Temperature and pH-responsive nano-hydrogel drug delivery system based on lysine-modified poly (vinylcaprolactam).

BACKGROUND: Smart materials capable of responding to external stimuli are noteworthy candidates in designing drug delivery systems. In many of the recent research, temperature and pH have been recognized as the main stimulating factors in designing systems for anti-cancer drugs delivery systems. PURPOSE: In this study, thermo and pH-responsive character of a nano-carrier drug delivery platform based on lysine modified poly (vinylcaprolactam) hydrogel conjugated with doxorubicin was assessed. METHODS: Poly (vinylcaprolactam) cross-linked with poly (ethyleneglycol) diacrylate was prepared via RAFT polymerization, and the prepared structure was linked with lysine through ring-opening. The anti-cancer drug doxorubicin, was linked to lysine moiety of the prepared structure via Schiff-base reaction. The prepared platform was characterized by 1HNMR and FT-IR, while molecular weight characterization was performed by size exclusion chromatography. The temperature-responsive activity was evaluated using differential scanning calorimetry and dynamic light scattering. In vitro release pattern in simulated physiologic pH at 37°C was compared with acidic pH attributed to tumor site and elevated temperature. The anticancer efficiency of the drug-conjugated structure was evaluated in breast cancer cell line MCF-7 in 24 and 48 h, and cell uptake assay was performed on the same cell line. CONCLUSION: According to the results, well-structure defined smart pH and temperature responsive nano-hydrogel was prepared. The enhanced release rates are observed at acidic pH and elevated temperature. We have concluded that the doxorubicin-conjugated nanoparticle results in higher cellular uptakes and more cytotoxicity

Ancient Migratory Events in the Middle East: New Clues from the Y-Chromosome Variation of Modern Iranians

Knowledge of high resolution Y-chromosome haplogroup diversification within Iran provides important geographic context regarding the spread and compartmentalization of male lineages in the Middle East and southwestern Asia. At present, the Iranian population is characterized by an extraordinary mix of different ethnic groups speaking a variety of Indo-Iranian, Semitic and Turkic languages. Despite these features, only few studies have investigated the multiethnic components of the Iranian gene pool. In this survey 938 Iranian male DNAs belonging to 15 ethnic groups from 14 Iranian provinces were analyzed for 84 Y-chromosome biallelic markers and 10 STRs. The results show an autochthonous but non-homogeneous ancient background mainly composed by J2a sub-clades with different external contributions. The phylogeography of the main haplogroups allowed identifying post-glacial and Neolithic expansions toward western Eurasia but also recent movements towards the Iranian region from western Eurasia (R1b-L23), Central Asia (Q-M25), Asia Minor (J2a-M92) and southern Mesopotamia (J1-Page08). In spite of the presence of important geographic barriers (Zagros and Alborz mountain ranges, and the Dasht-e Kavir and Dash-e Lut deserts) which may have limited gene flow, AMOVA analysis revealed that language, in addition to geography, has played an important role in shaping the nowadays Iranian gene pool. Overall, this study provides a portrait of the Y-chromosomal variation in Iran, useful for depicting a more comprehensive history of the peoples of this area as well as for reconstructing ancient migration routes. In addition, our results evidence the important role of the Iranian plateau as source and recipient of gene flow between culturally and genetically distinct population

KIR gene content diversity in four Iranian populations

Killer cell immunoglobulin-like receptors (KIR) regulate natural killer cell response against infection and malignancy. KIR genes are variable in the number and type, thereby discriminating individuals and populations. Herein, we analyzed the KIR gene content diversity in four native populations of Iran. The KIR genomic diversity was comparable between Bakhtiari and Persian and displayed a balance of A and B KIR haplotypes, a trend reported in Caucasian and African populations. The KIR gene content profiles of Arab and Azeri were comparable and displayed a preponderance of B haplotypes, a scenario reported in the natives of America, India, and Australia. A majority of the B haplotype carriers of Azeri and Arab had a centromeric gene-cluster (KIR2DS2-2DL2-2DS3-2DL5). Remarkably, this cluster was totally absent from the American natives but occurred at highest frequencies in the natives of India and Australia in combination with another gene cluster at the telomeric region (KIR3DS1-2DL5-2DS5-2DS1). Therefore, despite having similar frequencies of B haplotypes, the occurrence of B haplotype-specific KIR genes, such as 2DL2, 2DL5, 3DS1, 2DS1, 2DS2, 2DS3, and 2DS5 in Azeri and Arab were substantially different from the natives of America, India, and Australia. In conclusion, each Iranian population exhibits distinct KIR gene content diversity, and the Indo-European KIR genetic signatures of the Iranians concur with geographic proximity, linguistic affinity, and human migrations

Nanopharmaceuticals and nanomedicines currently on the market: Challenges and opportunities

There has been a revolution in nanotechnology and nanomedicine. Since 1980, there has been a remarkable increase in approved nano-based pharmaceutical products. These novel nano-based systems can either be therapeutic agents themselves, or else act as vehicles to carry different active pharmaceutical agents into specific parts of the body. Currently marketed nanostructures include nanocrystals, liposomes and lipid nanoparticles, PEGylated polymeric nanodrugs, other polymers, protein-based nanoparticles and metal-based nanoparticles. A range of issues must be addressed in the development of these nanostructures. Ethics, market size, possibility of market failure, costs and commercial development, are some topics which are on the table to be discussed. After passing all the ethical and biological assessments, and satisfying the investors as to future profitability, only a handful of these nanoformulations, successfully obtained marketing approval. We survey the range of nanomedicines that have received regulatory approval and are marketed. We discuss ethics, costs, commercial development and possible market failure. We estimate the global nanomedicine market size and future growth. Our goal is to summarize the different approved nanoformulations on the market, and briefly cover the challenges and future outlook. © 2019 2018 Future Medicine Ltd

An evolutionary approach to the medical implications of the tumor necrosis factor receptor superfamily member 13B (TNFRSF13B) gene.

Coding variants in tumor necrosis factor receptor superfamily member 13B (TNFRSF13B) have been implicated in common variable immunodeficiency (CVID), but the functional effects of such mutations in relation to the development of the disease have not been entirely established. To examine the potential contribution of TNFRSF13B variants to CVID, we have applied an evolutionary approach by sequencing its coding region in 451 individuals belonging to 26 worldwide populations, in addition to controls, patients with CVID and selective IgA deficiency (IgAD) from Italy. The low level of geographical structure for the observed genetic diversity and the several neutrality tests performed confirm the absence of recent population-specific selective pressures, suggesting that TNFRSF13B may be involved also in innate immune functions, rather than in adaptive immunity only. A slight excess of rare derived alleles was found in patients with CVID, and thus some of these variants may contribute to the disease, implying that CVID probably fits the rare variants rather than the common disease/common variant paradigm. This also confirms the previous suggestion that TNFRSF13B defects alone do not cause CVID and that such an extremely heterogeneous immunodeficiency might be more likely related to additional, still unknown environmental and genetic factors

An evolutionary approach to the medical implications of the tumor necrosis factor receptor superfamily member 13B (TNFRSF13B) geneTNFRSF13B evolution and CVID

13 páginas.-- et al.Coding variants in tumor necrosis factor receptor superfamily member 13B (TNFRSF13B) have been implicated in common variable immunodeficiency (CVID), but the functional effects of such mutations in relation to the development of the disease have not been entirely established. To examine the potential contribution of TNFRSF13B variants to CVID, we have applied an evolutionary approach by sequencing its coding region in 451 individuals belonging to 26 worldwide populations, in addition to controls, patients with CVID and selective IgA deficiency (IgAD) from Italy. The low level of geographical structure for the observed genetic diversity and the several neutrality tests performed confirm the absence of recent population-specific selective pressures, suggesting that TNFRSF13B may be involved also in innate immune functions, rather than in adaptive immunity only. A slight excess of rare derived alleles was found in patients with CVID, and thus some of these variants may contribute to the disease, implying that CVID probably fits the rare variants rather than the common disease/common variant paradigm. This also confirms the previous suggestion that TNFRSF13B defects alone do not cause CVID and that such an extremely heterogeneous immunodeficiency might be more likely related to additional, still unknown environmental and genetic factors.Peer reviewe

Bacterial components as naturally inspired nano-carriers for drug/gene delivery and immunization: Set the bugs to work?

Drug delivery is a rapidly growing area of research motivated by the nanotechnology revolution, the ideal of personalized medicine, and the desire to reduce the side effects of toxic anti-cancer drugs. Amongst a bewildering array of different nanostructures and nanocarriers, those examples that are fundamentally bio-inspired and derived from natural sources are particularly preferred. Delivery of vaccines is also an active area of research in this field. Bacterial cells and their components that have been used for drug delivery, include the crystalline cell-surface layer known as �S-layer� bacterial ghosts, bacterial outer membrane vesicles, and bacterial products or derivatives (e.g. spores, polymers, and magnetic nanoparticles). Considering the origin of these components from potentially pathogenic microorganisms, it is not surprising that they have been applied for vaccines and immunization. The present review critically summarizes their applications focusing on their advantages for delivery of drugs, genes, and vaccines. © 2018 Elsevier Inc