging applications. A short general review of the surface properties of powders (contact angle, superficial tension) is proposed, followed by a presentation of liquid marbles’ properties (superficial characteristics, elasticity, self-propulsion etc.). Finally, applications of liquid marbles are discussed, mainly as helpful and yet to be exploited structures in the pharmaceutical and medical field. Innovative pharmaceutical forms (Pickering emulsions) are also means of use taken into account as applications which need further investigation

Quality Control of Different Types of Honey and Propolis Collected from Romanian Accredited Beekeepers and Consumer’s Risk Assessment

Honey is a natural product recognized and appreciated for its nutritional value and therapeutic potential. However, the quality of bee honey is essential because various contaminants can seriously affect consumers’ health. In the experimental part of the work, we analyzed different types of honey (linden, black locust, rapeseed and multifloral honey) and propolis, which were collected from Romanian accredited beekeepers who placed beehives in two areas characterized by different industrial activity: area 1 (A1) is an area with intense industrial activity, with other industries existing nearby, including a refinery, while area 2 (A2) is entirely devoid of industrial activity, but with moderate agricultural activity. A total of 144 samples were collected, twelve samples for each variety of honey, propolis and soil, corresponding to each area analyzed. In addition, seven heavy metals and three pesticides were tested for in the samples collected. Finally, the correlation between the degree of contamination with soil pollutants and the contamination of the bee products harvested from the analyzed areas was studied. Cadmium, lead, copper, zinc and the sum of DDT metabolites exceeded the maximum allowable levels in honey samples, with differences between different types of honey

Development, Optimization and In Vitro/In Vivo Characterization of Collagen-Dextran Spongious Wound Dressings Loaded with Flufenamic Acid

The aim of this study was the development and optimization of some topical collagen-dextran sponges with flufenamic acid, designed to be potential dressings for burn wounds healing. The sponges were obtained by lyophilization of hydrogels based on type I fibrillar collagen gel extracted from calf hide, dextran and flufenamic acid, crosslinked and un-crosslinked, and designed according to a 3-factor, 3-level Box-Behnken experimental design. The sponges showed good fluid uptake ability quantified by a high swelling ratio. The flufenamic acid release profiles from sponges presented two stages—burst effect resulting in a rapid inflammation reduction, and gradual delivery ensuring the anti-inflammatory effect over a longer burn healing period. The resistance to enzymatic degradation was monitored through a weight loss parameter. The optimization of the sponge formulations was performed based on an experimental design technique combined with response surface methodology, followed by the Taguchi approach to select those formulations that are the least affected by the noise factors. The treatment of experimentally induced burns on animals with selected sponges accelerated the wound healing process and promoted a faster regeneration of the affected epithelial tissues compared to the control group. The results generated by the complex sponge characterization indicate that these formulations could be successfully used for burn dressing applications

Quality Control of Different Types of Honey and Propolis Collected from Romanian Accredited Beekeepers and Consumer’s Risk Assessment

Honey is a natural product recognized and appreciated for its nutritional value and therapeutic potential. However, the quality of bee honey is essential because various contaminants can seriously affect consumers’ health. In the experimental part of the work, we analyzed different types of honey (linden, black locust, rapeseed and multifloral honey) and propolis, which were collected from Romanian accredited beekeepers who placed beehives in two areas characterized by different industrial activity: area 1 (A1) is an area with intense industrial activity, with other industries existing nearby, including a refinery, while area 2 (A2) is entirely devoid of industrial activity, but with moderate agricultural activity. A total of 144 samples were collected, twelve samples for each variety of honey, propolis and soil, corresponding to each area analyzed. In addition, seven heavy metals and three pesticides were tested for in the samples collected. Finally, the correlation between the degree of contamination with soil pollutants and the contamination of the bee products harvested from the analyzed areas was studied. Cadmium, lead, copper, zinc and the sum of DDT metabolites exceeded the maximum allowable levels in honey samples, with differences between different types of honey

Chitosan-Based In Situ Gels for Ocular Delivery of Therapeutics: A State-of-the-Art Review

Ocular in situ gels are a promising alternative to overcome drawbacks of conventional eye drops because they associate the advantages of solutions such as accuracy and reproducibility of dosing, or ease of administration with prolonged contact time of ointments. Chitosan is a natural polymer suitable for use in ophthalmic formulations due to its biocompatibility, biodegradability, mucoadhesive character, antibacterial and antifungal properties, permeation enhancement and corneal wound healing effects. The combination of chitosan, pH-sensitive polymer, with other stimuli-responsive polymers leads to increased mechanical strength of formulations and an improved therapeutic effect due to prolonged ocular contact time. This review describes in situ gelling systems resulting from the association of chitosan with various stimuli-responsive polymers with emphasis on the mechanism of gel formation and application in ophthalmology. It also comprises the main techniques for evaluation of chitosan in situ gels, along with requirements of safety and ocular tolerability

COVID-19-Current Therapeutical Approaches and Future Perspectives

The ongoing pandemic of coronavirus disease (COVID-19) stimulated an unprecedented international collaborative effort for rapid diagnosis, epidemiologic surveillance, clinical management, prevention, and treatment. This review focuses on the current and new therapeutical approaches, summarizing the viral structure and life cycle, with an emphasis on the specific steps that can be interfered by antivirals: (a) inhibition of viral entry with anti-spike monoclonal antibodies; (b) inhibition of the RNA genome replication with nucleosidic analogs blocking the viral RNA polymerase; (c) inhibition of the main viral protease (Mpro), which directs the formation of the nonstructural proteins. An overview of the immunomodulatory drugs currently used for severe COVID-19 treatment and future therapeutical options are also discussed

Collagen-Polyvinyl Alcohol-Indomethacin Biohybrid Matrices as Wound Dressings

The aim of this study is to design, develop and evaluate new biohybrid sponges based on polymers (collagen and polyvinyl alcohol) with and without indomethacin as anti-inflammatory drug model to be used for tissue regeneration in wound healing. Type I fibrillar collagen in the form of a gel and different concentrations of polyvinyl alcohol were mixed together to prepare composite gels. Both control samples, without indomethacin and with indomethacin, were obtained. All samples were crosslinked with glutaraldehyde. By freeze-drying of hydrogels, the spongious forms (matrices) were obtained. The matrices were characterized by FT-IR spectroscopy, scanning electron microscopy (SEM), water absorption, enzymatic degradation and in vitro indomethacin release. The pharmacological effect of the spongious biohybrid matrices was determined on an experimental model of burns induced to Wistar rats. The SEM images showed a porous structure with interconnected pores. Collagen sponges present a structure with pore sizes between 20 and 200 µm, which became more and more compact with polyvinyl alcohol addition. The FT-IR showed interactions between collagen and polyvinyl alcohol. The enzymatic degradation indicated that the most stable matrix is the one with the ratio 75:25 of collagen:polyvinyl alcohol (ACI75), the other ones being degradable in time. The kinetic data of indomethacin release from matrices were fitted with different kinetic models and highlighted a biphasic release of the drug. Such kinetic profiles are targeted in skin wound healing for which important aspects are impaired inflammation and local pain. The treatment with sponges associated with anti-inflammatory drug had beneficial effects on the healing process in experimentally induced burns compared to the corresponding matrices without indomethacin and the classical treated control group