Alzheimer Disease: Clues from traditional and complementary medicine.

Despite modern medicine's incredible innovation and resulting accumulation of valuable knowledge, many of the world's most problematic diseases such as Alzheimer Disease (AD) still lack effective cures and treatments. Western medicine has revealed many genetic, cellular, and molecular processes that characterize AD such as protein aggregation and inflammation. As the need for novel and effective treatments increases, researchers have turned towards traditional medicine as a resource. Modern, evidence based research examining traditional and complementary remedies for AD has generated promising results within the last decade. Animal based products inhibiting cellular toxicity, anti-inflammatory nutraceuticals such as omega-3 fatty acids, and plant based compounds derived from herbal medicine demonstrate viability as neuroprotective treatments and possible application in developing pharmaceuticals. Analysis of antioxidant, anti-inflammatory, and neuroprotective phytochemicals used in various traditional medicines around the world reveal potential to ameliorate and prevent the devastating neurodegeneration observed in AD.

Understanding nutrition and immunity in disease management.

As we search for answers to modern medicine's most prevalent and challenging problems, the relationship between nutrition, immunity, and biological function of various natural compounds are preimminent. Nutritional research involving genomics provides rational capabilities for preventing disease. Scientific advances in genomic sequencing reveal opportunities for exploring diet-health relationships and potential for individual, genotype based dietary recommendations. Utilizing molecular and genetic technology to analyze impact of nutrition on genomics and metabolism reveals that nutrients may influence certain innate and/or acquired immune functions. By analyzing immune mechanisms including their cells and complex molecules, animal models have offered relevant insight that clarifies interrelations between immunity and nutrition. Plant products also provide numerous resources through bioengineering for designing novel pharmaceuticals. Having long been employed successfully in traditional and folk medicines, plant compounds exhibit anti-inflammatory, antimicrobial, and angiogenic activity. As a result, we now have a promising arsenal for successful application of bioactive compounds.

Transient Expression of Lumbrokinase (PI239) in Tobacco (Nicotiana tabacum) Using a Geminivirus-Based Single Replicon System Dissolves Fibrin and Blood Clots.

Lumbrokinases, a group of fibrinolytic enzymes extracted from earthworm, have been widely used to prevent and treat various cardiovascular diseases. They specifically target fibrin to effectively degrade thrombi without major side effects. Plant expression systems are becoming potential alternative expression platforms for producing pharmaceutical proteins. In this work, a lumbrokinase (PI239) was produced from a plant system. Both wild-type (WT) and plant codon-optimized (OP) PI239 gene sequences were synthesized and cloned into a geminivirus-based single-vector DNA replicon system. Both vectors were independently expressed in tobacco (Nicotiana tabacum) leaves transiently by agroinfiltration. Overexpressed PI239 resulted in sudden tissue necrosis 3 days after infiltration. Remaining proteins were purified through His-tag affinity chromatography and analyzed with SDS-PAGE and Western blot methods. Purified PI239 successfully degraded artificial fibrin with relative activity of 13,400 U/mg when compared with commercial lumbrokinase product. In vitro tests demonstrated that plant-derived PI239 dissolved human blood clots and that the plant expression system is capable of producing functional PI239.

Exploiting leech saliva to treat osteoarthritis: A provocative perspective.

Plant and animal-derived products are crucial components in complementary and alternative medicine. Although modern medicine has provided numerous innovations and advancements, these often fail to reveal new and dependable, inexpensive treatments nor real cures that are relatively free of adverse side effects. We present evidence that hirudotherapy, which utilizes leeches, improves certain diseases, including osteoarthritis. Osteoarthritis, a disease in joints, could benefit from use of medicinal peptides found in leech saliva, components of its immune system.

Right Median Nerve Electrical Stimulation for Acute Traumatic Coma Patients.

The right median nerve as a peripheral portal to the central nervous system can be electrically stimulated to help coma arousal after traumatic brain injury (TBI). The present study set out to examine the efficacy and safety of right median nerve electrical stimulation (RMNS) in a cohort of 437 comatose patients after severe TBI from August 2005 to December 2011. The patients were enrolled 2 weeks after their injury and assigned to the RMNS group (n=221) receiving electrical stimulation for 2 weeks or the control group (n = 216) treated by standard management according to the date of birth in the month. The baseline data were similar. After the 2-week treatment, the RMNS-treated patients demonstrated a more rapid increase of the mean Glasgow Coma Score, although statistical significance was not reached (8.43 ± 4.98 vs. 7.47 ± 5.37, p = 0.0532). The follow-up data at 6-month post-injury showed a significantly higher proportion of patients who regained consciousness (59.8% vs. 46.2%, p = 0.0073). There was a lower proportion of vegetative persons in the RMNS group than in the control group (17.6% vs. 22.0%, p = 0.0012). For persons regaining consciousness, the functional independence measurement (FIM) score was higher among the RMNS group patients (91.45 ± 8.65 vs. 76.23 ± 11.02, p < 0.001). There were no unique complications associated with the RMNS treatment. The current study, although with some limitations, showed that RMNS may serve as an easy, effective, and noninvasive technique to promote the recovery of traumatic coma in the early phase.

Corals and their potential applications to integrative medicine.

Over the last few years, we have pursued the use and exploitation of invertebrate immune systems, most notably their humoral products, to determine what effects their complex molecules might exert on humans, specifically their potential for therapeutic applications. This endeavor, called "bioprospecting," is an emerging necessity for biomedical research. In order to treat the currently "untreatable," or to discover more efficient treatment modalities, all options and potential sources must be exhausted so that we can provide the best care to patients, that is, proceed from forest and ocean ecosystems through the laboratory to the bedside. Here, we review current research findings that have yielded therapeutic benefits, particularly as derived from soft and hard corals. Several applications have already been demonstrated, including anti-inflammatory properties, anticancer properties, bone repair, and neurological benefits.

Diversity, evolution, and therapeutic applications of small RNAs in prokaryotic and eukaryotic immune systems.

Recent evidence supports that prokaryotes exhibit adaptive immunity in the form of CRISPR (Clustered Regularly Interspersed Short Palindromic Repeats) and Cas (CRISPR associated proteins). The CRISPR-Cas system confers resistance to exogenous genetic elements such as phages and plasmids by allowing for the recognition and silencing of these genetic elements. Moreover, CRISPR-Cas serves as a memory of past exposures. This suggests that the evolution of the immune system has counterparts among the prokaryotes, not exclusively among eukaryotes. Mathematical models have been proposed which simulate the evolutionary patterns of CRISPR, however large gaps in our understanding of CRISPR-Cas function and evolution still exist. The CRISPR-Cas system is analogous to small RNAs involved in resistance mechanisms throughout the tree of life, and a deeper understanding of the evolution of small RNA pathways is necessary before the relationship between these convergent systems is to be determined. Presented in this review are novel RNAi therapies based on CRISPR-Cas analogs and the potential for future therapies based on CRISPR-Cas system components.

A short note on how tied fights affect cortisol levels.

Previous work exploring the interrelationships between sex steroids (e.g. androgens, testosterones and 11-ketotestosterones) and social behavior in teleosts suggest that mirror-elicited aggression in cichlid fish may not trigger a hormonal response. Using the Mozambique tilapia (Oreochromis mossambicus) to analyze immune responses as a result of social stress, we measured levels of cortisol and melatonin using Enzyme-Linked Immunosorbent Assay (ELISA) assays. In this work, we demonstrated that cortisol concentrations are significantly lower yet the levels of melatonin remain unchanged in tilapia that are fighting their mirror image. Our results suggested that in tied fights, certain hormone levels remain unchanged (e.g. androgens) due to the lack of melatonin induction.

Timing of surgery after long-course neoadjuvant chemoradiotherapy for rectal cancer: a systematic review of the literature.

BACKGROUND: Neoadjuvant long-course chemoradiotherapy is commonly used to improve the local control and resectability of locally advanced rectal cancer, with surgery performed after an interval of a number of weeks. OBJECTIVE: We report an evidence-based systematic review of published data supporting the optimal time to perform surgical resection after long-course neoadjuvant therapy. DATA SOURCES: A systematic literature search was undertaken of the MEDLINE and Embase electronic databases from 1995 to 2012. STUDY SELECTION: English language articles were included that compared outcomes following rectal cancer surgery performed at different times after a long course of neoadjuvant radiation-based therapy. INTERVENTIONS: : Patients received a long course of neoadjuvant therapy followed by radical surgical resection after an interval period. MAIN OUTCOME MEASURES: The rates of tumor response, R0 resection, sphincter preservation, surgical complications, and disease recurrence were the primary outcomes measured. RESULTS: Fifteen studies were identified: 1 randomized controlled trial, 1 prospective nonrandomized interventional study, and 13 observational studies. Studies compared time intervals that varied between <5 days and >12 weeks, with a large degree of variation in what the standard interval length was considered to be. Four of the 7 studies that reported rates of pathological complete response identified significantly higher rates with an extended interval between chemoradiotherapy and surgery; 3 of 8 studies demonstrated increased primary tumor downstaging with a longer interval. No significant differences have been consistently demonstrated in rates of surgical complications, sphincter preservation, or long-term recurrence and survival. LIMITATIONS: Neoadjuvant regimes, indications for neoadjuvant therapy, and time intervals after chemoradiotherapy were heterogeneous between studies; consequently, meta-analysis could not be performed. CONCLUSIONS: There is limited evidence to support decisions regarding when to resect rectal cancer following chemoradiotherapy. There may be benefits in prolonging the interval between chemoradiotherapy and surgery beyond the 6 to 8 weeks that is commonly practiced. However, outcomes need to be studied further in robust randomized studies.

Three cases of an unusual pattern of invasion in malignant Brenner tumors.

Ovarian malignant Brenner tumors are rare neoplasms that are typically admixed with benign and borderline Brenner tumor elements. We report 3 cases of an unusual variant of malignant Brenner tumor where the infiltrative malignant component arose directly from a benign Brenner tumor rather than from borderline elements and did not exhibit a desmoplastic stromal response. Borderline elements were present in 1 case, but the invasive component did not arise from these. Our cases highlight that an absence of a borderline element should not dissuade the pathologist from diagnosing a malignant Brenner tumor.

Origin of innate immune responses: revelation of food and medicinal applications.

Much is known about the strong ecological impact that earthworms ( Qiu Yǐn; Pheretima) have on soil in terms of fertility, nutrient production, and tilling. Even more interesting though is the impact they have had on our understanding of innate immunity, and from this discovery, there has been a simultaneous recognition of their potential through their historical use as food and their use in treatment of certain chronic health problems that often afflict humans. This bifurcating growing knowledge base has stemmed from centuries of honing and practicing traditional and complementary forms of medicine such as Ayurveda (India) Traditional Chinese Medicine (China), Kampo (Japan), and Traditional Korean Medicine (Korea). Earthworms (Dilong) have also been credited as a model for research concerning the nervous and endocrine systems. One of the reasons behind the earthworm's tremendous impact on research into these biomedical endeavors is partly due to its lack of ethical restrictions, like those imposed on vertebrate models. Using invertebrate models as opposed to mice or other mammalian models bypasses ethical concerns. Moreover, financial constraints consistently hover over biological research that requires living subjects, preferably mammals. Earthworms are a rich source of several vital biological macromolecules and other nutrients. They have long been used as food in several cultures such as the Ye'Kuana in Venezuela, the Maori in New Zealand, and the nomadic populations in Papua New Guinea. Earthworms and their nutritious products have been shown to exert significant effects in treating humans for disorders of inflammation and blood coagulation. One area that continues to be examined is the earthworm's ability to regenerate lost appendages, and these effects have been extended to mammals. Evidence reveals that earthworm extracts may actually promote the regeneration of damaged nerves. This presentation will explore how earthworms may reveal significant advances and conclusions that decipher innate immunity. This is intimately associated with them as sources of their various nutritional and medicinal benefits.

Recombinant protein production of earthworm lumbrokinase for potential antithrombotic application.

Earthworms have been used as a traditional medicine in China, Japan, and other Far East countries for thousands of years. Oral administration of dry earthworm powder is considered as a potent and effective supplement for supporting healthy blood circulation. Lumbrokinases are a group of enzymes that were isolated and purified from different species of earthworms. These enzymes are recognized as fibrinolytic agents that can be used to treat various conditions associated with thrombosis. Many lumbrokinase (LK) genes have been cloned and characterized. Advances in genetic technology have provided the ability to produce recombinant LK and have made it feasible to purify a single lumbrokinase enzyme for potential antithrombotic application. In this review, we focus on expression systems that can be used for lumbrokinase production. In particular, the advantages of using a transgenic plant system to produce edible lumbrokinase are described.

The danger theory: 20 years later.

The self-non-self theory has dominated immunology since the 1950s. In the 1990s, Matzinger and her colleagues suggested a new, competing theory, called the "danger theory." This theory has provoked mixed acclaim: enthusiasm and criticism. Here we assess the danger theory vis-à-vis recent experimental data on innate immunity, transplantation, cancers and tolerance to foreign entities, and try to elucidate more clearly whether danger is well defined.