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Background Cardiovascular diseases (CVDs) are the leading cause of death worldwide. Black pepper, the fruits of Piper nigrum L., is well known as “the king of spices” and used as seasoning and condiments globally. In addition to being an important food additive, black pepper is also used as a traditional medicine to treat vomiting, abdominal pain, and diarrhea, among others. Piperine is a major pungent alkaloid identified in the fruits of P. nigrum (black pepper), whose content is at a range of ~5–13%. Black pepper and piperine have shown protective effect on CVDs. Scope and approach Literature search was conducted to systematically review the cardiovascular protective effect of both black pepper and its major bioactive constituent piperine. Key findings and conclusions Black pepper was reported to regulate lipid metabolism, inflammation, and oxidation status in CVDs. Piperine exhibited beneficial effect by targeting many processes associated with atherosclerosis. Piperine is able to prevent lipid peroxidation, oxidized low-density lipoprotein uptake in macrophages, lipid droplet formation, and adhesion of inflammatory cells to endothelial monolayer, promote cholesterol efflux from macrophages, as well as improve lipid profile. Besides, piperine may ameliorate myocardial ischemia, cardiac injury, and cardiac fibrosis, exhibit antihypertensive and antithrombosis effect, as well as prevent arterial stenosis by inhibiting vascular smooth muscle cell proliferation. The summarized information could provide the basis to develop black pepper or piperine as a food additive to prevent or treat CVDs.

Ginger (Zingiber officinale Roscoe) is a common and widely used spice. It is rich in various chemical constituents, including phenolic compounds, terpenes, polysaccharides, lipids, organic acids, and raw fibers. Herein, we reviewed its effects on the vascular system. Studies utilizing cell cultures or animal models showed that ginger constituents alleviate oxidative stress and inflammation, increase nitric oxide synthesis, suppress vascular smooth muscle cell proliferation, promote cholesterol efflux from macrophages, inhibit angiogenesis, block voltage-dependent Ca2+ channels, and induce autophagy. In clinical trials, ginger was shown to have a favorable effect on serum lipids, inflammatory cytokines, blood pressure, and platelet aggregation. Taken together, these studies point to the potential benefits of ginger and its constituents in the treatment of hypertension, coronary artery disease, peripheral arterial diseases, and other vascular diseases.

The open innovation hub Digital Health and Patient Safety Platform (DHPSP) was recently established with the purpose to invigorate collaborative scientific research and the development of new digital products and personalized solutions aiming to improve human health and patient safety. In this study, we evaluated the effectiveness of a Twitter-based campaign centered on using the hashtag #DHPSP to promote the visibility of the DHPSP initiative. Thus, tweets containing #DHPSP were monitored for five weeks for the period 20.10.2020–24.11.2020 and were analyzed with Symplur Signals (social media analytics tool). In the study period, a total of 11,005 tweets containing #DHPSP were posted by 3020 Twitter users, generating 151,984,378 impressions. Analysis of the healthcare stakeholder-identity of the Twitter users who used #DHPSP revealed that the most of participating user accounts belonged to individuals or doctors, with the top three user locations being the United States (501 users), the United Kingdom (155 users), and India (121 users). Analysis of co-occurring hashtags and the full text of the posted tweets further revealed that the major themes of attention in the #DHPSP Twitter-community were related to the coronavirus disease 2019 (COVID-19), medicine and health, digital health technologies, and science communication in general. Overall, these results indicate that the #DHPSP initiative achieved high visibility and engaged a large body of Twitter users interested in the DHPSP focus area. Moreover, the conducted campaign resulted in an increase of DHPSP member enrollments and website visitors, and new scientific collaborations were formed. Thus, Twitter campaigns centered on a dedicated hashtag prove to be a highly efficient tool for visibility-promotion, which could be successfully utilized by healthcare-related open innovation platforms or initiatives.

Scavenger receptor class B type I (SR-BI) protein is an integral membrane glycoprotein. SR-BI is emerging as a multifunctional protein, which regulates autophagy, efferocytosis, cell survival and inflammation. It is well known that SR-BI plays a critical role in lipoprotein metabolism by mediating cholesteryl esters selective uptake and the bi-directional flux of free cholesterol. Recently, SR-BI has also been identified as a potential marker for cancer diagnosis, prognosis, or even a treatment target. Natural products are a promising source for the discovery of new drug leads. Multiple natural products were identified to regulate SR-BI protein expression. There are still a number of challenges in modulating SR-BI expression in cancer and in using natural products for modulation of such protein expression. In this review, our purpose is to discuss the relationship between SR-BI protein and cancer, and the molecular mechanisms regulating SR-BI expression, as well as to provide an overview of natural products that regulate SR-BI expression.

Rutin is one of the most common dietary polyphenols found in vegetables, fruits, and other plants. It is metabolized by the mammalian gut microbiota and absorbed from the intestines, and becomes bioavailable in the form of conjugated metabolites. Rutin exhibits a plethora of bioactive properties, making it an extremely promising phytochemical. Numerous studies demonstrate that rutin can act as a chemotherapeutic and chemopreventive agent, and its anticancer effects can be mediated through the suppression of cell proliferation, the induction of apoptosis or autophagy, and the hindering of angiogenesis and metastasis. Rutin has been found to modulate multiple molecular targets involved in carcinogenesis, such as cell cycle mediators, cellular kinases, inflammatory cytokines, transcription factors, drug transporters, and reactive oxygen species. This review summarizes the natural sources of rutin, its bioavailability, and in particular its potential use as an anticancer agent, with highlighting its anticancer mechanisms as well as molecular targets. Additionally, this review updates the anticancer potential of its analogs, nanoformulations, and metabolites, and discusses relevant safety issues. Overall, rutin is a promising natural dietary compound with promising anticancer potential and can be widely used in functional foods, dietary supplements, and pharmaceuticals for the prevention and management of cancer.

Four diets, formulated with and without stevia and with and without exogenous xylanase, following a 2 × 2 factorial design, were prepared. Each diet was fed ad libitum to birds in eight pens (three birds in each pen) in a randomised block design. It was found that birds fed xylanase grew faster, used the feed more efficiently and had an increased concentration of hepatic α-tocopherol and vitamin E concentrations (P < 0.05). Feeding stevia did not affect growth performance (P > 0.05), but increased hepatic CoQ10 (P = 0.05), lutein, zeaxanthin and total carotenoids (P < 0.001) concentrations. There were no dietary stevia by xylanase interactions (P > 0.05) for any of the studied variables. The results showed that alone, dietary stevia and dietary xylanase can improve the antioxidative status of birds through enhancing dietary antioxidant availability.

BackgroundThe banana (Musa spp.) plant produces elongated and edible fruit. The two main parthenocarpic species of banana are Musa accuminata Colla and Musa balbisiana Colla. There are several health-promoting and disease-preventing effects of Musa accuminata Colla, which are attributed to its important bioactive compounds, including phenolics, carotenoids, biogenic amines, phytosterols, and volatile oils, found in the stem, fruit, pseudostem, leaf, flower, sap, inner trunk, root, and inner core. Banana possesses numerous pharmacological activities, such as antioxidant, immunomodulatory, antimicrobial, antiulcerogenic, hypolipidemic, hypoglycemic, leishmanicidal, anthelmintic, and anticancer properties. Various individual studies have reported anticancer effects of different components of the banana plant. However, according to our understanding, an up-to-date, systematic, and critical analysis of existing scientific results has not yet been carried out.ObjectivesThis review aims to include a thorough assessment of banana and its phytochemicals for cancer prevention and therapy with a focus on cellular and molecular mechanisms of action.MethodsThe available research studies on anticancer activities of banana extracts, fractions and pure compounds were collected using various scholarly databases, such as PubMed, ScienceDirect, and Scopus, based on predetermined selection criteria.ResultsVarious banana extracts, fractions, and phytoconstituents, including ferulic acid, protocatechualdehyde, 2-pentanone, 4-epicyclomusalenone, cycloeucalenol acetate, and chlorogenic acid, have been shown to exhibit cancer preventative and anticancer activities in breast, cervical, colorectal, esophageal, hepatic, oral, prostate, and skin cancers. Bioactive components present in bananas have exhibited antiproliferative, cell cycle arrest-inducing, apoptotic, anti-adhesive, anti-invasive, and antiangiogenic effects through modulation of diverse, dysregulated oncogenic signaling pathways.ConclusionBased on the critical analysis of available literature, banana products and phytoconstituents show enormous potential for future development of drugs for cancer prevention and therapy. However, more mechanistic studies and well-designed clinical trials should be performed to establish its efficacy.

Inflammation is a marker of arterial disease stemming from cholesterol-dependent to -independent molecular mechanisms. In recent years, the role of inflammation in atherogenesis has been underpinned by pharmacological approaches targeting systemic inflammation that have led to a significant reduction in cardiovascular disease (CVD) risk. Although the use of nutraceuticals to prevent CVD has largely focused on lipid-lowering (e.g, red-yeast rice and omega-3 fatty acids), there is growing interest and need, especially now in the time of coronavirus pandemic, in the use of nutraceuticals to reduce inflammatory markers, and potentially the inflammatory CVD burden, however, there is still not enough evidence to confirm this. Indeed, diet is an important lifestyle determinant of health and can influence both systemic and vascular inflammation, to varying extents, according to the individual nutraceutical constituents. Thus, the aim of this Position Paper is to provide the first attempt at recommendations on the use of nutraceuticals with effective anti-inflammatory properties.

Foam cell formation and further accumulation in the subendothelial space of the vascular wall is a hallmark of atherosclerotic lesions. Targeting foam cell formation in the atherosclerotic lesions can be a promising approach to treat and prevent atherosclerosis. The formation of foam cells is determined by the balanced effects of three major interrelated biologic processes, including lipid uptake, cholesterol esterification, and cholesterol efflux. Natural products are a promising source for new lead structures. Multiple natural products and pharmaceutical agents can inhibit foam cell formation and thus exhibit antiatherosclerotic capacity by suppressing lipid uptake, cholesterol esterification, and/or promoting cholesterol ester hydrolysis and cholesterol efflux. This review summarizes recent findings on these three biologic processes and natural products with demonstrated potential to target such processes. Discussed also are potential future directions for studying the mechanisms of foam cell formation and the development of foam cell-targeted therapeutic strategies.

Total-scale quantitative research literature analysis on the food toxicology scientific field has yet to be conducted. In this work, we identified and analysed food toxicology publications in the existing scientific literature. A literature search was performed with the online Web of Science database. Full records and cited references of the 73,099 identified manuscripts were imported into VOSviewer software for analysis. This research field has been growing steadily since the 1990s. Article to review ratio was 7.4:1. The publications were mainly related to toxicology, environmental sciences, food science and technology, pharmacology/pharmacy and biochemistry/molecular biology. The United States and China are major contributors to food toxicology research, followed by other European and Asian countries. The prolific authors have formed three major clusters within a citation network. Toxic or hazardous chemicals related to food with high citations included aflatoxin, dioxin, fumonisin, malondialdehyde, mycotoxin, ochratoxin, phthalate, and polychlorinated biphenyl.

Discovery and development of new potentially selective anticancer agents are necessary to prevent a global cancer health crisis. Currently, alternative medicinal agents derived from plants have been extensively investigated to develop anticancer drugs with fewer adverse effects. Among them, steroidal alkaloids are conventional secondary metabolites that comprise an important class of natural products found in plants, marine organisms and invertebrates, and constitute a judicious choice as potential anti-cancer leads. Traditional medicine and modern science have shown that representatives from this compound group possess potential antimicrobial, analgesic, anticancer and anti-inflammatory effects. Therefore, systematic and recapitulated information about the bioactivity of these compounds, with special emphasis on the molecular or cellular mechanisms, is of high interest. In this review, we methodically discuss the in vitro and in vivo potential of the anticancer activity of natural steroidal alkaloids and their synthetic and semi-synthetic derivatives. This review focuses on cumulative and comprehensive molecular mechanisms, which will help researchers understand the molecular pathways involving steroid alkaloids to generate a selective and safe new lead compound with improved therapeutic applications for cancer prevention and therapy. In vitro and in vivo studies provide evidence about the promising therapeutic potential of steroidal alkaloids in various cancer cell lines, but advanced pharmacokinetic and clinical experiments are required to develop more selective and safe drugs for cancer treatment.

Ethnopharmacological relevance The genus Vanda (Family: Orchidaceae) comprises about 73 species mainly distributed in Southeast Asia. Plants belonging to this genus are being used in the traditional medicine systems in Asian countries specially in India, Nepal, China and Bangladesh. Aim of the review The aim of this work was to review the scientific work about medicinal orchids of the genus Vanda regarding their traditional uses, reported bioactive components, and pharmacological activities. Materials and methods The information related to traditional uses, pharmacological activities, and bioactive compounds was systematically collected from the scientific literature databases including SciFinder, Scopus, PubMed and Google Scholar, published books and conference proceedings. Results The literature survey revealed diverse traditional uses of different species of Vanda, mainly against indigestion, wounds, hepatitis, dyspepsia, bronchitis, piles, rheumatism, and bone fracture. However, only few of them are investigated scientifically for their chemical constituents and pharmacological activities. Bioactive compounds including eucomic acid derivatives, phenanthrene derivatives and other phenolic compounds are reported from Vanda species. Different extracts were so far evaluated for number of pharmacological activities including neuroprotective, anti-aging, antimicrobial, anti-inflammatory, antioxidant, membrane stabilizing, wound healing and hepato-protective activities. Conclusion Vanda spp. are of much significance as ornamental flowers, but also used widely in traditional medicines and have potential for their diverse pharmacological activities. However, many members of the genus Vanda need further detailed studies regarding chemical constituents and mechanism-based pharmacological activities. Similarly, further studies should also focus on the conservation, cultivation and sustainable utilization of these species.

Intrinsic or acquired drug resistance, adverse drug reactions and tumor heterogeneity between and within cancer patients limit the efficacy of clinical management of advanced cancers. To overcome these barriers, predictive biomarkers have recently emerged to guide medical oncologists in the selection of cancer patients who will respond to various anticancer treatments and to improve the toxicity to benefit ratio. Notably, targeted therapy has significantly benefited from these advances, but the application of predictive biomarkers have been a bit slower with some drugs derived from natural sources such as trabectedin, cabazitaxel and alvocidib. In this paper, we discuss some recent advances regarding the use of cancer biomarkers to predict efficacy of some selected natural compounds with a focus on human clinical studies.

Cardiovascular disorders are leading mortality causes worldwide, often with a latent evolution. Vascular health depends on endothelial function, arterial stiffness, and the presence of atherosclerotic plaques. Preventive medicine deserves special attention, focusing on modifiable cardiovascular risk factors, including diet. A diet rich in fruits and vegetables has well-known health benefits, especially due to its polyphenolic components. Anthocyanins, water-soluble flavonoid species, responsible for the red-blue color in plants and commonly found in berries, exert favorable effects on the endothelial function, oxidative stress, inhibit COX-1, and COX-2 enzymes, exert antiatherogenic, antihypertensive, antiglycation, antithrombotic, and anti-inflammatory activity, ameliorate dyslipidemia and arterial stiffness. The present review aims to give a current overview of the mechanisms involved in the vascular protective effect of anthocyanins from the human diet, considering epidemiological data, in vitro and in vivo preclinical research, clinical observational, retrospective, intervention and randomized studies, dietary and biomarker studies, and discussing preventive benefits of anthocyanins and future research directions.

Background On January 30, 2020, the World Health Organization’s Emergency Committee declared the rapid, worldwide spread of COVID-19 a global health emergency. Since then, tireless efforts have been made to mitigate the spread of the disease and its impact, and these efforts have mostly relied on nonpharmaceutical interventions. By December 2020, the safety and efficacy of the first COVID-19 vaccines were demonstrated. The large social media platform Twitter has been used by medical researchers for the analysis of important public health topics, such as the public’s perception on antibiotic use and misuse and human papillomavirus vaccination. The analysis of Twitter-generated data can be further facilitated by using Twitter’s built-in, anonymous polling tool to gain insight into public health issues and obtain rapid feedback on an international scale. During the fast-paced course of the COVID-19 pandemic, the Twitter polling system has provided a viable method for gaining rapid, large-scale, international public health insights on highly relevant and timely SARS-CoV-2–related topics. Objective The purpose of this study was to understand the public’s perception on the safety and acceptance of COVID-19 vaccines in real time by using Twitter polls. Methods We developed 2 Twitter polls to explore the public’s views on available COVID-19 vaccines. The surveys were pinned to the Digital Health and Patient Safety Platform Twitter timeline for 1 week in mid-February 2021, and Twitter users and influencers were asked to participate in and retweet the polls to reach the largest possible audience. Results The adequacy of COVID-19 vaccine safety (ie, the safety of currently available vaccines; poll 1) was agreed upon by 1579 out of 3439 (45.9%) Twitter users. In contrast, almost as many Twitter users (1434/3439, 41.7%) were unsure about the safety of COVID-19 vaccines. Only 5.2% (179/3439) of Twitter users rated the available COVID-19 vaccines as generally unsafe. Poll 2, which addressed the question of whether users would undergo vaccination, was answered affirmatively by 82.8% (2862/3457) of Twitter users, and only 8% (277/3457) categorically rejected vaccination at the time of polling. Conclusions In contrast to the perceived high level of uncertainty about the safety of the available COVID-19 vaccines, we observed an elevated willingness to undergo vaccination among our study sample. Since people's perceptions and views are strongly influenced by social media, the snapshots provided by these media platforms represent a static image of a moving target. Thus, the results of this study need to be followed up by long-term surveys to maintain their validity. This is especially relevant due to the circumstances of the fast-paced pandemic and the need to not miss sudden rises in the incidence of vaccine hesitancy, which may have detrimental effects on the pandemic’s course.

Microbial polysaccharides (MPs) offer immense diversity in structural and functional properties. They are extensively used in advance biomedical science owing to their superior biodegradability, hemocompatibility, and capability to imitate the natural extracellular matrix microenvironment. Ease in tailoring, inherent bio-activity, distinct mucoadhesiveness, ability to absorb hydrophobic drugs, and plentiful availability of MPs make them prolific green biomaterials to overcome the significant constraints of cancer chemotherapeutics. Many studies have demonstrated their application to obstruct tumor development and extend survival through immune activation, apoptosis induction, and cell cycle arrest by MPs. Synoptic investigations of MPs are compulsory to decode applied basics in recent inclinations towards cancer regimens. The current review focuses on the anticancer properties of commercially available and newly explored MPs, and outlines their direct and indirect mode of action. The review also highlights cutting-edge MPs-based drug delivery systems to augment the specificity and efficiency of available chemotherapeutics, as well as their emerging role in theranostics.

Background Virtual reality (VR) and augmented reality (AR) have recently become popular research themes. However, there are no published bibliometric reports that have analyzed the corresponding scientific literature in relation to the application of these technologies in medicine. Objective We used a bibliometric approach to identify and analyze the scientific literature on VR and AR research in medicine, revealing the popular research topics, key authors, scientific institutions, countries, and journals. We further aimed to capture and describe the themes and medical conditions most commonly investigated by VR and AR research. Methods The Web of Science electronic database was searched to identify relevant papers on VR research in medicine. Basic publication and citation data were acquired using the “Analyze” and “Create Citation Report” functions of the database. Complete bibliographic data were exported to VOSviewer and Bibliometrix, dedicated bibliometric software packages, for further analyses. Visualization maps were generated to illustrate the recurring keywords and words mentioned in the titles and abstracts. Results The analysis was based on data from 8399 papers. Major research themes were diagnostic and surgical procedures, as well as rehabilitation. Commonly studied medical conditions were pain, stroke, anxiety, depression, fear, cancer, and neurodegenerative disorders. Overall, contributions to the literature were globally distributed with heaviest contributions from the United States and United Kingdom. Studies from more clinically related research areas such as surgery, psychology, neurosciences, and rehabilitation had higher average numbers of citations than studies from computer sciences and engineering. Conclusions The conducted bibliometric analysis unequivocally reveals the versatile emerging applications of VR and AR in medicine. With the further maturation of the technology and improved accessibility in countries where VR and AR research is strong, we expect it to have a marked impact on clinical practice and in the life of patients.

Age-related diseases for which there are no effective treatments include cardiovascular diseases; neurodegenerative diseases such as Alzheimer's disease; eye disorders such as cataract and age-related macular degeneration; and, more recently, Severe Acute Respiratory Syndrome (SARS-CoV-2). These diseases are associated with plasma and/or tissue increases in cholesterol derivatives mainly formed by auto-oxidation: 7-ketocholesterol, also known as 7-oxo-cholesterol, and 7β-hydroxycholesterol. The formation of these oxysterols can be considered as a consequence of mitochondrial and peroxisomal dysfunction, leading to increased in oxidative stress, which is accentuated with age. 7-ketocholesterol and 7β-hydroxycholesterol cause a specific form of cytotoxic activity defined as oxiapoptophagy, including oxidative stress and induction of death by apoptosis associated with autophagic criteria. Oxiaptophagy is associated with organelle dysfunction and in particular with mitochondrial and peroxisomal alterations involved in the induction of cell death and in the rupture of redox balance. As the criteria characterizing 7-ketocholesterol- and 7β-hydroxycholesterol-induced cytotoxicity are often simultaneously observed in major age-related diseases (cardiovascular diseases, age-related macular degeneration, Alzheimer's disease) the involvement of these oxysterols in the pathophysiology of the latter seems increasingly likely. It is therefore important to better understand the signalling pathways associated with the toxicity of 7-ketocholesterol and 7β-hydroxycholesterol in order to identify pharmacological targets, nutrients and synthetic molecules attenuating or inhibiting the cytotoxic activities of these oxysterols. Numerous natural cytoprotective compounds have been identified: vitamins, fatty acids, polyphenols, terpenes, vegetal pigments, antioxidants, mixtures of compounds (oils, plant extracts) and bacterial enzymes. However, few synthetic molecules are able to prevent 7-ketocholesterol- and/or 7β-hydroxycholesterol-induced cytotoxicity: dimethyl fumarate, monomethyl fumarate, the tyrosine kinase inhibitor AG126, memantine, simvastatine, Trolox, dimethylsufoxide, mangafodipir and mitochondrial permeability transition pore (MPTP) inhibitors. The effectiveness of these compounds, several of which are already in use in humans, makes it possible to consider using them for the treatment of certain age-related diseases associated with increased plasma and/or tissue levels of 7-ketocholesterol and/or 7β-hydroxycholesterol.

Previous evidence has shown a link between neurodegenerative diseases, including Parkinson's disease (PD), and melatonin. The data in the literature about the impact of the hormone under different experimental PD conditions are quite controversial, and its effect on memory impairment in the disease is very poorly explored. The current research was aimed at investigating the role of melatonin pretreatment on memory and motor behavior in healthy rats and those with the partial 6-hydroxydopamine (6-OHDA) model of PD. All rodents were pretreated with melatonin (20 mg/kg, intraperitoneally) for 5 days. At 24 h and 7 days after the first treatment for healthy rats, and at the second and third week post-lesion for those with PD, the animals were tested behaviorally (apomorphine-induced rotations, rotarod, and passive avoidance tests). The neurochemical levels of dopamine (DA), acetylcholine (ACh), noradrenaline (NA), and serotonin (Sero) in the brain were also determined. The results showed that in healthy animals, melatonin pretreatment had amnestic and motor-suppressive effects and did not change the levels of measured brain neurotransmitters. In animals with PD, melatonin pretreatment exerted a neuroprotective effect, manifested as a significantly decreased number of apomorphine-induced rotations, reduced number of falls in the rotarod test, and improved memory performance. The brain DA and ACh concentrations in the same animals were restored to the control levels, and those of NA and Sero did not change. Our results demonstrate a beneficial effect of melatonin on memory and motor disturbance in 6-OHDA-lesioned rats.

Aging is associated with a drastic decline in fertility/fecundity and with an increased risk of pregnancy complications. Resveratrol (RES), a natural polyphenolic compound, has shown anti-oxidant and anti-inflammatory activities in both human and animal models, thus representing a potential therapeutic and prophylactic anti-aging supplement. Here, we investigated whether preconceptional resveratrol supplementation improved reproductive outcomes in mid-aged (8-month-old) and old (12-month-old) C57BL/6J female mice. Female siblings were cohoused and assigned to either RES or vehicle supplementation to drinking water for 10 consecutive weeks. Subsequently, females were mated with non-supplemented males and their pregnancy outcomes were monitored. RES improved mating success in old, but not in mid-aged females, and prevented the occurrence of delivery complications in the latter. These results indicate that preconceptional RES supplementation could partially improve age-related reproductive complications, but it was not sufficient to restore fecundity in female mice at a very advanced age.

Open innovation in medical and pharmaceutical research has grown steadily over the last decade. However, the performance of the published literature in terms of the scientific impact and gaining social media attention remains largely unexplored. The scientific literature of open innovation was examined by means of bibliometric analyses to identify the most prolific authors, organizations, countries, journals, research areas, and recurring terms. By accessing the Web of Science Core Collection and Altmetric electronic databases, citation-related and Altmetric data were evaluated. Public-private partnerships and a selection of newly introduced potential novel drugs in the analyzed publications were identified. North America and Europe were the major literature contributors. Research outputs were mainly published in journals focused on business and economics, pharmacology and pharmacy, and engineering. Many pharmaceutical and biotechnological companies contributed to the analyzed publications, with higher mean citation counts and social media attention (Altmetric score) than nonindustry articles. Public-private partnerships fostered financial support, sharing of expertise and intellectual property, and research collaborations. In summary, open innovation might serve as a powerful strategy to both benefit the involved industry entities and accelerate the development of solutions and products for the betterment of human health.

Nanopharmaceuticals and nanonutraceuticals research has been lately receiving a lot of scientific attention. We aimed to identify the top 100 most cited original articles of the scientific area, analyze their research themes, major contributors regarding authors, institutions, countries and journals. The bibliometric data was extracted from the Web of Science electronic database. Data was further processed by a bibliometric software, VOSviewer, to generate bubble maps to visualize the results. Inter-institutional and international collaboration networks were constructed to further understand the cooperation between different study centers. Results revealed that over 60% of the articles were published in the 2000s. As of November 2019, the articles were cited 5763665 times, with 20.1261.8 citations per year. The majority of the most prolific institutions were based in the United States. Besides the United States, China, South Korea, Canada and Germany contributed heavily to the 100 articles. Some popular themes included drug delivery, tumor, toxicity / biocompatibility and biodistribution. Regarding composition materials, gold, silver and polymeric nanoparticles were the most commonly used., Atanas G. Atanasov acknowledges the support by the Polish KNOW (Leading National Research Centre) Scientific Consortium “Healthy Animal-Safe Food,” decision of Ministry of Science and Higher Education No. 05-1/KNOW2/2015. The support of the research project: Nutraceutica come supporto nutrizionale nel paziente oncologico, CUP: B83D18000140007, Italy is acknowledged., info:eu-repo/semantics/publishedVersion

The use of natural antioxidants, in particular polyphenols such as dihydroquercetin (DHQ), in animal nutrition have recently increased in popularity. This may partly be due to the risk of increased incidences of heat stress associated with raising livestock in warmer ambient temperatures, facilitated by global warming, reducing antioxidant capacity. The current research demonstrates the effect of dietary DHQ, vitamin E and standard or high ambient temperatures on growth performance, energy and nutrient metabolism, gastrointestinal tract development (GIT), jejunal villus morphometry and antioxidant status in broiler chickens. Each of the four experimental diets were fed to 16 pens of five birds, which were allocated to four rooms (four pens in each room). The temperature in two rooms was maintained at a constant 35 °C (high temperature; HT), and the temperature in the other two rooms was gradually reduced from 27 °C at 7d of age to 22 °C at 20d of age (standard temperature; ST). Rearing birds at HT reduced: feed intake, weight gain, weight of small intestine, total GIT, liver, spleen, heart, villus height, villus surface area and lowered blood glutationperoxidase (GSH-Px). Dietary DHQ increased blood GSH-Px and total antioxidant status, increased heart weight and reduced caecal size. When fed separately, DHQ and vitamin E improved hepatic vitamin E concentration. Feeding vitamin E increased spleen and liver weights. When fed together, DHQ and vitamin E reduced villus height, villus height to crypt depth ratio and villus surface area. Temperature and antioxidants did not affect energy and nutrient metabolism. There were no effects of dietary antioxidants on growth performance of broiler chickens and there were no mortalities. At present it is unclear if feeding antioxidants (in particular DHQ) at different levels, using different dietary formulations, and rearing birds under a range of environmental conditions may be effective at enhancing production performance and bird health in hot ambient climates.

The ligand-activated farnesoid X receptor is an emerging therapeutic target for the development of drugs against metabolic syndrome-related diseases. In this context, selective bile acid receptor modulators represent a novel concept for drug development. Selective bile acid receptor modulators act in a target gene- or tissue-specific way and are therefore considered less likely to elicit unwanted side effects. Based on leoligin, a lignan-type secondary plant metabolite from the alpine plant Leontopodium nivale ssp. alpinum, 168 synthesized structural analogs were screened in a farnesoid X receptor in silico pharmacophore-model. Fifty-six virtual hits were generated. These hits were tested in a cell-based farnesoid X receptor transactivation assay and yielded 7 farnesoid X receptor-activating compounds. The most active one being LT-141A, with an EC50 of 6 µM and an Emax of 4.1-fold. This analog did not activate the G protein-coupled bile acid receptor, TGR5, and the metabolic nuclear receptors retinoid X receptor α, liver X receptors α/β, and peroxisome proliferator-activated receptors β/γ. Investigation of different farnesoid X receptor target genes characterized LT-141A as selective bile acid receptor modulators. Functional studies revealed that LT-141A increased cholesterol efflux from THP-1-derived macrophages via enhanced ATP-binding cassette transporter 1 expression. Moreover, cholesterol uptake in differentiated Caco-2 cells was significantly decreased upon LT-141A treatment. In conclusion, the leoligin analog LT-141A selectively activates the nuclear receptor farnesoid X receptor and has an influence on cholesterol transport in 2 model systems.

Objective: Medical errors represent a leading cause of patient morbidity and mortality. The aim of this study was to quantitatively analyze the existing scientific literature on medical errors in order to gain new insights in this important medical research area. Study Design: Web of Science database was used to identify relevant publications, and bibliometric analysis was performed to quantitatively analyze the identified articles for prevailing research themes, contributing journals, institutions, countries, authors, and citation performance. Results: In total, 12,415 publications concerning medical errors were identified and quantitatively analyzed. The overall ratio of original research articles to reviews was 8.1:1, and temporal subset analysis revealed that the share of original research articles has been increasing over time. The United States contributed to nearly half (46.4%) of the total publications, and 8 of the top 10 most productive institutions were from the United States, with the remaining 2 located in Canada and the United Kingdom. Prevailing (frequently mentioned) and highly impactful (frequently cited) themes were errors related to drugs/medications, applications related to medicinal information technology, errors related to critical/intensive care units, to children, and mental conditions associated with medical errors (burnout, depression). Conclusions: The high prevalence of medical errors revealed from the existing literature indicates the high importance of future work invested in preventive approaches. Digital health technology applications are perceived to be of great promise to counteract medical errors, and further effort should be focused to study their optimal implementation in all medical areas, with special emphasis on critical areas such as intensive care and pediatric units.

Increased cholesterol efflux from macrophage foam cells in the subendothelial space confers protection against atherosclerosis. Soraphen A, a myxobacterial macrolactone, is an inhibitor of acetyl coenzyme A carboxylases (ACC), which control fatty acid synthesis and oxidation. To assess a potential direct link between macrophage cholesterol efflux and ACC inhibition, we examined [3H]-cholesterol efflux from human THP-1-derived foam cells in the presence of soraphen A. We dissected underlying molecular events by western blot analyses, RT-qPCR, reporter gene and coactivator recruitment assays as well as relative quantification of free and total cholesterol. Soraphen A increased cholesterol efflux from macrophage foam cells via upregulation of the cholesterol transporter ATP-binding cassette transporter A1 (ABCA1). Soraphen A enhanced transcription of ABCA1 in an LXR-dependent manner, however, without direct binding to the ligand-binding domain of this nuclear receptor. Soraphen A elevated the cellular level of free cholesterol, and failed to activate LXR upon exogenous supplementation with fatty acids or inhibition of cholesterol synthesis. Thus, impeded conversion from acetyl- to malonyl-CoA by soraphen A may lead to more unesterified cholesterol and thus potential LXR agonists. The present study reveals ACC inhibition as a previously unrecognized mechanism to regulate macrophage cholesterol efflux via indirect LXR activation and ABCA1 upregulation.

Over the last few years, the application of nanotechnology to nutraceuticals has been rapidly growing due to its ability to enhance the bioavailability of the loaded active ingredients, resulting in improved therapeutic/nutraceutical outcomes. The focus of this work is nanoprebiotics and nanoprobiotics, terms which stand for the loading of a set of compounds (e.g., prebiotics, probiotics, and synbiotics) in nanoparticles that work as absorption enhancers in the gastrointestinal tract. In this manuscript, the main features of prebiotics and probiotics are highlighted, together with the discussion of emerging applications of nanotechnologies in their formulation. Current research strategies are also discussed, in particular the promising use of nanofibers for the delivery of probiotics. Synbiotic-based nanoparticles represent an innovative trend within this area of interest. As only few experimental studies on nanoprebiotics and nanoprobiotics are available in the scientific literature, research on this prominent field is needed, covering effectiveness, bioavailability, and safety aspects., The authors acknowledge the support of the research project: Nutraceutica come supporto nutrizionale nel paziente oncologico, CUP: B83D18000140007. E. B. Souto acknowledges the sponsorship of the projects M-ERA-NET-0004/2015-PAIRED and UIDB/04469/2020 (strategic fund), receiving support from the Portuguese Science and Technology Foundation, Ministry of Science and Education (FCT/MEC) through national funds, and co-financed by FEDER, under the Partnership Agreement PT2020., info:eu-repo/semantics/publishedVersion

Pain represents an unpleasant sensation linked to actual or potential tissue damage. In the early phase, the sensation of pain is caused due to direct stimulation of the sensory nerve fibers. On the other hand, the pain in the late phase is attributed to inflammatory mediators. Current medicines used to treat inflammation and pain are effective; however, they cause severe side effects, such as ulcer, anemia, osteoporosis, and endocrine disruption. Increased attention is recently being focused on the examination of the analgesic potential of phytoconstituents, such as glycosides of traditional medicinal plants, because they often have suitable biological activities with fewer side effects as compared to synthetic drugs. The purpose of this article is to review for the first time the current state of knowledge on the use of glycosides from medicinal plants to induce analgesia and anti-inflammatory effect. Various databases and search engines, including PubMed, ScienceDirect, Scopus, Web of Science and Google Scholar, were used to search and collect relevant studies on glycosides with antinociceptive activities. The results led to the identification of several glycosides that exhibited marked inhibition of various pain mediators based on different well-established assays. Additionally, these glycosides were found to induce most of the analgesic effects through cyclooxygenase and lipoxygenase pathways. These findings can be useful to identify new candidates which can be clinically developed as analgesics with better bioavailability and reduced side effects. Graphical abstract Analgesic mechanisms of plant glycosides.

Excessive alcohol consumption is the cause of several diseases and thus is of a major concern for society. Worldwide alcohol consumption has increased by many folds over the past decades. This urgently calls for intervention and relapse counteract measures. Modern pharmacological solutions induce complete alcohol self-restraint and prevent relapse, but they have many side effects. Natural products are most promising as they cause fewer adverse effects. Here we discuss in detail the medicinal plants used in various traditional/folklore medicine systems for targeting alcohol abuse. We also comprehensively describe preclinical and clinical studies done on some of these plants along with the possible mechanisms of action.

The current study provides a comprehensive overview and analysis of the lignan literature. Data for the current study were extracted from the electronic Web of Science Core Collection database via the search string TOPIC = (lignan*) and processed by the VOSviewer software. The search yielded 10,742 publications. The ratio of original articles to reviews was 14.6:1. Over 80% of the analyzed papers have been published since the year 2000 and nearly 50% since the year 2010. Many of the publications were focused on pharmacology, chemistry, and plant sciences. The United States and Asian countries, such as China, Japan, South Korea, and India, were the most productive producers of lignan publications. Among the 5 most productive institutions was the University of Helsinki in Finland, the country that ranked 9th. Nineteen journals collectively published 3,607 lignan publications and were considered as core journals. Their impact factor did not correlate with the proportion of uncited papers. Highly cited publications usually mentioned phytoestrogen, isoflavone, daidzein, enterodiol, enterolactone, equol, genistein, and isoflavonoid. Cancer (e.g., breast cancer), cardiovascular disease, and antioxidation were the major themes. Clinical trials were estimated to contribute to 0.21.1% of the analyzed body of literature, so more of them should be conducted in the future to substantiate the beneficial effects and optimal dose of lignan intake in humans. Moreover, researchers can refer to these findings for future research directions and collaborations., AA acknowledges the support by the Polish KNOW (Leading National Research Centre) Scientific Consortium “Healthy Animal—Safe Food,” decision of the Ministry of Science and Higher Education No. 05-1/KNOW2/2015. EN and AS acknowledge the support of the research project Nutraceutica come supporto nutrizionale nel paziente oncologico, CUP: B83D18000140007., info:eu-repo/semantics/publishedVersion

Eudragit S100-coated chitosan microspheres (S100Ch) are proposed as a new oral delivery system for green tea polyphenon-60 (PP60). PP60 is a mixture of polyphenolic compounds, known for its active role in decreasing oxidative stress and metabolic risk factors involved in diabetes and in other chronic diseases. Chitosan-PP60 microspheres prepared by an emulsion cross-linking method were coated with Eudragit S100 to ensure the release of PP60 in the terminal ileum. Different core&ndash, coat ratios of Eudragit and chitosan were tested. Optimized chitosan microspheres were obtained with a chitosan:PP60 ratio of 8:1 (Ch-PP608:1), rotation speed of 1500 rpm, and surfactant concentration of 1.0% (m/v) achieving a mean size of 7.16 &micro, m. Their coating with the enteric polymer (S100Ch-PP60) increased the mean size significantly (51.4 &micro, m). The in vitro modified-release of PP60 from S100Ch-PP60 was confirmed in simulated gastrointestinal conditions. Mathematical fitting models were used to characterize the release mechanism showing that both Ch-PP608:1 and S100Ch-PP60 fitted the Korsmeyers&ndash, Peppas model. The antioxidant activity of PP60 was kept in glutaraldehyde-crosslinked chitosan microspheres before and after their coating, showing an IC50 of 212.3 &micro, g/mL and 154.4 &micro, g/mL, respectively. The potential of chitosan microspheres for the delivery of catechins was illustrated, with limited risk of cytotoxicity as shown in Caco-2 cell lines using the 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The beneficial effects of green tea and its derivatives in the management of metabolic disorders can be exploited using mucoadhesive chitosan microspheres coated with enteric polymers for colonic delivery.

We compared the neuroprotective action of three natural bio-antioxidants (AOs): ellagic acid (EA), &alpha, lipoic acid (LA), and myrtenal (Myrt) in an experimental model of Parkinson&rsquo, s disease (PD) that was induced in male Wistar rats through an intrastriatal injection of 6-hydroxydopamine (6-OHDA). The animals were divided into five groups: the sham-operated (SO) control group, striatal 6-OHDA-lesioned control group, and three groups of 6-OHDA-lesioned rats pre-treated for five days with EA, LA, and Myrt (50 mg/kg, intraperitoneally- i.p.), respectively. On the 2nd and the 3rd week post lesion, the animals were subjected to several behavioral tests: apomorphine-induced rotation, rotarod, and the passive avoidance test. Biochemical evaluation included assessment of main oxidative stress parameters as well as dopamine (DA) levels in brain homogenates. The results showed that all three test compounds improved learning and memory performance as well as neuromuscular coordination. Biochemical assays showed that all three compounds substantially decreased lipid peroxidation (LPO) levels, and restored catalase (CAT) activity and DA levels that were impaired by the challenge with 6-OHDA. Based on these results, we can conclude that the studied AOs demonstrate properties that are consistent with significant antiparkinsonian effects. The most powerful neuroprotective effect was observed with Myrt, and this work represents the first demonstration of its anti-Parkinsonian impact.

Acute and chronic physical exercises may enhance the development of statin-related myopathy. In this context, the recent (2019) guidelines of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS) for the management of dyslipidemias recommend that, although individuals with dyslipidemia should be advised to engage in regular moderate physical exercise (for at least 30 min daily), physicians should be alerted with regard to myopathy and creatine kinase (CK) elevation in statin-treated sport athletes. However it is worth emphasizing that abovementioned guidelines, previous and recent ESC/EAS consensus papers on adverse effects of statin therapy as well as other previous attempts on this issue, including the ones from the International Lipid Expert Panel (ILEP), give only general recommendations on how to manage patients requiring statin therapy on regular exercises. Therefore, these guidelines in the form of the Position Paper are the first such an attempt to summary existing, often scarce knowledge, and to present this important issue in the form of step-by-step practical recommendations. It is critically important as we might observe more and more individuals on regular exercises/athletes requiring statin therapy due to their cardiovascular risk.

Fenugreek seeds are widely used in Asia and other places of the world for their nutritive and medicinal properties. In Asia, fenugreek seeds are also recommended for geriatric populations. Here, we evaluated for the first time the effect of fenugreek seed feed supplementation on the liver antioxidant defense systems in aging mice. The study was conducted on 12-months aged mice which were given fenugreek seed dietary supplement. We evaluated the activities of various antioxidant defense enzymes such as superoxide dismutase (SOD), glutathione reductase (GR), and glutathione peroxidase (GPx), and also estimated the phenolics and free radical scavenging properties in mice liver upon fenugreek supplementation. The estimation of SOD, GPx, and GR activities in aged mice liver revealed a significant (p &lt, 0.01) difference among all the liver enzymes. Overall, this study reveals that fenugreek seed dietary supplementation has a positive effect on the activities of the hepatic antioxidant defense enzymes in the aged mice.

The essential oil from Croton argyrophyllus Kunth is known for its antiproliferative, anti-inflammatory, antinociceptive, and anticancer activities, and is recognized as a source of phytochemicals for potential use in pharmaceutic and food sectors. Solid lipid nanoparticles (SLN) have been produced to load Croton argyrophyllus (CA) Kunth essential oil (CAEO) and its antioxidant properties evaluated in vitro as a new approach for the treatment of neurodegenerative diseases. Cetyl palmitate SLN loading CAEO (CAEO-SLN) with a mean particle size of 201.4 &plusmn, 2.3 nm (polydispersity index 0.211) have been produced by hot high-pressure homogenisation. The release of the oil followed the Korsmeyers-Peppas model. The risk of lipid peroxidation has been determined by applying the production of thiobarbituric acid-reactive substances (TBARS) standard assay. The antioxidant activity was determined by the capacity of the antioxidants existing in CAEO to scavenge the stable radical DPPH&bull, The cytotoxicity of CA Kunth essential oil-loaded SLN (CAEO-SLN) was evaluated in a human cell line SH-SY5Y (derived from human neuroblastoma) by determining the reduction of the yellow dye 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT). Both free essential oil (fEO) and loaded essential oil (CAEO-SLN) were demonstrated to inhibit the Fenton reaction. CAEO-SLN showed DPPH&bull, radical scavenging capacity. The loading of the oil into cetyl palmitate SLN reduced the risk of cytotoxicity.

The natural tridecapeptide neurotensin has been emerged as a promising therapeutic scaffold for the treatment of neurological diseases and cancer. In this work, we aimed to identify the top 100 most cited original research papers as well as recent key studies related to neurotensins. The Web of Science Core Collection database was searched and the retrieved research articles were analyzed by using the VOSviewer software. The most cited original articles were published between 1973 and 2013. The top-cited article was by Carraway and Leeman reporting the discovery of neurotensin in 1973. The highly cited terms were associated with hypotension and angiotensin-converting-enzyme. The conducted analysis reveals the therapeutic potentials of neurotensin, and further impactful research toward its clinical development is warrantied., MG Georgieva, AA Balacheva, TI Pajpanova, L Milella, AG Atanasov and NT Tzvetkov acknowledge the support by the Bulgarian National Science Found (BNSF) under grant number KP-06-OPR 03/8., info:eu-repo/semantics/publishedVersion

We have developed a new cationic solid lipid nanoparticle (SLN) formulation, composed of Compritol ATO 888, poloxamer 188 and cetyltrimethylammonium bromide (CTAB), to load perillaldehyde 1,2-epoxide, and surface-tailored with a monoclonal antibody for site-specific targeting of human epithelial growth receptor 2 (HER2). Perillaldehyde 1,2-epoxide-loaded cationic SLN (cPa-SLN), with a mean particle size (z-Ave) of 275.31 &plusmn, 4.78 nm and polydispersity index (PI) of 0.303 &plusmn, 0.081, were produced by high shear homogenization. An encapsulation efficiency of cPa-SLN above 80% was achieved. The release of perillaldehyde 1,2-epoxide from cationic SLN followed the Korsemeyer&ndash, Peppas kinetic model, which is typically seen in nanoparticle formulations. The lipid peroxidation of cPa-SLN was assessed by the capacity to produce thiobarbituric acid-reactive substances, while the antioxidant activity was determined by the capacity to scavenge the stable radical DPPH. The surface functionalization of cPa-SLN with the antibody was done via streptavidin-biotin interaction, monitoring z-Ave, PI and ZP of the obtained assembly (cPa-SLN-SAb), as well as its stability in phosphate buffer. The effect of plain cationic SLN (c-SLN, monoterpene free), cPa-SLN and cPa-SLN-SAb onto the MCF-7 cell lines was evaluated in a concentration range from 0.01 to 0.1 mg/mL, confirming that streptavidin adsorption onto cPa-SLN-SAb improved the cell viability in comparison to the cationic cPa-SLN.

In recent years, there has been a great deal of attention toward the molecular machinery relevant to age-related progression controlled through the external intervention of polyphenols- an epigenetic-modulating diet. Natural products modulate cellular longevity through histone post-translational modification and can also induce the upregulation of autophagy, thus reducing the level of acetyl coenzyme A (AcCoA). In addition, the effect of caloric restriction (CR) on cancer-related chronic inflammation is of great significance in aging. In line with this, SIRT1 protein levels are expanded in response to calorie restriction mimetics (CRM), in this way acting as autophagy inducers relevant to cancer prevention.

Phytol (PYT) is a diterpene member of the long-chain unsaturated acyclic alcohols. PYT and some of its derivatives, including phytanic acid (PA), exert a wide range of biological effects. PYT is a valuable essential oil (EO) used as a fragrance and a potential candidate for a broad range of applications in the pharmaceutical and biotechnological industry. There is ample evidence that PA may play a crucial role in the development of pathophysiological states. Focusing on PYT and some of its most relevant derivatives, here we present a systematic review of reported biological activities, along with their underlying mechanism of action. Recent investigations with PYT demonstrated anxiolytic, metabolism-modulating, cytotoxic, antioxidant, autophagy- and apoptosis-inducing, antinociceptive, anti-inflammatory, immune-modulating, and antimicrobial effects. PPARs- and NF-κB-mediated activities are also discussed as mechanisms responsible for some of the bioactivities of PYT. The overall goal of this review is to discuss recent findings pertaining to PYT biological activities and its possible applications.

Natural products are gaining much momentum worldwide because they have a broad spectrum of biological effects and present excellent opportunities for bioproducts development. With this fact, this study has been designed to investigate for the first time the effects of the ethyl acetate (EA), methanolic (MeOH), and water (W) extracts of Lotus aegaeus (La) and Iberis sempervirens (Is) on key enzymes as well as to quantify antioxidant capacities. The total phenolic and flavonoid content were determined using colorimetric methods and the individual phenolic compounds were assessed by LC–MS/MS analysis. Quercetin hexoside was the dominant compound in L. aegaeus, particularly in methanol extract, while the ethyl acetate and methanol extracts of I. sempervirens were characterized by the presence scopoletin and hinic acid. The antioxidant abilities of the investigated extracts were tested using different assays including free radical scavenging, reducing power, phosphomolybdenum, and metal chelating. All the extracts showed strong antioxidant abilities. For both species, the ethyl acetate extracts were more potent against cholinesterases and α-amylase, while the methanol extracts were most active against α-glucosidase. Only the water extract, followed by methanol of I. sempervirens exhibited notable inhibitory activity against tyrosinase. In addition, the dominant compounds were docked against tyrosinase and α-glucosidase to investigate their predicted binding affinity and interactions with the active site. In conclusion, L. aegaeus and I. sempervirens showed potent biological attributes, which advocates for further studies to explore their potential use as phytopharmaceuticals.

Alkaloids are well-studied secondary metabolites, with recent preclinical studies evidencing that many of them exhibit anti-cancer, anti-depressant, anti-nociceptive, anti-inflammatory, anti-pyretic, anti-platelet, anti-oxidant, and anti-bacterial properties. Aconitum is a genus rich of diverse alkaloids. More than 450 alkaloids have been identified in a variety of species. Songorine is a C20 diterpenoid alkaloid and 12-keto analog of napelline, isolated from Aconitum soongaricum and was associated with a heterogeneous panel of biological functions. However, the bioactivity profile of this natural product has not been reviewed up to now. The present manuscript aims to summarize the most important biological activities associated with songorine administration in preclinical models. The most significant data found in the scientific literature were evaluated in order to summarize the potential clinical utility of songorine in a diverse spectrum of pathologies and conditions. Songorine and its derivatives have many pharmacological effects including anti-arrhythmic, anti-cardiac-fibrillation, excitation of synaptic transmission, anxiolytic effects, anti-nociceptive, anti-inflammatory, anti-arthritis effects, and a regenerative effect in a skin excision wound animal model. Despite its outstanding pharmacotherapeutic potential, songorine has never been tested in clinical trials. Therefore, further evaluation is required to better evaluate its clinical utility.

The dysregulation of autophagy is involved in the pathogenesis of a broad range of diseases, and accordingly universal research efforts have focused on exploring novel compounds with autophagy-modulating properties. While a number of synthetic autophagy modulators have been identified as promising cancer therapy candidates, autophagy-modulating phytochemicals have also attracted attention as potential treatments with minimal side effects. In this review, we firstly highlight the importance of autophagy and its relevance in the pathogenesis and treatment of cancer. Subsequently, we present the data on common phytochemicals and their mechanism of action as autophagy modulators. Finally, we discuss the challenges associated with harnessing the autophagic potential of phytochemicals for cancer therapy.

Background Food choices represent a highly significant approach to combat human obesity. Dietary intake of lipids, especially polyunsaturated and monounsaturated fatty acids, is gaining popularity in the effort to reduce or eliminate the occurrence of obesity. Pecan (Carya illinoinensis) nuts are an abundant source of these dietary fatty acids. Moreover, they are a rich source of epigallocatechin-3-gallate (EGCG), a polyphenol with a variety of health-beneficial properties. Scope and approach In this review, we summarize the literature reports examining physiological effects associated with pecan nuts consumption and described effects of their bioactive constituents. Key findings and conclusions The growing body of evidence suggests including pecan nuts into obesity management strategies. The consumption of pecan nuts can mitigate inflammation by reducing the extent of the synthesis of inflammatory mediator molecules. Pecan nuts can also counteract the pro-inflammatory effects of a diet rich in commonly overconsumed saturated fatty acids, characteristic of the Western diet. Additionally, consumption of pecans and other nuts has been linked to reduced risk of physiological parameters associated with cardiovascular disease or metabolic disorders. Diets enriched with tree nuts and peanuts can modulate the blood level of cholesterol, adiposity, and insulin resistance. Almonds and walnuts have been so far the most studied nuts, and studies with them have led to a greater understanding of the protective effects of diverse tree nuts on human physiology. In this review, we summarize the available data indicating that pecan nuts exert similar health-promoting benefits.

Mechanisms how colorectal cancer (CRC) cells penetrate blood micro-vessel endothelia and metastasise is poorly understood. To study blood endothelial cell (BEC) barrier breaching by CRC emboli, an in vitro assay measuring BEC-free areas underneath SW620 cell spheroids, so called “circular chemorepellent induced defects” (CCIDs, appearing in consequence of endothelial retraction), was adapted and supported by Western blotting, EIA-, EROD- and luciferase reporter assays. Inhibition of ALOX12 or NF-κB in SW620 cells or BECs, respectively, caused attenuation of CCIDs. The FDA approved drugs vinpocetine [inhibiting ALOX12-dependent 12(S)-HETE synthesis], ketotifen [inhibiting NF-κB], carbamazepine and fenofibrate [inhibiting 12(S)-HETE and NF-κB] significantly attenuated CCID formation at low μM concentrations. In the 5-FU-resistant SW620-R/BEC model guanfacine, nifedipine and proadifen inhibited CCIDs stronger than in the naive SW620/BEC model. This indicated that in SW620-R cells formerly silent (yet unidentified) genes became expressed and targetable by these drugs in course of resistance acquisition. Fenofibrate, and the flavonoids hispidulin and apigenin, which are present in medicinal plants, spices, herbs and fruits, attenuated CCID formation in both, naive- and resistant models. As FDA-approved drugs and food-flavonoids inhibited established and acquired intravasative pathways and attenuated BEC barrier-breaching in vitro, this warrants testing of these compounds in CRC models in vivo.

Mitochondria play a pivotal role in cellular energy-generating processes and are considered master regulators of cell life and death fate. Mitochondrial function integrates signalling networks in several metabolic pathways controlling neurogenesis and neuroplasticity. Indeed, dysfunctional mitochondria and mitochondrial-dependent activation of intracellular stress cascades are critical initiating events in many human neurodegenerative or neurodevelopmental diseases including Down syndrome (DS). It is well established that trisomy of human chromosome 21 can cause DS. DS is associated with neurodevelopmental delay, intellectual disability and early neurodegeneration. Recently, molecular mechanisms responsible for mitochondrial damage and energy deficits have been identified and characterized in several DS-derived human cells and animal models of DS. Therefore, therapeutic strategies targeting mitochondria could have great potential for new treatment regimens in DS. The purpose of this review is to highlight recent studies concerning mitochondrial impairment in DS, focusing on alterations of the molecular pathways controlling mitochondrial function. We will also discuss the effects and molecular mechanisms of naturally occurring and chemically synthetized drugs that exert neuroprotective effects through modulation of mitochondrial function and attenuation of oxidative stress. These compounds might represent novel therapeutic tools for the modulation of energy deficits in DS.

Concanavalin A (ConA)-induced hepatitis is an experimental model of human autoimmune hepatitis induced in rodents by i.v. injection of Con A. The disease is characterized by increase in serum levels of transaminases and massive immune infiltration of the livers. Type 1, type 2, and type 17 cytokines play a pathogenic role in the development of ConA-induced hepatitis. To understand further the immunoregulatory mechanisms operating in the development and regulation of ConA-induced hepatitis, we have evaluated the role of the anti-inflammatory pathway Nrf2/HO-1/CO (Nuclear Factor E2-related Factor 2/Heme Oxygenase-1/Carbon Monoxide) in this condition and determined whether the in vivo administration of CO via the CO-releasing molecule (CORM) CORM-A1, influences serological and histological development of Con-A-induced hepatitis. We have firstly evaluated in silico the genes belonging to the Nrf2/HO-1/CO pathway that are involved in the pathogenesis of autoimmune hepatitis (AIH). The data obtained from the in silico study demonstrate that a significant number of genes modulated in the liver of ConA-challenged mice belong to the Nrf2 pathway; on the other hand, the administration of CORM-A1 determines an improvement in several sero-immunological and histological parameters, and it is able to modulate genes identified by the in silico analysis. Collectively, our data indicate that the Nrf2/HO-1/CO pathway is fundamental for the regulation of the immune responses, and that therapeutic intervention aimed at its modulation by CORM-A1 may represent a valuable strategy to be considered for the treatment of autoimmune hepatitis in humans.

Citrinin (CIT) is a mycotoxin which causes contamination in the food and is associated with different toxic effects. A web search on CIT has been conducted covering the timespan since 1946. The accumulated data indicate that CIT is produced by several fungal strains belonging to Penicillium, Aspergillus and Monascus genera, and is usually found together with another nephrotoxic mycotoxin, ochratoxin A. Although, it is evident that CIT exposure can exert toxic effects on the heart, liver, kidney, as well as reproductive system, the mechanism of CIT-induced toxicity remains largely elusive. It is still controversial what are the genotoxic and mutagenic effects of CIT. Until now, its toxic effect has been linked to the CIT-mediated oxidative stress and mitochondrial dysfunction in biological systems. However, the toxicity strongly depends on its concentration, route, frequency and time of exposure, as well as from the used test systems. Besides the toxic effects, CIT is also reported to possess a broad spectrum of bioactivities, including antibacterial, antifungal, and potential anticancer and neuro-protective effects in vitro. This systematic review presents the current state of CIT research with emphasis on its bioactivity profile.

Background Neanotis wightiana (Wall. ex Wight & Arn) W.H. Lewis has been used in traditional medicine in India for the treatment of liver disorders. In fact, this plant is frequently used by the local people of Tripura for the treatment of liver disorder problems. In previous study on this plant we have isolated a hepatoprotective saponin, neanoside A. Purpose Evaluation of in vivo hepatoprotective effects of isolated compounds from N. wightiana aerial parts on serum hepatic-biomarkers in CCl4- induced hepatotoxicity in rats to validate the traditional use of the plant. Study design This study was designed to isolate more hepatoprotective compounds from N. wightiana aerial parts and evaluate their in vivo hepatoprotective activity in animal model. Methods The phytochemicals from the polar n-butanol fraction of methanolic extract of N. wightiana aerial parts were isolated by repeated column chromatography over Diaion HP-20 and silica gel. Among the isolated three compounds, two were known triterpenoids, ursolic acid and oleanolic acid. The new compound was named neanoside B and its structure was established as naphthalene diglucoside 1 on the basis of extensive spectroscopic (including 2D NMR) analysis. Furthermore, the hepatoprotective activity of 1 was evaluated on CCl4 -induced hepatic injured rats by oral administration at three doses (5, 10 mg and 20 mg/kg) for 7 d and the assay of serum hepatic injury marker enzymes, SGPT, SGOT, ALP and bilirubin contents and histopathological changes of injured liver tissue after 7 d The herbal hepatoprotective drug, silymarin (100 mg/kg) was as positive control. Results The structure of the new compound, neanoside B (1) was elucidated as 1,4-dihydroxy-2-(methoxymethyl)naphthalen-3-yl-methyl-3-β- d -glucopyranosyl-(1→6)-β- d -glucopyranoside on the basis of extensive spectroscopic (including 2D-NMR) and chemical studies. The compound 1 exhibited significant in vivo hepatoprotective effect at the tested doses of 5, 10 and 20 mg/kg bw in CCl4-induced hepatotoxicity in rats. In a dose-dependent manner, 1 normalized the elevated levels of hepatic injury marker enzymes, serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase (ALP) and total bilirubin and ameliorated the damage of liver tissue by reducing the necrosis and vacuoles. Possibly compound 1 ameliorated the hepatic damage in hepatotoxic rats by improving the antioxidant status. The higher dose (20 mg/kg) showed more hepatoprotective effect by reducing the elevated levels of SGPT, SGOT, ALP and bilirubin content to 388.5 ± 2.156, 160.7 ± 3.00, 198.6 ± 4.562 and 0.652 ± 0.036 IU/ml, respectively, compared to the levels in the control group (583.2 ± 6.922, 324.6 ± 4.711, 263.9 ± 4.939 and 1.533 ± 0.042 IU/ml, respectively) and the effect was comparable to that of the positive control silymarin (100 mg/kg bw) (389.4 ± 6.348, 167.9 ± 4.289, 203.3 ± 4.448 and 0.816 ± 0.030 IU/ml, respectively). Conclusions This study indicated that isolated neanoside B (1) from Neanotis wightiana could be a potential drug in liver disorders. Further study in pharmacokinetics and long-term toxicity of compound 1 is requested for its clinical setting as effective drug in liver disorders.