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Alzheimer's disease (AD) is a growing problem worldwide. Since ABCA7's identification as a risk gene, it has been extensively researched for its role in the disease. We review its recently characterized structure and what the mechanistic insights teach us about its function. We furthermore provide an overview of identified ABCA7 mutations, their presence in different ancestries and protein domains and how they might cause AD. For ABCA7 PTC variants and a VNTR expansion, haploinsufficiency is proposed as the most likely mode‐of‐action, although splice events could further influence disease risk. Overall, the need to better understand expression of canonical ABCA7 and its isoforms in disease is indicated. Finally, ABCA7's potential functions in lipid metabolism, phagocytosis, amyloid deposition, and the interplay between these three, is described. To conclude, in this review, we provide a comprehensive overview and discussion about the current knowledge on ABCA7 in AD, and what research questions remain. Highlights: Alzheimer's risk‐increasing variants in ABCA7 can be found in up to 7% of AD patients.We review the recently characterized protein structure of ABCA7.We present latest insights in genetics, expression patterns, and functions of ABCA7. [ABSTRACT FROM AUTHOR]

Saudi Arabia has an overall smoking rate of 15.9%. The link between smoking and periodontal disease has been studied extensively. It is possible for human gingival fibroblasts to accumulate nicotine intracellularly over a period of four hours. Additionally, unmetabolized nicotine is released into the environment. Tobacco presence can impair tissue inflammation, wound healing, and organ development. To counterbalance tobacco toxins, vitamin C has been added to a variety of products. This study aims to analyze the RNA expression of antioxidant, anti-inflammatory, and wound healing proteins in human gingival fibroblasts from smokers and nonsmokers using polymerase chain reaction. hGFs were extracted from clinically healthy periodontium sites of adult male subjects. Both heavy cigarette smokers and never-smokers participated as subjects. Cells were cultured and subcultured in supplemented growth medium. Vitamin C was inducted in the medium at the experimental 6th passage. RNA expression analysis (qRT-PCR) was performed to analyze adhesion, proliferation, and extracellular matrix expression. The results revealed marked expression of a wound healing gene (VEGF-A) in never-smokers (p value = 0.016). GPX3 and SOD3 represent antioxidants that are highly expressed in treated never-smoker cells. SOD2 significantly increased (p value = 0.016) in smokers after vitamin C exposure. The anti-inflammatory markers IL-6 and IL-8 were lower among smokers than among nonsmokers (p < 0.0001). Tobacco smoking suppressed gingival fibroblasts' abilities to regenerate, heal, combat inflammation, and resist free radicals. Vitamin C at cellular levels was beneficial and should be considered in the treatment component of smokers in the dental clinic. [ABSTRACT FROM AUTHOR]

Smoking and the severity of periodontal disease have long been associated. In Saudi Arabia, tobacco smoking is rising, contributing to the increased demand for products that counter its detrimental effects. The antioxidant properties of vitamin C (vit C) make it a powerful countermeasure to tobacco toxicity. Observation of these effects on human gingival fibroblasts (hGFs) would suggest use of vitamin C in future dental applications. To examine the proliferation, adhesion, and expression of extracellular RNA in human gingival fibroblasts extracted from cigarette smokers when compared to never-smokers, in association with vitamin C. Human gingival fibroblasts were extracted from Periodontal free sites of healthy adult male participants. Group 1; consisted of Heavy cigarette smokers (n = 1) while group 2 was never-smokers (n = 1). Collected cells were cultured and subcultured in supplemented growth medium. Vitamin C was then induced in the medium at the experimental sixth passage. RNA expression analysis using quantitative reverse transcriptase-polymerase chain reaction was performed to analyze the adhesion, proliferation, and extracellular matrix expression. Expression of the adhesion gene (CD44) in the smoker group was significantly downregulated than never-smoker group (p-value = 0.024). After the induction of vitamin C, the smoker samples showed a significant improvement in their gene expression levels. The extracellular genes involved in this study (COL1A1 , LAMA3 , and TGFB3) were significantly affected by the smoking status. In addition, the proliferation of MK167 and CCNB1 genes in smokers and never-smokers was increased. Cigarette smoking affects the overall properties of human gingival fibroblasts' adhesion, proliferation, and extra-cellular matrix formation. Furthermore, the addition of vitamin C affects these cellular properties in a positive manner. [ABSTRACT FROM AUTHOR]

BACKGROUND: There is emerging evidence that matrix metalloproteinase (MMP)-2 plays a crucial role in cancer invasion/metastasis. However, little evidence is available about the connections of multidrug resistance protein 1 (MDR1) and cancer invasion/metastasis so far. AIM: To investigate the expression of MDR1 and MMP2 in primary breast tumors and their corresponding metastasized lymph nodes. MATERIALS AND METHODS: Only lymph nodes which were pathologically identified as metastases were included in this study to compare with the corresponding primary tumor. We determined the expression of MDR1 and MMP2 in primary breast tumor and its metastasized lymph node specimens of 21 patients. The quantitative real-time polymerase chain reaction (Q-RT-PCR) technique was used to assess the MDR1 and MMP2 RNA expression levels in primary breast tumor and lymph nodal specimens. Target gene copies were normalized using beta-actin (beta-actin) gene copies. Tumor characteristics and number of metastatic lymph nodes were gathered from the pathology reports. RESULTS: The Q-RT-PCR data showed that MDR1 expression in metastasized lymph node was higher than that of their corresponding primary tumors (p < 0.05), MMP2 expression in metastasized lymph nodes was also even higher compared with their matched primary tumors (p < 0.01). But SPSS bivariate correlation analysis revealed that MDR1 expression in lymph node was not correlated with MMP-2 expression in lymph node, number of metastasized lymph nodes and tumor size (p > 0.05). MDR1 expression in primary tumors was highly correlated with in corresponding lymph node metastases (p < 0.01 r = 0.795). CONCLUSIONS: All those indicated that MMP-2 should play an important role in the lymph node metastasis. However, further clinical studies with larger sample size need to be performed to verify these findings. [ABSTRACT FROM AUTHOR]

Abstract: Placental alkaline phosphatase (PLAP), encoded by the ALPP gene, is produced by the fetal side of the placenta. This enzyme displays strong genetic variability. Some of the variants were reported to be associated with pathology of pregnancy. We show here that the two most common ALPP allelic variants, Pl1 and Pl2 , differ in mRNA expression level. This differential expression was independent of the parental origin and probably results from linkage disequilibrium with the sequence variation rs2014683G>A in the ALPP gene promoter that was shown to have allele-specific binding patterns to placental nuclear proteins. The possible role of this allelic-specific expression in placenta-related pathology is discussed. [Copyright &y& Elsevier]

Malignant pleural mesothelioma is an aggressive malignancy for which surgical treatment is an option for a subset of patients. A gene ratio test based on the relative expression levels of four genes has been validated in clinical trials to predict which patients will benefit from surgical therapy. A description of the test properties and the independent predictors for outcome are provided. [Copyright &y& Elsevier]