Fermenting Acerola (Malpighia emarginata D.C.) and Guava (Psidium guayaba L.) Fruit Processing Co-Products with Probiotic Lactobacilli to Produce Novel Potentially Synbiotic Circular Ingredients.

This study evaluated the effects of acerola and guava fruit processing co-products fermented with probiotic Lactobacillus acidophilus LA-05 and Lacticaseibacillus paracasei L-10 on the abundance of different intestinal bacterial groups and microbial metabolic activity during 48 h of in vitro fecal fermentation. Digested fermented fruit co-products increased the relative abundance of beneficial bacterial groups while overall decreasing or maintaining the relative abundance of non-beneficial bacterial groups, suggesting selective stimulatory effects on beneficial bacterial intestinal populations. The fermented co-products stimulated microbial metabolic activity due to decreased pH, sugar consumption, short-chain fatty acid production, phenolic compound and metabolic profile alteration, and high antioxidant capacity during fecal fermentation. Acerola and guava co-products have high nutritional value and bioactive compounds whose fermentation with probiotics improves their potential functionalities. The results show that fermented fruit co-products could induce beneficial changes in the relative abundance of several bacterial groups as well as in the metabolic activity of the human intestinal microbiota. These results highlight their potential as novel and circular candidates for use as synbiotic ingredients.

Exercise as medicine! Physical activity mitigated the impact of the COVID-19 pandemic on depressive symptoms in adults with depression.

We investigated the longitudinal association between physical activity (PA) and symptoms of depression and anxiety in people with depression during the COVID-19 pandemic. We used data from baseline (June 2020) to wave 3 (June 2021) of the PAMPA Cohort, an ambispective cohort with adults in south Brazil. The Hospital Anxiety and Depression Scale assessed depressive and anxiety symptoms in all waves. Participants reported frequency (minutes), type (aerobic, strength, combined), and place (out of home, at home) of physical activity at baseline. Generalized linear models were used to investigate the interaction between time and PA, adjusting for possible confounding variables. Subjective memory decline was assessed using multivariate Cox proportional hazard regression models to obtain adjusted hazard ratio (HR) and respective 95% confidence interval (CI). Participants (n = 424) with self-reported clinically diagnosed depression were included. We observed a non-linear increase trajectory of depression during the first year of the COVID-19 pandemic. PA was associated with a slower trajectory of depressive (slope: -1.89; 95%CI: -3.34, -0.43 points) but not anxiety (slope: -1.33; 95%CI: -2.93, 0.25 points) symptoms during the COVID-19 pandemic. Participants who continued physically active from pre-pandemic in wave 1 showed a lower risk of subjective memory decline during follow-up than those who persisted inactive in the same period (HR: 0.52; 95%CI: 0.30, 0.89). PA attenuated the impact of the COVID-19 pandemic on depressive symptoms in adults living with depression in south Brazil. Regularity of physical activity was associated with fewer depression and anxiety symptoms and a lower risk of subjective memory decline.

Longitudinal impact of leisure-time physical activity on pain intensity and daily activity limitation in people with low back pain. Findings from the PAMPA cohort.

OBJECTIVE: We aimed to prospectively evaluate the association between leisure-time physical activity and outcomes related to low back pain (LBP), such as pain intensity and daily activity limitation. METHODS: We analyzed data from the PAMPA (Prospective Study about Mental and Physical Health) cohort, a longitudinal study with adults residing in Southern Brazil. Participants answered an online-based, self-administered questionnaire. Physical activity was assessed as minutes per week, and those who reported engaging in 150 min/week or more were considered active. We also assessed the types of activities participants engaged. Pain intensity was assessed with a numeric pain rating scale (from 0 to 10), and participants reported whether their pain restricted their daily activities. Generalized linear models were used to investigate the association between physical activity and LBP outcomes. RESULTS: Data from 991 individuals (82.7% women) aged 38.9 ± 13.9 were analyzed. Pain intensity was higher in those inactive in waves one (ß: 0.54; 95 % CI 0.23, 0.86), three (ß: 0.38; 95% CI 0.02, 0.75), and four (ß: 0.48; 95% CI 0.06, 0.90). Also, being physically inactive at wave one was associated with a higher probability of daily activity limitation at waves two (IRR 1.77; 95% CI 1.27; 2.46), three (IRR 1.63; 95% CI 1.17, 2.29), and four (IRR 1.73; 95% CI 1.20, 2.50). CONCLUSION: Not practicing at least 150 min/week of physical activity resulted in higher levels of pain and an increased risk of daily activity limitation in individuals with LBP. Moreover, various forms of activities have shown to be advantageous in alleviating pain among this group.

IL-27 maintains cytotoxic Ly6C+ γδ T cells that arise from immature precursors.

In mice, γδ-T lymphocytes that express the co-stimulatory molecule, CD27, are committed to the IFNγ-producing lineage during thymic development. In the periphery, these cells play a critical role in host defense and anti-tumor immunity. Unlike αß-T cells that rely on MHC-presented peptides to drive their terminal differentiation, it is unclear whether MHC-unrestricted γδ-T cells undergo further functional maturation after exiting the thymus. Here, we provide evidence of phenotypic and functional diversity within peripheral IFNγ-producing γδ T cells. We found that CD27+ Ly6C- cells convert into CD27+Ly6C+ cells, and these CD27+Ly6C+ cells control cancer progression in mice, while the CD27+Ly6C- cells cannot. The gene signatures of these two subsets were highly analogous to human immature and mature γδ-T cells, indicative of conservation across species. We show that IL-27 supports the cytotoxic phenotype and function of mouse CD27+Ly6C+ cells and human Vδ2+ cells, while IL-27 is dispensable for mouse CD27+Ly6C- cell and human Vδ1+ cell functions. These data reveal increased complexity within IFNγ-producing γδ-T cells, comprising immature and terminally differentiated subsets, that offer new insights into unconventional T-cell biology.

Influence of fluoride characteristics on tooth surface protection in an erosive condition: A multifaceted characterization approach.

OBJECTIVE: To evaluate the effect of fluoride consistency and composition to protect enamel and dentin against the dental erosion. MATERIALS AND METHODS: Bovine enamel and dentin specimens were treated with artificial saliva, neutral fluoride gel (NFG), acidulated phosphate fluoride gel (AFG), neutral fluoride foam (NFF), and acidulated phosphate fluoride foam. The samples were subjected to cycling. Micro energy-dispersive X-ray fluorescence spectrometry, surface roughness (Ra), contact angle (CA), and scanning electron microscopy (SEM) were performed. Composition, CA and Ra data were analyzed by ANOVA and multiple comparison test (p < 0.05). RESULTS: The dentin protected had a significantly higher mineral content than in the control. Eroded unprotected enamel had higher Ra values than normal surfaces. Fluoride treatments increased the Ra in dentin samples. AFG increased the CA in enamel. Fluoride foams increased CA in dentin with reduced mineral loss. SEM analysis found a deposited layer on enamel treated with AFG and remnants of deposits on dentin treated with NFG and NFF. CONCLUSION: Regardless of the form of application, fluoride provided protection against erosion, however with different levels. CLINICAL SIGNIFICANCE: Applying the adequate fluoride form is relevant since the formulations have different effects on both enamel and dentin.

Pleonotoquinones, Cytotoxic Oxepinenaphthoquinones from Pleonotoma jasminifolia.

Two unusual naphthoquinones, named here as pleonotoquinones A (1) and B (2), were isolated along with two known anthraquinones (3 and 4) via chromatographic separations of an ethyl acetate extract of the roots of Pleonotoma jasminifolia. Compounds 1 and 2 are the first examples of quinones bearing a 2-methyloxepine moiety. The compounds were isolated with the aid of mass spectrometry and molecular networking, and their structures were resolved using 1D and 2D NMR and HRESIMS data. The isolated compounds were evaluated for their antiproliferative activity against human cancer cell lines, and compounds 1 and 2 displayed cytotoxicity against human colon cancer HCT116 cells (IC50 = 2.6 µM for compound 1 and IC50 = 4.3 µM for compound 2) and human liver cancer HepG2 cells (IC50 = 1.9 µM for compound 1 and IC50 = 6.4 µM for compound 2).

Revealing the Satellite DNA Content in Ancistrus sp. (Siluriformes: Loricariidae) by Genomic and Bioinformatic Analysis.

INTRODUCTION: Eukaryotic genomes are composed of simple, repetitive sequences, including satellite DNAs (satDNA), which are noncoding sequences arranged in tandem arrays. These sequences play a crucial role in genomic functions and innovations, influencing processes such as the maintenance of nuclear material, the formation of heterochromatin and the differentiation of sex chromosomes. In this genomic era, advances in next-generation sequencing and bioinformatics tools have facilitated the exhaustive cataloging of repetitive elements in genomes, particularly in non-model species. This study focuses on the satDNA content of Ancistrus sp., a diverse species of fish from the Loricariidae family. The genus Ancistrus shows significant karyotypic evolution, with extensive variability from the ancestral diploid number. METHODS: By means of bioinformatic approaches, 40 satDNA families in Ancistrus sp., constituting 5.19% of the genome were identified. Analysis of the abundance and divergence landscape revealed diverse profiles, indicating recent amplification and homogenization of these satDNA sequences. RESULTS: The most abundant satellite, AnSat1-142, constitutes 2.1% of the genome, while the least abundant, AnSat40-52, represents 0.0034%. The length of the monomer repeat varies from 16 to 142 base pairs, with an average length of 61 bp. These results contribute to understanding the genomic dynamics and evolution of satDNAs in Ancistrus sp. CONCLUSION: The study underscores the variability of satDNAs between fish species and provides valuable information on chromosome organization and the evolution of repetitive elements in non-model organisms.

Characterization of flours from the aroeira leaf (Schinus terebinthifolius Raddi), obtained by different drying methods.

The present work aimed at the development and characterization of aroeira leaf flour (Schinus terebinthifolius Raddi), obtained by lyophilization and drying in an air circulation oven. The technological, physical, physico-chemical, morphological, functional, and microbiological aspects were analyzed. Physico-chemical analysis identified the following properties with values provided respectively for fresh leaves (FOin) and flours (FES and FLIO): low water activity (0.984, 0.370, 0.387 g/100 g), moisture (64.52, 5.37, 7.97 g /100 g), ash (2.69, 6.51, and 6.89 g/100 g), pH (0.89, 4.45, 4.48 g/100 g), lipids (0.84, 1.67, 5.23 g/100 g), protein (3.29, 8.23, 14.12 g/100 g), carbohydrates (17.02, 53.12, 33.02 g/100 g), ascorbic acid (19.70, 34.20, 36.90 mg/100 g). Sources of fiber from plant leaves and flours (11.64, 25.1, 32.89 g/100 g) showed increased levels of luminosity. For NMR, the presence of aliphatic and aromatic compounds with olefinic hydrogens and a derivative of gallic acid were detected. The most abundant minerals detected were potassium and calcium. Micrographs identified the presence of irregular, non-uniform, and sponge-like particles. The main sugars detected were: fructose, glucose, and maltose. Malic, succinic, citric, lactic, and formic acids were found. Fifteen phenolic compounds were identified in the samples, highlighting: kaempferol, catechin, and caffeic acid. The values ​​found for phenolics were (447, 716.66, 493.31 mg EAG/100 g), flavonoids (267.60, 267.60, 286.26 EC/100 g). Antioxidant activity was higher using the ABTS method rather than FRAP for analysis of FOin, FES, and FLIO. Since the flours of the aroeira leaf have an abundant matrix of nutrients with bioactive properties and antioxidant activity, they have a potential for technological and functional use when added to food.

Interspecific cytogenomic comparison reveals a potential chromosomal centromeric marker in Proceratophrys frog species.

Among the repetitive elements, satellite DNA (SatDNA) emerges as extensive arrays of highly similar tandemly repeated units, spanning megabases in length. Given that the satDNA PboSat01-176, previously characterized in P. boiei, prompted our interest for having a high abundance in P. boiei and potential for centromeric satellite, here, we employed various approaches, including low coverage genome sequencing, followed by computational analysis and chromosomal localization techniques in four Proceratophrys species and, investigating the genomic presence and sharing, as well as its potential for chromosomal centromere marker in Proceratophrys frog species. Our findings demonstrate that PboSat01-176 exhibits high abundance across all four Proceratophrys species, displaying distinct characteristics that establish it as the predominant repetitive DNA element in these species. The satellite DNA is prominently clustered in the peri/centromeric region of the chromosomes, particularly in the heterochromatic regions. The widespread presence of PboSat01-176 in closely related Proceratophrys species reinforces the validity of the library hypothesis for repetitive sequences. Thus, this study highlighted the utility of the satDNA family PboSat01-176 as a reliable centromeric marker in Proceratophrys species, with potential to be applied in other species of anuran amphibians. The observed sharing and maintenance of this sequence within the genus suggest possibilities for future research, particularly through expanded sampling to elucidate parameters that underlie the library hypothesis and the evolutionary dynamics of satDNA sequences.

Paradoxical activation of oncogenic signaling as a cancer treatment strategy.

Cancer homeostasis depends on a balance between activated oncogenic pathways driving tumorigenesis and engagement of stress-response programs that counteract the inherent toxicity of such aberrant signaling. While inhibition of oncogenic signaling pathways has been explored extensively, there is increasing evidence that overactivation of the same pathways can also disrupt cancer homeostasis and cause lethality. We show here that inhibition of Protein Phosphatase 2A (PP2A) hyperactivates multiple oncogenic pathways and engages stress responses in colon cancer cells. Genetic and compound screens identify combined inhibition of PP2A and WEE1 as synergistic in multiple cancer models by collapsing DNA replication and triggering premature mitosis followed by cell death. This combination also suppressed the growth of patient-derived tumors in vivo. Remarkably, acquired resistance to this drug combination suppressed the ability of colon cancer cells to form tumors in vivo. Our data suggest that paradoxical activation of oncogenic signaling can result in tumor suppressive resistance.

Analysis of Lower Limb Amputations in Brazil's Public Health System over 13 Years.

OBJECTIVE: Understanding the causes of amputation is crucial for defining health policies that seek to avoid such an outcome, but only a few studies have investigated the epidemiology of patients submitted to amputations in developing countries. The objective of this study was to analyse all lower limb amputations performed in the public health system in Brazil over a 13 year period, evaluating trends in the number of cases, patient demographics, associated aetiologies, hospital length of stay, and in hospital mortality rate. METHODS: This was a retrospective, population based analysis of all lower limb amputations performed in the Brazilian public health system between 1 January 2008 and 31 December 2020. Using a public database, all types of amputations were selected, defining the number of procedures, their main aetiologies, anatomical level of limb loss, demographic data, regional distribution, and other variables of interest. RESULTS: A total of 633 455 amputations were performed between 2008 and 2020, mostly (55.6%) minor amputations, predominantly in males (67%). There was an upward trend in the number of amputations, determined mainly by the increase in major amputations (50.4% increase in the period). Elderly individuals have the highest rates of amputation. Diabetes mellitus (DM) is becoming the main primary diagnosis associated with amputations over the years. The highest in hospital mortality rate occurred after major amputations and was associated with peripheral arterial disease (PAD). CONCLUSION: Amputation rates in Brazil show an upward trend. DM is becoming the most frequent associated primary diagnosis, although PAD is the diagnosis most associated with major amputations and in hospital death.

A Preterm Rat Model for Pain Studies.

This research delves into the consequences of consistent pinprick stimulation on preterm offspring to ascertain its long-term implications for pain sensitivity. The primary objective of this protocol was to investigate the impact of neonatal pinprick stimuli on the pain threshold in the later stages of life using a preterm rat model. By establishing this model, we aim to advance the research on understanding and managing early postnatal pain associated with prematurity. The findings of this study indicate that while the baseline thresholds to mechanical stimuli remained unaffected, there was a notable increase in mechanical hypersensitivity following complete Freund's adjuvant (CFA) injection in adult rats. Interestingly, compared with male rats, female rats demonstrated heightened inflammatory hypersensitivity. Notably, maternal behavior, the weight of the litters, and the growth trajectory of the offspring remained unchanged by the stimulation. The manifestation of altered nociceptive responses in adulthood after neonatal painful stimuli could be indicative of changes in sensory processing and the functioning of glucocorticoid receptors. However, further research is needed to understand the underlying mechanisms involved and to develop interventions for the consequences of prematurity and neonatal pain in adults.

TcSERPIN, an inhibitor that interacts with cocoa defense proteins and has biotechnological potential against human pathogens.

In plants, serpins are a superfamily of serine and cysteine protease inhibitors involved in stress and defense mechanisms, with potential for controlling agricultural pests, making them important biotechnological tools. The objective of this study was to characterize a serpin from Theobroma cacao, called TcSERPIN, to identify its endogenous targets and determine its function and biotechnological potential. TcSERPIN has 390 amino acid residues and shows conservation of the main active site, RCL. Cis-elements related to light, stress, hormones, anaerobic induction, cell cycle regulation and defense have been identified in the gene's regulatory region. TcSERPIN transcripts are accumulated in different tissues of Theobroma cacao. Furthermore, in plants infected with Moniliophtora perniciosa and Phytophthora palmivora, the expression of TcSERPIN was positively regulated. The protein spectrum, rTcSERPIN, reveals a typical ß-sheet pattern and is thermostable at pH 8, but loses its structure with temperature increases above 66°C at pH 7. At the molar ratios of 0.65 and 0.49, rTcSERPIN inhibited 55 and 28% of the activity of papain from Carica papaya and trypsin from Sus scrofa, respectively. The protease trap containing immobilized rTcSERPIN captured endogenous defense proteins from cocoa extracts that are related to metabolic pathways, stress and defense. The evaluation of the biotechnological potential against geohelminth larvae showed that rTcSERPIN and rTcCYS4 (Theobroma cacao cystatin 4) reduced the movement of larvae after 24 hours. The results of this work show that TcSERPIN has ideal biochemical characteristics for biotechnological applications, as well as potential for studies of resistance to phytopathogens of agricultural crops.

Chemical profile and evaluation of the pharmacological activity of the dry extract and fraction of ethyl acetate obtained from the leaves of Mimosa caesalpiniifolia.

ETHNOPHARMACOLOGICAL RELEVANCE: Mimosa caesalpiniifolia (Sansão-do-Campo) is a native species of the caatinga in northeastern Brazil that has been studied for its potential anti-inflammatory and antidepressant activity. It is popularly consumed as a medicinal plant and its pharmacological benefits are evidenced in the literature. AIM OF THE STUDY: The present work was carried out to promote the chemical profile and evaluate the pharmacological activity of the dry extract and the ethyl acetate fraction obtained from the dry leaves of Mimosa caesalpiniifolia. MATERIALS AND METHODS: The leaves were collected in the municipality of Alfenas-MG and subjected to drying, followed by division in a knife mill. The preparation of the dry extract was carried out by the extraction method using simple percolation and the fraction was obtained by liquid-liquid partition. Part of the extractive solution was concentrated in a rotary evaporator followed by a drying process using the spray technique with the addition of colloidal silicon dioxide. The dry extract (33.33%) showed a higher yield in mass when compared to the yield of the ethyl acetate fraction (19.67%). The in vivo pharmacological evaluation was conducted with a total of 82 male Wistar rats that underwent cecal ligation and perforation surgery to induce the inflammatory process. One week after surgery, these animals were treated for 7 days with the dry extract and the ethyl acetate fraction and submitted to behavioral tests (open field and forced swimming). RESULTS: The chemical results were obtained through analysis by HPLC-PDA coupled to a mass spectrometer, enabling the verification of the presence of phenolic acids, flavonoids, aglycones, and glycosides, in addition to tannins. This corroborates with data present in the literature for the genus Mimosa sp. Some compounds had their structure determined, where they were identified as catechin (m/z 288.97), cassiaocidentalin A (m/z 560.75), and procyanidin B2 [(epi)catechin-(epi)catechin; m/z 576.83)]. It was found that the animals that were submitted to the treatment did not present statistically significant results, demonstrating that the pharmacological action evaluated in the test was not highlighted in this type of experiment. The groups that underwent treatment had an aggravated locomotor activity. CONCLUSIONS: The results found with the chemical study contributed to the knowledge of the plant species studied. On the other hand, further studies are needed to provide a better understanding of the pharmacological evaluation of Mimosa caesalpiniifolia.

Effects of Simulated Gastrointestinal Conditions on Combined Potentially Probiotic Limosilactobacillus fermentum 296, Quercetin, and/or Resveratrol as Bioactive Components of Novel Nutraceuticals.

This study evaluated the effects of simulated gastrointestinal conditions (SGIC) on combined potentially probiotic Limosilactobacillus fermentum 296 (~ 10 log CFU/mL), quercetin (QUE, 160 mg), and/or resveratrol (RES, 150 mg) as the bioactive components of novel nutraceuticals. Four different nutraceuticals were evaluated during exposure to SGIC and analyzed the plate counts and physiological status of L. fermentum 296, contents and bioaccessibility of QUE and RES, and antioxidant capacity. Nutraceuticals with QUE and RES had the highest plate counts (4.94 ± 0.32 log CFU/mL) and sizes of live cell subpopulations (28.40 ± 0.28%) of L. fermentum 296 after SGIC exposure. An index of injured cells (Gmean index, arbitrary unit defined as above 0.5) indicated that part of L. fermentum 296 cells could be entered the viable but nonculturable state when the nutraceuticals were exposed to gastric and intestinal conditions while maintaining vitality. The nutraceuticals maintained high contents (QUE ~ 29.17 ± 0.62 and RES ~ 23.05 mg/100 g) and bioaccessibility (QUE ~ 41.0 ± 0.09% and RES ~ 67.4 ± 0.17%) of QUE and RES, as well as high antioxidant capacity (ABTS assay ~ 88.18 ± 1.16% and DPPH assay 75.54 ± 0.65%) during SGIC exposure, which could be linked to the protective effects on L. fermentum 296 cells. The developed nutraceuticals could cross along the gastrointestinal tract with high concentrations of functioning potentially probiotic cells and bioavailable phenolic compounds to exert their beneficial impacts on consumer health, being an innovative strategy for the co-ingestion of these bioactive components.

National Cross-Sectional Epidemiological Analysis of the Impact of Pandemic COVID-19 on Vascular Procedures in Public Health System: 521,069 Procedures Over 4 Years.

BACKGROUND: During the COVID-19 pandemic, there was a dramatic increase in healthcare demand. Resources were redirected to care patients with COVID-19. Therefore, surgical treatments were affected, including those of vascular diseases. There are no studies evaluating the whole impact of the COVID-19 pandemic, considering all types of vascular procedures, both elective and urgent, in a large country. The aim of the present study was to analyze the impact on all types of vascular procedures performed in Brazilian public hospitals during the COVID-19 pandemic. METHODS: Cross-sectional population-based analysis of publicly available data referring to vascular procedures. Surgeries 2 years before the pandemic onset (2018-2019) and 2 years during pandemic (2020-2021) were included. RESULTS: We observed a total of 521,069 procedures. Decrease was observed in elective abdominal aortic aneurysm repairs both open surgery (P = 0.001) and endovascular surgery (P < 0.001), emergency open abdominal repairs (P = 0.005), elective thoracic aortic aneurysm repairs (P = 0.007), elective open peripheral aneurysm repairs (P = 0.038), carotid endarterectomies (P < 0.001) and angioplasties (P = 0.001), open revascularizations for peripheral arterial disease (P < 0.001), surgical treatment of chronic venous disease (P < 0.001) and sympathectomies for hyperhidrosis (P < 0.001). However, there was an increase of lower limb amputations (P = 0.027) and vena cava filter placements (P = 0.005). There was a reduction of almost US$17 million in financial investments. CONCLUSIONS: The reorganization of health systems led to a significant reduction in vascular procedures and decrease in financial investments. On the other hand, there was a significant increase in the number of lower limb amputations and vena cava filter placements.

Branched copolymer surfactants impart thermoreversible gelation to LAPONITE® gels.

This investigation seeks to integrate LAPONITE® clay gels with thermoresponsive branched copolymer surfactants (BCSs) to develop advanced functional materials with temperature-induced sol-gel behaviour. It is known that a diverse range of molecules adsorb strongly to clays which may be used to control liberation of the species in healthcare applications, and as such the development of polymer/clay hybrid materials which can add function to the native clay behaviour are of great interest. BCS were synthesised with a structure that encompasses poly(ethylene glycol)methacrylate (PEGMA), ethylene glycol dimethacrylate (EGDMA), and dodecanethiol (DDT), conferring versatile and tuneable thermoresponsive attributes. Systematic modulation of the monomer : DDT/initiator ratio was used to facilitate the synthesis of BCS architectures spanning a range of molecular weights. Through application of small-amplitude oscillatory shear (SAOS) rheology and small-angle neutron scattering (SANS) in conjunction with controlled temperature variations, the sol-gel transition dynamics of these nanocomposite materials were elucidated. Complementary insights into the mechanisms underpinning this transition and temperature-induced alterations in the constituents are gleaned through the utilization of SANS techniques employing contrast-matching methodologies to mitigate clay and polymer scattering interference. It is found that heating systems from room- to body- temperature induces self-assembly of BCS in the bulk aqueous phase with concurrent structuration of clay in gel-forming samples with lower number average molecular weight (Mn). SANS study unpicks this phenomenon to find that gelation occurs with concurrent aggregation of BCS in the bulk, inducing clay-clay interactions only in lower Mn BCS systems with large nanoaggregates.

Cleomin Exerts Acute Antinociceptive Effects in Mice via GABAB and Muscarinic Receptors.

Cleomin, a 1,3-oxazolidine-2-thione, was recently isolated from Neocalyptrocalyx longifolium, a species traditionally used for treating painful conditions. Reports about the pharmacological activities of cleomin are lacking. Here, the antinociceptive effects of cleomin were investigated using mice models of pain, namely the formalin, the cold plate, and the tail flick tests. Motor integrity was assessed in the rota-rod test. Antagonism assays and in silico docking analyses were performed to investigate the putative mechanisms of action. Cleomin (12.5-25 mg/kg), at doses that did not induce motor impairment, induced dose-dependent antinociception in both early and late phases of the formalin test and reduced nociceptive behaviors in both the cold plate and tail flick tests. Pretreatments with phaclofen and atropine attenuated the antinociceptive effects of cleomin, implicating the involvement of GABAB and muscarinic receptors. In silico docking studies suggested satisfactory coupling between cleomin and GABAB and M2 receptors, hence corroborating their role in cleomin's activity. Pretreatments with naloxone, yohimbine, bicuculline, and methysergide did not affect the antinociception of cleomin. In silico pharmacokinetics prediction showed a good drug ability profile of cleomin. In conclusion, cleomin promoted antinociception mediated by GABAB and muscarinic receptors. These findings support further investigation of the analgesic potential of cleomin.

The Essential Oil from Conyza bonariensis (L.) Cronquist (Asteraceae) Exerts an In Vitro Antimelanoma Effect by Inducing Apoptosis and Modulating the MAPKs, NF-κB, and PKB/AKT Signaling Pathways.

The characterization and cytotoxicity of the essential oil from Conyza bonariensis (L.) aerial parts (CBEO) were previously conducted. The major compound was (Z)-2-lachnophyllum ester (EZ), and CBEO exhibited significant ROS-dependent cytotoxicity in the melanoma cell line SK-MEL-28. Herein, we employed the Molegro Virtual Docker v.6.0.1 software to investigate the interactions between the EZ and Mitogen-Activated Protein Kinases (MAPKs), the Nuclear Factor kappa B (NF-κB), and the Protein Kinase B (PKB/AKT). Additionally, in vitro assays were performed in SK-MEL-28 cells to assess the effect of CBEO on the cell cycle, apoptosis, and these signaling pathways by flow cytometry and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay using MAPKs inhibitors. CBEO induced a significant increase in the sub-G1 peak, as well as biochemical and morphological changes characteristic of apoptosis. The in-silico results indicated that EZ interacts with Extracellular Signal-Regulated Kinase 1 (ERK1), c-Jun N-terminal Kinase 1 (JNK1), p38α MAPK, NF-κB, and PKB/AKT. Moreover, CBEO modulated the ERK1/2, JNK, p38 MAPK, NF-κB, and PKB/AKT activities in SK-MEL-28 cells. Furthermore, CBEO's cytotoxicity against SK-MEL-28 cells was significantly altered in the presence of MAPKs inhibitors. These findings support the in vitro antimelanoma effect of CBEO through apoptosis induction, and the modulation of ERK, JNK, p38 MAPK, NF-κB, and PKB/AKT activities.