Antifungal Proteins with Antiproliferative Activity on Cancer Cells and HIV-1 Enzyme Inhibitory Activity from Medicinal Plants and Medicinal Fungi.

A variety of fungi, plants, and their different tissues are used in Traditional Chinese Medicine to improve health, and some of them are recommended for dietary therapy. Many of these plants and fungi contain antifungal proteins and peptides which suppress spore germination and hyphal growth in phytopathogenic fungi. The aim of this article is to review antifungal proteins produced by medicinal plants and fungi used in Chinese medicine which also possess anticancer and human immunodeficiency virus-1 (HIV-1) enzyme inhibitory activities.

Tuber Lectins with Potentially Exploitable Bioactivities.

Lectins are a group of proteins or glycoproteins with various potentially exploitable bioactivities and have been capturing more interest recently. They have been isolated and reported from various tissues of a diversity of plant species. Tubers are modified and enlarged plant structures derived from stems or roots that are used for nutrient storage and asexual reproduction. A number of plants such as yam, taro and potato are grown for their edible tubers, and lectins are found to be one of the major storage proteins. These lectins exhibit potent bioactivities encompassing mitogenic, antitumor, antimicrobial, immunomodulatory, antioxidative, hypoglycemic, insecticidal and nematicidal activities. They are potential resources for development into functional or healthy foods and targets for food protein researchers.

Prognostic Utility of Initial Lactate in Patients With Acute Drug Overdose: A Validation Cohort.

STUDY OBJECTIVE: Previous studies have suggested that the initial emergency department (ED) lactate concentration may be an important prognostic indicator for inhospital mortality from acute drug poisoning. We conduct this cohort study to formally validate the prognostic utility of the initial lactate concentration in a larger, distinct patient population with acute drug overdose. METHODS: This observational, prospective, cohort study was conducted during 5 years at 2 urban teaching hospitals. Consecutive adult ED patients with acute drug overdose had serum lactate levels tested as part of clinical care. The primary outcome was inpatient fatality. Receiver operating characteristics were plotted to determine optimal cut points, test characteristics, area under the curve, odds ratios, and 95% confidence intervals (CIs). RESULTS: Of 3,739 patients screened, 1,406 were analyzed (56% women; mean age 43.1 years) and 24 died (1.7%). The difference in mean initial lactate concentration was 5.9 mmol/L (95% CI 3.4 to 8.1 mmol/L) higher in patients who died compared with survivors. The area under the curve for prediction of fatality was 0.85 (95% CI 0.73 to 0.95). The optimal lactate cut point for fatality was greater than or equal to 5.0 (odds ratio 34.2; 95% CI 13.7 to 84.2; 94.7% specificity). Drug classes for which lactate had the highest utility were salicylates, sympathomimetics, acetaminophen, and opioids (all area under the curve ≥0.97); lowest utility was for diuretics and angiotensin-converting enzyme inhibitors. CONCLUSION: Initial lactate concentration is a useful biomarker for early clinical decisionmaking in ED patients with acute drug overdose. Studies of lactate-tailored management for these patient populations are warranted.

Apoptosis and Anti-cancer Drug Discovery: The Power of Medicinal Fungi and Plants.

The purpose of this account is to review the compounds capable of eliciting mitochondria-mediated apoptosis in cancer cells produced by medicinal fungi and plants. The medicinal fungi discussed encompass Cordyceps, Ganoderma species, Coriolus versicolor and Hypsizygus marmoreus. The medicinal plants discussed comprise Astragalus complanatus, Dendrobium spp, Dioscorea spp, Glycyrrhiza spp, Panax notoginseng, Panax ginseng, and Momordica charantia. These compounds have the potential of development into anticancer drugs.

Motor deficits, impaired response inhibition, and blunted response to methylphenidate following neonatal exposure to decabromodiphenyl ether.

Decabromodiphenyl ether (decaBDE) is an applied brominated flame retardant that is widely-used in electronic equipment. After decades of use, decaBDE and other members of its polybrominated diphenyl ether class have become globally-distributed environmental contaminants that can be measured in the atmosphere, water bodies, wildlife, food staples and human breastmilk. Although it has been banned in Europe and voluntarily withdrawn from the U.S. market, it is still used in Asian countries. Evidence from epidemiological and animal studies indicate that decaBDE exposure targets brain development and produces behavioral impairments. The current study examined an array of motor and learning behaviors in a C57BL6/J mouse model to determine the breadth of the developmental neurotoxicity produced by decaBDE. Mouse pups were given a single daily oral dose of 0 or 20mg/kg decaBDE from postnatal day 1 to 21 and were tested in adulthood. Exposed male mice had impaired forelimb grip strength, altered motor output in a circadian wheel-running procedure, increased response errors during an operant differential reinforcement of low rates (DRL) procedure and a blunted response to an acute methylphenidate challenge administered before DRL testing. With the exception of altered wheel-running output, exposed females were not affected. Neither sex had altered somatic growth, motor coordination impairments on the Rotarod, gross learning deficits during operant lever-press acquisition, or impaired food motivation. The overall pattern of effects suggests that males are more sensitive to developmental decaBDE exposure, especially when performing behaviors that require effortful motor output or when learning tasks that require sufficient response inhibition for their successful completion.

Therapeutic potentials of short interfering RNAs.

Short interfering RNA (siRNA) is one of the members of the family of RNA interference (RNAi). Coupled with the RNA-induced silencing complex (RISC), siRNA is able to trigger the cleavage of target RNAs which serve as a defensive system against pathogens. Meanwhile, siRNA in gene silencing opens a new avenue for the treatment of various diseases. SiRNA can effectively inhibit viral infection and replication and suppress tumorigenesis and various inflammation-associated diseases and cardiovascular diseases by inactivation of viral genes and downregulation of oncogene expression. Recently, endogenous siRNAs (endo-siRNAs) were discovered in the reproductive cells of animals which may be associated with regulation of cell division. Structural modification of siRNA enhances the delivery, specificity and efficacy and bioavailability to the target cells. There are at least five categories of siRNA delivery systems including viral vectors, lipid-based nanoparticles, peptide-based nanoparticles, polymer-based nanoparticles and inorganic small molecules like metal ions, silica and carbon. Sufficient preclinical and clinical studies supported that siRNA may be a potential medicine for targeted therapy of various diseases in the near future.

Antifreeze Proteins from Diverse Organisms and their Applications: An Overview.

Antifreeze proteins are ice-binding or ice-structuring proteins that prevent water from freezing by adsorbing to the ice surface and stopping the growth of minute ice crystals to large crystals in a non-colligative manner. The antifreeze proteins are found in species like fish, arthropods, plants, algae, fungi, yeasts and bacteria. The diversity, distribution and classification of antifreeze proteins were highlighted in this review. Antifreeze proteins help the organisms adapt to and survive in subzero temperature environments. The distribution of antifreeze proteins in different species appears to be the outcome of a combination of independent evolutionary events, probably the convergent evolution or horizontal gene transfer. Benefits can be derived from the frost resistance of these organisms. Their potential applications have been recognized in food processing, cryopreservation, cryosurgery, fishery and agricultural industries and anti-icing materials development. This review includes information on the current understanding of antifreeze proteins. A discussion on interactions and mechanisms involving ice recognition and adsorption was also included.

Mannose Binding Lectin: A Potential Biomarker for Many Human Diseases.

The innate immune system plays a modulatory role in producing an inflammatory response during microbial infection and tissue regeneration. Mannose-binding lectin (MBL) is a predominant constituent of the innate immune system which initiates one of the complement activation, the lectin pathway. The activation of the complement system is also associated with many human diseases. We, therefore, try to summarize herewith the prognostic value of early detection of serum mannose-binding lectin (MBL) and measurement of its levels. The variant alleles and single nucleotide substitutions in MBL2 gene associated with MBL polymorphism are responsible for an increased risk of infection. Based on the currently available evidence, the role of MBL in humans is a double facet; sometimes its presence is associated with deterioration of the pathological condition while in other cases it is an important part of the body defense system. The importance of the determination of serum MBL as a diagnostic biomarker is duly addressed and then substitution of plasma-purified or recombinant MBL which can be a potential therapeutic for the treatment of human diseases is also highlighted. We have summarized in this article the pivotal roles of MBL in the early pathophysiology of various diseases and shown that MBL serves as a novel therapeutic target.

Snake venom toxins: toxicity and medicinal applications.

Snake venoms are complex mixtures of small molecules and peptides/proteins, and most of them display certain kinds of bioactivities. They include neurotoxic, cytotoxic, cardiotoxic, myotoxic, and many different enzymatic activities. Snake envenomation is a significant health issue as millions of snakebites are reported annually. A large number of people are injured and die due to snake venom poisoning. However, several fatal snake venom toxins have found potential uses as diagnostic tools, therapeutic agent, or drug leads. In this review, different non-enzymatically active snake venom toxins which have potential therapeutic properties such as antitumor, antimicrobial, anticoagulating, and analgesic activities will be discussed.

Fungal proteinaceous compounds with multiple biological activities.

Fungi comprise organisms like molds, yeasts and mushrooms. They have been used as food or medicine for a long time. A large number of fungal proteins or peptides with diverse biological activities are considered as antibacterial, antifungal, antiviral and anticancer agents. They encompass proteases, ribosome inactivating proteins, defensins, hemolysins, lectins, laccases, ribonucleases, immunomodulatory proteins, and polysaccharopeptides. The target of the present review is to update the status of the various bioactivities of these fungal proteins and peptides and discuss their therapeutic potential.

A hemagglutinin isolated from Northeast China black beans induced mitochondrial dysfunction and apoptosis in colorectal cancer cells.

Incidence of colorectal cancer is closely related with the lifestyle, especially the dietary habits of patients. Epidemiological researches have demonstrated a negative correlation between legume consumption and colorectal cancer incidence. Lectins/hemagglutinins are a type of carbohydrate binding proteins which are abundantly stored in legumes. Their eminent pH-stability allows them to survive digestion and remain active in the intestine where they may have direct contact with colorectal tumors. It is therefore interesting to explore the direct interaction between lectins/hemagglutinins and colorectal cancer. In the present research, we reported a detailed research on the interaction between a hemagglutinin isolated from an edible legume with two colorectal cancer cell lines. This hemagglutinin (NCBBH) was found to first bind to tumor cell membrane as early as 30min post treatment and was gradually transported inside the cytoplasm within 3h, with some of it localized in the Golgi apparatus and some in the lysosomes. After its entrance, the hemagglutinin induced aggregation of the Golgi apparatus, which in turn adversely affected the transportation of protein from endoplasmic reticulum (ER) to the Golgi apparatus, resulting in protein accumulation in ER and ER stress. The hemagglutinin-treated cells also manifested severe mitochondrial malformation and membrane depolarization, accompanied by obvious apoptosis characteristics, like chromatin condensation, phosphatidylserine exposure and caspase activation. Collectively, our results indicate that the hemaggltuinin could successfully enter the cytoplasm of colorectal cancer cells and adversely affect their growth, providing a mechanism in support of the application of edible legumes to the prevention and treatment of colorectal cancer.

Bovine Lactoferrampin, Human Lactoferricin, and Lactoferrin 1-11 Inhibit Nuclear Translocation of HIV Integrase.

This study aimed to investigate fragments derived from human and bovine lactoferrins for ability to inhibit nuclear translocation of HIV-1 integrase. It was shown that human lactoferricin, human lactoferrin 1-11, and bovine lactoferrampin reduced nuclear distribution of HIV-1 integrase. Bovine lactoferrampin could inhibit both the activity and nuclear translocation of HIV-1 integrase. Human lactoferrampin, bovine lactoferricin, and bovine lactoferrin 1-11 had no effect on HIV-1 integrase nuclear translocation. Human lactoferrampin which inhibited the activity of integrase did not prevent its nuclear translocation. Human lactoferricin and lactoferrin 1-11 did not inhibit HIV-1 integrase nuclear translocation despite their ability to attenuate the enzyme activity. The discrepancy between the findings on reduction of HIV-1 activity and inhibition of nuclear translocation of HIV-1 integrase was due to the different mechanisms involved. A similar reasoning can also be applied to the different inhibitory potencies of the milk peptides on different HIV enzymes, i.e., nuclear translocation.

Marine natural products with anti-inflammatory activity.

Chronic inflammation is believed to play crucial roles in the pathogenesis of various diseases. Several types of drugs are used to treat inflammatory disorders, but they cause adverse side effects. Natural products are alternatives to these drugs which offer hope for discovery of bioactive lead compounds that may be developed into drugs for treatment of inflammatory disorders. The biological and chemical diversity of marine habitats constitutes a sizeable reservoir of novel compounds. Some of them, like sesquiterpenoids, diterpenes, steroids, polysaccharides, alkaloids, fatty acids, proteins, and other chemical compounds, isolated from marine organisms are found to exhibit anti-inflammatory activity. This review reports some recent (2011-2015) investigations and examples of marine natural products and their synthetic derivatives with anti-inflammatory activity. It also highlights those compounds that are currently undergoing preclinical or clinical evaluation.

Biological activities of ribosome-inactivating proteins and their possible applications as antimicrobial, anticancer, and anti-pest agents and in neuroscience research.

Ribosome-inactivating proteins (RIPs) are enzymes which depurinate ribosomal RNA (rRNA), thus impeding the process of translation resulting in inhibition of protein synthesis. They are produced by various organisms including plants, fungi and bacteria. RIPs from plants are linked to plant defense due to their antiviral, antifungal, antibacterial, and insecticidal activities in which they can be applied in agriculture to combat microbial pathogens and pests. Their anticancer, antiviral, embryotoxic, and abortifacient properties may find medicinal applications. Besides, conjugation of RIPs with antibodies or other carriers to form immunotoxins has been found useful to research in neuroscience and anticancer therapy.

Proteins, peptides, polysaccharides, and nucleotides with inhibitory activity on human immunodeficiency virus and its enzymes.

Human immunodeficiency virus (HIV), the causative agent of acquired immune deficiency syndrome, has claimed innumerable lives in the past. Many biomolecules which suppress HIV replication and also other biomolecules that inhibit enzymes essential to HIV replication have been reported. Proteins including a variety of milk proteins, ribosome-inactivating proteins, ribonucleases, antifungal proteins, and trypsin inhibitors; peptides comprising cathelicidins, defensins, synthetic peptides, and others; polysaccharides and polysaccharopeptides; nucleosides, nucleotides, and ribozymes, demonstrated anti-HIV activity. In many cases, the mechanism of anti-HIV action has been elucidated. Strategies have been devised to augment the anti-HIV potency of these compounds.

Chitosan: An Update on Potential Biomedical and Pharmaceutical Applications.

Chitosan is a natural polycationic linear polysaccharide derived from chitin. The low solubility of chitosan in neutral and alkaline solution limits its application. Nevertheless, chemical modification into composites or hydrogels brings to it new functional properties for different applications. Chitosans are recognized as versatile biomaterials because of their non-toxicity, low allergenicity, biocompatibility and biodegradability. This review presents the recent research, trends and prospects in chitosan. Some special pharmaceutical and biomedical applications are also highlighted.

Antiviral activities of whey proteins.

Milk contains an array of proteins with useful bioactivities. Many milk proteins encompassing native or chemically modified casein, lactoferrin, alpha-lactalbumin, and beta-lactoglobulin demonstrated antiviral activities. Casein and alpha-lactalbumin gained anti-HIV activity after modification with 3-hydroxyphthalic anhydride. Many milk proteins inhibited HIV reverse transcriptase. Bovine glycolactin, angiogenin-1, lactogenin, casein, alpha-lactalbumin, beta-lactoglobulin, bovine lactoferrampin, and human lactoferrampin inhibited HIV-1 protease and integrase. Several mammalian lactoferrins prevented hepatitis C infection. Lactoferrin, methylated alpha-lactalbumin and methylated beta-lactoglobulin inhibited human cytomegalovirus. Chemically modified alpha-lactalbumin, beta-lactoglobulin and lysozyme, lactoferrin and lactoferricin, methylated alpha-lactalbumin, methylated and ethylated beta-lactoglobulins inhibited HSV. Chemically modified bovine beta-lactoglobulin had antihuman papillomavirus activity. Beta-lactoglobulin, lactoferrin, esterified beta-lactoglobulin, and esterified lactoferrindisplayed anti-avian influenza A (H5N1) activity. Lactoferrin inhibited respiratory syncytial virus, hepatitis B virus, adenovirus, poliovirus, hantavirus, sindbis virus, semliki forest virus, echovirus, and enterovirus. Milk mucin, apolactoferrin, Fe(3+)-lactoferrin, beta-lactoglobulin, human lactadherin, bovine IgG, and bovine kappa-casein demonstrated antihuman rotavirus activity.

Marine Peptides: Bioactivities and Applications.

Peptides are important bioactive natural products which are present in many marine species. These marine peptides have high potential nutraceutical and medicinal values because of their broad spectra of bioactivities. Their antimicrobial, antiviral, antitumor, antioxidative, cardioprotective (antihypertensive, antiatherosclerotic and anticoagulant), immunomodulatory, analgesic, anxiolytic anti-diabetic, appetite suppressing and neuroprotective activities have attracted the attention of the pharmaceutical industry, which attempts to design them for use in the treatment or prevention of various diseases. Some marine peptides or their derivatives have high commercial values and had reached the pharmaceutical and nutraceutical markets. A large number of them are already in different phases of the clinical and preclinical pipeline. This review highlights the recent research in marine peptides and the trends and prospects for the future, with special emphasis on nutraceutical and pharmaceutical development into marketed products.

A review of fish lectins.

Lectins have been reported from various tissues of a diversity of fish species including Japanese eel, conger eel, electric eel, bighead carp, gibel carp, grass carp, Arabian Gulf catfish, channel catfish, blue catfish, catfish, pike perch, perch, powan, zebrafish, toxic moray, cobia fish, steelhead trout, Japanese trout, Atlantic salmon, chinook salmon, olive rainbow smelt, rainbow smelt, white-spotted charr, tilapia, blue gourami, ayu, Potca fish, Spanish mackerel, gilt head bream, tench, roach, rudd, common skate, and sea lamprey. The tissues from which the lectins were isolated comprise gills, eggs, electric organ, stomach, intestine, and liver. Lectins have also been isolated from skin, mucus serum, and plasma. The lectins differ in molecular weight, number of subunits, glycosylation, sugar binding specificity and amino acid sequence. Their activities include antimicrobial, antitumor, immunoregulatory and a role in development.

Antibacterial products of marine organisms.

Marine organisms comprising microbes, plants, invertebrates, and vertebrates elaborate an impressive array of structurally diverse antimicrobial products ranging from small cyclic compounds to macromolecules such as proteins. Some of these biomolecules originate directly from marine animals while others arise from microbes associated with the animals. It is noteworthy that some of the biomolecules referred to above are structurally unique while others belong to known classes of compounds, peptides, and proteins. Some of the antibacterial agents are more active against Gram-positive bacteria while others have higher effectiveness on Gram-negative bacteria. Some are efficacious against both Gram-positive and Gram-negative bacteria and against drug-resistant strains as well. The mechanism of antibacterial action of a large number of the chemically identified antibacterial agents, possible synergism with currently used antibiotics, and the issue of possible toxicity on mammalian cells and tissues await elucidation. The structural characteristics pivotal to antibacterial activity have been ascertained in only a few studies. Demonstration of efficacy of the antibacterial agents in animal models of bacterial infection is highly desirable. Structural characterization of the active principles present in aqueous and organic extracts of marine organisms with reportedly antibacterial activity would be desirable.