Paving Luteolin Therapeutic Potentialities and Agro-Food-Pharma Applications: Emphasis on in Vivo Pharmacological Effects and Bioavailability Traits

Luteolin is a naturally occurring secondary metabolite belonging to the class of flavones. As many other natural flavonoids, it is often found in combination with glycosides in many fruits, vegetables, and plants, contributing to their biological and pharmacological value. Many preclinical studies report that luteolin present excellent antioxidant, anticancer, antimicrobial, neuroprotective, cardioprotective, antiviral, and anti-inflammatory effects, and as a consequence, various clinical trials have been designed to investigate the therapeutic potential of luteolin in humans. However, luteolin has a very limited bioavailability, which consequently affects its biological properties and efficacy. Several drug delivery strategies have been developed to raise its bioavailability, with nanoformulations and lipid carriers, such as liposomes, being the most intensively explored. Pharmacological potential of luteolin in various disorders has also been underlined, but to some of them, the exact mechanism is still poorly understood. Given the great potential of this natural antioxidant in health, this review is aimed at providing an extensive overview on the in vivo pharmacological action of luteolin and at stressing the main features related to its bioavailability, absorption, and metabolism, while essential steps determine its absolute health benefits and safety profiles. In addition, despite the scarcity of studies on luteolin bioavailability, the different drug delivery formulations developed to increase its bioavailability are also listed here.This study was partially supported by Çanakkale Onsekiz Mart Üniversitesi (Scientific Research Projects, ID: FYL-2017-1339 and FBA-2017-1268)

Production, Transmission, Pathogenesis, and Control of Dengue Virus: A Literature-Based Undivided Perspective

Dengue remains one of the most serious and widespread mosquito-borne viral infections in human beings, with serious health problems or even death. About 50 to 100 million people are newly infected annually, with almost 2.5 billion people living at risk and resulting in 20,000 deaths. Dengue virus infection is especially transmitted through bites of Aedes mosquitos, hugely spread in tropical and subtropical environments, mostly found in urban and semiurban areas. Unfortunately, there is no particular therapeutic approach, but prevention, adequate consciousness, detection at earlier stage of viral infection, and appropriate medical care can lower the fatality rates. This review offers a comprehensive view of production, transmission, pathogenesis, and control measures of the dengue virus and its vectors.This work was supported by CONICYT PIA/APOYO CCTE AFB170007

Lasia spinosa Chemical Composition and Therapeutic Potential: A Literature-Based Review

Lasia spinosa (L.) is used ethnobotanically for the treatment of various diseases, including rheumatoid arthritis, inflammation of the lungs, bleeding cough, hemorrhoids, intestinal diseases, stomach pain, and uterine cancer. This review is aimed at summarizing phytochemistry and pharmacological data with their molecular mechanisms of action. A search was performed in databases such as PubMed, Science Direct, and Google Scholar using the keywords: "Lasia spinosa,"then combined with "ethnopharmacological use,""phytochemistry,"and "pharmacological activity."This updated review included studies with in vitro, ex vivo, and in vivo experiments with compounds of known concentration and highlighted pharmacological mechanisms. The research results showed that L. spinosa contains many important nutritional and phytochemical components such as alkanes, aldehydes, alkaloids, carotenoids, flavonoids, fatty acids, ketones, lignans, phenolics, terpenoids, steroids, and volatile oil with excellent bioactivity. The importance of this review lies in the fact that scientific pharmacological evidence supports the fact that the plant has antioxidant, anti-inflammatory, antimicrobial, cytotoxic, antidiarrheal, antihelminthic, antidiabetic, antihyperlipidemic, and antinociceptive effects, while protecting the gastrointestinal system and reproductive. Regarding future toxicological and safety data, more research is needed, including studies on human subjects. In light of these data, L. spinosa can be considered a medicinal plant with effective bioactives for the adjuvant treatment of various diseases in humans.This work was supported by Comisión Nacional de Investigación Científica y Tecnológica (CONICYT) PIA/APOYO CCTE AFB170007. N.C.-M. acknowledges the Portuguese Foundation for Science and Technology under the Horizon 2020 Program (PTDC/PSI-GER/28076/2017)

Therapeutic Potential of Isoflavones with an Emphasis on Daidzein

Daidzein is a phytoestrogen isoflavone found in soybeans and other legumes. The chemical composition of daidzein is analogous to mammalian estrogens, and it could be useful with a dual-directional purpose by substituting/hindering with estrogen and estrogen receptor (ER) complex. Hence, daidzein puts forth shielding effects against a great number of diseases, especially those associated with the control of estrogen, such as breast cancer, diabetes, osteoporosis, and cardiovascular disease. However, daidzein also has other ER-independent biological activities, such as oxidative damage reduction acting as an antioxidant, immune regulator as an anti-inflammatory agent, and apoptosis regulation, directly linked to its potential anticancer effects. In this sense, the present review is aimed at providing a deepen analysis of daidzein pharmacodynamics and its implications in human health, from its best-known effects alleviating postmenopausal symptoms to its potential anticancer and antiaging properties.N.M. acknowledges the Portuguese Foundation for Science and Technology under the Horizon 2020 Program (PTDC/PSI-GER/28076/2017). M. T-M was funded by a grant from the Programa Postdoctoral Margalida Comas-Comunidad Autónoma de las Islas Baleares (PD/050/2020). The authors also acknowledge that some of the icons used in figures are adapted from Flaticon

Pancreatic cancer and depression: myth and truth

<p>Abstract</p> <p>Background</p> <p>Various studies reported remarkable high incidence rates of depression in cancer patients compared with the general population. Pancreatic cancer is still one of the malignancies with the worst prognosis and therefore it seems quite logical that it is one of the malignancies with the highest incidence rates of major depression.</p> <p>However, what about the scientific background of this relationship? Is depression in patients suffering from pancreatic cancer just due to the confrontation with a life threatening disease and its somatic symptoms or is depression in this particular group of patients a feature of pancreatic cancer per se?</p> <p>Discussion</p> <p>Several studies provide evidence of depression to precede the diagnosis of pancreatic cancer and some studies even blame it for its detrimental influence on survival. The immense impact of emotional distress on quality of life of cancer patients enhances the need for its early diagnosis and adequate treatment. Knowledge about underlying pathophysiological mechanisms is required to provide the optimal therapy.</p> <p>Summary</p> <p>A review of the literature on this issue should reveal which are the facts and what is myth.</p

Anticonvulsant effects of aerial parts of Passiflora incarnata extract in mice: involvement of benzodiazepine and opioid receptors

<p>Abstract</p> <p>Background</p> <p>Passion flower (<it>Passiflora incarnata</it>) is used in traditional medicine of Europe and South America to treat anxiety, insomnia and seizure. Recently, it has shown antianxiety and sedative effects in human.</p> <p>Methods</p> <p>In this study, anticonvulsant effects of hydro- alcoholic extract of Passiflora, Pasipay, were examined by using pentylentetrazole model (PTZ) on mice. Pasipay, diazepam, and normal saline were injected intraperitoneally at the doses 0.4–0.05 mg/kg, 0.5–1 mg/kg and 10 ml/kg respectively 30 minutes before PTZ (90 mg/kg, i.p). The time taken before the onset of clonic convulsions, the duration of colonic convulsions, and the percentage of seizure and mortality protection were recorded. For investigating the mechanism of Pasipay, flumazenil (2 mg/kg, i.p) and naloxone (5 mg/kg, i.p) were also injected 5 minutes before Pasipay.</p> <p>Results</p> <p>An ED₅₀value of Pasipay in the PTZ model was 0.23 mg/kg (%95 CL: 0.156, 0.342). Pasipay at the dose of 0.4 mg/kg prolonged the onset time of seizure and decreased the duration of seizures compared to saline group (p < 0.001). At the dose of 0.4 mg/kg, seizure and mortality protection percent were 100%. Flumazenil and naloxone could suppress anticonvulsant effects of Pasipay.</p> <p>Conclusion</p> <p>It seems that Pasipay could be useful for treatment absence seizure and these effects may be related to effect of it on GABAergic and opioid systems. More studies are needed in order to investigate its exact mechanism.</p

Essential omega‐3 fatty acids are depleted in sea ice and pelagic algae of the Central Arctic Ocean

Microalgae are the main source of the omega‐3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), essential for the healthy development of most marine and terrestrial fauna including humans. Inverse correlations of algal EPA and DHA proportions (% of total fatty acids) with temperature have led to suggestions of a warming‐induced decline in the global production of these biomolecules and an enhanced importance of high latitude organisms for their provision. The cold Arctic Ocean is a potential hotspot of EPA and DHA production, but consequences of global warming are unknown. Here, we combine a full‐seasonal EPA and DHA dataset from the Central Arctic Ocean (CAO), with results from 13 previous field studies and 32 cultured algal strains to examine five potential climate change effects; ice algae loss, community shifts, increase in light, nutrients, and temperature. The algal EPA and DHA proportions were lower in the ice‐covered CAO than in warmer peripheral shelf seas, which indicates that the paradigm of an inverse correlation of EPA and DHA proportions with temperature may not hold in the Arctic. We found no systematic differences in the summed EPA and DHA proportions of sea ice versus pelagic algae, and in diatoms versus non‐diatoms. Overall, the algal EPA and DHA proportions varied up to four‐fold seasonally and 10‐fold regionally, pointing to strong light and nutrient limitations in the CAO. Where these limitations ease in a warming Arctic, EPA and DHA proportions are likely to increase alongside increasing primary production, with nutritional benefits for a non‐ice‐associated food web

A Self-Organizing Algorithm for Modeling Protein Loops

Protein loops, the flexible short segments connecting two stable secondary structural units in proteins, play a critical role in protein structure and function. Constructing chemically sensible conformations of protein loops that seamlessly bridge the gap between the anchor points without introducing any steric collisions remains an open challenge. A variety of algorithms have been developed to tackle the loop closure problem, ranging from inverse kinematics to knowledge-based approaches that utilize pre-existing fragments extracted from known protein structures. However, many of these approaches focus on the generation of conformations that mainly satisfy the fixed end point condition, leaving the steric constraints to be resolved in subsequent post-processing steps. In the present work, we describe a simple solution that simultaneously satisfies not only the end point and steric conditions, but also chirality and planarity constraints. Starting from random initial atomic coordinates, each individual conformation is generated independently by using a simple alternating scheme of pairwise distance adjustments of randomly chosen atoms, followed by fast geometric matching of the conformationally rigid components of the constituent amino acids. The method is conceptually simple, numerically stable and computationally efficient. Very importantly, additional constraints, such as those derived from NMR experiments, hydrogen bonds or salt bridges, can be incorporated into the algorithm in a straightforward and inexpensive way, making the method ideal for solving more complex multi-loop problems. The remarkable performance and robustness of the algorithm are demonstrated on a set of protein loops of length 4, 8, and 12 that have been used in previous studies

Past, present, and future of global health financing : a review of development assistance, government, out-of-pocket, and other private spending on health for 195 countries, 1995-2050

Background Comprehensive and comparable estimates of health spending in each country are a key input for health policy and planning, and are necessary to support the achievement of national and international health goals. Previous studies have tracked past and projected future health spending until 2040 and shown that, with economic development, countries tend to spend more on health per capita, with a decreasing share of spending from development assistance and out-of-pocket sources. We aimed to characterise the past, present, and predicted future of global health spending, with an emphasis on equity in spending across countries. Methods We estimated domestic health spending for 195 countries and territories from 1995 to 2016, split into three categories-government, out-of-pocket, and prepaid private health spending-and estimated development assistance for health (DAH) from 1990 to 2018. We estimated future scenarios of health spending using an ensemble of linear mixed-effects models with time series specifications to project domestic health spending from 2017 through 2050 and DAH from 2019 through 2050. Data were extracted from a broad set of sources tracking health spending and revenue, and were standardised and converted to inflation-adjusted 2018 US dollars. Incomplete or low-quality data were modelled and uncertainty was estimated, leading to a complete data series of total, government, prepaid private, and out-of-pocket health spending, and DAH. Estimates are reported in 2018 US dollars, 2018 purchasing-power parity-adjusted dollars, and as a percentage of gross domestic product. We used demographic decomposition methods to assess a set of factors associated with changes in government health spending between 1995 and 2016 and to examine evidence to support the theory of the health financing transition. We projected two alternative future scenarios based on higher government health spending to assess the potential ability of governments to generate more resources for health. Findings Between 1995 and 2016, health spending grew at a rate of 4.00% (95% uncertainty interval 3.89-4.12) annually, although it grew slower in per capita terms (2.72% [2.61-2.84]) and increased by less than $1 per capita over this period in 22 of 195 countries. The highest annual growth rates in per capita health spending were observed in upper-middle-income countries (5.55$ 8.0 trillion (7.8-8.1) in 2016 (comprising 8.6% [8.4-8.7] of the global economy and $10.3 trillion [10.1-10.6] in purchasing-power parity-adjusted dollars), with a per capita spending of US$ 5252 (5184-5319) in high-income countries, $491 (461-524) in upper-middle-income countries,$ 81 (74-89) in lower-middle-income countries, and $40 (38-43) in low-income countries. In 2016, 0.4$ 9.5 billion, 24.3% of total DAH), although spending on other infectious diseases (excluding tuberculosis and malaria) grew fastest from 2010 to 2018 (6.27% per year). The leading sources of DAH were the USA and private philanthropy (excluding corporate donations and the Bill & Melinda Gates Foundation). For the first time, we included estimates of China's contribution to DAH ($644.7 million in 2018). Globally, health spending is projected to increase to$ 15.0 trillion (14.0-16.0) by 2050 (reaching 9.4% [7.6-11.3] of the global economy and $ 21.3 trillion [19.8-23.1] in purchasing-power parity-adjusted dollars), but at a lower growth rate of 1.84% (1.68-2.02) annually, and with continuing disparities in spending between countries. In 2050, we estimate that 0.6% (0.6-0.7) of health spending will occur in currently low-income countries, despite these countries comprising an estimated 15.7% of the global population by 2050. The ratio between per capita health spending in high-income and low-income countries was 130.2 (122.9-136.9) in 2016 and is projected to remain at similar levels in 2050 (125.9 [113.7-138.1]). The decomposition analysis identified governments' increased prioritisation of the health sector and economic development as the strongest factors associated with increases in government health spending globally. Future government health spending scenarios suggest that, with greater prioritisation of the health sector and increased government spending, health spending per capita could more than double, with greater impacts in countries that currently have the lowest levels of government health spending. Interpretation Financing for global health has increased steadily over the past two decades and is projected to continue increasing in the future, although at a slower pace of growth and with persistent disparities in per-capita health spending between countries. Out-of-pocket spending is projected to remain substantial outside of high-income countries. Many low-income countries are expected to remain dependent on development assistance, although with greater government spending, larger investments in health are feasible. In the absence of sustained new investments in health, increasing efficiency in health spending is essential to meet global health targets.Peer reviewe