Novel 4-Azapregnene Derivatives as Potential Anticancer Agents: Synthesis, Antiproliferative Activity and Molecular Docking Studies.

A series of novel 21E-arylidene-4-azapregn-5-ene steroids has been successfully designed, synthesized and structurally characterized, and their antiproliferative activity was evaluated in four different cell lines. Within this group, the 21E-(pyridin-3-yl)methylidene derivative exhibited significant cytotoxic activity in hormone-dependent cells LNCaP (IC50 = 10.20 µM) and T47-D cells (IC50 = 1.33 µM). In PC-3 androgen-independent cells, the steroid 21E-p-nitrophenylidene-4-azapregn-5-ene was the most potent of this series (IC50 = 3.29 µM). Considering these results, the 21E-(pyridin-3-yl)methylidene derivative was chosen for further biological studies on T47-D and LNCaP cells, and it was shown that this azasteroid seems to lead T47-D cells to apoptotic death. Finally, molecular docking studies were performed to explore the affinity of these 4-azapregnene derivatives to several steroid targets, namely 5α-reductase type 2, estrogen receptor α, androgen receptor and CYP17A1. In general, compounds presented higher affinity to 5α-reductase type 2 and estrogen receptor α.

Fungal diversity and mycotoxins detected in maize stored in silo-bags: a review.

Silo-bags are hermetic storage systems that inhibit fungal growth because of their atmosphere with low humidity, as well as low pH and O2 concentrations, and a high CO2 concentration. If a silo-bag with stored maize loses its hermetic nature, it favors the development of fungi and the production of mycotoxins. To the best of our knowledge, this is the first review on the diversity of fungal species and mycotoxins that were reported in maize stored under the environmental conditions provided by silo-bags. The genera Penicillium, Aspergillus and Fusarium were found more frequently, whereas Acremonium spp., Alternaria sp., Candida sp., Cladosporium sp., Debaryomyces spp., Epiconum sp., Eupenicillium spp., Eurotium sp., Eurotium amstelodami, Hyphopichia spp., Hyphopichia burtonii, Moniliella sp., Wallemia sp. and genera within the orden Mucorales were reported less recurrently. Despite finding a great fungal diversity, all of the studies focused their investigations on a small group of toxins: fumonisins (FBs), aflatoxins (AFs), deoxynivalenol (DON), zearalenone (ZEA), patulin (PAT), toxin T2 (T2) and ochratoxin (OT). Of the FBs, fumonisin B1 and fumonisin B2 presented higher incidence percentages, followed by fumonisin B3 . Of the AFs, the only one reported was aflatoxin B1. The mycotoxins DON, ZEA and OT were found with lower incidences, whereas PAT and T2 were not detected. Good management practices of the silo-bags are necessary to achieve a hermetically sealed environment, without exchange of gases and water with the external environment during the storage period. © 2022 Society of Chemical Industry.

Sperm chromatin protamination influences embryo development in unsexed and sexed bull semen.

Sex selection through sperm sorting offers advantages in regards selection pressure in high-producing livestock. However, the sex-sorting process results in sperm membrane and DNA damage that ultimately decrease fertility. We hypothesized that given the role of protamines in DNA packaging, protamine deficiency could account, at least partially, for the DNA damage observed following sperm sex sorting. To test this, we compared protamine status between unsexed and sexed spermatozoa from two bulls using the fluorochrome chromomycin A3 (CMA3) and flow cytometry. Then, we assessed embryo development following in vitro fertilization (IVF) using the same sperm treatments. Overall, sperm protamination was not different between sexed and unsexed semen. However, one of the two bulls displayed higher rates of protamine deficiency for both unsexed and sexed semen (P < 0.05). Moreover, unsexed semen from this bull yielded lower blastocyst (P < 0.05) and blastocyst hatching rates than unsexed sperm from the other bull. CMA3-positive staining was negatively correlated with cleavage (R2 85.1, P = 0.003) and blastocyst hatching (R2 87.6, P = 0.006) rates in unsexed semen. In conclusion, while the sex-sorting process had no effect on sperm protamine content, we observed a bull effect for sperm protamination, which correlated to embryo development rates following IVF.

Highlights on Steroidal Arylidene Derivatives as a Source of Pharmacologically Active Compounds: A Review.

Steroids constitute a unique class of chemical compounds, playing an important role in physiopathological processes, and have high pharmacological interest. Additionally, steroids have been associated with a relatively low toxicity and high bioavailability. Nowadays, multiple steroidal derivatives are clinically available for the treatment of numerous diseases. Moreover, different structural modifications on their skeleton have been explored, aiming to develop compounds with new and improved pharmacological properties. Thus, steroidal arylidene derivatives emerged as a relevant example of these modifications. This family of compounds has been mainly described as 17ß-hydroxysteroid dehydrogenase type 1 and aromatase inhibitors, as well as neuroprotective and anticancer agents. Besides, due to their straightforward preparation and intrinsic chemical reactivity, steroidal arylidene derivatives are important synthetic intermediates for the preparation of other compounds, particularly bearing heterocyclic systems. In fact, starting from arylidenesteroids, it was possible to develop bioactive steroidal pyrazolines, pyrazoles, pyrimidines, pyridines, spiro-pyrrolidines, amongst others. Most of these products have also been studied as anti-inflammatory and anticancer agents, as well as 5α-reductase and aromatase inhibitors. This work aims to provide a comprehensive overview of steroidal arylidene derivatives described in the literature, highlighting their bioactivities and importance as synthetic intermediates for other pharmacologically active compounds.

New Estrone Oxime Derivatives: Synthesis, Cytotoxic Evaluation and Docking Studies.

The interest in the introduction of the oxime group in molecules aiming to improve their biological effects is increasing. This work aimed to develop new steroidal oximes of the estrane series with potential antitumor interest. For this, several oximes were synthesized by reaction of hydroxylamine with the 17-ketone of estrone derivatives. Then, their cytotoxicity was evaluated in six cell lines. An estrogenicity assay, a cell cycle distribution analysis and a fluorescence microscopy study with Hoechst 3358 staining were performed with the most promising compound. In addition, molecular docking studies against estrogen receptor α, steroid sulfatase, 17ß-hydroxysteroid dehydrogenase type 1 and ß-tubulin were also accomplished. The 2-nitroestrone oxime showed higher cytotoxicity than the parent compound on MCF-7 cancer cells. Furthermore, the oximes bearing halogen groups in A-ring evidenced selectivity for HepaRG cells. Remarkably, the Δ9,11-estrone oxime was the most cytotoxic and arrested LNCaP cells in the G2/M phase. Fluorescence microscopy studies showed the presence of condensed DNA typical of prophase and condensed and fragmented nuclei characteristic of apoptosis. However, this oxime promoted the proliferation of T47-D cells. Interestingly, molecular docking studies estimated a strong interaction between Δ9,11-estrone oxime and estrogen receptor α and ß-tubulin, which may account for the described effects.

Chemical composition and antifungal properties of commercial essential oils against the maize phytopathogenic fungus Fusarium verticillioides.

The aim of the present study was to analyze the chemical composition of Curcuma longa, Pimenta dioica, Rosmarinus officinalis, and Syzygium aromaticum essential oils (EOs) and their antifungal and anti-conidiogenic activity against Fusarium verticillioides. The chemical profile of the EOs was determined by GC/MS. The antifungal and anti-conidiogenic activities were evaluated by the agar dilution method. The tested concentrations were 1000ppm, 500ppm, 250ppm and 125ppm. S. aromaticum EO exhibited the highest antifungal effect, followed by P. dioica and to a lesser extent C. longa. The major compounds of these EOs were eugenol (88.70% in S. aromaticum and 16.70% in P. dioica), methyl eugenol (53.09% in P. dioica), and α-turmerone (44.70%), ß-turmerone (20.67%), and Ar-turmerone (17.27%) in C. longa. Rosmarinus officinalis poorly inhibited fungal growth; however, it was the only EO that inhibited conidial production, with its major components being 1,8-cineole (53.48%), α-pinene (15.65%), and (-)-camphor (9.57%). Our results showed that some compounds are capable of decreasing mycelial growth without affecting sporulation, and vice versa. However, not all the compounds of an EO are responsible for its bioactivity. In the present work, we were able to identify different major compounds or mixtures of major compounds that were responsible for antifungal and anti-conidiogenic effects. Further experiments combining these pure components are necessary in order to achieve a highly bioactive natural formulation against the phytopathogenic fungus F. verticillioides.

Line Immunoassay for Confirmation and Discrimination of Human T-Cell Lymphotropic Virus Infections in Inconclusive Western Blot Serum Samples from Brazil.

Difficulties in confirming and discriminating human T-cell lymphotropic virus type 1 (HTLV-1) and HTLV-2 infections by serological Western blot (WB) assays (HTLV Blot 2.4; MP Biomedicals) have been reported in Brazil, mainly in HIV/AIDS patients, with a large number of WB-indeterminate and WB-positive but HTLV-untypeable results. Nonetheless, a line immunoassay (LIA) (INNO-LIA HTLV-I/II; Fujirebio) provided enhanced specificity and sensitivity for confirming HTLV-1/2 infections. To add information concerning the improved ability of the LIA in relation to WB when applied to samples of individuals from different risk groups from Brazil, we performed the present study. Three groups were analyzed: group 1 (G1), with 62 samples from HIV/AIDS patients from São Paulo, SP (48 WB indeterminate and 14 HTLV untypeable); group 2 (G2), with 24 samples from patients with hepatitis B or hepatitis C from São Paulo (21 WB indeterminate and 3 HTLV untypeable; 17 HIV seropositive); and group 3 (G3), with 25 samples from an HTLV outpatient clinic in Salvador, Bahia (16 WB indeterminate and 9 HTLV untypeable; all HIV seronegative). Overall, the LIA confirmed HTLV-1/2 infection (HTLV-1, HTLV-2, or HTLV) in 66.1% (G1), 83.3% (G2), and 76.0% (G3) of samples. Interestingly, the majority of WB-indeterminate results were confirmed by the LIA as being HTLV-2 positive in G1 and G2 but not in G3, in which the samples were defined as being HTLV-1 or HTLV positive. These results agree with the virus types that circulate in such patients of different regions in Brazil and emphasize that the LIA is the best serological test for confirming HTLV-1 and HTLV-2 infections, independently of being applied in HTLV-monoinfected or HTLV-coinfected individuals.

Performance of Commercially Available Serological Screening Tests for Human T-Cell Lymphotropic Virus Infection in Brazil.

Serological screening for human T-cell lymphotropic virus type 1 (HTLV-1) is usually performed using enzyme-linked immunosorbent assay (ELISA), particle agglutination, or chemiluminescence assay kits. Due to an antigen matrix improvement entailing the use of new HTLV antigens and changes in the format of HTLV screening tests, as well as newly introduced chemiluminescence assays (CLIAs), a systematic evaluation of the accuracy of currently available commercial tests is warranted. We aimed to assess the performance of commercially available screening tests for HTLV infection diagnosis. A diagnostic accuracy study was conducted on a panel of 397 plasma samples: 200 HTLV-negative plasma samples, 170 HTLV-positive plasma samples, and 27 plasma samples indeterminate by Western blotting (WB). WB-indeterminate samples (i.e., those yielding no specific bands for HTLV-1 and/or HTLV-2) were assessed by PCR, and the results were used to compare agreement among the commercially available ELISA screening tests. For performance analysis, WB-indeterminate samples were excluded, resulting in a final study panel of 370 samples. Three ELISA kits (Murex HTLV-1/2 [Murex], anti-HTLV-1/2 SYM Solution [SYM Solution], and Gold ELISA HTLV-1/2 [Gold ELISA]) and one CLIA kit (Architect rHTLV-1/2) were evaluated. All screening tests demonstrated 100% sensitivity. Concerning the HTLV-negative samples, the SYM Solution and Gold ELISA kits had specificity values of >99.5%, while the Architect rHTLV-1/2 test presented 98.1% specificity, followed by Murex, which had a specificity of 92.0%. Regarding the 27 samples with WB-indeterminate results, after PCR confirmation, all ELISA kits showed 100% sensitivity but low specificity. Accuracy findings were corroborated by the use of Cohen's kappa value, which evidenced slight and fair agreement between PCR analysis and ELISAs for HTLV infection diagnosis. Based on the data, we believe that all evaluated tests can be safely used for HTLV infection screening.

Use of platelet-rich plasma on in vitro maturation during bovine embryo production.

One of the crucial aspects to be considered for successful in vitro production (IVP) of embryos is the composition of the various media used throughout the stages of this reproductive biotechnology. The cell culture media employed should fulfill the metabolic requirements of both gametes during oocyte maturation and sperm development, as well as the embryo during its initial cell divisions. Most IVP protocols incorporate blood serum into the media composition as a source of hormones, proteins, growth factors, and nutrients. Numerous studies have suggested Platelet-Rich Plasma (PRP) as a substitute for fetal sera in cell culture, particularly for stem cells. Therefore, the objective of this study is to assess the potential use of PRP as a replacement for fetal bovine serum (FBS) during oocyte maturation for in vitro production of bovine embryos. During in vitro maturation (IVM), cumulus-oocyte complexes (COCs) were allocated into the following experimental groups: Group G1 (IVM medium with 5% PRP); Group G2 (MIV medium with 5% PRP and 5% SFB); Group G3 (MIV medium with 5% SFB); and Group G4 (MIV medium without either PRP or SFB). Subsequently, the cumulus-oocyte complexes were fertilized with semen from a single bull, and the resulting zygotes were cultured for seven days. Cleavage and blastocyst formation rates were assessed on days 2 and 7 of embryonic development, respectively. The quality of matured COCs was also evaluated by analyzing the gene expression of HSP70, an important protein associated with cellular stress. The results demonstrated that there were no significant differences among the experimental groups in terms of embryo production rates, both in the initial cleavage stages and blastocyst formation (except for the G4 group, which exhibited a lower blastocyst formation rate on D7, as expected). This indicates that PRP could be a cost-effective alternative to SFB in the IVP of embryos.

Synthesis, In Vitro Biological Evaluation of Antiproliferative and Neuroprotective Effects and In Silico Studies of Novel 16E-Arylidene-5α,6α-epoxyepiandrosterone Derivatives.

Steroids constitute an important class of pharmacologically active molecules, playing key roles in human physiology. Within this group, 16E-arylideneandrostane derivatives have been reported as potent anti-cancer agents for the treatment of leukemia, breast and prostate cancers, and brain tumors. Additionally, 5α,6α-epoxycholesterol is an oxysterol with several biological activities, including regulation of cell proliferation and cholesterol homeostasis. Interestingly, pregnenolone derivatives combining these two modifications were described as potential neuroprotective agents. In this research, novel 16E-arylidene-5α,6α-epoxyepiandrosterone derivatives were synthesized from dehydroepiandrosterone by aldol condensation with different aldehydes followed by a diastereoselective 5α,6α-epoxidation. Their cytotoxicity was evaluated on tumoral and non-tumoral cell lines by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Furthermore, the assessment of the neuroprotective activity of these derivatives was performed in a dopaminergic neuronal cell line (N27), at basal conditions, and in the presence of the neurotoxin 6-hydroxydopamine (6-OHDA). Interestingly, some of these steroids had selective cytotoxic effects in tumoral cell lines, with an IC50 of 3.47 µM for the 2,3-dichlorophenyl derivative in the breast cancer cell line (MCF-7). The effects of this functionalized epoxide on cell proliferation (Ki67 staining), cell necrosis (propidium iodide staining), as well as the analysis of the nuclear area and near neighbor distance in MCF-7 cells, were analyzed. From this set of biological studies, strong evidence of the activation of apoptosis was found. In contrast, no significant neuroprotection against 6-OHDA-induced neurotoxicity was observed for the less cytotoxic steroids in N27 cells. Lastly, molecular docking simulations were achieved to verify the potential affinity of these compounds against important targets of steroidal drugs (androgen receptor, estrogen receptor α, and 5α-reductase type 2, 17α-hydroxylase-17,20-lyase and aromatase enzymes). This in silico study predicted a strong affinity between most novel steroidal derivatives and 5α-reductase and 17α-hydroxylase-17,20-lyase enzymes.

Endophytic Trichoderma species from rubber trees native to the Brazilian Amazon, including four new species.

Fungi belonging to the genus Trichoderma have been widely recognized as efficient controllers of plant diseases. Although the majority of isolates currently deployed, thus far, have been isolated from soil, endophytic Trichoderma spp. is considered to be a promising option for application in biocontrol. In this study, 30 endophytic Trichoderma isolates-obtained from the leaves, stems, and roots of wild Hevea spp. in the Brazilian Amazon-were analyzed using specific DNA barcodes: sequences of internal transcribed spacers 1 and 2 of rDNA (ITS region), genes encoding translation elongation factor 1-α (TEF1-α), and the second largest subunit of RNA polymerase II (RPB2). The genealogical concordance phylogenetic species recognition (GCPSR) concept was used for species delimitation. A phylogenetic analysis showed the occurrence of Trichoderma species, such as T. erinaceum, T. ovalisporum, T. koningiopsis, T. sparsum, T. lentiforme, T. virens, and T. spirale. Molecular and morphological features resulted in the discovery of four new species, such as T. acreanum sp. nov., T. ararianum sp. nov., T. heveae sp. nov., and T. brasiliensis sp. nov. The BI and ML analyses shared a similar topology, providing high support to the final trees. The phylograms show three distinct subclades, namely, T. acreanum and T. ararianum being paraphyletic with T. koningiopsis; T. heveae with T. subviride; and T. brasiliensis with T. brevicompactum. This study adds to our knowledge of the diversity of endophytic Trichoderma species in Neotropical forests and reveals new potential biocontrol agents for the management of plant diseases.

New Scaffolds of Proteasome Inhibitors: Boosting Anticancer Potential by Exploiting the Synergy of In Silico and In Vitro Methodologies.

Cancer is a complex multifactorial disease whose pathophysiology involves multiple metabolic pathways, including the ubiquitin-proteasome system, for which several proteasome inhibitors have already been approved for clinical use. However, the resistance to existing therapies and the occurrence of severe adverse effects is still a concern. The purpose of this study was the discovery of novel scaffolds of proteasome inhibitors with anticancer activity, aiming to overcome the limitations of the existing proteasome inhibitors. Thus, a structure-based virtual screening protocol was developed using the structure of the human 20S proteasome, and 246 compounds from virtual databases were selected for in vitro evaluation, namely proteasome inhibition assays and cell viability assays. Compound 4 (JHG58) was shortlisted as the best hit compound based on its potential in terms of proteasome inhibitory activity and its ability to induce cell death (both with IC50 values in the low micromolar range). Molecular docking studies revealed that compound 4 interacts with key residues, namely with the catalytic Thr1, Ala20, Thr21, Lys33, and Asp125 at the chymotrypsin-like catalytic active site. The hit compound is a good candidate for additional optimization through a hit-to-lead campaign.

MTHFR Polymorphisms and Cardiac Parameters in Patients with Diabetic Retinopathy.

BACKGROUND: Diabetes Mellitus (DM) is directly associated with cardiovascular dysfunctions and microvascular complications, such as diabetic retinopathy (DR). The association between DR and increased risks of developing cardiovascular diseases has been described. The low activity of the Methylenetetrahydrofolate reductase (MTHFR), an enzyme involved in the metabolism of homocysteine, can lead to hyperhomocysteinemia that has already been related to cardiac outcomes and resistance to insulin. The A1298C and C677T polymorphisms in the MTHFR can reduce enzyme activity. OBJECTIVE: The study aims to analyze the association between MTHFR genotypes and cardiac parameters in patients with DR. METHODS: DM patients diagnosed with DR (n=65) were categorized and compared according to MTHFR genotypes A1298C (AA and AC+CC groups) and C677T (CC and CT+TT) groups; biochemical, cardiological, anthropometric, genetic, lifestyle and vitamin B9 and B12 consumption variables. Fischer's exact test and Poisson regression were performed to assess the relationship between variables. RESULTS: Comparing echocardiographic and electrocardiogram parameters within genotypic groups, we found a significant association between left atrial dilation and C677T polymorphism. Left atrium diameter was higher in the T allele carriers (CT+TT group), with a prevalence ratio of 0.912. This association was confirmed in the regression model, including confounding variables. The other cardiac structural and functional parameters studied were not significantly associated with the A1298C or C677T genotypes. CONCLUSION: The MTHFR C677T genotype may contribute to atrial remodeling in RD patients. We found an association between the diameter of the left atrium and the T allele of the MTHFR C677T polymorphism in patients with DR.

Effect of Carbon Sources on the Production of Volatile Organic Compounds by Fusarium verticillioides.

The aim of the present study was to evaluate the effect of different carbon sources on the hydrocarbon-like volatile organic compounds (VOCs) of Fusarium verticillioides strain 7600 through a Principal Component Analysis approach, and to explore their diesel potential by using data from the literature. The fungus was cultivated in GYAM culture medium, and five carbon sources were evaluated: glucose, sucrose, xylose, lactose, and fructose. The VOCs were collected using a close-loop apparatus and identified through GC-MS. The same profile of 81 VOCs was detected with all treatments, but with different relative percentages among carbon sources. The production of branched-chain alkanes (30 compounds) ranged from 25.80% to 38.64%, straight-chain alkanes (12 compounds) from 22.04% to 24.18%, benzene derivatives (12 compounds) from 7.48% to 35.58%, and the biosynthesis of branched-chain alcohols (11 compounds) was from 6.82% to 16.71%, with lower values for the remaining groups of VOCs. Our results show that F. verticillioides has the metabolic potential to synthesize diesel-like VOCs. Further research should include the optimization of culture conditions other than carbon sources to increase the production of certain groups of VOCs.

Insecticidal Activity of Essential Oils against Mealybug Pests (Hemiptera: Pseudococcidae): A Systematic Review and Meta-Analysis.

Most mealybugs of the Pseudococcidae family are important pests of agriculture and ornamental gardens. Our aim was to perform a review and meta-analysis on 14 published scientific articles on the insecticidal activity of essential oils (EOs) against mealybug species of the Pseudococcidae family. Data on (1) species, genus, families, and plant parts from which the EO was extracted; (2) the main compounds of each EO; (3) the highest and lowest concentrations tested; and (4) the application method used for the toxicological studies was collected from each study. The metafor package (R software) was used to perform a three-level random effects meta-analysis. The families Lamiaceae, Rutaceae, Myrtaceae, Zingiberaceae and Euphorbiaceae and the genera Citrus, Cymbopogon, Syzygium, Cinnamomum and Jatropha were the most used among the studies. According to the results from the meta-analyses, 13 out of 24 genera analyzed were effective against mealybugs. All methods were effective, but fumigation and indirect contact were the most frequently used methodologies. The results obtained from the present review and meta-analysis could be used for the potential development of natural biopesticide formulations against mealybugs belonging to the Pseudococcidae family.

Exploring Contact Toxicity of Essential Oils against Sitophilus zeamais through a Meta-Analysis Approach.

Sitophilus zeamais is a primary pest of maize. Our aim was to perform a qualitative review and meta-analyses with 56 scientific articles published from 1 January 2000 to 1 October 2022 dealing with direct (topical application) and indirect (impregnation of essential oils, EOs, onto filter paper or maize grains) contact toxicity of EOs against S. zeamais. Three independent meta-analyses of single means of LD50 (direct contact) and LC50 (indirect contact) were conducted using a random effect model. Essential oils more frequently evaluated were those belonging to Asteraceae, Apiaceae, Lamiaceae, Myrtaceae, Piperaceae, and Rutaceae. The LC50 global mean values were 33.19 µg/insect (CI95 29.81-36.95) for topical application; 0.40 µL/cm2 (CI95 0.25-0.65) for filter paper indirect contact; and 0.50 µL/g maize (CI95 0.27-0.90) for maize grains indirect contact. The species Carum carvi, Salvia umbratica, Ilicium difengpi, Periploca sepium, Cephalotaxus sinensis, Murraya exotica, Rhododendron anthopogonoides, Ruta graveolens, Eucalyptus viminalis, Ocotea odorifera, Eucalyptus globulus, Eucalyptus dunnii, Anethum graveolens, Ilicium verum, Cryptocarya alba, Azadirachta indica, Chenopodium ambrosioides, Cupressus semperivens, Schinus molle, Piper hispidinervum, Mentha longifolia, and Croton pulegiodorus showed LC50 or LD50 values lower than the global means, indicating good insecticidal properties. Our results showed that EOs have great potential to be used as bioinsecticides against S. zeamais.

10ß-Hydroxyestra-1,4-diene-3,17-dione as potential antiproliferative agent: in vitro biological evaluation and in silico studies.

10ß-Hydroxyestra-1,4-diene-3,17-dione (HEDD) is a natural product described as having neuroprotective activity. However, the cytotoxic properties of this quinol are barely studied. Thus, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed in six cell lines (MCF-7, T47-D, LNCaP, HepaRG, Caco-2 and NHDF). Additionally, an in vitro estrogenicity assay and a cell viability analysis together with in silico molecular docking studies were carried out in order to understand the potential mechanism of cytotoxicity. Computational predictions of its pharmacokinetic and toxicity properties were also performed. Surprisingly, HEDD displayed marked cytotoxic activity, particularly against hormone-dependent cancer cells and the flow cytometry analysis revealed that HEDD markedly reduced the viability of hepatic cancer cells. Molecular docking studies suggested a high affinity towards the estrogen receptor α and 17ß-hydroxysteroid dehydrogenase type 1. Moreover, it was predicted that HEDD may have good oral bioavailability and a low maximum tolerated dose in humans.

Potential role of Limosilactobacillus fermentum as a probiotic with anti-diabetic properties: A review.

Oxidative stress, inflammation, and gut microbiota impairments have been implicated in the development and maintenance of diabetes mellitus. Strategies capable of recovering the community of commensal gut microbiota and controlling diabetes mellitus have increased in recent years. Some lactobacilli strains have an antioxidant and anti-inflammatory system capable of protecting against oxidative stress, inflammation, and diabetes mellitus. Experimental studies and some clinical trials have demonstrated that Limosilactobacillus fermentum strains can beneficially modulate the host antioxidant and anti-inflammatory system, resulting in the amelioration of glucose homeostasis in diabetic conditions. This review presents and discusses the currently available studies on the identification of Limosilactobacillus fermentum strains with anti-diabetic properties, their sources, range of dosage, and the intervention time in experiments with animals and clinical trials. This review strives to serve as a relevant and well-cataloged reference of Limosilactobacillus fermentum strains capable of inducing anti-diabetic effects and promoting health benefits.

BRAX, Brazilian labeled chest x-ray dataset.

Chest radiographs allow for the meticulous examination of a patient's chest but demands specialized training for proper interpretation. Automated analysis of medical imaging has become increasingly accessible with the advent of machine learning (ML) algorithms. Large labeled datasets are key elements for training and validation of these ML solutions. In this paper we describe the Brazilian labeled chest x-ray dataset, BRAX: an automatically labeled dataset designed to assist researchers in the validation of ML models. The dataset contains 24,959 chest radiography studies from patients presenting to a large general Brazilian hospital. A total of 40,967 images are available in the BRAX dataset. All images have been verified by trained radiologists and de-identified to protect patient privacy. Fourteen labels were derived from free-text radiology reports written in Brazilian Portuguese using Natural Language Processing.

Metabolic impact of the VDR rs1544410 in diabetic retinopathy.

AIMS: To investigate the association between BsmI and DM2 in patients with and without DR and to correlate with clinical parameters in a population in northeastern Brazil. METHODS: Cross-sectional case-control study in which data were collected from 285 individuals, including 128 patients with DM2 and 157 with DR. Clinical, biochemical and anthropometric parameters were analyzed, in addition to the single nucleotide polymorphism (SNP) BsmI of the VDR gene (rs1544410), genotyped by PCR-RFLP. RESULTS: In the DR group we found a greater number of patients using insulin therapy (p = 0.000) and with longer duration of DM2 (p = 0.000), in addition to higher serum creatinine values (p = 0.001). Higher fasting glucose levels and higher frequency of insulinoterapy were independently observed in patients with DR and b allele carriers, when compared to BB. CONCLUSION: The association of the bb/Bb genotypes (rs1544410) of the VDR gene with increased blood glucose levels and insulinoterapy may represent worse glicemic control in rs1544410 b allele carriers in DR Latin American individuals.