Design,Synthesis and Enzymatic Inhibition of Novel Unusual Amino Acids as a Transition State Analogue of Amyloid Precursor Protein Peptide

International Journal of Peptide Research and Therapeutics - β-secretase 1 (BACE1) plays a pivotal role in the pathology of Alzheimer?s disease via accumulation beta amyloid in the...     

The interaction of high and low-risk human papillomavirus genotypes increases the risk of developing genital warts: A population-based cohort study

Cervical cancer is among the most common type of cancers in women and is associated with human papillomavirus (HPV) infection. Genital warts are also reported to be linked with HPV infection types 11 and 6. In turn, clinical characteristics and morphological features of warts may be useful in the prediction of prognosis and in making treatment decisions. Thus, we have investigated the association of high and low-risk HPVs genotype with genital wart risk, as well as pathological and cytological information in cases recruited from a population-based cohort study of 1380 patients. Patients infected with HPV genotype 6 or 11 had an increased risk of having warts, with OR of 2.34 (95% CI: 0.955-5.737, P = 0.06). Also, this association was enhanced in the presence of high plus low-risk HPV for having genital wart (OR: 2.814; 95%: 1.208-6.55, P = 0.017) and cases having high-risk HPV (OR: 2.329; 95% CI: 1.029-5.269, P = 0.042). Moreover, we observed patients with genital warts having CIN2/3, indicating the importance of informing the physician to the patient to prevent more severe lesions. Our data demonstrated that patients with both low/high-risk HPV types had an increased risk of developing genital warts and persistent infection with HPV was a necessary precursor for the increase in cervical lesions.     

Evaluation of the two polymorphisms rs1801133 in MTHFR and rs10811661 in CDKN2A/B in breast cancer

The 5,10-Methylenetetrahydrofolate reductase (MTHFR) was the rate-limiting enzyme in the methyl cycle, which was encoded by the MTHFR gene. MTHFR played a key role in homocysteine plasma level and was associated with the risk of breast cancer. The cyclin-dependent kinase (CDK) inhibitor (CDKN2A/B) was the tumor suppressor in the cell cycle regulation. The single-nucleotide polymorphism was thought to be associated with the predisposition of breast cancer and in subsequent immune response in different populations. The current study was conducted on a peripheral blood sample of 100 Iranian women with breast carcinoma and 142 cancer-free healthy female volunteers. The TaqMan real-time polymerase chain reaction technique was applied for genotyping of participants. The correlation of both variants and demographic data were investigated with the risk of breast cancer. Our data showed that the MTHFR allele T and TT genotype had the higher prevalence in patients (P < 0.0001) than the control group. The frequency of risk C allele into the CDKN2A/B rs10811661 was 72%. The correlations of menarche and underlying hormonal disorder with the risk of breast cancer were investigated; also our results showed that the menopause status was statistically significant between patients and controls (P = 0.036). Our investigations demonstrated that the MTHFR rs180113 and CDKN2A/B rs10811661 had a significant correlation with the elevated risk of breast cancer and they might be potentially valuable to apply as a prognostic factor for individual health care.     

Vaccines for colorectal cancer: an update

Colorectal cancer (CRC) is known as the third most common and fourth leading cancer associated death worldwide. The occurrence of metastasis has remained as a critical challenge in CRC, so that distant metastasis (mostly to the liver) has been manifested in about 20%-25% of patients. Several screening approaches have introduced for detecting CRC in different stages particularly in early stages. The standard treatments for CRC are surgery, chemotherapy and radiotherapy, in alone or combination. Immunotherapy is a set of novel approaches with the aim of remodeling the immune system battle with metastatic cancer cells, such as immunomodulatory monoclonal antibodies (immune checkpoint inhibitors), adoptive cell transfer (ACT) and cancer vaccine. Cancer vaccines are designed to trigger the intense response of immune system to tumor-specific antigens. In two last decades, introduction of new cancer vaccines and designing several clinical trials with vaccine therapy, have been taken into consideration in colon cancer patients. This review will describe the treatment approaches with the special attention to vaccines applied to treat colorectal cancer.     

Effects of Aluminum on the Growth of Tea Plant and Activation of Antioxidant System

The origin and distribution of carbonic anhydrase (CA), which could accelerate karst processes, are explored in this paper. The soil samples used in the study were collected from four different kinds of karst ecosystems of Southwest China. The results indicate that CA activity could be detected in surface layer soils, and that CA activity varied obviously among the soils in different karst ecosystems. Of the four kinds of karst site, the mean CA activity of the surface soil in Misuga, Liupanshui, which had the lowest vegetation cover, was the lowest with 0.02 U g ^–1 dry soil. Nongla and Jinfu mountain, where there is abundant vegetable species diversity and dense vegetation, had higher mean CA activity in the surface soil with 3.83 U g ^–1 dry soil and 3.13 U g ^–1 dry soil, respectively. Moreover, there was certain difference in CA activities of soils among different kinds of karst landscape in the same kind of karst ecosystem. On the other hand, the higher CA activity could be detected in the soils in the vicinity of the plant roots, and CA activity in soil exhibited both obvious seasonal and vertical changes. These facts implied that plant roots and soil microorganisms might serve as important sources of CA. Besides, the results indicate that CA activity is found in bacteria, actinomycetes and fungi. Actinomycetes had higher intracellular CA activity, while fungi had higher extracellular CA activity. This study shows that higher microbial CA activities are found in Jinfu Mountain, while lower microbial CA activities are found in Misuga, Liupanshui.     

<Emphasis Type="Bold">Role of microRNAs and their target genes in salinity response in plant</Emphasis>s

We examined the effects of 2,4-epibrassinolide (EBR) application on photosynthesis, antioxidant enzyme activity, and Rubisco activase (RCA) gene expression in wheat (Triticum aestivum L.) seedlings under a combination of drought and heat stress. The net photosynthetic rates (P_n) of wheat seedlings decreased significantly, the photosynthetic capability was inhibited, and the activities of superoxide (SOD), peroxidase (POD), catalase (CAT), and RCA as well as the initial and total activity of Rubisco declined under the combined stress. These decreases and inhibitory effects were significantly ameliorated by exogenous EBR application. Three subunits (45–46, 41–42, and 38–39 kDa) of RCA were observed in wheat seedlings. The abundances of the 38–39 kDa and 41–42 kDa subunits were significantly lower in plants subjected to stressful conditions than in unstressed plants. Interestingly, a marked increase in 45–46 kDa RCA was observed under heat or heat combined with drought stress. The abundance of 38–39 kDa RCA in seedlings exposed to heat, drought, or their combination was significantly enhanced by EBR pretreatment, which paralleled the changes in initial Rubisco activity and P_n, but was not consistent with observed mRNA abundance. These results indicated that the larger subunit of RCA (45–46 kDa), which is more thermostable and increased in response to moderate heat stress, and the smaller isoform (38–39 kDa) of RCA may play important roles in maintaining the photosynthetic capability by EBR under stress conditions.     

Inhibitor of PI3K/Akt Signaling Pathway Small Molecule Promotes Motor Neuron Differentiation of Human Endometrial Stem Cells Cultured on Electrospun Biocomposite Polycaprolactone/Collagen Scaffolds

Small molecules as useful chemical tools can affect cell differentiation and even change cell fate. It is demonstrated that LY294002, a small molecule inhibitor of phosphatidylinositol 3-kinase (PI3K)/Akt signal pathway, can inhibit proliferation and promote neuronal differentiation of mesenchymal stem cells (MSCs). The purpose of this study was to investigate the differentiation effect of Ly294002 small molecule on the human endometrial stem cells (hEnSCs) into motor neuron-like cells on polycaprolactone (PCL)/collagen scaffolds. hEnSCs were cultured in a neurogenic inductive medium containing 1 μM LY294002 on the surface of PCL/collagen electrospun fibrous scaffolds. Cell attachment and viability of cells on scaffolds were characterized by scanning electron microscope (SEM) and 3-(4,5-dimethylthiazoyl-2-yl)2,5-diphenyltetrazolium bromide (MTT) assay. The expression of neuron-specific markers was assayed by real-time PCR and immunocytochemistry analysis after 15 days post induction. Results showed that attachment and differentiation of hEnSCs into motor neuron-like cells on the scaffolds with Ly294002 small molecule were higher than that of the cells on tissue culture plates as control group. In conclusion, PCL/collagen electrospun scaffolds with Ly294002 have potential for being used in neural tissue engineering because of its bioactive and three-dimensional structure which enhances viability and differentiation of hEnSCs into neurons through inhibition of the PI3K/Akt pathway. Thus, manipulation of this pathway by small molecules can enhance neural differentiation.