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Ethylhexyl methoxycinnamate (EHMC) (CAS number: 5466-77-3) and butyl methoxydibenzoylmethane (BMDM) (CAS number: 70356-09-1) are important sunscreens. However, frequent application of large amounts of these compounds may reflect serious environmental impact, once it enters the environment through indirect release via wastewater treatment or immediate release during water activities. In this article, we reviewed the toxicological effects of EHMC and BMDM on aquatic ecosystems and the human consequences. According to the literature, EHMC and BMDM have been detected in water samples and sediments worldwide. Consequently, these compounds are also present in several marine organisms like fish, invertebrates, coral reefs, marine mammals, and other species, due to its bioaccumulation potential. Studies show that these chemicals are capable of damaging the aquatic beings in different ways. Further, bioaccumulation studies have shown that EHMC biomagnifies through trophic levels, which makes human seafood consumption a concern because the higher position in the trophic chain, the more elevate levels of ultraviolet (UV) filters are detected, and it is established that EHMC present adverse effects on the human organism. In contrast, there are no studies on the BMDM bioaccumulation and biomagnification potential. Different strategies can be adopted to avoid the damage caused by sunscreens in the environment and human organism. Two of them include the use of natural photoprotectors, such as polyphenols, in association with UV filters in sunscreens and the development of new and safer UV filters. Overall, this review shows the importance of studying the impacts of sunscreens in nature and developing safer sunscreens and formulations to safeguard marine fauna, ecosystems, and humans.

This Clinical Practice Guideline on the systemic treatment of Psoriasis includes the recommendations elaborated by a panel of experts from the Latin American Psoriasis Society SOLAPSO, who assessed the quality of the available evidence using the GRADE system and the PICO process to guide the literature search. To answer each question, the experts discussed the results of randomized controlled trials, observational studies and metanalysis evaluating the interventions identified (non-biologics, biologics and phototherapy) in different populations of patients with moderate to severe plaque-psoriasis, which was summarized in Tables ad-hoc. The main end-points considered to assess efficacy were PASI 50, 75, 90 and 100, PGA 0-1 and significant improvement of health-related quality of life. Specific adverse events, either severe or leading to treatment interruption, were also evaluated. The 31 recommendations included in this CPG follow the structure proposed by GRADE: direction (for or against) and strength (strong or weak). The goal of this CPG is to improve the management of patients with psoriasis by recommending interventions of proved benefit and providing a reference standard for the treating physician. Adhering to the contents of this CPG does not guarantee therapeutic success. The final decision on the specific treatment is the responsibility of the physician based on the individual circumstances and considering the values, the preferences and the opinions of the patient or caregivers.

Acyldepsipeptide (ADEP) is an exploratory antibiotic with a novel mechanism of action. ClpP, the proteolytic core of the caseinolytic protease, is deregulated towards unrestrained proteolysis. Here, we report on the mechanism of ADEP resistance in Firmicutes. This bacterial phylum contains important pathogens that are relevant for potential ADEP therapy. For Staphylococcus aureus, Bacillus subtilis, enterococci and streptococci, spontaneous ADEP‐resistant mutants were selected in vitro at a rate of 10−6. All isolates carried mutations in clpP. All mutated S. aureus ClpP proteins characterised in this study were functionally impaired; this increased our understanding of the mode of operation of ClpP. For molecular insights, crystal structures of S. aureus ClpP bound to ADEP4 were determined. Well‐resolved N‐terminal domains in the apo structure allow the pore‐gating mechanism to be followed. The compilation of mutations presented here indicates residues relevant for ClpP function and suggests that ADEP resistance will occur at a lower rate during the infection process., ClpP mutant analysis: ADEP antibiotics select ClpP out‐of‐function mutations in Firmicutes in vitro. Studying these ClpP defects provides a map of amino acids relevant for the function of ClpP. Several mutated ClpP proteins were purified, and their diverse impairments were characterised. A new S. aureus ClpP:ADEP co‐crystal structure shows an electrostatic network stabilising the N‐terminal gate.

Recently, many efforts have been made to develop N-methyl-D-aspartic acid receptor antagonists for treating different pathological conditions such as thrombo-embolic stroke, traumatic head injury, Huntington's, Parkinson's, and Alzheimer's diseases). However, as side-effects limit the use of most antagonists, new drugs are still required. In this work, we performed a (quantitative) structure-activity relationship analysis of 17 phenyl-amidine derivatives (1a-1q), reported as N-methyl-D-aspartic acid receptor antagonists, and used this data to rationally design the triazolyl-amidines. The best (quantitative) structure-activity relationship model constructed by multiple linear regression analysis presented high data fitting (R = 0.914) was able to explain 83.6% of the biological data variance (R(2) = 0.836), presented a satisfactory internal predictive ability (Q(2) = 0.609) and contained the descriptors (E(HOMO), Ovality and cLogP). Our assays confirmed that glutamate promotes an extensive cell death in avian neurons (77%) and 2a and 2b protected the neurons from the glutamate effect (from 77% to 27% and 45%, respectively). The results of neurotoxicity and cytotoxicity on Vero cells suggested the favorable profile of 2a and 2b. Also, the molecular modeling used to predict the activity, the interaction with the receptor and the pharmacokinetic and toxicity of the triazolyl-amidines pointed them as a promising class for further exploration as N-methyl-D-aspartic acid receptor antagonists.

Receptor-dependent four-dimensional quantitative structure–activity relationship (RD-4D-QSAR) studies were applied on a series of 21 peptides reversible inhibitors of Trypanosoma cruzi trypanothione reductase (TR) (Amino Acids, 20, 2001, 145). The RD-4D-QSAR (J Chem Inform Comp Sci, 43, 2003, 1591) approach can evaluate multiple conformations from molecular dynamics simulation and several superposition structure alignments inside a box composed by unitary cubic cells. The descriptors are the occupancy frequency of the atoms types inside the grid cells. We could develop 3D-QSAR models that were highly predictive (q2 above 0.71). The 3D-QSAR models can be visualized as a spatial map of atom types that are important on the comprehension of the ligand–enzyme interaction mechanism, pointing main pharmacophoric groups and TR subsites described in the literature. We were able also to identify some TR subsites for further development in the drug discovery process against tropical diseases not yet studied.

Proteases have received enormous interest from the research and medical communities because of their significant roles in several human diseases. Some examples include the involvement of thrombin in thrombosis, HIV-1 protease in Acquired Immune Deficiency Syndrome, cruzain in Trypanosoma cruzi infection, and membrane-type 1 matrix metalloproteinase in tumor invasion and metastasis. Many efforts has been undertaken to design effective inhibitors featuring potent inhibitory activity, specificity, and metabolic stability to those proteases involved in such pathologies. Protease inhibitors usually target the active site, but some of them act by other inhibitory mechanisms. The understanding of the structure-function relationships of proteases and inhibitors has an impact on new inhibitor drugs designing. In this paper, the structures of four proteases (thrombin, HIV-protease, cruzain, and a matrix metalloproteinase) are briefly reviewed, and used as examples of the importance of proteases for the development of new treatment strategies, leading to a longer and healthier life.

Traditionally, monoxenous trypanosomatid protozoa are not believed to infect vertebrate cells. Using light and electron microscopy, we show that the monoxenous trypanosomatids Crithidia deanei and Herpetomonas roitmani are able to infect dermal mouse fibroblasts in vitro. We present experimental evidence of phagocytosis of these trypanosomatids, and demonstrate their survival in vertebrate cells. This paper raises the question about the role of C. deanei and H. roitmani, and perhaps other monoxenous trypanosomatid species, in opportunistic infections of immunocompromised individuals and cutaneos lesions in vertebrate hosts.