Extract of Araçá-Boi and Its Major Phenolic Compound, Trans-Cinnamic Acid, Reduce Viability and Inhibit Migration of Human Metastatic Melanoma Cells.

Cutaneous melanoma is an aggressive type of skin cancer that is recognized for its high metastatic potential and the challenges it presents in its treatment. There has been increasing interest in plant extracts and their potential applications in melanoma. The present study aimed to investigate the content of individual phenolic compounds in araçá-boi extract, evaluate their antioxidant activity, and explore their effects on cell viability, migration properties, oxidative stress levels, and protein expression in the human metastatic melanoma cell line SK-MEL-28. HPLC-DAD analysis identified 11 phenolic compounds in the araçá-boi extract. Trans-cinnamic acid was the main phenolic compound identified; therefore, it was used alone to verify its contribution to antitumor activities. SK-MEL-28 melanoma cells were treated for 24 h with different concentrations of araçá-boi extract and trans-cinnamic acid (200, 400, 600, 800, and 1600 µg/mL). Both the araçá-boi extract and trans-cinnamic acid reduced cell viability, cell migration, and oxidative stress in melanoma cells. Additionally, they modulate proteins involved in apoptosis and inflammation. These findings suggest the therapeutic potential of araçá-boi extract and its phenolic compounds in the context of melanoma, especially in strategies focused on preventing metastasis. Additional studies, such as the analysis of specific signaling pathways, would be valuable in confirming and expanding these observations.

Current treatment of Psoriasis triggered by Cytokine Storm and future immunomodulation strategies.

Psoriasis is a chronic condition caused by an inflammation mediated mainly by cytokines and T cells. In COVID-19, the same type of imbalance is common, generating the Cytokine Storm and promoting a worsening in the skin conditions of patients with autoimmune disorders, such as Psoriasis. In this context, one of the main mediators of immune responses presented by SARS-CoV-2 infected patients is the Purinergic System. This immunological resource is capable of stimulating the hyperinflammatory state presented by infected individuals, mainly by the activity of the P2X7 receptor, culminating in the Cytokine Storm and consequently in the Psoriasis crisis. Currently, different drugs are used for patients with Psoriasis, such as immunosuppressants and small molecules; however, the safety of these drugs in infected patients has not been analyzed yet. In this context, studies are being developed to evaluate the possible administration of these traditional drugs to COVID-19 patients with Psoriasis crisis. Along with that, researchers must evaluate the potential of administrating P2X7 antagonists to these patients as well, improving both the systemic and the dermatological prognostics of patients, by reducing the Cytokine Storm and its general effects, but also avoiding the provocation of Psoriasis crisis.

Rosmarinic acid modulates purinergic signaling and induces apoptosis in melanoma cells.

Cancer cases have increased worldwide. Cutaneous melanoma (CM), a highly metastatic skin cancer, largely contributes to global statistical cancer death data. Research has shown that rosmarinic acid (RA) is a promising phenolic compound with antineoplastic properties. Thus, we investigated the effects of RA on apoptosis-inducing in melanoma cells, purinergic signaling modulation, and cytokine levels. We treated SK-MEL-28 cells for 24 h with different concentrations of RA and assessed the apoptosis, CD39, CD73, and A2A expression, and cytokine levels. We found RA-induced apoptosis in melanoma cells. Regarding the purinergic system, we verified that RA downregulated the expression of CD73 and A2A, specially at high concentrations of treatment. Additionally, RA increased IL-6, IL-4, IL-10, IFN-γ, and TNF-α levels. Our in vitro results confirm RA's potential to be used to induce melanoma cell apoptosis, having CD73 and A2A as targets when reversion of immune suppression is desired. Further studies in animal models and clinical trials focusing on RA's modulation of purinergic signaling in melanoma are required.

Takotsubo syndrome as an outcome of the use of checkpoint inhibitor therapy in patients with COVID-19.

Takotsubo Syndrome (TS) is a heart disease caused by extreme exposure of the body to physical or psychological stress. In the context of COVID-19, the virus can be a significant source of stress, with particular attention being paid to the cytokine storm as a cause of damage to the body. New research shows that the production of specific cytokines is linked to the activation of immune checkpoint proteins such as PD-1, PD-L1, and CTLA-4 on T cells. Although initially beneficial in combating infections, it can suppress defense and aid in disease progression. Therefore, checkpoint inhibitor therapy has been highlighted beyond oncological therapies, given its effectiveness in strengthening the immune system. However, this treatment can lead to excessive immune responses, inflammation, and stress on the heart, which can cause Takotsubo Syndrome in patients. Several studies investigate the direct link between this therapy and cardiac injuries in these patients, which can trigger TS. From this perspective, we must delve deeper into this treatment and consider its effects on the prognosis against SARS-CoV-2 infection.

Hydroalcoholic Extract of Centella asiatica and Madecassic Acid Reverse Depressive-Like Behaviors, Inflammation and Oxidative Stress in Adult Rats Submitted to Stress in Early Life.

Major depressive disorder (MDD) is a severe disorder that causes enormous loss of quality of life, and among the factors underlying MDD is stress in maternal deprivation (MD). In addition, classic pharmacotherapy has presented severe adverse effects. Centella asiatica (C. asiatica) demonstrates a potential neuroprotective effect but has not yet been evaluated in MD models. This study aimed to evaluate the effect of C. asiatica extract and the active compound madecassic acid on possible depressive-like behavior, inflammation, and oxidative stress in the hippocampus and serum of young rats submitted to MD in the first days of life. Rats (after the first day of birth) were separated from the mother for 3 h a day for 10 days. When adults, these animals were divided into groups and submitted to treatment for 14 days. After subjecting the animals to protocols of locomotor activity in the open field and behavioral despair in the forced swimming test, researchers then euthanized the animals. The hippocampus and serum were collected and analyzed for the inflammatory cytokines and oxidative markers. The C. asiatica extract and active compound reversed or reduced depressive-like behaviors, inflammation in the hippocampus, and oxidative stress in serum and hippocampus. These results suggest that C. asiatica and madecassic acid have potential antidepressant action, at least partially, through anti-inflammatory and antioxidant profiles.

Curcumin modulates purinergic signaling and inflammatory response in cutaneous metastatic melanoma cells.

Cutaneous melanoma (CM) poses a therapeutic challenge due to its aggressive nature and often limited response to conventional treatments. Exploring novel therapeutic targets is essential, and natural compounds have emerged as potential candidates. This study aimed to elucidate the impact of curcumin, a natural compound known for its anti-inflammatory, antioxidant, and anti-tumor properties, on metastatic melanoma cells, focusing on the purinergic system and immune responses. Human melanoma cell line SK-Mel-28 were exposed to different curcumin concentrations for either 6 or 24 h, after which we assessed components related to the purinergic system and the inflammatory cascade. Using RT-qPCR, we assessed the gene expression of CD39 and CD73 ectonucleotidases, as well as adenosine deaminase (ADA). Curcumin effectively downregulated CD39, CD73, and ADA gene expression. Flow cytometry analysis revealed that curcumin significantly reduced CD39 and CD73 protein expression at specific concentrations. Moreover, the A2A receptor's protein expression decreased across all concentrations. Enzymatic activity assays demonstrated that curcumin modulated CD39, CD73, and ADA activities, with effects dependent on concentration and duration of treatment. Extracellular ATP levels increased after 24 h of curcumin treatment, emphasizing its role in modulating hydrolytic activity. Curcumin also displayed anti-inflammatory properties by reducing NLRP3 gene expression and impacting the levels of key inflammatory cytokines. In conclusion, this study unveils the potential of curcumin as a promising adjuvant in CM treatment. Curcumin modulates the expression and activity of crucial components of the purinergic system and exhibits anti-inflammatory effects, indicating its potential therapeutic role in combating CM. These findings underscore curcumin's promise and warrant further investigation in preclinical and clinical settings for melanoma management.

The impacts of obesity in rheumatoid arthritis and insights into therapeutic purinergic modulation.

Rheumatoid Arthritis (RA) is an autoimmune condition responsible for the impairment of synovia and joints, endangering the functionality of individuals and contributing to mortality. Currently, obesity is increasing worldwide, and recent studies have suggested an association between such condition and RA. In this sense, obese individuals present a lower capacity for achieving remission and present more intense symptoms of the disease, demonstrating a link between both disorders. Different studies aim to understand the possible connection between the conditions; however, few is known in this sense. Therefore, knowing that obesity can alter the activity of multiple body systems, this work's objective is to evaluate the main modifications caused by obesity, which can be linked to the pathophysiology of RA, highlighting as relevant topics obesity's negative impact triggering systemic inflammation, intestinal dysbiosis, endocrine disbalances. Furthermore, the relationship between oxidative stress and obesity also deserves to be highlighted, considering the influence of reactive oxygen species (ROS) accumulation in RA exacerbation. Additionally, many of those characteristics influenced by obesity, along with the classic peculiarities of RA pathophysiology, can also be associated with purinergic signaling. Hence, this work suggests possible connections between the purinergic system and RA, proposing potential therapeutic targets against RA to be studied.

Peripheral biomarkers as a predictor of poor prognosis in severe cases of COVID-19.

We evaluated glycemia and triglyceride, hepatic, muscular, and renal damage markers, redox profile, and leptin and ghrelin hormone levels in COVID-19 patients. We also conducted statistical analysis to verify the potential of biomarkers to predict poor prognosis and the correlation between them in severe cases. We assessed glycemia and the levels of triglycerides, hepatic, muscular, and renal markers in automatized biochemical analyzer. The leptin and ghrelin hormones were assessed by the ELISA assay. Severe cases presented high glycemia and triglyceride levels. Hepatic, muscular, and renal biomarkers were altered in severe patients. Oxidative stress status was found in severe COVID-19 patients. Severe cases also had increased levels of leptin. The ROC curves indicated many biomarkers as poor prognosis predictors in severe cases. The Spearman analysis showed that biomarkers correlate between themselves. Patients with COVID-19 showed significant dysregulation in the levels of several peripheral biomarkers. We bring to light that a robust panel of peripheral biomarkers and hormones predict poor prognosis in severe cases of COVID-19 and biomarkers correlate with each other. Early monitoring of these biomarkers may lead to appropriate clinical interventions in patients infected by SARS-CoV2.

Cytokine storm in human monkeypox: A possible involvement of purinergic signaling.

Some evidence has indicated that monkeypox can induce a cytokine storm. Purinergic signaling is a cell pathway related to the cytokine storm. However, the precise mechanisms that lead to cytokine storms in monkeypox infections and the possible involvement of purinergic signaling in the immune response to this virus remain unknown. In this review article, we aimed to highlight a body of scientific evidence that consolidates the role of the cytokine storm in monkeypox infection and proposes a new hypothesis regarding the roles of purinergic signaling in this immune-mediated mechanism. We further suggested some purinergic signaling modulators to mitigate the deleterious and aggravating effects of immune dysregulation in human monkeypox virus infection by inhibiting P2X3, P2X7, P2Y2, and P2Y12, reducing inflammation, and activating A1 and A2A receptors to promote an anti-inflammatory response.

Cutaneous melanoma and purinergic modulation by phenolic compounds.

Cutaneous melanoma is a complex pathology that still has only treatments that lack efficiency and offer many adverse effects. Due to this scenario emerges the need to analyze other possible treatments against this disease, such as the effect of phenolic compounds. These substances have proven antitumor effects, but still have not been fully explored as a form of therapy to combat melanoma. Also, the purinergic receptors, along with its system molecules, take part in the formation of tumors from many pathways, such as the actions of ectoenzymes and receptors activity, especially P2Rs family, and are formed by structures that can be modulated by the phenolic compounds. Therefore, more studies have to be made with the aim of explaining the purinergic system activity in carcinogenesis of cutaneous melanoma and the effects of its modulation by phenolic compound, in order to enable the development of new therapies to combat this aggressive and feared cancer.

Implications of COVID-19 in Parkinson's disease: the purinergic system in a therapeutic-target perspective to diminish neurodegeneration.

The pathophysiology of Parkinson's disease (PD) is marked by degeneration of dopaminergic neurons in the substantia nigra. With advent of COVID-19, which is closely associated with generalized inflammation and multiple organ dysfunctions, the PD patients may develop severe conditions of disease leading to exacerbated degeneration. This condition is caused by the excessive release of pro-inflammatory markers, called cytokine storm, that is capable of triggering neurodegenerative conditions by affecting the blood-brain barrier (BBB). A possible SARS-CoV-2 infection, in serious cases, may compromise the immune system by triggering a hyperstimulation of the neuroimmune response, similar to the pathological processes found in PD. From this perspective, the inflammatory scenario triggers oxidative stress and, consequently, cellular dysfunction in the nervous tissue. The P2X7R seems to be the key mediator of the neuroinflammatory process, as it acts by increasing the concentration of ATP, allowing the influx of Ca2+ and the occurrence of mutations in the α-synuclein protein, causing activation of this receptor. Thus, modulation of the purinergic system may have therapeutic potential on the effects of PD, as well as on the damage caused by inflammation of the BBB, which may be able to mitigate the neurodegeneration caused by diseases. Considering all the processes of neuroinflammation, oxidative stress, and mitochondrial dysfunction that PD propose, we can conclude that the P2X7 antagonist acts in the prevention of viral diseases, and it also controls purinergic receptors formed by multi-target compounds directed to self-amplification circuits and, therefore, may be a viable strategy to obtain the desired disease-modifying effect. Thus, purinergic system receptor modulations have a high therapeutic potential for neurodegenerative diseases such as PD.

Chemical profile and biological properties of the Piper corcovadense C.DC. essential oil.

The essential oil from Piper corcovadense D.DC. (EOPc), an important plant belonging to the Piperaceae family, which is commonly found in the northern region of Brazil and poorly explored scientifically, was used in this study. Thus, the EOPc was characterized chemically by Gas Chromatography/Mass Spectrometry (GC/MS) and the antioxidant and antimicrobial activities and their potential effects on cutaneous melanoma (SK-MEL-28) and healthy peripheral blood mononuclear (PBMC) cells were determined. The major compounds identified in the EOPc were: trans-sesquisabinene hydrate, trans-caryophyllene, ß-pinene, trans-ß-farnesene, 14-hydroxycaryophyllene, limonene and p-cymene. The EOPc demonstrated antioxidant activity as evaluated by Folin-Ciocalteu reagent (FC) reducing capacity, DPPH, and ABTS methods. The values found were respectively 5.41 ± 0.17 mg GAE mL-1 (GAE: Gallic acid equivalent), 2.88 ± 0.17 µmol TE mL-1 (TE: Trolox equivalent) and 6.26 ± 0.02 µmol TE mL-1. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined for different bacterial strains. The EOPc at a concentration of 2.61 µg mL-1 exhibited both bactericidal and bacteriostatic properties against Escherichia coli. The EOPc showed potential antitumor activity as it reduced the cell viability of human cutaneous melanoma cells SK-MEL-28. Besides, the EOPc did not exhibit cytotoxic activity against healthy PBMCs, indicating that it does not harm healthy cells at the tested concentrations. The EOPc increased the levels of ROS at concentrations of 250 µg mL-1. The EOPc also did not stimulate the mobilization of endogenous antioxidant defenses, as assessed by total thiol (PSH) and non-protein thiols (NPSH). Thus, the study suggests that the EOPc has antioxidant and antimicrobial properties due to the presence of specific compounds. It also exhibits antitumor potential against cutaneous melanoma cells while showing no cytotoxicity to healthy PBMCs. It directly influenced ROS levels at the highest tested concentration in the cells, suggesting an antitumor effect related to the intrinsic apoptosis pathway. Nevertheless, while the study has initial findings, the results are promising and indicate an attractive biological potential of P. corcovadense, mainly in human cutaneous melanoma cells.

Amyotrophic Lateral Sclerosis in Long-COVID Scenario and the Therapeutic Potential of the Purinergic System in Neuromodulation.

Amyotrophic lateral sclerosis (ALS) involves the degeneration of motor neurons and debilitating and possibly fatal symptoms. The COVID-19 pandemic directly affected the quality of life of this group, and the SARS-CoV-2 infection accelerated the present neuroinflammatory process. Furthermore, studies indicate that the infection may have led to the development of the pathology. Thus, the scenario after this pandemic presents "long-lasting COVID" as a disease that affects people who have been infected. From this perspective, studying the pathophysiology behind ALS associated with SARS-CoV-2 infection and possible supporting therapies becomes necessary when we understand the impact on the quality of life of these patients. Thus, the purinergic system was trained to demonstrate how its modulation can add to the treatment, reduce disease progression, and result in better prognoses. From our studies, we highlight the P2X7, P2X4, and A2AR receptors and how their activity can directly influence the ALS pathway.

Effects of calcium supplementation on changes in the IL2, IL4, IL6, IL10 axes and oxidative stress in pregnant women at risk for pre-eclampsia.

BACKGROUND: Pregnant women with hypertensive disorders are at increased risk for inflammatory diseases and oxidative stress. The dilemma raised by the best dosage of calcium supplementation on these factors is evident. The aim of the current study was to examine the effects of calcium on biomarkers of the purinergic system, inflammation and oxidative stress, which are factors contributing to vascular damage in pregnant women at high risk of pre-eclampsia. METHODS: A prospective, double-blind and placebo-controlled study conducted with 101 women at risk of pre-eclampsia were randomized to take 500 mg calcium/day or 1,500 mg calcium/day or placebo for 6 weeks from the 20th gestational week until delivery. Fasting blood samples were collected at the beginning of the study and 6 weeks after the intervention. RESULTS: Taking calcium supplements (500 mg calcium/day) led to a significant increase in ATP hydrolysis (p < 0.05), NTPDase activity with increased hydrolysis of ADP and AMP nucleotides in platelets and lymphocytes. In the intragroup analysis IL-2, IL-6, IL-4 and interferon-É£ presented lower values in the calcium 1,500 mg/day group (p < 0.005). Oxidative stress was assessed by TBARS pro-oxidant marker, with an increase for the calcium groups when compared to the placebo group. The Vitamin C antioxidant marker presented a significant increase (p < 0.005) for the group that received high calcium doses. CONCLUSIONS: Calcium administration for 6 weeks had antioxidant action and positively modulated the purinergic system and inflammatory markers in pregnant women at risk of pre-eclampsia.

Current Pharmacology and Modulation of the Purinergic System in Takotsubo Syndrome Triggered by Cytokine Storm.

Studies show that with the COVID-19 pandemic, the world's population went through multiple stress and anxiety factors, generating serious psychological problems, in addition, the virus also caused damage and physical stress to those contaminated. In this way, the intense emotional experiences and stressful effects on the body caused by SARS-CoV-2 are capable of triggering the excessive release of catecholamines in the body. Thus, the framework of Takotsubo Syndrome is characterized by myocardial dysfunction as a response of cardiac receptors to the spillage of such hormones in an unregulated way in the human body. The purinergic system plays a central role in this process, as it actively participates in actions responsible for the syndromic cascade, such as the stress generated by the cytokine storm triggered by the virus and the stimulation of deregulated catecholamine release. Therefore, further pharmacological studies on the role of purines in this pathology should be developed in order to avoid the evolution of the syndrome and to modulate its P1 and P2 receptors aiming at developing means of reversing or treating the Takotsubo Syndrome.

Redox imbalance and inflammation: A link to depression risk in brazilian pesticide-exposed farmers.

This study aims to elucidate the mechanisms linking occupational pesticide exposure to depression among rural workers from Maravilha, Brazil. We assessed the mental health, oxidative, and inflammatory profiles of farmers exposed to pesticides (N = 28) and compared them to an urban control group without occupational exposure to pesticides (N = 25). Data on sociodemographic, occupational history, and clinical records were collected. Emotional states were evaluated using the State-Trait Anxiety Inventory (STAI) and Beck Depression Inventory (BDI). Biochemical, hematological, inflammatory, and redox parameters were examined in blood samples from both groups. Results showed educational disparities between groups and unveiled a concerning underutilization of personal protective equipment (PPEs) among farmers. Glyphosate was the predominant pesticide used by farmers. Farmers exhibited higher BDI scores, including more severe cases of depression. Additionally, elevated levels of creatinine, ALT, AST, and LDH were observed in farmers, suggesting potential renal and hepatic issues due to pesticide exposure. Oxidative stress markers, such as increased lipid peroxidation and superoxide dismutase (SOD) activity, along with decreased catalase (CAT) activity and ascorbic acid levels, were noted in the pesticide-exposed group compared to controls. Elevated levels of inflammatory cytokines, particularly IL-1ß, IL-6 and TNF-α, were also observed in pesticide-exposed group. Our findings suggest that inflammation, oxidative distress and lower educational levels may be associated with depression in pesticide-exposed farmers. This study highlights the impact of occupational pesticide exposure on the mental health of rural workers. The underuse of PPEs and the link between depressive symptoms, inflammation, and oxidative stress underscore the urgent need for improved safety measures in agricultural practices. Addressing these issues will contribute to a deeper understanding of the intricate relationship between environmental exposures and mental health outcomes.

The outcomes of growth hormone therapy in the obstructive sleep apnea parameters of Prader-Willi syndrome patients: a systematic review.

PURPOSE: Prader-Willi syndrome is a serious genetic condition, capable of causing endocrinological imbalance, which has as one of its main treatments the growth hormone therapy. However, this therapy still causes some uncertainty concerning its effects on the respiratory parameters of those patients, especially in cases of obstructive sleep apnea, therefore, presenting a need for the analysis of the relationship between the therapy and the otolaryngologic condition. METHODS: A systematic review following the PRISMA model was developed, with searches for keywords made in the databases PubMed (MEDLINE), Scopus, and Web of Science and registration in the PROSPERO platform (CRD42023404250). RESULTS: Three randomized controlled trials were considered eligible for inclusion in the review. None of the studies demonstrated statistically significant modifications in the obstructive sleep apnea parameters of Prader-Willi patients related to the growth hormone administration. CONCLUSIONS: Growth hormone therapy is safe for Prader-Willi syndrome patients when analyzing their obstructive sleep apnea parameters.

Efeitos da suplementação do cálcio sobre marcadores da pré-eclâmpsia: ensaio clínico randomizado / Efectos de los suplementos de calcio en marcadores de preeclampsia: ensayo clínico aleatorizado / Effects of calcium supplementation on markers of preeclampsia: randomized clinical trial

Resumo Objetivo Analisar os efeitos da suplementação de cálcio nos marcadores da pré-eclâmpsia ao longo do tempo, comparando o uso de cálcio em alta e baixa dosagem em mulheres grávidas com hipertensão. Métodos Trata-se de ensaio clínico randomizado com três grupos paralelos, placebo controlado, realizado no ambulatório de referência para o pré-natal de alto risco na Região Sul do Brasil, com análise de intenção de tratar e seguimento após quatro e oito semanas. A intervenção consistiu na ingestão de cálcio 500mg/dia, cálcio 1500mg/dia e placebo. Os dados foram analisados segundo um modelo generalizado de estimação de equações mistas adotando α 0,05. Resultados O efeito do cálcio em baixa e alta dosagem na evolução ao longo do tempo foi mantido entre os grupos, mesmo após o ajuste para os fatores de confusão. Houve diferença significativa nos parâmetros analisados na interação tempo e grupo (p <0,000) e diminuição nas médias de 12,3mmHg na PAS, 9,2 mmHg na PAD, 3,2 mg/dl creatinina e 7,2 mg/dl proteinúria para o grupo cálcio 500mg/dia. Os resultados foram semelhantes para o grupo com suplementação máxima. Conclusão O cálcio melhorou o prognóstico vascular em mulheres grávidas com hipertensão ao reduzir os níveis pressóricos e os marcadores da pré-eclâmpsia.

Resumen Objetivo Analizar los efectos de los suplementos de calcio en los marcadores de preeclampsia a lo largo del tiempo, comparando el uso de calcio en dosis altas y bajas en mujeres embarazadas con hipertensión. Métodos Se trata de un ensayo clínico aleatorizado con tres grupos paralelos, placebo controlado realizado en consultorios externos de referencia en el control prenatal de alto riesgo en la Región Sur de Brasil, con análisis de intención de tratar y seguimiento luego de cuatro y ocho semanas. La intervención consistió en la ingesta de calcio 500 mg/día, calcio 1500 mg/día y placebo. Los datos se analizaron de acuerdo con un modelo generalizado de estimación de ecuaciones mixtas adoptando α 0,05. Resultados El efecto del calcio en dosis bajas y altas en la evolución a lo largo del tiempo se mantuvo entre los grupos, inclusive después de los ajustes por los factores de confusión. Hubo diferencia significativa en los parámetros analizados en la interacción tiempo y grupo (p <0,000) y reducción de los promedios de 12,3 mmHg en la PAS, 9,2 mmHg en la PAD, 3,2 mg/dl creatinina y 7,2 mg/dl proteinuria en el grupo calcio 500 mg/día. Los resultados fueron parecidos en el grupo con suplemento en dosis máxima. Conclusión El calcio mejoró el pronóstico vascular en mujeres embarazadas con hipertensión al reducir los niveles de presión y los marcadores de preeclampsia. Registro Brasileiro de Ensaios Clínicos: RBR-9ngb95

Abstract Objective To analyze the effects of calcium supplementation on markers of preeclampsia over time by comparing the use of high- and low-dose calcium in hypertensive pregnant women. Methods This is a randomized clinical trial, placebo controlled, with three parallel groups carried out at the reference outpatient clinic for high-risk prenatal care in the South Region of Brazil, with intention-to-treat analysis and follow-up after four and eight weeks. The intervention consisted of ingesting calcium 500mg/day, calcium 1500mg/day and placebo. Data were analyzed according to a generalized mixed equation estimation model adopting α 0.05. Results The effect of low- and high-dose calcium on evolution over time was maintained between groups, even after adjustment for confounding factors. There was a significant difference in the parameters analyzed in the time and group interaction (p <0.000) and a decrease in the means of 12.3 mmHg in SBP, 9.2 mmHg in DBP, 3.2 mg/dl creatinine and 7.2 mg/dl proteinuria for the 500mg calcium/day group. The results were similar for the maximal supplementation group. Conclusion Calcium improved vascular prognosis in hypertensive pregnant women by reducing blood pressure levels and markers of preeclampsia. Brazilian Registry of Clinical Trials: RBR-9ngb95

COVID-19, Anxiety, and Body Mass Index Increase Leptin Levels: a Cross-sectional Multicentric Study.

Although many efforts have been made to understand the pathophysiological mechanisms of COVID-19, critical gaps remain to be explored. This study aimed to investigate potential alterations in adipokine levels (specifically adiponectin, leptin, and resistin) among individuals with COVID-19. Within this population, we further assessed the association between these markers with both, body mass index (BMI) and psychiatric symptoms. This cross-sectional study included an age- and sex-matched sample of adults with COVID-19 (cases) and without COVID-19 (controls). We evaluated the severity of psychiatric symptoms, BMI, and adipokines. Individuals with COVID-19 presented greater BMI, stress levels, and leptin levels when compared to controls. Leptin levels were greater in individuals with moderate/severe COVID-19 as compared to individuals with COVID-19 who were asymptomatic or having mild symptoms. Leptin levels were positively correlated with BMI, severity of depressive and anxiety symptoms, and stress levels in the total sample. Leptin levels were also positively correlated with BMI, severity of anxiety symptoms, and stress levels in controls. In cases, there was a positive correlation between adiponectin and the severity of depressive symptoms and stress levels and leptin/resistin with BMI. A linear regression model revealed that BMI, severity of anxiety symptoms, and the diagnosis of COVID-19 are independently associated with increased leptin levels. Thus, leptin levels seem to be impacted by the COVID-19 infection, anxiety, and BMI.

Curcumin promotes apoptosis of human melanoma cells by caspase 3.

Cutaneous melanoma (CM) is a malignant neoplasm with a high metastatic rate that shows poor response to systemic treatments in patients with advanced stages. Recently, studies have highlighted the antineoplastic potential of natural compounds, such as polyphenols, in the adjuvant therapy context to treat CM. The objective of the present study was to evaluate the effect of different concentrations of curcumin (0.1-100 µM) on the metastatic CM cell line SK-MEL-28. The cells were treated for 6 and 24 h with different concentrations of curcumin. Cell viability was assessed by 3-(4,5-dimethyl-2thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and fluorescence microscopy. The apoptotic-inducing potential was detected by annexin V flow cytometry. The wound healing assay was used to verify cell migration after the curcumin exposition. The redox profile was evaluated by levels of the pro-oxidant markers reactive oxygen species (ROS) and Nitric oxide (NOx) and antioxidants of total thiols (PSH) and nonprotein thiols. The gene expression and enzymatic activity of caspase 3 were evaluated by reverse transcription-quantitative polymerase chain reaction and a sensitive fluorescence assay, respectively. Curcumin significantly decreased the cell viability of SK-MEL-28 cells at both exposure times. It also induced apoptosis at the highest concentration tested (p < .0001). SK-MEL-28 cell migration was inhibited by curcumin after treatment with 10 µM (p < .0001) and 100 µM (p < .0001) for 6 and 24 h (p = .0006 and p < .0001, respectively). Furthermore, curcumin significantly increased levels of ROS and NOx. Finally, curcumin was capable of increasing the gene expression at 10 µM (p = .0344) and 100 µM (p = .0067) and enzymatic activity at 10 µM (p = .0086) and 100 µM (p < .0001) of caspase 3 after 24 h. For the first time, we elucidated in our study that curcumin increases ROS levels, promoting oxidative stress that activates the caspase pathway and culminates in SK-MEL-28 metastatic CM cell death.