抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Statistical method for testing the neutral mutation hypothesis by DNA polymorphism.

Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction

Gold nanoparticles (GNPs) with controlled geometrical, optical, and surface chemical properties are the subject of intensive studies and applications in biology and medicine. To date, the ever increasing diversity of published examples has included genomics and biosensorics, immunoassays and clinical chemistry, photothermolysis of cancer cells and tumors, targeted delivery of drugs and antigens, and optical bioimaging of cells and tissues with state-of-the-art nanophotonic detection systems. This critical review is focused on the application of GNP conjugates to biomedical diagnostics and analytics, photothermal and photodynamic therapies, and delivery of target molecules. Distinct from other published reviews, we present a summary of the immunological properties of GNPs. For each of the above topics, the basic principles, recent advances, and current challenges are discussed (508 references).

Gold nanoparticles in biomedical applications: recent advances and perspectives

The immune system has evolved to protect the host from a universe of pathogenic microbes that are themselves constantly evolving. The immune system also helps the host eliminate toxic or allergenic substances that enter through mucosal surfaces. Central to the immune system's ability to mobilize a response to an invading pathogen, toxin, or allergen is its ability to distinguish self from nonself. The host uses both innate and adaptive mechanisms to detect and eliminate pathogenic microbes, and both of these mechanisms include self-nonself discrimination. This overview identifies key mechanisms used by the immune system to respond to invading microbes and other exogenous threats and identifies settings in which disturbed immune function exacerbates tissue injury.

/pdf/overview-of-the-immune-response-2is735zjhy.pdf

Overview of the Immune Response

Herbal drug technology is used for converting botanical materials into medicines, where standardization and quality control with proper integration of modern scientific techniques and traditional knowledge is important. The use of chromatographic techniques and marker compounds to standardize botanical preparations has limitations because of their variable sources and chemical complexity. DNA-based molecular markers have utility in the fields like taxonomy, physiology, embryology, genetics, etc. DNA-based techniques have been widely used for authentication of plant species of medicinal importance. Pharmacognosy mainly addresses quality-related issues using routine botanical and organoleptic parameters of crude drugs, and chemoprofiling-assisted characterization with chromatographic and spectroscopic techniques. The new pharmacognosy includes all the aspects of drug development and discovery, where biotechnology-driven applications play an important role. Current focus on chemotype-driven fingerprinting and related techniques requires integration with genotype-driven molecular techniques so that an optimal characterization of botanical materials is possible. This review provides a brief account of various DNA-based technologies that are useful in genotyping and quick identification of botanicals with suitable examples.

Molecular markers in herbal drug technology

Nanomaterials have gained tremendous importance in biology and medicine because they can be used as carriers for delivering small molecules such as drugs, proteins, and genes. We report herein the binding of the hormone insulin to gold nanoparticles and its application in transmucosal delivery for the therapeutic treatment of diabetes mellitus. Insulin was loaded onto bare gold nanoparticles and aspartic acid-capped gold nanoparticles and delivered in diabetic Wistar rats by both oral and intranasal (transmucosal) routes. Our principle observations are that there is a significant reduction of blood glucose levels (postprandial hyperglycemia) when insulin is delivered using gold nanoparticles as carriers by the transmucosal route in diabetic rats. Furthermore, control of postprandial hyperglycemia by the intranasal delivery protocol is comparable to that achieved using the standard subcutaneous administration used for type I diabetes mellitus, thus showing considerable promise for further development.

Gold nanoparticles as carriers for efficient transmucosal insulin delivery.

Cyclin-dependent kinases (Cdk) and their associated pathways represent some of the most attractive targets for the development of anticancer therapeutics. Based on antitumor activity in animal models, a variety of Cdk inhibitors are undergoing clinical evaluation either as a single agent or in combination with other approved drugs. In our anticancer drug discovery program, a novel series of flavones have been synthesized for evaluation against the activity of Cdk4-D1. This enzyme catalyzes the phosphorylation of retinoblastoma protein, thus inhibiting its function. We have identified a series of potent Cdk4-D1 inhibitors with IC(50) below 250 nmol/L. In this report, we have described the properties of one of the best compound, P276-00 of the flavone's series. P276-00 shows 40-fold selectivity toward Cdk4-D1, compared with Cdk2-E. The specificity toward 14 other related and unrelated kinases was also determined. P276-00 was found to be more selective with IC(50)s <100 nmol/L for Cdk4-D1, Cdk1-B, and Cdk9-T1, as compared with other Cdks, and less selective for non-Cdk kinases. It showed potent antiproliferative effects against various human cancer cell lines, with an IC(50) ranging from 300 to 800 nmol/L and was further compared for its antiproliferative activity against cancer and normal fibroblast cell lines. P276-00 was found to be highly selective for cancer cells as compared with normal fibroblast cells. To delineate its mechanism of action, the effect of P276-00 on cell cycle proteins was studied in human breast cancer cell line (MCF-7) and human non-small cell lung carcinoma (H-460). A significant down-regulation of cyclin D1 and Cdk4 and a decrease in Cdk4-specific pRb Ser(780) phosphorylation was observed. P276-00 produced potent inhibition of Cdk4-D1 activity that was found to be competitive with ATP and not with retinoblastoma protein. The compound also induced apoptosis in human promyelocytic leukemia (HL-60) cells, as evidenced by the induction of caspase-3 and DNA ladder studies. These data suggest that P276-00 has the potential to be developed as an anti-Cdk chemotherapeutic agent.

https://mct.aacrjournals.org/content/molcanther/6/3/918.full.pdf

In vitro antitumor properties of a novel cyclin-dependent kinase inhibitor, P276-00.

Considerable clinical and experimental evidence now supports the idea that deficiencies or imbalances in certain highly unsaturated fatty acids may contribute to a range of common developmental disorders including Attention Deficit Hyperactivity Disorder (ADHD) Few intervention studies with LCPUFA supplementation have reported inconsistent and marginal results This pilot study evaluates the effect of alpha linolenic acid (ALA)-rich nutritional supplementation in the form of flax oil and antioxidant emulsion on blood fatty acids composition and behavior in children with ADHD Post-supplementation levels of RBC membrane fatty acids were significantly higher than pretreatment levels as well as the levels in control There was significant improvement in the symptoms of ADHD reflected by reduction in total hyperactivity scores of ADHD children derived from ADHD rating scale

Supplementation with flax oil and vitamin C improves the outcome of Attention Deficit Hyperactivity Disorder (ADHD)

Traditional Indian medicine—Ayurveda—classifies the human population into three major constituents or Prakriti known as Vata, Pitta and Kapha types. Earlier, we have demonstrated a proof of concept to support genetic basis for Prakriti. The descriptions in Ayurveda indicate that individuals with Pitta Prakriti are fast metabolizers while those of Kapha Prakriti are slow metabolizers. We hypothesized that different Prakriti may have different drug metabolism rates associated with drug metabolizing enzyme (DME) polymorphism. We did CYP2C19 (Phase I DME) genotyping in 132 unrelated healthy subjects of either sex by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. We observed significant association between CYP2C19 genotype and major classes of Prakriti types. The extensive metabolizer (EM) genotype (*1/*1, *1/*2, *1/*3) was found to be predominant in Pitta Prakriti (91%). Genotype (*1/*3) specific for EM group was present only in Pitta Prakriti. Poor metabolizer (PM) genotype (*2/*2, *2/*3, *3/*3) was highest (31%) in Kapha Prakriti when compared with Vata (12%) and Pitta Prakriti (9%). Genotype (*2/*3) which is typical for PM group was significant in Kapha Prakriti (odds ratio = 3.5, P =  .008). We observed interesting correlations between CYP2C19 genotypes and Prakriti with fast and slow metabolism being one of the major distinguishing and differentiating characteristics. These observations are likely to have significant impact on phenotype-genotype correlation, drug discovery, pharmacogenomics and personalized medicine.

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Kalpana Joshi

Papers

Molecular markers in herbal drug technology

Gold nanoparticles as carriers for efficient transmucosal insulin delivery.

In vitro antitumor properties of a novel cyclin-dependent kinase inhibitor, P276-00.

Supplementation with flax oil and vitamin C improves the outcome of Attention Deficit Hyperactivity Disorder (ADHD)

Traditional Medicine to Modern Pharmacogenomics: Ayurveda Prakriti Type and CYP2C19 Gene Polymorphism Associated with the Metabolic Variability