Safety evaluation of the food enzyme pectinesterase from the genetically modified Trichoderma reesei strain RF6201.

The food enzyme pectinesterase (pectin pectylhydrolase; EC 3.1.1.11) is produced with the genetically modified Trichoderma reesei strain RF6201 by AB Enzymes GmbH. The genetic modifications do not give rise to safety concerns. The food enzyme was considered free from viable cells of the production organism and its DNA. It is intended to be used in five food manufacturing processes: fruit and vegetable processing for juice production, fruit and vegetable processing for products other than juices, production of wine and wine vinegar, coffee demucilation and production of plant extracts as flavouring preparations. Since residual amounts of the total organic solids (TOS) are removed during the coffee demucilation and the production of flavouring extracts, dietary exposure was calculated only for the remaining three food processes. It was estimated to be up to 0.532 mg TOS/kg body weight (bw) per day in European populations. Genotoxicity tests did not indicate a safety concern. The systemic toxicity was assessed by means of a repeated dose 90-day oral toxicity study in rats. The Panel identified a no observed adverse effect level of 1,000 mg TOS/kg bw per day, the highest dose tested, which, when compared with the estimated dietary exposure, resulted in a margin of exposure of at least 1,880. A search for the similarity of the amino acid sequence of the food enzyme to known allergens was made and two matches were found with pollen allergens. The Panel considered that, under the intended conditions of use, the risk of allergic reactions upon dietary exposure, particularly in individuals sensitised to pollen allergens, cannot be excluded. Based on the data provided, the Panel concluded that this food enzyme does not give rise to safety concerns under the intended conditions of use.

Safety evaluation of the food enzyme endo-polygalacturonase from the genetically modified Trichoderma reesei strain RF6197.

The food enzyme endo-polygalacturonase ((1-4)-α-d-galacturonan glycanohydrolase; EC 3.2.1.15) is produced with the genetically modified Trichoderma reesei strain RF6197 by AB Enzymes GmbH. The genetic modifications do not give rise to safety concerns. The food enzyme was considered free from viable cells of the production organism and its DNA. It is intended to be used in five food manufacturing processes: fruit and vegetable processing for juice production, fruit and vegetable processing for products other than juices, production of wine and wine vinegar, coffee demucilation and production of plant extracts as flavouring preparations. Since residual amounts of the total organic solids (TOS) are removed during the coffee demucilation and the production of flavouring extracts, dietary exposure was calculated only for the remaining three food processes. It was estimated to be up to 0.156 mg TOS/kg body weight (bw) per day in European populations. Genotoxicity tests did not indicate a safety concern. The systemic toxicity was assessed by means of a repeated dose 90-day oral toxicity study in rats. The Panel identified a no observed adverse effect level of 1,000 mg TOS/kg bw per day, the highest dose tested, which, when compared with the estimated dietary exposure, resulted in a margin of exposure of at least 6,410. A search for the similarity of the amino acid sequence of the food enzyme to known allergens was made and matches were found with a number of pollen allergens. The Panel considered that, under the intended conditions of use, the risk of allergic reactions by dietary exposure, particularly in individuals sensitised to pollen cannot be excluded. Based on the data provided, the Panel concluded that this food enzyme does not give rise to safety concerns under the intended conditions of use.

Emulsion Electrospinning of PLLA/PVA/Chitosan with Hypericum perforatum L. as an Antibacterial Nanofibrous Wound Dressing.

Chronic wounds are one of the most severe health problems that affect millions of people worldwide. These types of injuries impair healing and lead to life-threatening complications. Therefore, suitable wound dressing materials are essential to prevent the risk of infection and to provide an excellent healing environment. The present research reports the development of an electrospun Poly (L-lactic acid) (PLLA)/Poly (vinyl alcohol) (PVA)/Chitosan (CS) wound dressing material, produced via emulsion electrospinning in a single step using homogeneous gel-like suspensions of two different and incompatible polymer solutions. The electrospun PLLA/PVA/CS fiber mats were loaded with two different amounts of Hypericum perforatum L. (HP) (2.5% and 5.0% owf). The results revealed that the produced electrospun PLLA/PVA/CS fiber mats displayed ideal properties as a wound dressing due to a total porosity, wettability, water vapor transmission rate (WVTR), and swelling properties similar to those reported for the extracellular matrix (ECM) of the skin, mainly when 2.5% owf HP was incorporated. Moreover, the electrospun PLLA/PVA/CS fiber mats containing HP were able to prevent the growth of gram-positive bacterium Staphylococcus aureus (S. aureus) without causing cytotoxicity to normal human dermal fibroblasts (NHDF). These findings suggest that these electrospun dressing mats are helpful for preventing wound infections as well as an appropriate support and microenvironment for wound healing.

Parestesia do nervo alveolar inferior decorrente de procedimentos cirúrgicos e suas formas de tratamentos / Paresthesi of the lower alveolar nerve resulting from surgical procedures and its forms of treatment

Nas cirurgias odontológicas é possível que ocorra alguns acidentes ou complicações que podem interferir no dia a dia do paciente. A lesão do nervo alveolar inferior é uma complicação decorrente de cirurgias orais que podem causar um distúrbio de sensibilidade transitória ou persistente, na região do lábio inferior e na região delimitada do forame mentoniano e hemi-arco da mucosa. O diagnóstico da parestesia pode ser feito através de testes mecanoceptivos e nocioceptivos em que o profissional escolherá para qual melhor se adapte no paciente. O objetivo do presente trabalho foi abordar por meio de uma revisão de literatura as formas de diagnóstico e tratamento da parestesia do nervo alveolar inferior decorrentes de cirurgias orais. As bases de dados utilizadas para confecção desta revisão são encontradas nas bibliotecas virtuais eletrônicas: BVS (Biblioteca Virtual em Saúde), LILACS (Literatura Latino-Americana e do Caribe em Ciências da Saúde) e Pubmed. Como critério de inclusão foram selecionados artigos publicados de 2012 a 2022 em língua inglesa, portuguesa e espanhola. Após a leitura do título e resumo dos resultados da pesquisa e aplicação dos critérios de inclusão e exclusão dentre eles foram excluídos 883, pois não se enquadravam no nosso critério de inclusão. No final, foram selecionados 13 estudos por meio de base de dados, que serviram de base para esta revisão. Concluímos que as formas de tratamento para a parestesia na literatura, são um pouco escassas e conflitantes, mas relata que o uso da laserterapia e acupuntura tem sido uma forma de tratamento com um bom índice de sucesso, e para os casos que não sejam suficientes tais tratamentos, pode-se optar por uma cirurgia(AU)

In dental surgeries it is possible to have some accidents or complications that can interfere with the patient's day. Injury to the inferior alveolar nerve is a complication resulting from oral surgeries that can cause a disturbance of sensitivity that can be transient or persistent in the region of the lower lip and in the delimited region of the mental foramen and hemiarch of the mucosa. The diagnosis of paresthesia can be made through mechanoceptive and nocioceptive tests that the professional will choose, which best suits the patient. The objective of the present work is to approach, through a literature review, the forms of diagnosis and treatment aimed at inferior alveolar nerve paresthesia resulting from oral surgeries. The databases used for this review are found in the virtual electronic libraries: VHL (Virtual Health Library), LILACS (Latin American and Caribbean Literature on Health Sciences) and Pubmed. As inclusion criteria, articles published from 2012 to 2022 in English, Portuguese and Spanish were selected. After reading the title and summary of the research results and applying the inclusion and exclusion criteria, 883 were excluded, as they did not meet our inclusion criteria. In the end, 13 studies were selected from the database, which served as the basis for this review. We conclude that the forms of treatment for paresthesia in the literature are a little scarce and conflicting, but it reports that the use of laser therapy and acupuncture has been a form of treatment with a good success rate, and for cases that are not enough, such treatments, one can opt for surgery(AU)

Effects of Hippotherapy on Postural Control in Children With Cerebral Palsy: A Systematic Review.

PURPOSE: To summarize and update the current knowledge on the effectiveness of hippotherapy on postural control in children with cerebral palsy. METHODS: Using a systematic review methodology, the electronic databases PubMed, Virtual Health Library, PEDro, Scielo, Embase, and Web of Science were searched for eligible articles from 2011 up to September 2021. Quality assessment of eligible studies was performed using the PEDro scale. RESULTS: There were 239 identified studies. Eight clinical trials were selected. The total sample consisted of 264 individuals, with 134 allocated to the experimental group (hippotherapy) and 130 individuals to the control group (conventional therapy). Most studies had moderate to high methodological quality. CONCLUSIONS: Hippotherapy can be an effective intervention to improve several aspects related to postural control, such as static balance (especially in the sitting posture), dynamic balance, and alignment (body posture) in children aged 3 to 16 years, particularly with spastic hemiplegia or diplegia. WHAT THIS ADDS TO THE EVIDENCE: This review summarizes studies that explore potential effects of hippotherapy on postural control in children with cerebral palsy.

Study of the viability of using lipase-hydrolyzed commercial vegetable oils to produce microbially conjugated linolenic acid-enriched milk.

This work studied the viability of using vegetable oils as precursor substrates to develop a dairy product enriched in microbial conjugated linoleic (CLA) and conjugated linolenic (CLNA) acids. Hydrolysis of hempseed, flaxseed (FSO) and soybean (SBO) oils was tested with Candida rugosa (CRL), Pseudomonas fluorescens, or Pancreatic porcine lipases. FSO and SBO, previously hydrolyzed with CRL, were further selected for cow's milk CLA/CLNA-enrichment with Bifidobacterium breve DSM 20091. Thereafter, higher substrate concentrations with hydrolyzed FSO were tested. For all tested oils, CRL revealed the best degrees of hydrolysis (>90 %). Highest microbial CLA/CLNA yield in milk was achieved with hydrolyzed FSO, which led to the appearance of mainly CLNA isomers (0.34 mg/g). At higher substrate concentrations, maximum yield was 0.88 mg/g CLNA. Therefore, it was possible to enrich milk with microbial CLNA using vegetable oil, but not with CLA, nor develop a functional product that can deliver a reliable effective dose.

Mapping key neuropeptides involved in the melanocortin system in Atlantic salmon (Salmo salar) brain.

The melanocortin system is a key regulator of appetite and food intake in vertebrates. This system includes the neuropeptides neuropeptide y (NPY), agouti-related peptide (AGRP), cocaine- and amphetamine-regulated transcript (CART), and pro-opiomelanocortin (POMC). An important center for appetite control in mammals is the hypothalamic arcuate nucleus, with neurons that coexpress either the orexigenic NPY/AGRP or the anorexigenic CART/POMC neuropeptides. In ray-finned fishes, such a center is less characterized. The Atlantic salmon (Salmo salar) has multiple genes of these neuropeptides due to whole-genome duplication events. To better understand the potential involvement of the melanocortin system in appetite and food intake control, we have mapped the mRNA expression of npy, agrp, cart, and pomc in the brain of Atlantic salmon parr using in situ hybridization. After identifying hypothalamic mRNA expression, we investigated the possible intracellular coexpression of npy/agrp and cart/pomc in the tuberal hypothalamus by fluorescent in situ hybridization. The results showed that the neuropeptides were widely distributed, especially in sensory and neuroendocrine brain regions. In the hypothalamic lateral tuberal nucleus, the putative homolog to the mammalian arcuate nucleus, npya, agrp1, cart2b, and pomca were predominantly localized in distinct neurons; however, some neurons coexpressed cart2b/pomca. This is the first demonstration of coexpression of cart2b/pomca in the tuberal hypothalamus of a teleost. Collectively, our data suggest that the lateral tuberal nucleus is the center for appetite control in salmon, similar to that of mammals. Extrahypothalamic brain regions might also be involved in regulating food intake, including the olfactory bulb, telencephalon, midbrain, and hindbrain.

Medium-chain triglycerides and conjugated linolenic acids in functional yogurts: impact of GIT and potential biological activities.

In recent years, bioactive lipids particularly medium-chain triglycerides and conjugated linolenic fatty acids have obtained more attention due to their possible applicability in obesity metabolism modulation. These compounds are capable to increase thermogenesis and reduce weight gain through the modulation of key neurohormones such as leptin and adiponectin. The purpose of this work was to develop functional yogurts through the addition of coconut (rich in medium-chain fatty acids) or pomegranate oils (rich in conjugated linolenic acids). The presence of these oils led to a significant alteration in the nutritional value of yogurts, showing a capacity to reduce the accumulation of lipids in hepatocytes and increase the release of triglycerides in adipocytes. These results demonstrate that functional yogurts can be a valuable strategy for obesity prevention.

Is low-level laser therapy effective in the treatment of herpes labialis? Systematic review and meta-analysis.

The objective of this systematic review is to evaluate the effectiveness of low-level laser therapy in the treatment of herpes labialis. The searches were carried out independently by 2 researchers and the articles were selected through the electronic databases according to the inclusion and exclusion criteria previously established. Initially, 480 articles were found, of which 7 randomized clinical trials and 1 clinical trial were selected. In total, 928 patients were included. In the meta-analysis, the mean healing time for laser use was significant, showing a mean reduction of 1.37 [CI 95% = 0.92 to 1.82] days for tissue healing (p < 0.0001). In the meta-analysis to evaluate the time for crust formation, there was no significant difference between the groups and no significant reduction in the mean time for crust formation (p = 0.150). Only one of the selected studies had a low risk of bias. The use of low-level laser proved to be effective in the treatment of herpes labialis. However, due to the high risk of bias in the included studies, there is a need to carry out new standardized studies to prove the effectiveness of this therapy.

Vapor-Phase of Essential Oils as a Promising Solution to Prevent Candida Vaginal Biofilms Caused by Antifungal Resistant Strains.

BACKGROUND: Vulvovaginal candidiasis (VVC) is a disease with high incidence, a huge impact on the quality of life and health of women, and which represents a great challenge to treat. The growing need to apply antifungal intensive therapies have contributed to an emergence of drug-resistant Candida strains. Thus, effective therapeutic options, to meet the antifungal-resistance challenge and to control high resilient biofilms, are urgently needed. This study aimed to investigate the antifungal activity of essentials oils (EOs) on drug-resistant Candida vaginal isolates. METHOD: Therefore, the antimicrobial effect of tea tree, niaouli, white thyme, and cajeput EOs on the planktonic growth of Candida isolates was initially evaluated by an agar disc diffusion method. Then, the vapor-phase effect of tea tree EO (VP-TTEO) on biofilm formation and on pre-formed biofilms was evaluated by crystal violet staining, XTT reduction assay, colony forming units' enumeration, and scanning electron microscopy. RESULTS: The results revealed high antifungal activity of EOs against drug-resistant Candida isolates. Additionally, the VP-TTEO showed a significant inhibitory effect on the biofilm formation of all tested isolates and was able to provoke an expressive reduction in mature Candida albicans biofilms. CONCLUSIONS: Overall, this study suggests that the VP-EO may be a promising solution that is able to prevent biofilm-related VVC caused by antifungal-resistant strains.

Effects of different amendments on the quality of burnt eucalypt forest soils - A strategy for ecosystem rehabilitation.

The magnitude of forest fires' impacts on the environment is directly related to the changes induced on soil physical, chemical and biological properties. Using available organic resources to rehabilitate burnt forest soils can help reduce post-fire soil fertility loss, accelerating ecosystem recovery. In the present study, the potential of four soil amendments: a mycotechnosol, a eucalypt residue mulch, dredged sediments from a freshwater lagoon and an organic-mineral biofertilizer, to improve the quality of burnt forest soils in terms of organic matter, carbon, nitrogen and phosphorus contents, was evaluated. Two experiments were set-up, one in a recently burnt eucalypt plantation and another in the laboratory using soils from the same area, to assess the effects of the amendments on soil quality, with both experiments lasting for 7 months. The effects of the amendments on nutrient leaching along the soil profile were also evaluated in the laboratory, to investigate possible negative impacts on groundwater and surface water quality. All amendments increased the organic matter and nutrient contents of burnt soils, confirming their potential for ecosystem rehabilitation. The biofertilizer, however, was found to promote nutrient losses by leaching, largely owing to its high solubility, increasing the risk of contamination of ground and surface waters. Using available organic resources to rehabilitate burnt forests as was done in the present work complies with the idea of a circular economy, being key for the sustainability of forest ecosystems.

Pomegranate Oil's Potential as an Anti-Obesity Ingredient.

In recent years, pomegranate oil has obtained more attention due to its content of conjugated linolenic acids and possible application in the prevention of many diseases. The purpose of this work was to evaluate the potential ability of pomegranate oil to modulate obesity-related metabolism and immune response using in vitro models. In this regard, pomegranate oil was characterized in terms of fatty acids profile, tocopherols and phytosterols, and antioxidant capacity. After evaluation of the safety profile, pomegranate oil's capacity to modulate obesity-related metabolism was evaluated through adipolysis and adipokines secretion quantification in 3T3-L1 differentiated adipocytes and hepatic lipid accumulation assay in Hep G2 hepatocytes. The immunomodulatory activity was evaluated in Caco-2 cells by quantification of pro-inflammatory cytokines IL-6, IL-8, and TNF-α. This oil showed high antioxidant capacity and was mainly composed of conjugated fatty acid, namely punicic acid. Its chemical composition was responsible for its capacity to reduce the lipid accumulation in Hep G2 cells and 3T3-L1 differentiated adipocytes. In short, pomegranate oil shows great potential for the development of functional foods and nutraceuticals targeting obesity.

Correction: Martins et al. Cannabis-Based Products for the Treatment of Skin Inflammatory Diseases: A Timely Review. Pharmaceuticals 2022, 15, 210.

The authors would like to make the following corrections about the published paper [...].

Folic acid-mesoporous silicon nanoparticles enhance the anticancer activity of the p73-activating small molecule LEM2.

Many drugs with anticancer potential fail in their translation to the clinics due to problems related to pharmacokinetics. LEM2 is a new dual inhibitor of MDM2/mutp53-TAp73 interactions with interesting in vitro anticancer activity, which opens new hopes as an unconventional anticancer therapeutic strategy against cancers lacking p53 or with impaired p53 pathways. As others xanthone derivatives, LEM2 has limited aqueous solubility, posing problems to pursue in vivo assays, and therefore limiting its potential clinical translation. In this work, a mesoporous silicon (PSi)-based nanodelivery system was developed with folate functionalization (APTES-TCPSi-PEG-FA) for targeted delivery, which successfully increased LEM2 solubility when compared to bulk LEM2, evidenced in payload release study. Such effect was reflected on the increase of LEM2 cytotoxicity in HCT116 and MDA-MB-231 cancer cells when treated with LEM2-loaded APTES-TCPSi-PEG-FA, by reducing cell viability lower than 50% in comparison with bulk LEM2. Despite the reduced LEM2 loading degree, which still limits its application in further in vivo assays, the results obtained herein recognize PSi-based nanodelivery systems as a promising strategy to improve LEM2 anticancer activity and bioavailability, which will be relevant for the potential use of this potent TAp73 activator in anticancer therapy.

Bioluminescent Models to Evaluate the Efficiency of Light-Based Antibacterial Approaches.

The emergence of microbial resistance to antimicrobials among several common pathogenic microbial strains is an increasing problem worldwide. Thus, it is urgent to develop not only new antimicrobial therapeutics to fight microbial infections, but also new effective, rapid, and inexpensive methods to monitor the efficacy of these new therapeutics. Antimicrobial photodynamic therapy (aPDT) and antimicrobial blue light (aBL) therapy are receiving considerable attention for their antimicrobial potential and represent realistic alternatives to antibiotics. To monitor the photoinactivation process provided by aPDT and aBL, faster and more effective methods are required instead of laborious conventional plating and overnight incubation procedures. Bioluminescent microbial models are very interesting in this context. Light emission from bioluminescent microorganisms is a highly sensitive indication of their metabolic activity and can be used to monitor, in real time, the effects of antimicrobial agents and therapeutics. This chapter reviews the efforts of the scientific community concerning the development of in vitro, ex vivo, and in vivo bioluminescent bacterial models and their potential to evaluate the efficiency of aPDT and aBL in the inactivation of bacteria.

Relaxing the "second brain": nutrients and bioactive compounds as a therapeutic and preventive strategy to alleviate oxidative stress in the enteric nervous system.

The enteric nervous system (ENS) regulates several functional and immunological processes in the gastrointestinal tract. However, some diseases can disrupt the ENS functionality, impacting the behavior of enteric neurons and enteric glial cells by increasing the accumulation of reactive oxygen species. Oxidative stress is considered to be a trigger for alterations in these cells' morphology, density, and neurochemical patterns. In light of this, nutritional strategies are a growing field of investigation regarding their potential to modulate enteric neurons and enteric glial cells through reduced reactive oxygen species production. Moreover, several lines of evidence show that nutrients are related to counteracting oxidative stress. Some studies have evaluated the potential of nutrients with antioxidant roles (such as amino acids, polyphenols, prebiotics, vitamins, and specific extracts obtained from foods) to modulate the ENS. Thus, this review discusses how bioactive compounds and nutrients can impact the ENS by alleviating oxidative stress.

Reações adversas do montelucaste no tratamento da asma pediátrica: uma revisão integrativa da literatura / Adverse reactions of montelukast in the treatment of pediatric asthma: an integrative literature review / Reacciones adversas de montelukast en el tratamiento del asma pediátrico: una revisión integrativa de la literatura

Buscou-se analisar as reações adversas do montelucaste quando prescrito para o tratamento da asma pediátrica. Revisão integrativa da literatura utilizando as bases de dados: U.S. National Library of Medicine (PubMed), Biblioteca Virtual da Saúde (BVS), SCOPUS e Business Source Complete (EBSCO), empregando os descritores: "asthma", "pediatric", "montelukast" e "adverse effects", unidos pelo booleano "AND''. Incluíram-se artigos na íntegra; publicados nos últimos 5 anos; redigidos em português, inglês ou espanhol; pesquisados em humanos e com uma relação com o nosso objetivo. Excluíram-se os que se enquadravam em nossos critérios de exclusão.Foram identificados 53 artigos, dos quais 11 compuseram a amostra final desta revisão. A exposição ao montelucaste foi associada a uma chance 2 vezes maior de reações neuropsiquiátricas em um dos artigos analisados, porém os estudos ainda não forneceram uma explicação fisiopatológica em comum. Reações neuropsiquiátricas foram as de maior prevalência, representando mais de 90% da amostra.

We analyzed the adverse reactions of montelukast when prescribed for the treatment of pediatric asthma. This is an integrative literature review using the databases: U.S. National Library of Medicine (PubMed), Virtual Health Library (BVS), SCOPUS and Business Source Complete (EBSCO), using the descriptors: "asthma", "pediatric", "montelukast" and "adverse effects", connected by the Boolean " AND''. Articles in full were included, published in the last 5 years, written in Portuguese, English or Spanish, researched in humans and related to our objective. Those that met our exclusion criteria were excluded. Fifty-three articles were identified, of which 11 comprised the final sample of this review. Exposure to montelukast was associated with a 2-fold greater chance of neuropsychiatric reactions in one of the articles analyzed, but the studies have not yet provided a common pathophysiological explanation. Neuropsychiatric reactions were the most prevalent, representing more than 90% of the sample.

Se intentó analizar las reacciones adversas de montelukast cuando se prescribe para el tratamiento del asma pediátrica. Revisión integrativa de la literatura usando las bases de datos: U.S. National Library of Medicine (PubMed), Virtual Health Library (BVS), SCOPUS y Business Source Complete (EBSCO), utilizando los descriptores: "asma", "pediátrico", "montelukast" y "efectos adversos", unidos por el booleano " Y". Se incluyeron artículos completos, publicados en los últimos 5 años, escritos en portugués, inglés o español, investigados en humanos y relacionados con nuestro objetivo. Se excluyeron aquellos que cumplieron con nuestros criterios de exclusión. Se identificaron cincuenta y tres artículos, de los cuales 11 constituyeron la muestra final de esta revisión. La exposición a montelukast se asoció con una probabilidad 2 veces mayor e reacciones neurosiquiátricas en uno de los artículos analizados, pero los estudios aún no han proporcionado una explicación fisiopatológica común. Las reacciones neurosiquiátricas fueron las más prevalentes, representando más del 90% de la muestra

Cannabis-Based Products for the Treatment of Skin Inflammatory Diseases: A Timely Review.

The use of natural products in dermatology is increasingly being pursued due to sustainability and ecological issues, and as a possible way to improve the therapeutic outcome of chronic skin diseases, relieving the burden for both patients and healthcare systems. The legalization of cannabis by a growing number of countries has opened the way for researching the use of cannabinoids in therapeutic topical formulations. Cannabinoids are a diverse class of pharmacologically active compounds produced by Cannabis sativa (phytocannabinoids) and similar molecules (endocannabinoids, synthetic cannabinoids). Humans possess an endocannabinoid system involved in the regulation of several physiological processes, which includes naturally-produced endocannabinoids, and proteins involved in their transport, synthesis and degradation. The modulation of the endocannabinoid system is a promising therapeutic target for multiple diseases, including vascular, mental and neurodegenerative disorders. However, due to the complex nature of this system and its crosstalk with other biological systems, the development of novel target drugs is an ongoing challenging task. The discovery of a skin endocannabinoid system and its role in maintaining skin homeostasis, alongside the anti-inflammatory actions of cannabinoids, has raised interest in their use for the treatment of skin inflammatory diseases, which is the focus of this review. Oral treatments are only effective at high doses, having considerable adverse effects; thus, research into plant-based or synthetic cannabinoids that can be incorporated into high-quality, safe topical products for the treatment of inflammatory skin conditions is timely. Previous studies revealed that such products are usually well tolerated and showed promising results for example in the treatment of atopic dermatitis, psoriasis, and contact dermatitis. However, further controlled human clinical trials are needed to fully unravel the potential of these compounds, and the possible side effects associated with their topical use.

Role of ATP-binding Cassette Transporters in Sorafenib Therapy for Hepatocellular Carcinoma: An Overview.

BACKGROUND: Molecular therapy with sorafenib remains the mainstay for advancedstage hepatocellular carcinoma. Notwithstanding, treatment efficacy is low, with few patients obtaining long-lasting benefits due to the high chemoresistance rate. OBJECTIVE: To perform, for the first time, an overview of the literature concerning the role of adenosine triphosphate-binding cassette (ABC) transporters in sorafenib therapy for hepatocellular carcinoma. METHODS: Three online databases (PubMed, Web of Science, and Scopus) were searched, from inception to October 2020. Study selection, analysis, and data collection were independently performed by two authors. RESULTS: The search yielded 224 results; 29 were selected for inclusion. Most studies were pre-clinical, using HCC cell lines; three used human samples. Studies highlight the effect of sorafenib in decreasing ABC transporters expression. Conversely, it is described the role of ABC transporters, particularly multidrug resistance protein 1 (MDR-1), multidrug resistance-associated proteins 1 and 2 (MRP-1 and MRP-2) and ABC subfamily G member 2 (ABCG2) in sorafenib pharmacokinetics and pharmacodynamics, being key resistance factors. Combination therapy with naturally available or synthetic compounds that modulate ABC transporters may revert sorafenib resistance by increasing absorption and intracellular concentration. CONCLUSION: A deeper understanding of ABC transporters' mechanisms may provide guidance for developing innovative approaches for hepatocellular carcinoma. Further studies are warranted to translate the current knowledge into practice and paving the way to individualized therapy.

Biodegradation of water-accommodated aromatic oil compounds in Arctic seawater at 0 °C.

Oil spills in Arctic marine environments are expected to increase concurrently with the expansion of shipping routes and petroleum exploitation into previously inaccessible ice-dominated regions. Most research on oil biodegradation focusses on the bulk oil, but the fate of the water-accommodated fraction (WAF), mainly composed of toxic aromatic compounds, is largely underexplored. To evaluate the bacterial degradation capacity of such dissolved aromatics in Greenlandic seawater, microcosms consisting of 0 °C seawater polluted with WAF were investigated over a 3-month period. With a half-life (t1/2) of 26 days, m-xylene was the fastest degraded compound, as measured by gas chromatography - mass spectrometry. Substantial slower degradation was observed for ethylbenzene, naphthalenes, phenanthrene, acenaphthylene, acenaphthene and fluorenes with t1/2 of 40-105 days. Colwellia, identified by 16S rRNA gene sequencing, was the main potential degrader of m-xylene. This genus occupied up to 47 % of the bacterial community until day 10 in the microcosms. Cycloclasticus and Zhongshania aliphaticivorans, potentially utilizing one-to three-ringed aromatics, replaced Colwellia between day 10 and 96 and occupied up to 6 % and 23 % of the community, respectively. Although most of the WAF can ultimately be eliminated in microcosms, our results suggest that the restoration of an oil-impacted Arctic environment may be slow as most analysed compounds had t1/2 of over 2-3 months and the detrimental effects of a spill towards the marine ecosystem likely persist during this time.