Nutraceuticals in Viral Infections: An Overview of the Immunomodulating Properties.

Nutraceuticals, including vitamin D, vitamin A, zinc, lactoferrin, polyphenols coenzyme Q, magnesium, and selenium, are implicated in the modulation of the complex molecular pathways involved in the immune response against viral pathogens. A common element of the activity of nutraceuticals is their ability to enhance the innate immune response against pathogens by acting on the major cellular subsets and inducing the release of pro-inflammatory cytokines and antimicrobial peptides. In some cases, this action is accompanied by a direct antimicrobial effect, as evidenced in the specific case of lactoferrin. Furthermore, nutraceuticals act through complex molecular mechanisms to minimize the damage caused by the activation of the immune system against pathogens, reducing the oxidative damage, influencing the antigen presentation, enhancing the differentiation and proliferation of regulatory T cells, driving the differentiation of lymphocyte subsets, and modulating the production of pro-inflammatory cytokines. In this paper, we review the main molecular mechanisms responsible for the immunomodulatory function of nutraceuticals, focusing on the most relevant aspects for the prevention and treatment of viral infections.

Effective Antiviral Medicinal Plants and Biological Compounds Against Central Nervous System Infections: A Mechanistic Review.

BACKGROUND AND OBJECTIVE: Infectious diseases are amongst the leading causes of death in the world and central nervous system infections produced by viruses may either be fatal or generate a wide range of symptoms that affect global human health. Most antiviral plants contain active phytoconstituents such as alkaloids, flavonoids, and polyphenols, some of which play an important antiviral role. Herein, we present a background to viral central nervous system (CNS) infections, followed by a review of medicinal plants and bioactive compounds that are effective against viral pathogens in CNS infections. METHODS: A comprehensive literature search was conducted on scientific databases including: PubMed, Scopus, Google Scholar, and Web of Science. The relevant keywords used as search terms were: "myelitis", "encephalitis", "meningitis", "meningoencephalitis", "encephalomyelitis", "central nervous system", "brain", "spinal cord", "infection", "virus", "medicinal plants", and "biological compounds". RESULTS: The most significant viruses involved in central nervous system infections are: Herpes Simplex Virus (HSV), Varicella Zoster Virus (VZV), West Nile Virus (WNV), Enterovirus 71 (EV71), Japanese Encephalitis Virus (JEV), and Dengue Virus (DENV). The inhibitory activity of medicinal plants against CNS viruses is mostly active through prevention of viral binding to cell membranes, blocking viral genome replication, prevention of viral protein expression, scavenging reactive Oxygen Species (ROS), and reduction of plaque formation. CONCLUSION: Due to the increased resistance of microorganisms (bacteria, viruses, and parasites) to antimicrobial therapies, alternative treatments, especially using plant sources and their bioactive constituents, appear to be more fruitful.

Inhibitory effect of melatonin on Mst1 ameliorates myocarditis through attenuating ER stress and mitochondrial dysfunction.

Viral myocarditis has been found to be one of the leading causes of sudden death in young adults. However, no effective drugs have been developed to intervene the progression of myocarditis. Accordingly, the present study is carried out to explore the protective role played by melatonin in the setting of viral myocarditis with a focus on Mst1-Hippo pathway, mitochondrial dysfunction and ER stress. Cardiac function was determined via echocardiographic examination. Mitochondrial function and ER stress were detected via ELISA, western blots, and immunofluorescence. Our data demonstrated that virus injection induced cardiac dysfunction as evidenced by reduced contractile function in myocardium. Besides, LDH release assay and western blotting analysis demonstrated that cardiomyocyte death was activated by virus injection. Interestingly, melatonin treatment improved cardiac function and repressed virus-mediated cardiomyocyte apoptosis. At the molecular levels, mitochondrial dysfunction was induced by virus infection, as indicated by mitochondrial membrane potential reduction, mPTP opening rate elevation and caspase-9-related apoptosis activation. Besides, ER stress parameters were also elevated in virus-treated cardiomyocytes. Interestingly, melatonin treatment maintained mitochondrial dysfunction and repressed ER stress. To the end, we found that Mst1 was upregulated by virus infection; this effect was attenuated through supplementation with melatonin. However, Mst1 overexpression reduced the beneficial impact exerted by melatonin on cardiomyocyte viability, mitochondrial function and ER homeostasis. Our study illustrated that melatonin treatment attenuated viral myocarditis via sustaining cardiomyocyte viability, repressing mitochondrial dysfunction and inhibiting ER stress in a manner dependent on Mst1 inhibition.

Clothianidin seed-treatment has no detectable negative impact on honeybee colonies and their pathogens.

Interactions between multiple stressors have been implicated in elevated honeybee colony losses. Here, we extend our landscape-scale study on the effects of placement at clothianidin seed-treated oilseed rape fields on honeybees with an additional year and new data on honeybee colony development, swarming, mortality, pathogens and immune gene expression. Clothianidin residues in pollen, nectar and honeybees were consistently higher at clothianidin-treated fields, with large differences between fields and years. We found large variations in colony development and microbial composition and no observable negative impact of placement at clothianidin-treated fields. Clothianidin treatment was associated with an increase in brood, adult bees and Gilliamella apicola (beneficial gut symbiont) and a decrease in Aphid lethal paralysis virus and Black queen cell virus - particularly in the second year. The results suggest that at colony level, honeybees are relatively robust to the effects of clothianidin in real-world agricultural landscapes, with moderate, natural disease pressure.

Virucidal, antiviral and immunomodulatory activities of ß-escin and Aesculus hippocastanum extract.

OBJECTIVES: ß-Escin, one of the constituents of Aesculus hippocastanum L. (Hippocastanaceae) seed extract (AH), inhibits NF-κB activation, which plays an important role in HSV-1 replication. The aim was to examine the antiherpetic activity of ß-escin and AH, as well as their effect on the activation of NF-κB and AP-1 and cytokine secretion in epithelial cells and macrophages. METHODS: Cell viability was evaluated using MTT assay, and antiviral and virucidal activity was determined by plaque assay. The effect on NF-κB and AP-1 signalling pathways activation was determined by a luciferase reporter assay, and cytokine production was measured by ELISA. KEY FINDINGS: ß-Escin and AH had virucidal and anti-HSV-1 activities, and the antiviral activity was discovered for other enveloped viruses (VSV and Dengue). Moreover, ß-escin and AH significantly reduced NF-κB and AP-1 activation and cytokine production in macrophages stimulated with HSV-1 and TLRs ligands. However, an enhanced activation of these pathways and an increase in the levels of pro-inflammatory cytokines in ß-escin and AH-treated HSV-1-infected epithelial cells were found. CONCLUSIONS: This study demonstrates virucidal and broad-spectrum antiviral activities for ß escin and AH. Besides, ß-escin and AH modulate cytokine production depending on the stimuli (viral or non-viral) and the cell type under study.

Endocytic Transport as a Drug Target in Infectious Diseases.

Components of the extracellular environment can be transported into cells by molecular mechanisms collectively termed endocytosis. Cells typically use a multitude of such internalization pathways. These endocytic transport pathways have a wide range of implications for physiological regulation as well as pathological processes. Many infectious diseases, for example, involve internalization of the pathogen into the cell as part of the infection process. Selective interference with the endocytic transport of a microbe, thus, represents a therapeutic strategy that may prevent infections or decrease the rate of their progression. Herein, we provide a brief review of strategies for discovery of novel anti-infection drugs and their pharmacological implications.

Olfactory vector hypothesis for encephalitis lethargica.

Viruses have long been implicated in the pathogenesis of classical encephalitis lethargica, which was first described by Constantin von Economo in 1917. In this article, I propose the hypothesis that an airborne virus travels along the olfactory conduit to infect the olfactory bulb; this local infection or induced neuroinflammation, in turn, retrogradely targets certain neuronal populations with sleep-wake regulatory functions in the hypothalamus and midbrain, leading to the development of wakeful inactivity, a hallmark clinical feature of the disease. Furthermore, the olfactory vector hypothesis may also explain the pathomechanism of the debilitating complication of the disease, i.e., postencephalitic parkinsonism, in terms of a recently discovered nigro-olfactory projection.

Respiratory protease/antiprotease balance determines susceptibility to viral infection and can be modified by nutritional antioxidants.

The respiratory epithelium functions as a central orchestrator to initiate and organize responses to inhaled stimuli. Proteases and antiproteases are secreted from the respiratory epithelium and are involved in respiratory homeostasis. Modifications to the protease/antiprotease balance can lead to the development of lung diseases such as emphysema or chronic obstructive pulmonary disease. Furthermore, altered protease/antiprotease balance, in favor for increased protease activity, is associated with increased susceptibility to respiratory viral infections such as influenza virus. However, nutritional antioxidants induce antiprotease expression/secretion and decrease protease expression/activity, to protect against viral infection. As such, this review will elucidate the impact of this balance in the context of respiratory viral infection and lung disease, to further highlight the role epithelial cell-derived proteases and antiproteases contribute to respiratory immune function. Furthermore, this review will offer the use of nutritional antioxidants as possible therapeutics to boost respiratory mucosal responses and/or protect against infection.

Conducting nanosponge electroporation for affordable and high-efficiency disinfection of bacteria and viruses in water.

High-efficiency, affordable, and low energy water disinfection methods are in great need to prevent diarrheal illness, which is one of the top five leading causes of death over the world. Traditional water disinfection methods have drawbacks including carcinogenic disinfection byproducts formation, energy and time intensiveness, and pathogen recovery. Here, we report an innovative method that achieves high-efficiency water disinfection by introducing nanomaterial-assisted electroporation implemented by a conducting nanosponge filtration device. The use of one-dimensional (1D) nanomaterials allows electroporation to occur at only several volts, which is 2 to 3 orders of magnitude lower than that in traditional electroporation applications. The disinfection mechanism of electroporation prevents harmful byproduct formation and ensures a fast treatment speed of 15,000 L/(h·m(2)), which is equal to a contact time of 1 s. The conducting nanosponge made from low-cost polyurethane sponge coated with carbon nanotubes and silver nanowires ensures the device's affordability. This method achieves more than 6 log (99.9999%) removal of four model bacteria, including Escherichia coli, Salmonella enterica Typhimirium, Enterococcus faecalis, and Bacillus subtilis, and more than 2 log (99%) removal of one model virus, bacteriophage MS2, with a low energy consumption of only 100 J/L.

Roadblocks to translational challenges on viral pathogenesis.

Distinct roadblocks prevent translating basic findings in viral pathogenesis into therapies and implementing potential solutions in the clinic. An ongoing partnership between the Volkswagen Foundation and Nature Medicine resulted in an interactive meeting in 2012, as part of the "Herrenhausen Symposia" series. Current challenges for various fields of viral research were recognized and discussed with a goal in mind--to identify solutions and propose an agenda to address the translational barriers. Here, some of the researchers who participated at the meeting provide a concise outlook at the most pressing unmet research and clinical needs, identifying these key obstacles is a necessary step towards the prevention and cure of human viral diseases.

[Disease survey and pathogen identification on Notopterygium incisum in Gansu province].

Six diseases have been found after disease surveys on Notopterygium incisum in Gansu province during 2004 to 2007. They were brown spot (Ascochyta levistici), powdery mildew (Erysiphe heraclei), grey spot (Alternaria sp. ; Alternaria burnsii), leaf spot (Septoria dearnessii), angular leaf spot (Pleospora sp.), leaf streak (Phoma sp.), bacterial angular leaf spot and a virus disease. Bacterial angular leaf spot and powdery mildew are the urgent problems waiting to be solved effectively. All these diseases were reported for the first time in China.

[Radix isatidis and infectious diseases caused by viruses].

Radix Isatidis (Banlangen in Chinese), used to clearing away heat and toxic material, is a traditional Chinese medicinal (TCM) herb. It is frequently used for preventing and treating infectious diseases caused by viruses. To provide scientific basis for the effect of Radix Isatidis on infectious diseases, the traditional effect and new research development on pharmacological activities are summarized in the review. According to the existed problems in the clinical application, the weak links and shortages of quality research and industrialized production of Radix Isatidis are discussed. It could present the new ideas for improving the technology of Radix Isatidis preparation, and promoting the rational use of the preparation in the clinical treatment.

Long-term care facilities: a cornucopia of viral pathogens.

OBJECTIVES: To determine the frequency and types of respiratory viruses circulating in Boston long-term care facilities (LTCFs) during a 3-year period. DESIGN: Observational. SETTING: Thirty-three Boston-area LTCFs over a 3-year period. PARTICIPANTS: Residents of long-term care who had previously participated in a trial of vitamin E supplementation and had paired serum samples available for viral analysis. MEASUREMENTS: Viral antibody titers to eight respiratory viruses (influenza A and B, respiratory syncytial virus (RSV), parainfluenza virus serotype three (PIV-3), PIV-2, human metapneumovirus (hMPV), and coronaviruses 229E and OC43) were measured using enzyme immunoassay at baseline and 53 weeks. Infection was defined as a more than quadrupling of viral titers. Clinical data on respiratory illnesses were collected throughout the study period. RESULTS: A total of 617 persons were enrolled in the trial. Of these, 382 (62%) had sera available for viral analysis. A total of 204 viral infections were documented in 157 subjects. Serological responses to all eight viruses were documented, with hMPV (12.8%) and coronavirus 229E (10.5%) being the most common and PIV-2 (2.4%) the least common. The occurrence of bronchitis (P=.007), pneumonia (P=.02), and any lower respiratory tract infection (P=.002) was significantly associated with having a viral diagnosis. CONCLUSION: A wide range of respiratory viruses cocirculates in LTCFs and contributes to respiratory illness morbidity in these populations.

General preadaptation of viral infectors to their hosts.

We tested the hypothesis of optimal adaptation of viral infectors to eukaryotic hosts, using (1) correlation in codon and amino acid usage between organisms, and (2) canonical correlation between groups of hosts and infectors. The codon correlations between parasites and hosts vary, being low between swine and African swine fever virus (ASF; r = 0.18), and highest between potato and potato virus X (r = 0.60). The correlations might indicate different stages of evolution toward optimal adaptation of the parasite codon distribution to the host tRNA pools. The amino acid correlations vary from r = 0.71 between pig and ASF, to 0.88 between catfish and its herpesvirus. It was observed that both in virus and hosts, there is a negative correlation between frequency of an amino acid and molecular weight. Therefore, it was advanced that viral infectors might be preadapted to their hosts because of similarities of the tRNA pools of hosts, and that evolution toward optimization would be dependent on the size of the divergence between the codon distributions of infector and host. Preadaptation does not imply origin of the virus by lateral transfer from the present host, since the correlation of the molecular weight of amino acids with their abundance in proteins is a general phenomenon.

Selenium and vitamin E status: impact on viral pathogenicity.

Selenium (Se), an essential trace element, and vitamin E, a lipid soluble antioxidant, are important mediators for protection against oxidative stress. Recent work has demonstrated that deficiencies in either Se or vitamin E result in increased viral pathogenicity and altered immune responses. Furthermore, deficiencies in either Se or vitamin E results in specific viral mutations, changing relatively benign viruses into virulent ones. Thus, host nutritional status should be considered a driving force for the emergence of new viral strains or newly pathogenic strains of known viruses.

Three-dimensional culture models for human viral diseases and antiviral drug development.

Researchers are recognizing the limitations of two-dimensional (2D) cell cultures, given the fact that they do not reproduce the morphology and biochemical features that the cells possess in the original tissue. As an alternative, the three-dimensional (3D) cell culture approach offers researchers the possibility to study cell growth and differentiation under conditions that more closely resemble the in vivo situation with regard to cell shape and cellular environment. Currently, 3D culture models are being employed in many areas of biomedical research because they offer a more realistic milieu than 2D cultures. The era of 2D culture techniques is moving towards a new epoch of culture systems in 3D. The present review is focused on topics of research on 3D cell cultures in virology and their use in antiviral drug development.

Dynamics of carbon, nitrogen and phosphorus in soil amended with irradiated, pasteurized and limed biosolids.

Sewage biosolids contain high concentrations of pathogens, which limits their use as soil amendment. This study investigated how application of lime (Ca(OH)2), irradiation, or pasteurization reduced pathogens in biosolids and how its application affected soil characteristics. A soil sampled outside the canopy of Mesquite trees (Prosopis laevigata) and from a pasture at Lerma (Mexico) was amended with treated or untreated biosolids, characterized and incubated aerobically while dynamics of carbon (C), nitrogen (N) and phosphorus (P) were monitored. Heavy metals concentrations in the biosolids were low, so it was of excellent quality (USEPA). The amount of pathogens in the biosolids made it a class "B" (USEPA) which can be used in forests. Only irradiation sufficiently reduced faecal coliforms to make it a class "A" biosolids without restrictions in application. C mineralization increased significantly when biosolids were added, but not concentrations of available P (P < 0.05). Ammonium (NH4+) concentrations in soil amended with biosolids were higher compared to unamended soil, but not the concentrations of nitrate (NO3-) except when biosolids treated with Ca(OH)2 was added to the Lerma soil.

[Selenium in health and disease]. / Selen w zdrowiu i chorobie.

Selenium deficiency occurs in many regions of the world including Poland. It leads to human body dysfunctions and diseases among which Keshan disease is the most known. Biologically active selenium is usually incorporated into proteins as selenocysteine, which is the most useful in nutritional supplementation. Selenium addition is important since many viruses are more pathogenic when deficiency of this element occurs.