Kisspeptin-10 Improves Testicular Redox Status but Does Not Alter the Unfolded Protein Response (UPR) That Is Downregulated by Hypothyroidism in a Rat Model.

Hypothyroidism compromises the testicular redox status and is associated with reduced sperm quality and infertility in men. In this regard, studies have demonstrated the antioxidant potential of kisspeptin in reproductive and metabolic diseases. In this study, we evaluate the effects of kisspeptin-10 (Kp10) on the testicular redox, as well as mediators of the unfolded protein response (UPR) in adult rats with hypothyroidism. Adult male Wistar rats were randomly separated into the Control (n = 15), Hypo (n = 13) and Hypo + Kp10 (n = 14) groups, and hypothyroidism was induced with 6-propyl-2-thiouracil (PTU) for three months. In the last month, half of the hypothyroid animals received Kp10. Testis samples were collected for enzymatic, immunohistochemical and/or gene evaluation of mediators of oxidative stress (TBARs, lipid hydroperoxides (LOOH), ROS, peroxynitrite, SOD, CAT and GPX), endoplasmic reticulum stress (GRP78, ATF6, PERK, CHOP, HO-1 and sXBP1) and antiapoptocytes (BCL-2). Hypothyroidism increased apoptosis index, TBARS and LOOH concentrations, and reduced testicular gene expression of Sod1, Sod2 and Gpx1, as well as the expression of Grp78, Atf6, Ho1 and Chop. Treatment with Kp10, in turn, reduced testicular apoptosis and the production of peroxynitrite, while increased SOD1 and GPX ½ expression, and enzymatic activity of CAT, but did not affect the lower expression of UPR mediators caused by hypothyroidism. This study demonstrated that hypothyroidism causes oxidative stress and dysregulated the UPR pathway in rat testes and that, although Kp10 does not influence the low expression of UPR mediators, it improves the testicular redox status, configuring it as an important antioxidant factor in situations of thyroid dysfunction.

Aryl Hydrocarbon Receptor as a Therapeutical Target of Environmentally Induced Skin Conditions.

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor, expressed in several tissues and involved in the response to environmental stressors. Studies have already associated exposure to environmental factors, such as organic air pollutants, products of the skin microbiota, and solar radiation, with the development/worsening of skin conditions, mediated by AhR. On the other hand, recent studies have shown that synthetic and natural compounds are able to modulate the activation of some AhR signaling pathways, minimizing the harmful response of these environmental stressors in the skin. Thus, AhR constitutes a new therapeutic target for the prevention or treatment of skin conditions induced by the skin exposome. Herein, an overview of potential AhR ligands and their biologic effects in environmentally induced skin conditions are presented. The literature survey pointed out divergences in the mechanism of action from a therapeutic perspective. Although most studies point to the benefits of ligand downregulation of AhR signaling, counteracting the toxic effects of environmental factors on the skin, some studies suggest the AhR ligand activation as a therapeutical mechanism for some skin conditions. Furthermore, both agonist and antagonist profiles were identified in the AhR modulation by the synthetic and natural compounds raised. Despite that, this target is still little explored, and further studies are needed to elucidate the molecular mechanisms involved and identify new AhR ligands with therapeutic potential. SIGNIFICANCE STATEMENT: The aryl hydrocarbon receptor (AhR) is involved in different skin physiological and pathological processes, including toxic mechanisms of environmental factors. Synthetic and natural AhR ligands have demonstrated therapeutic potential for skin conditions induced by these agents. Thus, a comprehensive understanding of the skin toxicity mechanisms involving the AhR, as well as the use of AhR modulators from a therapeutic perspective, provides an alternative approach to the development of new treatments for skin disorders induced by the exposome.

Redox profile and mediators of the unfolded protein response (UPR) in the placenta of rats during pregnancy.

CONTEXT: Proliferation, differentiation, migration and apoptosis of trophoblastic cells are influenced by hypoxia, as well as adequate modulation of oxidative stress and the unfolded protein response (UPR) pathway. AIMS: We aimed to evaluate the expression profile of redox and UPR mediators in the placenta of rats throughout pregnancy. METHODS: Placental expression of hypoxia-inducible factor 1α (HIF1α), 8-Hydroxy-2'-deoxyguanosine (8-OHdG), superoxide dismutase 1 (SOD1), glutathione peroxidase (GPX), catalase (Cat), activating transcription factor 6 (ATF6), protein kinase RNA-like endoplasmic reticulum kinase (PERK), 78 kD glucose-regulated protein (GRP78) and C/EBP-homologous protein (CHOP), as well as reactive oxygen species (ROS) and peroxynitrite production, were evaluated in Wistar rats on the 10th, 12th, 14th, 16th and 18th day of pregnancy (DP). KEY RESULTS: Increased immunostaining of HIF1α was observed on the 16th and 18th DP, while 8-OHdG and ROS production were greater on the 14th DP. SOD1 and Cat had increased immunostaining on the 14th and 18th DP, while staining of GPX1/2, GRP78 and CHOP was greater on the 18th DP. With regard to gene expression, Hif1α and Sod1 showed increased mRNA expression on the 12th and 16th DP, while Gpx1 had increased expression on the 10th and 16th DP. Cat , Perk and Grp78 gene expression was greater on the 14th DP, unlike Atf6 , which showed greater expression on the 12th DP. In contrast, Chop maintained increased expression from the 12th to the 18th DP. CONCLUSIONS: The placental expression of redox and UPR mediators in rats is influenced by gestational age, with greater expression in periods of greater HIF1α and 8-OHdG expression and at the end of the pregnancy. IMPLICATIONS: This study provides data on the physiological modulation of redox and UPR mediators during placental development in rats.

At the intersection of the model minority myth and antiblackness: From Asian American triangulation to recommendations for solidarity.

Asian Americans are situated in a triangulated role in a black-white racial hierarchy designed to legitimize white supremacy (Kim, 1999). However, little is known about the lived experiences of Asian American triangulation and even less so in the context of anti-Asian racism. The present study was initially designed to examine anti-Asian racism at the outset of the COVID-19 pandemic. Yet, in a sociopolitical climate described as a "racial reckoning," our study evolved to capture the process of racial triangulation and the interplay of anti-Asian racism and antiblackness. Based on the online responses of 201 Asian Americans (from over 32 U.S. states), four themes emerged to showcase the ways in which Asian Americans suffered from and recapitulated racial oppression: (a) anti-Asian racism is overlooked in the black-white racial discourse, (b) anti-Asian racism is not taken seriously, (c) anti-Asian racism is also perpetrated by people of color (POC), and (d) anti-Asian racism is deprioritized in the presence of anti-Black racism. Regarding participant recommendations to combat anti-Asian racism, our second research question focused on areas of convergence with dismantling anti-Black racism. Two key themes emerged: (a) foster Asian American pan-ethnic solidarity and (b) build and strengthen cross-racial coalitions (POC solidarity and White allyship). Altogether, our study descriptively captured the process of racial triangulation to showcase the manifestation and recapitulation of anti-Asian racism and antiblackness. While Asian Americans suffered as victims and perpetrators of racial oppression, they also recognized the need to dismantle white supremacy with racial solidarity, coalition-building, and advocacy. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Kisspeptin Suppresses Inflammasome-NLRP3 Activation and Pyroptosis Caused by Hypothyroidism at the Maternal-Fetal Interface of Rats.

Gestational diseases such as preeclampsia and gestational diabetes cause inflammasome activation and pyroptosis in the placenta and changes in placental kisspeptin levels. Although maternal hypothyroidism also reduces the kisspeptin/Kiss1R system at the maternal-fetal interface, there is still no information on whether this dysfunction causes inflammasome activation and pyroptosis in the placenta or influences the modulatory role of kisspeptin in these processes. This study aimed to evaluate whether hypothyroidism activates the inflammasome-NLRP3 pathway and pyroptosis at the maternal-fetal interface of rats and whether kisspeptin can modulate these processes. Hypothyroidism was induced in Wistar rats by the administration of propylthiouracil. Kisspeptin-10 (Kp10) treatment began on the 8th day of gestation (DG). Gene and/or protein expressions of NLRP3, Caspase 1, IL-1ß, IL-18, and Gasdermin D (Gsmd) were evaluated in the deciduae and placentae at the 18th DG. Hypothyroidism increased the decidual and placental stainings of NLRP3, IL-1ß, and Gasdermin D, and increased the gene expressions of Nlrp3, Ilß, and Il18 in the placenta and of Gsmd in the decidua. Treatment with Kp10 suppressed the increase in NLRP3/Nlrp3, IL-1ß, Il18, and Gasdermin D/Gsmd caused by hypothyroidism at the maternal-fetal interface. However, Kp10 increased the placental gene expressions of Casp1 and Il1ß. The findings demonstrated that maternal hypothyroidism activated the inflammasome-NLRP3 pathway and pyroptosis at the maternal-fetal interface of rats and that treatment with Kp10 was able to block these processes, thus suggesting that kisspeptin analogues may be promising in the treatment of gestational diseases that involve inflammasome activation and pyroptosis.

The Impact of Hydroxytyrosol on the Metallomic-Profile in an Animal Model of Alzheimer's Disease.

It is undeniable that as people get older, they become progressively more susceptible to neurodegenerative illnesses such as Alzheimer's disease (AD). Memory loss is a prominent symptom of this condition and can be exacerbated by uneven levels of certain metals. This study used inductively coupled plasma mass spectrometry (ICP-MS) to examine the levels of metals in the blood plasma, frontal cortex, and hippocampus of Wistar rats with AD induced by streptozotocin (STZ). It also tested the effects of the antioxidant hydroxytyrosol (HT) on metal levels. The Barnes maze behavior test was used, and the STZ group showed less certainty and greater distance when exploring the Barnes maze than the control group. The results also indicated that the control group and the STZ + HT group exhibited enhanced learning curves during the Barnes maze training as compared to the STZ group. The ICP-MS analysis showed that the STZ group had lower levels of cobalt in their blood plasma than the control group, while the calcium levels in the frontal cortex of the STZ + HT group were higher than in the control group. The most important finding was that copper levels in the frontal cortex from STZ-treated animals were higher than in the control group, and that the STZ + HT group returned to equivalent levels to the control group. The antioxidant HT can restore copper levels to their basal physiological state. This finding may help explain HT's potential beneficial effect in AD-patients.

Comparative cytogenetics among Boana species (Anura, Hylidae): focus on evolutionary variability of repetitive DNA.

Boana comprises a diverse genus of Neotropical treefrogs, currently rearranged into seven taxonomic species groups. Although cytogenetic studies have demonstrated diversity in its representatives, the chromosomal mapping of repetitive DNA sequences is still scarce. In this study, Boana albopunctata, Boana faber, and Boana prasina were subjected to in situ localization of different repetitive DNA units to evaluate trends of chromosomal evolution in this genus. Boana faber and B. prasina had 2n=24 chromosomes, while B. albopunctata has 2n=22 and an intra-individual variation related to the presence/absence of one B chromosome. The location of 45S rDNA sites was different in the analyzed karyotypes, corroborating with what was found in the distinct phylogenetic groups of Boana. We presented the first description of 5S rDNA in a Boana species, which showed markings resulting from transposition/translocation mechanisms. In situ localization of microsatellite loci proved to be a helpful marker for karyotype comparison in Boana, commonly with cis accumulation in the heterochromatin. On the other hand, genomic dispersion of microsatellites may be associated with hitchhiking effects during the spreading of transposable elements. The obtained results corroborated the independent diversification of these lineages of species from three distinct phylogenetic groups of Boana.

Detection of intestinal parasites in human faecal samples using dissolved air flotation.

OBJECTIVE: Ova and parasite (O&P) examination is recommended for the laboratory diagnosis of agents causing parasitic infections; however, this exam requires scientific and technological improvements to enhance its diagnostic validity. Dissolved air flotation (DAF) is an efficient technical principle separating suspended solids in a liquid medium. We aimed to develop and validate a new procedure for intestinal parasite detection with DAF. METHODS: In this study, we collected samples from 500 volunteers, screened them by direct examination, and transferred the material to tubes using the Three Faecal Test (TF-Test) for triplicate DAF tests. We evaluated physical-chemical parameters and DAF prototype components through quantifying parasites recovered from floated and non-floated regions of the flotation column. The DAF operation protocol was validated with the gold standard results. RESULTS: The 10% saturated volume proportion and cationic surfactant showed regularity and high parasite recovery (80%). Modifications of the needle device did not influence parasite recovery (p > 0.05). Sensitivity, specificity, accuracy and kappa agreement obtained with the DAF protocol were 91%, 100%, 93% and substantial (k = 0.64), respectively. CONCLUSION: The DAF principle could be used to process faecal samples in routine laboratory exams, enabling intestinal parasite detection.

Spectroscopic study of D1-A-D2-A terpolymer films for optoelectronic applications.

Several strategies have been considered in search of more efficient organic materials for charge transfer in photovoltaic devices. Among them, the integration of donor-acceptor (D-A) functional units on a conjugated copolymer has been widely applied. In this framework, we evaluated four terpolymers made up of donor moieties derived from 9,9-dioctylfluorene and 9-(heptadecan-9-yl)-9H-carbazole combined with 2,1,3-benzothiadiazole, the acceptor moiety, in different monomer ratios and polymerization routes (block and random microstructures). The preferred molecular orientation and charge transfer dynamics of the polymeric films were assessed by near edge X-ray absorption fine structure spectroscopy (NEXAFS) and resonant Auger electron spectroscopy (RAES) around the sulfur K-edge. Charge transfer times (τCT) were estimated by the Core-Hole Clock (CHC) method. Films with a high degree of organization were identified for the block terpolymer and random terpolymers with uneven amounts of donor units, showing a preferred orientation of the benzothiadiazole (BT) molecular plane parallel to the substrate surface. The values of τCT measured for all terpolymers were higher than those for typical polymers used in photovoltaic devices, which is not desirable for this type of optoelectronic application, but this may be correlated to the strong acceptor character of BT, the unit probed. To investigate the effect of film formation on the excited state behavior, steady-state and time-resolved photoluminescence measurements were also conducted. X-ray photoelectron spectroscopy (XPS) was employed to characterize the surface chemical composition of the terpolymer films. Based on the spectroscopic data the block copolymer appears to be the most suitable for the desired application.

Executive functions in school-aged children exposed to airborne manganese: A multilevel analysis.

Neuropsychological alterations have been identified in populations heavily exposed to metals with neurotoxic potential, such as manganese (Mn). This study examined the associations between Mn environmental exposure in school-aged children and executive functions, using structural equation modeling. Children, aged between 7 and 12 years (N = 181), were recruited from four elementary schools located in a region that is under the influence of atmospheric emissions from a ferro-manganese alloy plant in the municipality of Simões Filho, Bahia, Brazil. The following cognitive functions were evaluated: Intelligence, Inhibitory Control, Cognitive Flexibility, Verbal and Design Fluency, Verbal and Visual Working Memory and Attention. We performed structural equation modeling to identify the following executive functions latent variables: working memory, inhibitory control and cognitive flexibility. We further analyzed the relations between executive functions and Mn measured in hair (MnH) and toenails (MnTn) with linear mixed models, after controlling for co-variables. A positive effect at the individual level on working memory, inhibition control and cognitive flexibility was observed with MnTn after controlling for co-variables, but no association was found with MnH levels. However, children attending school most environmentally exposed to Mn emissions, which had the highest rate of Mn dust deposition, had the poorest scores on working memory. These findings suggest both benefits and risk of Mn on children's cognitive development.

Ethylhexyl methoxycinnamate and butyl methoxydibenzoylmethane: Toxicological effects on marine biota and human concerns.

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.

Eight-and-a-Half Syndrome Secondary to Neurotoxoplasmosis: A Rare Case Report.

Eight-and-a-half syndrome (EHS) is a neuro-ophthalmological condition characterised by horizontal gaze palsy, internuclear ophthalmoplegia, and ipsilateral facial palsy. Albeit rare, EHS is a well reported condition in the literature, with several reports presenting multiple aetiologies. Infarcts are the cause in more than half the cases. Human immunodeficiency virus (HIV)-related cases are rare, and are probably underreported in low- and middle-income countries. In this report, we describe EHS secondary to neurotoxoplasmosis in a 40-year-old HIV-positive Brazilian man. EHS secondary to neurotoxoplasmosis is a challenging diagnosis, with important differential diagnoses, notably for HIV patients.

Pyometra and estrous cycle modulate the uterine expression of the kisspeptin system and angiogenic and immune factors in cats.

Failures in hypothalamic kisspeptin/Kiss1r signaling are associated with infertility, and in vitro studies have shown that kisspeptin can modulate angiogenesis and immune activity. Because there is no in vivo research on the functional relationship between these factors in the reproductive system, especially in domestic cats, we evaluated the expression profile of kisspeptin/Kiss1r and angiogenic and immunological mediators in the genital tract of cyclic cats and of those with pyometra. The uterus of cats in diestrus exhibited greater gene and protein expression of Kiss1, as well as Vegf, Pigf, Mif, and Il6. In contrast, Kiss1r presented greater expression in proestrus/estrus, similarly to that observed for the immunostaining of INFγ, MIF, TNFα, and IL10. These factors were positively correlated with Kiss1 and/or Kiss1r, and a positive correlation between Kiss1 and Kiss1r was also observed in the uterus of cats during the estrous cycle. Cats with pyometra showed greater immunostaining of Kiss1 and Kiss1r on the endometrial surface and reduced immunostaining of Kiss1 in deep glands, whereas there was a significant reduction in Vegf, Pigf, Mif, and Il6 mRNA, and an increase in Tnf mRNA. The findings reveal that there is a gene correlation between kisspeptin/Kiss1r and angiogenic and immune mediators in the uterus of the domestic cat, which is modulated by the estrous cycle, and that pyometra affects the expression of these mediators. This study suggests, for the first time, a functional relationship between the Kiss/Kiss1r system and angiogenic and immune mediators in the female genital tract.

Kisspeptin/Kiss1r system and angiogenic and immunological mediators at the maternal-fetal interface of domestic cats.

The Kisspeptin/Kiss1r system is a key regulator of reproduction by stimulating gonadotrophin-releasing hormone and luteinizing hormone release, and in vitro studies have shown that Kisspeptin can modulate angiogenesis and immune function, factors that are also essential for reproduction However, there are no studies on the expression of Kisspeptin/Kiss1r at the maternal-fetal interface in domestic cats and its relationship with angiogenic and immunological mediators. Thus, our objective was to evaluate the spatiotemporal expression profile of Kisspeptin/Kiss1r and angiogenic and immunological mediators in the uterus and placenta of domestic cats during pregnancy. Uterus and placenta samples were collected from cats in mid pregnancy (N = 6) and late pregnancy (N = 6), in addition to uterus from non-pregnant cats in diestrus (N = 7), to evaluate protein and gene expression of kisspeptin (Kiss1), kisspeptin receptor (Kiss1r), vascular endothelial growth factor (VEGF), tyrosine kinase receptor (Flk-1), placental growth factor (PLGF), interferon gamma (INFγ), migration inhibiting factor (MIF), tumor necrosis factor (TNFα), interleukins (IL6 and IL10) by immunohistochemistry and quantitative polymerase chain reaction. Pregnancy increased the uterine expression of Kiss1 and Kiss1r, especially at the late pregnancy, in addition to upregulating INFy, MIF, Vegf, Il10, and Tnf and downregulating Plgf. Higher placental expression of Kiss1r and Plgf mRNA occurred at the late pregnancy, while the expression of Kiss1, VEGF, Flk-1, INFy, TNFα, Il6, and IL10 was higher in the mid of pregnancy. A positive correlation between Kiss1 and Tnf was observed in the placenta, while Kiss1r had a negative correlation with Infγ, Il6, and Il10. The findings reveal that Kisspeptin/Kiss1r and angiogenic and immunological mediators at the maternal-fetal interface of pregnant cat have a gene correlation and are modulated by the gestational age. These data suggest possible functional links of Kisspeptin in placental angiogenesis and immunology.

Cytogenotoxicity and protective effect of piperine and capsaicin on meristematic cells of Allium cepa L.

Piperine and capsaicin are important molecules with biological and pharmacological activities. This study aimed to evaluate the cytogenotoxic and protective effect of piperine and capsaicin on Allium cepa cells. A. cepa roots were exposed to negative (2% Dimethylsulfoxide) and positive (Methylmethanesulfonate, MMS, 10 µg/mL) controls, and four concentrations (25-200 µM) of piperine or capsaicin (alone) or associated before, simultaneously or after with the MMS. Only the lowest concentration of piperine (25 µM) showed a protective effect because it was not genotoxic. Piperine and capsaicin were cytotoxic (50, 100 and 200 µM). Piperine (50 to 200 µM) caused a significant increase in the total average of chromosomal alterations of in A. cepa cells. For capsaicin, the genotoxic effect was dose-dependent with a significant increase for all concentrations, highlighting the significant presence of micronuclei and nuclear buds for the two isolates. In general, bioactive compounds reduced the total average of chromosomal alterations against damage caused by MMS, mainly micronuclei and/or nuclear buds. Therefore, the two molecules were cytotoxic and genotoxic at the highest concentrations, and did not have cytoprotective action, and the lowest concentration of piperine demonstrated important chemopreventive activity.

Do breastfed children have a lower chance of developing mouth breathing? A systematic review and meta-analysis.

OBJECTIVE: Determine the association between breastfeeding and the development of mouth breathing in children. MATERIALS AND METHODS: Seven databases were searched for studies investigating the association between the type of feeding and the development of the breathing pattern in children. Descriptive analysis and meta-analysis were performed, with the calculation of the prevalence and likelihood (odds ratios (95% CI)) of mouth breathing according to the duration of breastfeeding. RESULTS: The overall prevalence of mouth breathing was 44% (95% CI: 38-49) (N total = 1182). Breastfeeding was a protection factor against the development of mouth breathing (OR = 0.62; 95% CI: 0.41-0.93). The likelihood of developing mouth breathing was 41% and 34% lower among children that were breastfed for more than 12 and more than 24 months, respectively. No association was found between exclusive breastfeeding for up to 6 months and the occurrence of mouth breathing (OR = 0.60; 95% CI: 0.31-1.18). CONCLUSIONS: Due to the scarcity of cohort studies that met the inclusion criteria and the low certainty of the evidence, no strong evidence-based conclusion can be drawn. However, breastfeeding should be encouraged due to its possible protective effect, evidenced by the substantial reduction in the prevalence of mouth breathing pattern when performed for up to 2 years. Exclusive breastfeeding was not associated with the development of the breathing pattern. CLINICAL RELEVANCE: The results reveal that breastfeeding can protect children from the development of mouth breathing. Thus, healthcare providers should offer support so that mothers feel prepared and encouraged to perform breastfeeding. TRIAL REGISTRATION: PROSPERO registry: CRD42017062172.

Use of crack cocaine increases tooth loss.

PURPOSE: To evaluate the occurrence of tooth loss among crack cocaine users. METHODS: A cross-sectional study was conducted with 106 crack cocaine users and 106 controls matched for age, gender, and tobacco use. Data were collected on socio-demographic characteristics, drug use, use of dental services, dental caries, periodontal disease, and the outcome (tooth loss). RESULTS: Crack cocaine users had a greater frequency of tooth loss (55.7% vs. 36.8%), severity of dental caries and periodontal disease and less use of dental services than the controls (P< 0.05). After adjustments, tooth loss was 46% more frequent among crack cocaine users (PR= 1.46; 95%, CI: 1.10-1.93) as well as significantly more frequent among non-whites, those older than 24 years of age and those with high dental caries severity. Occurrence of tooth loss was significantly higher among crack cocaine users. These findings can contribute to the planning and implementation of prevention strategies and oral health care for individuals with a chemical dependence. CLINICAL SIGNIFICANCE: The use of crack cocaine had a negative impact on the oral health of its users, leading to tooth loss and a greater severity of dental caries. These findings should be considered when planning prevention strategies to improve oral health in individuals addicted to crack cocaine.

Phytomodulatory proteins isolated from Calotropis procera latex promote glycemic control by improving hepatic mitochondrial function in HepG2 cells.

The medicinal uses of Calotropis procera are diverse, yet some of them are based on effects that still lack scientific support. Control of diabetes is one of them. Recently, latex proteins from C. procera latex (LP) have been shown to promote in vivo glycemic control by the inhibition of hepatic glucose production via AMP-activated protein kinase (AMPK). Glycemic control has been attributed to an isolated fraction of LP (CpPII), which is composed of cysteine peptidases (95%) and osmotin (5%) isoforms. Those proteins are extensively characterized in terms of chemistry, biochemistry and structural aspects. Furthermore, we evaluated some aspects of the mitochondrial function and cellular mechanisms involved in CpPII activity. The effect of CpPII on glycemic control was evaluated in fasting mice by glycemic curve and glucose and pyruvate tolerance tests. HepG2 cells was treated with CpPII, and cell viability, oxygen consumption, PPAR activity, production of lactate and reactive oxygen species, mitochondrial density and protein and gene expression were analyzed. CpPII reduced fasting glycemia, improved glucose tolerance and inhibited hepatic glucose production in control animals. Additionally, CpPII increased the consumption of ATP-linked oxygen and mitochondrial uncoupling, reduced lactate concentration, increased protein expression of mitochondrial complexes I, III and V, and activity of peroxisome-proliferator-responsive elements (PPRE), reduced the presence of reactive oxygen species (ROS) and increased mitochondrial density in HepG2 cells by activation of AMPK/PPAR. Our findings strongly support the medicinal use of the plant and suggest that CpPII is a potential therapy for prevention and/or treatment of type-2 diabetes. A common epitope sequence shared among the proteases and osmotin is possibly the responsible for the beneficial effects of CpPII.

Regulation of Lin28a-miRNA let-7b-5p pathway in skeletal muscle cells by peroxisome proliferator-activated receptor delta.

Lin28a/miRNA let-7b-5p pathway has emerged as a key regulators of energy homeostasis in the skeletal muscle. However, the mechanism through which this pathway is regulated in the skeletal muscle has remained unclear. We have found that 8 wk of aerobic training (Tr) markedly decreased let-7b-5p expression in murine skeletal muscle, whereas high-fat diet (Hfd) increased its expression. Conversely, Lin28a expression, a well-known inhibitor of let-7b-5p, was induced by Tr and decreased by Hfd. Similarly, in human muscle biopsies, Tr increased LIN28 expression and decreased let-7b-5p expression. Bioinformatics analysis of LIN28a DNA sequence revealed that its enrichment in peroxisome proliferator-activated receptor delta (PPARδ) binding sites, which is a well-known metabolic regulator of exercise. Treatment of primary mouse skeletal muscle cells or C2C12 cells with PPARδ activators GW501516 and AICAR increased Lin28a expression. Lin28a and let-7b-5p expression was also regulated by PPARδ coregulators. While PPARγ coactivator-1α (PGC1α) increased Lin28a expression, corepressor NCoR1 decreased its expression. Furthermore, PGC1α markedly reduced the let-7b-5p expression. PGC1α-mediated induction of Lin28a expression was blocked by the PPARδ inhibitor GSK0660. In agreement, Lin28a expression was downregulated in PPARδ knocked-down cells leading to increased let-7b-5p expression. Finally, we show that modulation of the Lin28a-let-7b-5p pathway in muscle cells leads to changes in mitochondrial metabolism in PGC1α dependent fashion. In summary, we demonstrate that Lin28a-let-7b-5p is a direct target of PPARδ in the skeletal muscle, where it impacts mitochondrial respiration.

Insights and controversies on sunscreen safety.

Although sunlight provides several benefits, ultraviolet (UV) radiation plays an important role in the development of various skin damages such as erythema, photoaging, and photocarcinogenesis. Despite cells having endogenous defense systems, damaged DNA may not be efficiently repaired at chronic exposure. In this sense, it is necessary to use artificial defense strategies such as sunscreen formulations. UV filters should scatter, reflect, or absorb solar UV radiation in order to prevent direct or indirect DNA lesions. However, the safety of UV filters is a matter of concern due to several controversies reported in literature, such as endocrine alterations, allergies, increased oxidative stress, phototoxic events, among others. Despite these controversies, the way in which sunscreens are tested is essential to ensure safety. Sunscreen regulation includes mandatory test for phototoxicity, but photogenotoxicity testing is not recommended as a part of the standard photosafety testing program. Although available photobiological tests are still the first approach to assess photosafety, they are limited. Some existing tests do not always provide reliable results, mainly due to limitations regarding the nature of the assessed phototoxic effect, cell UV sensitivity, and the irradiation protocols. These aspects bring queries regarding the safety of sunscreen wide use and suggest the demand for the development of robust and efficient in vitro screening tests to overcome the existing limitations. In this way, Saccharomyces cerevisiae has stood out as a promising model to fill the gaps in photobiology and to complete the mandatory tests enabling a more extensive and robust photosafety assessment.