Overview of the Anticancer Potential of the "King of Spices" Piper nigrum and Its Main Constituent Piperine

The main limits of current anticancer therapy are relapses, chemoresistance, and toxic effects resulting from its poor selectivity towards cancer cells that severely impair a patient's quality of life. Therefore, the discovery of new anticancer drugs remains an urgent challenge. Natural products represent an excellent opportunity due to their ability to target heterogenous populations of cancer cells and regulate several key pathways involved in cancer development, and their favorable toxicological profile. Piper nigrum is one of the most popular spices in the world, with growing fame as a source of bioactive molecules with pharmacological properties. The present review aims to provide a comprehensive overview of the anticancer potential of Piper nigrum and its major active constituents-not limited to the well-known piperine-whose undeniable anticancer properties have been reported for different cancer cell lines and animal models. Moreover, the chemosensitizing effects of Piper nigrum in association with traditional anticancer drugs are depicted and its toxicological profile is outlined. Despite the promising results, human studies are missing, which are crucial for supporting the efficacy and safety of Piper nigrum and its single components in cancer patients

Janus Kinase Inhibitors and Coronavirus Disease (COVID)-19: Rationale, Clinical Evidence and Safety Issues

: We are witnessing a paradigm shift in drug development and clinical practice to fight the novel coronavirus disease (COVID-19), and a number of clinical trials have been or are being testing various pharmacological approaches to counteract viral load and its complications such as cytokine storm. However, data on the effectiveness of antiviral and immune therapies are still inconclusive and inconsistent. As compared to other candidate drugs to treat COVID-19, Janus Kinase (JAK) inhibitors, including baricitinib and ruxolitinib, possess key pharmacological features for a potentially successful repurposing: convenient oral administration, favorable pharmacokinetic profile, multifunctional pharmacodynamics by exerting dual anti-inflammatory and anti-viral effects. Baricitinib, originally approved for rheumatoid arthritis, received Emergency Use Authorization in November 2020 by the Food and Drug Administration in combination with remdesivir for the treatment of COVID-19 in hospitalized patients ≥ 2 years old who require supplemental oxygen, invasive mechanical ventilation, or extracorporeal membrane oxygenation. By July 2021, the European Medicines Agency is also expected to issue the opinion on whether or not to extend its use in hospitalised patients from 10 years of age who require supplemental oxygen. Ruxolitinib, approved for myelofibrosis, was prescribed in patients with COVID-19 within an open-label Emergency Expanded Access Plan. This review will address key milestones in the discovery and use of JAK inhibitors in COVID-19, from artificial intelligence to current clinical evidence, including real world experience, and critically appraise emerging safety issues, namely infections, thrombosis, and liver injury. An outlook to ongoing studies (clinicaltrials.gov) and unpublished pharmacovigilance data is also offered

The Alcoholic Bark Extract of Terminalia Arjuna Exhibits Cytotoxic and Cytostatic Activity on Jurkat Leukemia Cells

Abstract: Background: Natural products are characterized by complex chemical composition and are capable of concurrently modulate several signalling pathways. Considering the biological com- plexity of carcinogenesis, natural products represent key components of the therapeutic armamen- tarium for oncological diseases. The bark of Terminalia arjuna is used in traditional Ayurvedic medicine for its astringent, expectorant, cardiotonic, styptic, and antidysenteric properties. Along- side its traditional uses, Terminalia arjuna exhibits different biological activities including an- timutagenic and anticarcinogenic. Objective: This study was designed to evaluate the toxic effects of an alcoholic extract obtained from the bark of T. arjuna on a human T-lymphoblastic cell line (Jurkat). We explored the phyto- chemical composition and investigated the cytotoxic, cytostatic, genotoxic, and anti-genotoxic effects. Methods: The phytochemical composition was analyzed using spectrophotometric methods; all the biological endpoints were assessed through flow cytometry. Results: The phytochemical screening showed that polyphenols represent about 64% of the extract. Moreover, the extract was cytotoxic on Jurkat cells by inducing both apoptosis and necrosis and blocked the cell cycle in the G2/M phase. Additionally, it was found that the extract lacks any geno- toxic effect, but was not effective in protecting Jurkat cells from the DNA damage induced by H2O2 and etoposide. Conclusion: The results of our study show the toxic effects of Terminalia arjuna on Jurkat cells and confirm the pivotal role played by natural compounds in the oncological field. Further studies should be performed to better understand its clinical potential and deepen its toxicological profile

Discovery of Sulforaphane as an Inducer of Ferroptosis in U-937 Leukemia Cells: Expanding Its Anticancer Potential

In recent years, natural compounds have emerged as inducers of non-canonical cell death. The isothiocyanate sulforaphane (SFN) is a well-known natural anticancer compound with remarkable pro-apoptotic activity. Its ability to promote non-apoptotic cell-death mechanisms remains poorly investigated. This work aimed to explore the capacity of SFN to induce non-apoptotic cell death modalities. SFN was tested on different acute myeloid leukemia cell lines. The mechanism of cell death was investigated using a multi-parametric approach including fluorescence microscopy, western blotting, and flow cytometry. SFN triggered different cell-death modalities in a dose-dependent manner. At 25 μM, SFN induced caspase-dependent apoptosis and at 50 μM ferroptosis was induced through depletion of glutathione (GSH), decreased GSH peroxidase 4 protein expression, and lipid peroxidation. In contrast, necroptosis was not involved in SFN-induced cell death, as demonstrated by the non-significant increase in phosphorylation of receptor-interacting protein kinase 3 and phosphorylation of the necroptotic effector mixed lineage kinase domain-like pseudokinase. Taken together, our results suggest that the antileukemic activity of SFN can be mediated via both ferroptotic and apoptotic cell death modalities

Practice Theories and the \u201cCircuit of Culture\u201d: Integrating Approaches for Studying Material Culture

The paper compares two heuristic tools to understand how practice theory could be used to study the phenomena of material culture: the one summarized by Shove et Al. (2012) in The Dynamics of Social Practice: Everyday Life and How It Changes and the \u201ccircuit of culture\u201d proposed by Paul Du Gay et Al. in Doing Cultural Studies. The Case of the Sony Walkman (1997). The aim of the article is to test the possibility to integrate the use of these two tools. In order to fulfil this purpose, the article is comprised of two parts. The first part illustrates how the two heuristic tools are compatible and what advantages each have over the other. In the second part, both heuristic tools will be applied to explore two case studies, one regarding a technological artefact and another one regarding a type of agricultural practice

Combining excitation-emission matrix fluorescence spectroscopy, parallel factor analysis, cyclodextrin-modified micellar electrokinetic chromatography and partial least squares class-modelling for green tea characterization

In this study, an alternative analytical approach for analyzing and characterizing green tea (GT) samples is proposed, based on the combination of excitation–emission matrix (EEM) fluorescence spectroscopy and multivariate chemometric techniques. The three-dimensional spectra of 63 GT samples were recorded using a Perkin–Elmer LS55 luminescence spectrometer; emission spectra were recorded between 295 and 800 nm at excitation wavelength ranging from 200 to 290 nm, with excitation and emission slits both set at 10 nm. The excitation and emission profiles of two factors were obtained using Parallel Factor Analysis (PARAFAC) as a 3-way decomposition method. In this way, for the first time, the spectra of two main fluorophores in green teas have been found. Moreover, a cyclodextrin-modified micellar electrokinetic chromatography method was employed to quantify the most represented catechins and methylxanthines in a subset of 24 GT samples in order to obtain complementary information on the geographical origin of tea. The discrimination ability between the two types of tea has been shown by a Partial Least Squares Class-Modelling performed on the electrokinetic chromatography data, being the sensitivity and specificity of the class model built for the Japanese GT samples 98.70% and 98.68%, respectively. This comprehensive work demonstrates the capability of the combination of EEM fluorescence spectroscopy and PARAFAC model for characterizing, differentiating and analyzing GT samples

O CUIDADO EM SAÚDE E AS IMPLICAÇÕES PARA OS CUIDADORES DOMICILIARES

RESUMO: O artigo trata da temática do cuidado domiciliar em saúde, modalidade de atendimento que tem crescido em vários países, impulsionada pelas transições demográficas e epidemiológicas dos últimos anos. Com foco em duas experiências, o trabalho apresenta os resultados de uma pesquisa com o objetivo de analisar o perfil dos cuidadores de dois programas de atenção em saúde domiciliar sendo, um público e outro privado desenvolvido em cidades localizadas na Região da Grande Florianópolis. Trata-se de uma pesquisa qualitativa com aplicação de entrevistas com cuidadores de pessoas em internação domiciliar. Como principais resultados aponta-se que a família tem sido cada vez mais responsabilizada pelo cuidado em saúde, principalmente as mulheres alterando a dinâmica familiar que implica nas condições objetivas de vida

DETECTION OF WIDESPREAD HYDRATED MATERIALS ON VESTA BY THE VIR IMAGING SPECTROMETER ON BOARD THE DAWN MISSION

Water plays a key role in the evolution of terrestrial planets, and notably in the occurrence of Earth's oceans. However, the mechanism by which water has been incorporated into these bodies—including Earth—is still extensively debated. Here we report the detection of widespread 2.8 μm OH absorption bands on the surface of the asteroid Vesta by the VIR imaging spectrometer on board Dawn. These observations are surprising as Vesta is fully differentiated with a basaltic surface. The 2.8 μm OH absorption is distributed across Vesta's surface and shows areas enriched and depleted in hydrated materials. The uneven distribution of hydrated mineral phases is unexpected and indicates ancient processes that differ from those believed to be responsible for OH on other airless bodies, like the Moon. The origin of Vestan OH provides new insight into the delivery of hydrous materials in the main belt and may offer new scenarios on the delivery of hydrous minerals in the inner solar system, suggesting processes that may have played a role in the formation of terrestrial planets

Risk factors for mental disorder development in asylum seekers and refugees resettled in Western Europe and Turkey: Participant-level analysis of two large prevention studies

BackgroundIn asylum seekers and refugees, the frequency of mental disorders, such as depression, anxiety and post-traumatic stress disorder, is higher than the general population, but there is a lack of data on risk factors for the development of mental disorders in this population.AimThis study investigated the risk factors for mental disorder development in a large group of asylum seekers and refugees resettled in high- and middle-income settings.MethodsParticipant-level data from two randomized prevention studies involving asylum seekers and refugees resettled in Western European countries and in Turkey were pooled. The two studies randomized participants with psychological distress, but without a diagnosis of mental disorder, to the Self-Help Plus psychological intervention or enhanced care as usual. At baseline, exposure to potentially traumatic events was measured using the Harvard Trauma Questionnaire-part I, while psychological distress and depressive symptoms were assessed with the General Health Questionnaire and the Patient Health Questionnaire. After 3 and 6 months of follow-up, the proportion of participants who developed a mental disorder was calculated using the Mini International Neuropsychiatric Interview.ResultsA total of 1,101 participants were included in the analysis. At 3- and 6-month follow-up the observed frequency of mental disorders was 13.51% (115/851) and 24.30% (207/852), respectively, while the frequency estimates after missing data imputation were 13.95% and 23.78%, respectively. After controlling for confounders, logistic regression analysis showed that participants with a lower education level (p = .034), a shorter duration of journey (p = .057) and arriving from countries with war-related contexts (p = .017), were more at risk of developing mental disorders. Psychological distress (p = .004), depression (p = .001) and exposure to potentially traumatic events (p = .020) were predictors of mental disorder development.ConclusionsThis study identified several risk factors for the development of mental disorders in asylum seekers and refugees, some of which may be the target of risk reduction policies. The identification of asylum seekers and refugees at increased risk of mental disorders should guide the implementation of focused preventative psychological interventions