Antibody-Drug Conjugates-Evolution and Perspectives.

Antineoplastic therapy is one of the main research themes of this century. Modern approaches have been implemented to target and heighten the effect of cytostatic drugs on tumors and diminish their general/unspecific toxicity. In this context, antibody-drug conjugates (ADCs) represent a promising and successful strategy. The aim of this review was to assess different aspects regarding ADCs. They were presented from a chemical and a pharmacological perspective and aspects like structure, conjugation and development particularities alongside effects, clinical trials, safety issues and perspectives and challenges for future use of these drugs were discussed. Representative examples include but are not limited to the following main structural components of ADCs: monoclonal antibodies (trastuzumab, brentuximab), linkers (pH-sensitive, reduction-sensitive, peptide-based, phosphate-based, and others), and payloads (doxorubicin, emtansine, ravtansine, calicheamicin). Regarding pharmacotherapy success, the high effectiveness expectation associated with ADC treatment is supported by the large number of ongoing clinical trials. Major aspects such as development strategies are first discussed, advantages and disadvantages, safety and efficacy, offering a retrospective insight on the subject. The second part of the review is prospective, focusing on various plans to overcome the previously identified difficulties.

Geographic Variability of Berry Phytochemicals with Antioxidant and Antimicrobial Properties.

The aim of this study was to determine the variability of several chemical compounds and the antioxidant and antimicrobial activities of eight types of berries harvested from two different geographical regions in the same year. The analyses were performed on bilberry, black currant, gooseberry, red currant, raspberry, sea buckthorn, strawberry and sour cherry, which were handpicked during the summer of 2019, in the same periods when they are typically harvested for consumer purposes. Total anthocyanins content (TAC), total flavonoids content (TFC), total polyphenolic compounds (TPC), determination of the Ferric-Reducing Antioxidant Power (FRAP), determination of the DPPH free radical scavenging assay (RSA), determination of nine phenolic compounds by HPLC-UV assay and antimicrobial activity were determined for undiluted hydroalcoholic extracts of all the studied berries. The results showed that the berries from Romania were richer in antioxidant compounds than the berries from Russia. The TPC content varied between 4.13-22.2 mg GAE/g d.w., TFC between 3.33-8.87 mg QE/g d.w. and TAC between 0.13-3.94 mg/g d.w. The highest variability was determined for TPC. Regarding the antioxidant activity assessed by FRAP assay, values were between 6.02-57.23 µmols TE/g d.w. and values for the RSA method between 18.44-83.81%. From the eight types of berries analyzed, bilberries and raspberries had the highest antioxidant activity considering both regions and both determination methods. Not only the type, but also the environmental and cultivation conditions in which the berries grow, can lead to variations in their chemical composition. The extracted polyphenolic compounds from the studied berries showed antibacterial properties on pathogens, such as Escherichia coli, Bacillus subtilis and Staphyloccocus aureus. The inhibitory action on Salmonella typhi and fungi Candida albicans and Aspegillus niger was absent to very low. The antimicrobial activity of the hydroalcoholic extracts was dependent on the provenance of the berries, too.

Safety Profile of the Trastuzumab-Based ADCs: Analysis of Real-World Data Registered in EudraVigilance.

Trastuzumab (T) and tyrosine kinase inhibitors (TKIs) are among the first-line treatments recommended for HER2-positive breast cancer. More recently, antibody-drug conjugates (ADCs) such as trastuzumab deruxtecan (T-DXd) and trastuzumab emtansine (T-DM1) have been authorized, and they represent the second-line therapy in this type of cancer. The present study aimed to evaluate adverse drug reactions (ADRs) associated with T-based ADCs that were spontaneously reported in EudraVigilance-the European pharmacovigilance database. Out of 42,272 ADRs reported for currently approved ADCs on the market, 24% of ADRs were related to T-DM1, while 12% of ADRs were related to T-DXd. T-DM1 had a higher probability of reporting eye, ear and labyrinth, and cardiac and hepatobiliary ADRs, while T-DXd had a higher probability of reporting respiratory, thoracic and mediastinal, blood and lymphatic system, metabolism and nutrition, and gastrointestinal ADRs. The present research found that in terms of hematological disorders, T-DM1 and T-DXd had a higher probability of reporting ADRs than TKIs. Moreover, the data showed that T-DM1 seemed to have a higher risk of cardiotoxicity than T-DXd, while T-DXd had a higher probability of reporting metabolism and nutrition disorders than T-DM1.

A comparative study on the quality of air in offices and homes.

The main purpose of this study was to collect data on some of the factors that contribute to indoor air quality and to discomfort, in order to take the proper actions that can reduce the level of air pollution within houses and offices. To ascertain the contamination degree total bacterial counts, total fungal counts, suspended particulate matter, air temperature, and relative humidity have been determined. Additionally, mathematical statistical models have been elaborated for the total bacterial count, respirable particulate matter and humidity. A total number of 40 indoor air samples were collected from office and houses. The results shows that approximately 45% of the air samples from homes, and 45% of the air samples from offices had levels of total viable count higher than the recommended by "European Concerted Action-Indoor Air Quality and Its Impact on Man- Report No 12." For yeast and moulds it was observed that 40% of the air samples within homes, and 10% of the air samples within offices had levels of total viable count higher than the recommended. This highlights the need for frequent cleaning of offices and homes as well as the ventilation improvement for providing a healthy environment.

Comparative Antioxidant and Antimicrobial Activities of Several Conifer Needles and Bark Extracts.

Nowadays, an increased concern regarding using natural products for their health benefits can be observed. The aim of this study was to assess and compare several phenolic compounds found in 15- to 60-year-old Douglas fir, silver fir, larch, pine, and spruce needle and bark extracts and to evaluate their antioxidant and antimicrobial activities. Spectrophotometric assays were used to determine the total polyphenol content and the antioxidant activity that was assessed by using the DPPH• radical scavenging assay (RSA), the ferric reducing antioxidant power assay (FRAP), and the ABTS•+ radical cation scavenging assay (ABTS). The phytochemical content was determined by using high-performance liquid chromatography, and the antimicrobial activity was determined by assessing the minimal inhibition concentration (MIC). The results of the study show a total polyphenol content of 62.45-109.80 mg GAE/g d.w. and an antioxidant activity of 91.18-99.32% for RSA, 29.16-35.74 µmol TE/g d.w. for FRAP, and 38.23-53.57 µmol TE/g d.w. for ABTS. The greatest quantity of phenolic compound for most of the extracts was for (+)-catechin, and it had values between 165.79 and 5343.27 µg/g d.w. for these samples. The antimicrobial inhibition for all the extracts was the strongest for Staphylococcus aureus (MIC 62.5-125 µg/mL). The extracts analyzed could be used for their bioactive potential after further investigations.

Valorization of Grape Pomace and Berries as a New and Sustainable Dietary Supplement: Development, Characterization, and Antioxidant Activity Testing.

Grape pomace and berries represent natural sources of phytochemicals that can increase the quality of life of consumers by contributing to the prevention of chronic diseases; thus, the development of a dietary supplement was necessary. The raw material (r.m.) used for the development of the dietary supplement consisted of dried and powdered bilberries (Vaccinium myrtillus L.), red currants (Ribes rubrum L.), and red fermented pomaces (Vitis vinifera L.) from Feteasca Neagra and Cabernet Sauvignon cultivars. The particle size distribution, powder flow, total phenolic content (TPC), HPLC-DAD phenolic profile assessment, and radical scavenging assay (RSA) were employed for the analysis of the raw material. After encapsulation, the average mass and uniformity of mass, the disintegration, and the uniformity of content for the obtained capsules were performed to obtain a high-quality dietary supplement. All the assays performed complied to the compendial requirements and the TPC was determined at 9.07 ± 0.25 mg gallic acid equivalents/g r.m. and RSA at 48.32 ± 0.74%. The highest quantities of phenolic compounds determined were 333.7 ± 0.50 µg/g r.m. for chlorogenic acid, followed by rutin, ferulic acid, and (+)-catechin with 198.9 ± 1.60 µg/g r.m., 179.8 ± 0.90 µg/g r.m. and 118.7 ± 0.75 µg/g r.m., respectively. The results of this study can be used for the manufacturing and assessing of pilot scale-up capsule batches and thinking of quality assurance, we recommend that the industrial batch extracts should be standardized in polyphenols, and the manufacturing process should be validated.

Green Design of Novel Starch-Based Packaging Materials Sustaining Human and Environmental Health.

A critical overview of current approaches to the development of starch-containing packaging, integrating the principles of green chemistry (GC), green technology (GT) and green nanotechnology (GN) with those of green packaging (GP) to produce materials important for both us and the planet is given. First, as a relationship between GP and GC, the benefits of natural bioactive compounds are analyzed and the state-of-the-art is updated in terms of the starch packaging incorporating green chemicals that normally help us to maintain health, are environmentally friendly and are obtained via GC. Newer approaches are identified, such as the incorporation of vitamins or minerals into films and coatings. Second, the relationship between GP and GT is assessed by analyzing the influence on starch films of green physical treatments such as UV, electron beam or gamma irradiation, and plasma; emerging research areas are proposed, such as the use of cold atmospheric plasma for the production of films. Thirdly, the approaches on how GN can be used successfully to improve the mechanical properties and bioactivity of packaging are summarized; current trends are identified, such as a green synthesis of bionanocomposites containing phytosynthesized metal nanoparticles. Last but not least, bioinspiration ideas for the design of the future green packaging containing starch are presented.

Use of Yoghurt Enhanced with Volatile Plant Oils Encapsulated in Sodium Alginate to Increase the Human Body's Immunity in the Present Fight Against Stress.

(1) Background: The COVID-19 pandemic and the imposition of strict but necessary measures to prevent the spread of the new coronavirus have been, and still are, major stress factors for adults, children, and adolescents. Stress harms human health as it creates free radicals in the human body. According to various recent studies, volatile oils from various aromatic plants have a high content of antioxidants and antimicrobial compounds. An external supply of antioxidants is required to destroy these free radicals. The main purpose of this paper is to create a yoghurt with high antioxidant capacity, using only raw materials from Romania; (2) Methods: The bioactive components used to enrich the cow milk yoghurt were extracted as volatile oils out of four aromatic plants: basil, mint, lavender and fennel. Initially, the compounds were extracted to determine the antioxidant capacity, and subsequently, the antioxidant activity of the yoghurt was determined. The 2,2-diphenyl-1-picrylhy-drazyl (DPPH) method was used to determine the antioxidant activity; (3) Results: The results show that cow milk yoghurt enhanced with volatile oils of basil, lavender, mint and fennel, encapsulated in sodium alginate has an antioxidant and antimicrobial effect as a staple food with multiple effects in increasing the body's immunity. The antioxidant activity proved to be considerably higher than the control sample. The highest antioxidant activity was obtained on the first day of the analysis, decreasing onwards to measurements taken on days 10 and 20. The cow milk yoghurt enriched with volatile basil oil obtained the best results; (4) Conclusions: The paper shows that yoghurts with a high antioxidant capacity were obtained, using only raw materials from Romania. A healthy diet, compliance with safety conditions and finding appropriate and safe methods to increase the body's immunity is a good alternative to a major transition through harder times, such as pandemics. The creation of food products that include natural antioxidant compounds combines both the current great possibility of developing food production in Romania and the prevention and reduction of the effects caused by pandemic stress in the human body.

Bilberry (Vaccinium myrtillus L.) Extracts Comparative Analysis Regarding Their Phytonutrient Profiles, Antioxidant Capacity along with the In Vivo Rescue Effects Tested on a Drosophila melanogaster High-Sugar Diet Model.

Bilberries (Vaccinium myrtillus L.) have been reported to hold a plentitude of health-promoting properties beyond basic nutrition, mainly attributed to their anthocyanin content and antioxidant activity. In this article, we built the phytochemical profile of three wild bilberry fruit extract formulations (aqueous, methanolic, and hydro-methanolic) using UHPLC-ESI-MS/MS putative analysis, identifying 88 individual phytochemicals, mainly flavonoids (total content 8.41 ± 0.11 mg QE/g dw), free amino acids, polyphenols (total content 21.68 ± 0.19 mg GAE/g dw), carboxylic acids, and vitamins. Furthermore, the antioxidant activity of the extract was assessed, reaching 78.03 ± 0.16% DPPH free radical scavenging activity, comparable to literature values determined for bilberry extracts of other origin. Due to the increased prevalence of metabolic syndrome and based on the reviewed benefits of bilberries, we tested the most potent formulation of our bilberry extracts in this biological context. The in vivo rescue effect of a bilberry extract supplemented diet on Drosophila melanogaster was assessed by monitoring biochemical and genomic markers. Hemolymph trehalose levels were halved upon addition of 3% hydro-methanolic bilberry extract to a high-sugar (1.5 M sucrose) diet, as compared to the non-supplemented high-sugar diet. Noteworthy, the rescue seen for flies kept on the bilberry extract supplemented high-sugar diet appeared to parallel the trehalose levels observed in the case of the control diet (50 mM sucrose) flies. Moreover, next to the trehalose-lowering type of in vivo effects, other gene expression related rescues were also detected for genes such as InR, Akh, AstA, AstC, Irk, Npc2g, and CCHa2 upon supplementation of the high-sugar diet with our hydro-methanolic bilberry fruit extract. Our findings suggest that such a bilberry fruit extract could generate physiological and genomic type of compensatory mechanisms so that further translational approaches would advance the understanding of some human specific pathological conditions.

An overview of natural antimicrobials role in food.

The present paper aims to review the natural food preservatives with antimicrobial properties emphasizing their importance for the future of food manufacturing and consumers' health. The extraction procedures applied to natural antimicrobials will be considered, followed by the description of some natural preservatives' antimicrobial mechanism of action, including (i) membrane rupture with ATP-ase activity inhibition, (ii) leakage of essential biomolecules from the cell, (iii) disruption of the proton motive force and (iiii) enzyme inactivation. Moreover, a provenance-based classification of natural antimicrobials is discussed by considering the sources of origin for the major natural preservative categories: plants, animals, microbes and fungi. As well, the structure influence on the antimicrobial potential is considered. Natural preservatives could also constitute a viable alternative to address the critical problem of microbial resistance, and to hamper the negative side effects of some synthetic compounds, while meeting the requirements for food safety, and exerting no negative impact on nutritional and sensory attributes of foodstuffs.