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White matter lesions known as leukoaraiosis (LA) are cerebral white matter hyperintensities observed in elderly individuals. Currently, no reliable molecular biomarkers are available for monitoring their progression over time. To identify biomarkers for the onset and progression of LA, we analyzed whole blood-based, microRNA expression profiles of leukoaraiosis, validated those exhibiting significant microRNA changes in clinical subjects by means of quantitative real-time polymerase chain reactions and determined the function of miRNA in cell lines by means of microRNA mimic transfection assays. A total of seven microRNAs were found to be significantly down-regulated in leukoaraiosis. Among the microRNAs, hsa-miR-1972 was downregulated during the early onset phase of leukoaraiosis, as confirmed in independent patients, and it was found to target leukoaraiosis-dependent BAIAP3, decreasing its expression in 293T cell lines. Functional enrichment analysis revealed that significantly dysregulated miRNAs-mRNAs changes associated with the onset of leukoaraiosis were involved in neurogenesis, neuronal development, and differentiation. Taken together, the study identified a set of candidate microRNA biomarkers that may usefully monitor the onset and progression of leukoaraiosis. Given the enrichment of leukoaraiosis-associated microRNAs and mRNAs in neuron part and membrane system, BAIAP3 could potentially represent a novel target of hsa-miR-1972 in leukoaraiosis through which microRNAs are involved in the pathogenesis of white matter lesions.

Traditional Chinese Medicine (TCM) has been extensively used to ameliorate diseases in Asia for over thousands of years. However, owing to a lack of formal scientific validation, the absence of information regarding the mechanisms underlying TCMs restricts their application. After oral administration, TCM herbal ingredients frequently are not directly absorbed by the host, but rather enter the intestine to be transformed by gut microbiota. The gut microbiota is a microbial community living in animal intestines, and functions to maintain host homeostasis and health. Increasing evidences indicate that TCM herbs closely affect gut microbiota composition, which is associated with the conversion of herbal components into active metabolites. These may significantly affect the therapeutic activity of TCMs. Microbiota analyses, in conjunction with modern multiomics platforms, can together identify novel functional metabolites and form the basis of future TCM research.

Background and Objective: Cervical erosion is a common gynecological disease that increases the risk of human papillomavirus (HPV) infection and causes cervical lesions. Without prompt treatment, this disease may lead to the occurrence of cervical cancer. According to previous studies, the reproductive tract microbiome is closely related to the occurrence and development of a variety of gynecological diseases, but to date, there have been few studies on the composition of the genital tract flora and the local immune microenvironment of cervical erosion. Currently, the mechanism of interaction between the reproductive tract microbiome and cervical erosion remains unknown.Materials and Methods: A total of 11 healthy individuals and 15 patients with cervical erosion (including 11 HPV+ patients) were included recruited in this study. Vaginal secretion and cervical mucus were obtained from volunteers before and after treatment. Luminex multi-factor detection technology was used to detect and analyze cytokines, chemokines, and growth factors in the local immune microenvironment of the reproductive tract. A third-generation nanopore high-throughput sequencing platform was used to explore the characteristics of the reproductive tract microbial community structure of HPV+ and HPV− cervical erosion patients. Reproductive tract metabolomics was explored by liquid chromatography-mass spectrometry (LC-MS) for characterization.Results: Following 21 days of continuous treatment with Jinchuang gel, the smoothness of the cervical surface was restored for all of the 15 patients with cervical erosion, and 4 of the 11 HPV+ patients turned HPV−. After 84 days of continuous treatment, the remaining 7 HPV+ individuals turned negative of HPV−. Furthermore, tThe gel ingredients can improve the local proteolytic environment, reduce the inflammatory response, and promote wound healing. The microbial level of vagina showed that the gel ingredients increased the abundance of Lactobacillus and decreased the relative abundance of Pseudomonas, Megasphaera, and Hungateiclostridium, as well as the overall species diversity. Metabolites of Epicatechin, protocatechuic acid, and hydroxybenzoic acid metabolites with activities of anti-bacterial microbes and anti-inflammatory inflammation were effects increased, which subsequently decreased the levels of harmful metabolites (pipecolate, m-cresol, 2-hydroxy-2-methylbutyric acid, histamine, and other metabolites). Nicotinic acid and nicotinamide metabolism and the tryptophan metabolism pathway may be related involved to the occurrenceincidence of HPV+ in cervical erosion patients, and niacin and nicotinamide metabolism and the histidine metabolism pathway may be related contributed to the positive outcomes of treatment.Conclusion: It is speculated that the active ingredients play a role in wound healing, viral clearance, and immune regulation by regulating the activity of the NF-κB and MAPK signaling pathways.

Background Osteoporosis is a chronic bone metabolism disorder affecting millions of the world population. The RANKL/RANK/OPG signaling pathway has been confirmed to be the main regulator of osteoporosis. It is of great interest to identify appropriate therapeutic agents that can regulate the RANKL/RANK/OPG pathway. Baicalin (BA) is a well-known traditional Chinese medicine formula against various inflammatory diseases with a proven role of the RANKL/RANK/OPG pathway regulation. However, the potential effect of BA on osteoporosis and the mechanisms underlying this remain unclear. In the present study, we aimed to evaluate the efficacy of BA in the prevention of dexamethasone (DEX)-induced osteoporosis in zebrafish. Methods In this study, growth and development changes of zebrafish and calcein staining were assessed with a micrograph. The expression levels of RANKL and OPG and transcription factors in response to DEX induction and BA administration were evaluated by Western blotting and qRT-PCR. In addition, the intermolecular interactions of BA and RANKL were investigated by molecular docking. Results Results show that BA enhances the growth and development of dexamethasone (DEX)-induced osteoporosis in zebrafish larvae. Calcein staining and calcium and phosphorus determination revealed that BA ameliorates mineralization of DEX-induced osteoporosis zebrafish larvae. BA also regulates the expression of RANKL and OPG and hampers the changes in gene expression related to bone formation and resorption under the induction of DEX in zebrafish. It can be inferred by molecular docking that BA may interact directly with the extracellular domain of RANKL. Conclusion The findings, herein, reveal that BA ameliorates DEX-induced osteoporosis by regulation of the RANK/RANKL/OPG signaling pathway.

Background:Recurrence is the leading cause of treatment failure and death in patients with gastric cancer (GC). However, the mechanism underlying GC recurrence remains unclear, and prognostic markers are still lacking.Methods:We analyzed DNA methylation profiles in gastric cancer cases with shorter survival ( 3 years), and identified candidate genes associated with GC recurrence. Then, the biological effects of these genes on gastric cancer were studied.Results:A novel gene, magnesium-dependent phosphatase 1 (mdp1), was identified as a candidate gene whose DNA methylation was higher in GC samples from patients with shorter survival and lower in patients with longer survival. MDP1 protein was highly expressed in GC tissues with longer survival time, and also had a tendency to be expressed in highly differentiated GC samples. Forced expression of MDP1 in GC cell line BGC-823 inhibited cell proliferation, whereas the knockdown of MDP1 protein promoted cell growth. Overexpression of MDP1 in BGC-823 cells also enhanced cell senescence and apoptosis. Cytoplasmic kinase protein c-Jun N-terminal kinase (JNK) and signal transducer and activator of transcription 3 (Stat3) were found to mediate the biological function of MDP1.Conclusion:These results suggest that MDP1 protein suppresses the survival of gastric cancer cells and loss of MDP expression may benefit the recurrence of gastric cancer.

Background Vitamin D3 has been known to have an anticancer effect, but the mechanisms underlying this is poorly explored. The present study aimed to investigate the antitumor role of vitamin D3 on gastric cancer and mechanisms. Methods The Roche Elecsys platform was applied in retrospective studies to detect the role of 25-hydroxylvitamin D3 in adenocarcinoma and colony formation assay was conducted to verify the effect of 1, 25-dihydroxyvitamin D3 on the proliferation of gastric cancer cells. After the identification of hypermethylation of BMP3 CpG islands by bisulfite genomic sequencing (BGS), we further investigated the relationship of BMP3 expression and gastric carcinogenesis by Western blot analysis and gel electrophoresis mobility shift assay (EMSA). Results Here we show that low concentration of 1, 25-dihydroxyvitamin D3 links to can-cerization and significantly inhibits proliferation of undifferentiated gastric cancer cell lines SGC-7901 and BGC-823. BMP3 promoter hypermethylation was highly correlated with gastric tumor. Moreover, BMP3 expression was regulated by its promoter methylation in gastric cells. The further exploration of the relationship between 1, 25-dihydroxyvitamin D3 and BMP3 by EMSA results that 1, 25-dihydroxyvitamin D3 stimulates BMP3 expression by the inhibition of BMP3 promoter methylation in gastric tumor cells. Conclusion In combination with the data from clinical research, bioinformatics analysis and experimental verification, we propose that 1, 25-hydroxylvitamin D3 affects gastric cancer progression by repressing BMP3 promoter methylation.

Background: Suppression of tumorigenicity 5 (ST5) has been considered as a tumor suppressor gene in HeLa tumor cells. However, there is no report of ST5 expression or function in the progression of breast cancer.Methods: ST5 expression in different subtypes and pathological stages of breast cancer was determined by Oncomine database, Breast Cancer Gene-Expression Miner v4.4 (bc-GenExMiner v4.4) analysis and immunohistochemistry. Cell viability was measured by CCK8 assay and metastatic behavior was assessed using scratch wound model and Transwell. Flow cytometry was employed for cell cycle and apoptosis detection, and methylation-specific PCR (MSP) was used to detect methylation level.Results: ST5 was expressed at low level in different subtypes of breast cancer specimens compared to normal breast and there was a negative association between ST5 status and pathological stages of breast cancer patients. Additionally, ST5 was lower in cases of recurrent and invasive breast cancer than that in non-recurrent and non-invasive patients. In in vitro experiment, ST5 status was also negatively associated with the invasive capability of breast cancer cells, showing lower in MDA-MB-231 and SKBR3 cell lines than that in MCF-7 cells. ST5-downregulation promoted, while ST5-upregulation inhibited the tumour characteristics of MDA-MB-231 cells including cell viability, cell cycle and migration. And exogenous ST5 also elevated, but ST5 depletion limited the proportion of apoptotic cells in MDA-MB-231 cells. However, the alteration of ST5, no matter upregulation or downregulation, had no impact on tumour behaviors of MCF-7 cells. Mechanistically, ST5 protein ablation activated, while ST5-upregulation repressed the activities of phosphorylated JNK and ERK1/2, and subsequently the expression of c-Myc. Of note, low level of ST5 in breast cancer cells was possibly related with the aberrant methylation of ST5 promoter region.Conclusion: Our findings suggest that ST5 potentially acts as a tumor suppressor gene in invasive breast cancer through regulating ERK/JNK signaling pathway and provide a novel insight for breast cancer treatment.

Background Surgery combined with new adjuvant chemotherapy is the primary treatment for early stage invasive and advanced stage breast cancer. Growing evidence indicates that patients with ERα-positive breast cancer show poor response to chemotherapeutics. However, ERα-mediated drug-resistant mechanisms remain unclear. Methods Levels of WW domain-binding protein 2 (WBP2) and drug-resistant gene were determined by western blotting and RT-PCR, respectively. Cell viability was measured by preforming MTT assay. CD243 expression and apoptosis rate were evaluated by flow cytometry. Interactions of WBP2/ERα and ERα/MDR1 were detected by co-immunoprecipitation and chromatin immunoprecipitation (ChIP) assay, respectively. Results There was an intrinsic link between WBP2 and ERα in drug-resistant cancer cells. Upregulation of WBP2 in MCF7 cells increased the chemoresistance to doxorubicin, while RNAi-mediated knockdown of WBP2 in MCF7/ADR cells sensitised the cancer cells to doxorubicin. Further investigation in in vitro and in vivo models demonstrated that WBP2 expression was directly correlated with MDR1, and WBP2 could directly modulate MDR1 transcription through binding to ERα, resulting in increased chemotherapy drug resistance. Conclusions Our finding provides a new mechanism for the chemotherapy response of ERα-positive breast tumours, and WBP2 might be a key molecule for developing new therapeutic strategies to treat chemoresistance in breast cancer patients.

White matter lesions known as leukoaraiosis (LA) are cerebral white matter hyperintensities observed in elderly individuals. Currently, no reliable molecular biomarkers are available for monitoring their progression over time. To identify biomarkers for the onset and progression of LA, we analyzed whole blood-based, microRNA expression profiles of leukoaraiosis, validated those exhibiting significant microRNA changes in clinical subjects by means of quantitative real-time polymerase chain reactions and determined the function of miRNA in cell lines by means of microRNA mimic transfection assays. A total of seven microRNAs were found to be significantly down-regulated in leukoaraiosis. Among the microRNAs, hsa-miR-1972 was downregulated during the early onset phase of leukoaraiosis, as confirmed in independent patients, and it was found to target leukoaraiosis-dependent

Warfarin is a commonly prescribed and effective oral anticoagulant. Genetic polymorphisms associated with warfarin metabolism and sensitivity have been implicated in the wide inter-individual dose variation that is observed. Several algorithms integrating patients’ clinical characteristics and genetic polymorphism information have been explored to predict warfarin dose. However, most of these algorithms could explain only over half of the variation in a warfarin maintenance dose, suggesting that additional genetic factors may exist and need to be identified. Here, a drug absorption, distribution, metabolism and excretion (ADME) Core Panel Kit-based pharmacogenetic study was performed to screen for warfarin dose-associated SNP sites in Han-Chinese population patients taking warfarin therapy, and the screen was followed by pyrosequencing-based validation. Finally, we confirmed that the common variant rs9923231 in VKORC1 and two novel genes, SLC15A2 (rs1143671 and rs1143672) and SLCO1B3 (rs4149117 and rs7311358), are associated with the warfarin maintenance dose. As has been shown for those carriers with the variant rs9923231 in VKORC1, it was suggested that those subjects with homozygous minor alleles in those four SNPs should take a lower warfarin dose than those carrying the wild type alleles. Together with the established predictor rs9923231 in VKORC1, those four novel variants on SLC15A2 and SLCO1B3 should be considered as useful biomarkers for warfarin dose adjustment in clinical practice in Han-Chinese populations.

The roles of newly identified, non-conventional, native gut microbiota bacteria for promotion of health and even therapeutic purposes have rapidly attracted much more attention in contrast to the traditional probiotics. Detailed physiological and molecular evidences on isolation, identification and functional characterization of these various bacteria are rapidly gathering. These potentially beneficial bacteria are gradually grouped to form the next generation probiotics (NGP). Many bacterial species and strains belonging to Actinobacteria, Bacteroidetes, Firmicutes and Verrucomicrobia are gradually highlighted. Notably, NGP may have the potential of being treated as drugs (live biotherapeutic products, LBP); therefore, the requirements for grouping of NGP are much more stringent than traditional probiotics. Comprehensive understandings of effectiveness on amelioration of diseases, safety, physiological, genomic, and metabolomics characteristics, the drug susceptibility pattern and transfer of drug resistance genes, and potential virulence factors are mandatory. Besides, how NPG interact with the host to maintain intestinal integrity and host homeostasis has to be addressed. While most NGP products are currently not commercially available yet, this present review emphasizes the requirements of grouping newly identified microbiota bacteria as NGP. Furthermore, selection of specific functional bacteria to the strain level is essential. We also provide an overview of the potential NGP candidates that could be applied for targeted therapy on specific inflammation related diseases.

Background Vitamin D3 has been known to have an anticancer effect, but the mechanisms underlying this is poorly explored. The present study aimed to investigate the antitumor role of vitamin D3 on gastric cancer and mechanisms. Methods The Roche Elecsys platform was applied in retrospective studies to detect the role of 25-hydroxylvitamin D3 in adenocarcinoma and colony formation assay was conducted to verify the effect of 1, 25-dihydroxyvitamin D3 on the proliferation of gastric cancer cells. After the identification of hypermethylation of BMP3 CpG islands by bisulfite genomic sequencing (BGS), we further investigated the relationship of BMP3 expression and gastric carcinogenesis by Western blot analysis and gel electrophoresis mobility shift assay (EMSA). Results Here we show that low concentration of 1, 25-dihydroxyvitamin D3 links to can-cerization and significantly inhibits proliferation of undifferentiated gastric cancer cell lines SGC-7901 and BGC-823. BMP3 promoter hypermethylation was highly correlated with gastric tumor. Moreover, BMP3 expression was regulated by its promoter methylation in gastric cells. The further exploration of the relationship between 1, 25-dihydroxyvitamin D3 and BMP3 by EMSA results that 1, 25-dihydroxyvitamin D3 stimulates BMP3 expression by the inhibition of BMP3 promoter methylation in gastric tumor cells. Conclusion In combination with the data from clinical research, bioinformatics analysis and experimental verification, we propose that 1, 25-hydroxylvitamin D3 affects gastric cancer progression by repressing BMP3 promoter methylation.

Non-small cell lung cancer (NSCLC) patients with activating epidermal growth factor receptor (EGFR) mutations initially respond well to the EGFR tyrosine kinase inhibitors (TKIs) erlotinib and gefitinib. However, clinical efficacy is limited by the development of resistance. In most cases, this resistance is in the form of the T790M mutation. Here, we report the design, synthesis and biochemical evaluation of a novel series of irreversible EGFR tyrosine kinase inhibitors (EGFR-TKIs) that are derived from the anilinoquinazoline scaffold. Guided by molecular modeling, this series of analogs was evolved to target a cysteine residue in the ATP binding site via covalent bond formation and to achieve high levels of anti-tumor activity in cell cultures and in xenografts. The most promising compound 13c ((E) -N - (4 - (4 - (3-fluorobenzyloxy) -3- chlorophenylamino) -7-ethoxyquinazolin-6-yl) -3- ((S) -pyrrolidin-2-yl)acrylamide, which we named Transtinib) displayed strong anti-proliferative activity against the H1975 and A431 cell lines with IC50 values of 34 nM and 62 nM, respectively. In xenograft models, Transtinib significantly decreases tumor size for a prolonged period of time. These results suggest that Transtinib is a potential cancer therapeutic drug lead for the inhibition of mutant EGFR to overcome the development of resistance.

The objective of this study was to identify genes regulated by methylation that were involved in spermatogenesis failure in non-obstructive azoospermia (NOA). Testis biopsies of patients with NOA and OA (with normal spermatogenesis) were evaluated by microarray analysis to examine DNA methylation and mRNA expression using our established integrative approach. Of the coordinately hypermethylated and down-regulated gene list, zinc-finger CCHC-type containing 13 (ZCCHC13) was present within the nuclei of germ cells of testicular tissues according immunohistochemistry, and there was decreased protein expression in men with NOA compared with OA controls. Mechanistic analyses indicated that ZCCHC13 increased c-MYC expression through the p-AKT and p-ERK pathways. To confirm the changes in ZCCHC13 expression in response to methylation, 5-aza-2′-deoxycitidine (5-Aza), a hypomethylating agent, was administered to mouse spermatogonia GC-1 cells. We demonstrated that 5-Aza enhanced protein and mRNA expression of ZCCHC13 epigenetically, which was accompanied by activation of p-AKT and p-ERK signaling. Our data, for the first time, demonstrate that ZCCHC13 is an important signaling molecule that positively regulates the AKT/MAPK/c-MYC pathway and that methylation aberrations of ZCCHC13 may cause defects in testis development in human disease, such as NOA.

miRNAs are involved in various biological processes and different diseases through interacting with their target mRNAs. Therefore, deciphering miRNA targets is important for diagnostics and therapeutics. However, it is still complex and expensive to do large scale screening for miRNA alterations and identify their downstream miRNA targets. Recently, integrating analysis of miRNA expression profiles and mRNA expression levels has been used to successfully identify the most prominent interactions. Here, we present a protocol that combines both expression data and computational prediction to refine the microarray result for identifying the miRNA targets. Many details are also provided to help researchers choose more appropriate tools and methods for a given type of application. Available web-based resources and experimental conditions for functional enrichment and validation of miRNA targets are also summarized.

WW domain-binding protein 2 (WBP2) has been demonstrated as oncogenic in breast cancer. Many studies have revealed the WBP2 gene as a high-risk gene for leukoariaosis and cerebral white matter lesions is important in the pathologic stage of glioma development. This study aimed to illustrate the underlying mechanism by which WBP2 regulates the process of glioma development. The expression pattern of WBP2 in several tumor cells was determined, clarifying the carcinogenic action of WBP2 in glioma cells. Overexpression of WBP2 in glioma cells promoted cell proliferation and migration, and the number of S-phase cells, whereas the depletion of WBP2 by RNAi-mediated knockdown restrained cell growth and cell cycle progression. Upregulation of WBP2 significantly enhanced the tumorigenic ability of U251 cells in vivo. MS/GST pulldown assay identified α-enolase (ENO1) and Homer protein homolog 3 (Homer3) as novel potent interaction partners of WBP2. Knockdown of ENO1 or Homer3 allowed cell growth and migration to return to normal levels. Furthermore, in vitro and in vivo experiments indicated that the oncogenic role of WBP2 in glioma was through modulating ENO1 and glycolysis activity via the ENO1-PI3K/Akt signaling pathway. Collectively, these results reveal that WBP2 plays a vital role in the occurrence and development of glioma, indicating a target gene for glioblastoma treatment.

Src homology 2 (SH2)-containing protein tyrosine phosphatase 2 (SHP2), encoded by the human PTPN11 gene, is a ubiquitously expressed protein tyrosine phosphatase (PTP) that consists of two tandem Src homology (SH2) domains (N-SH2 and C-SH2), a PTP catalytic domain, and a C-terminal tail with tyrosyl phosphorylation sites. It plays critical roles in numerous cellular processes through the regulation of various signaling pathways in PTP catalytic activity-dependent and -independent manners. Dysfunction of SHP2 resulting from pathogenic mutations and aberrant expression leads to the dysregulation of multiple signaling pathways, thus contributing to different human disorders. Germline and somatic mutations in PTPN11 are involved in Noonan syndrome (NS), LEOPARD syndrome (LS), and hematological malignancies, as well as several solid tumors. In this report, we provide an overview of the current knowledge of the structure and function of SHP2, and further discuss the molecular and pathogenic mechanism of SHP2 in human diseases, with a special focus on tumorigenesis. Furthermore, we summarize that SHP2 might itself represent a potential drug target for cancer prevention and treatment. Ongoing research and development of SHP2-specific inhibitors would enhance this potential.

The feasibility of T-Cell receptor (TCR) gene therapy using a MART-1-specific TCR has been previously demonstrated in melanoma patients. However, it remains a challenge without a defined tumor-specific antigen in the therapy of hepatocellular carcinoma (HCC). In this study, through the analysis of clonal expansion of TCR Vβ subfamily and DNA sequencing, we identified TCR Vβ7.1_H3F7 as a potential therapeutic gene specifically for the HCC patients. Peripheral blood monouclear cells (PBMC) transfected with TCRV β7.1_H3F7 gene were specifically cytotoxic against HCC cells in vitro. Adoptive transfer of this transfected PBMC resulted in a marked suppression of HCC tumor development in the animal model. These results demonstrated the value of TCRV β7.1_H3F7 as a therapeutic gene specifically for HCC. More importantly, it provides a novel strategy for screening tumor-specific TCR genes, which may pave the way for TCR gene therapy in cancer patients currently without the defined tumor-specific antigens.

Parkinson's disease (PD) and cancer are often thought of as two sides of the same coin. At first glance, cancer and PD appear to have little in common. PD is caused by the degeneration of dopaminergic neurons, whereas cancer results from the uninhibited growth of tumor cells. Increasing numbers of genetic studies suggest that the pathogenesis of PD and cancer may involve similar genes, pathways, and mechanisms. The differences in the pathological and cellular mechanisms, and the associated genetic mutations, may result in two such divergent diseases. In this article, we highlight some molecular mechanisms and key biomarkers which might cause those two diseases from misfolding and degradation of proteins, mitochondrial damage, oxidative stress response, cell cycle control and DNA repair, and the PI3K/AKT/ mTOR pathway, in order to provide help to the understanding and treatment of these two diseases.

In the original version of this article the author name Xiaolei Chen was published incorrectly. This has been corrected to Xiao Lei Chen.

Vitamin D (VitD) comes from sunlight exposure and food intake. Apart from regulating calcium homeostasis and bone function, its levels also associate with the presence of development of adenocarcinoma. VitD can interact with VitD receptor (VDR), which heterodimerizes with retinoic X receptor (RXR) and then induces transcription of proteins that function in cell proliferation, differentiation, apoptosis, and angiogenesis. We reviewed and discussed the genes and their associated polymorphisms involved in the correlation between development of adenocarcinoma and VitD deficiency to highlight how VitD may be instrumental in cancerization. Furthermore, pilot epidemiological data show that the detection of 25-hydroxy-Vitamin D 3 ((36.5±10.7 nmol/L, n=129) vs (81.4±19.8 nmol/L, n=81)) can be a promising approach in cancer diagnosis. In this review, we suggest that 25-hydroxy-Vitamin D 3 can act as an indicator and/or risk assessment factor in early diagnosis, prognosis and treatment of adenocarcinoma.

Molecular medical research on aromatherapy has been steadily increasing for use as an adjuvant therapy in managing psychiatric disorders and to examine its therapeutic mechanisms. Most studies, as well as clinically applied experience, have indicated that various essential oils, such as lavender, lemon and bergamot can help to relieve stress, anxiety, depression and other mood disorders. Most notably, inhalation of essential oils can communicate signals to the olfactory system and stimulate the brain to exert neurotransmitters (e.g. serotonin and dopamine) thereby further regulating mood. However, little research has been done on the molecular mechanisms underlying these effects, thus their mechanism of action remains ambiguous. Several hypotheses have been proposed regarding the therapeutic mechanism of depression. These have mainly centered on possible deficiencies in monoamines, neurotrophins, the neuroendocrine system, c-AMP, cation channels as well as neuroimmune interactions and epigenetics, however the precise mechanism or mechanisms related to depression have yet to be elucidated. In the current study, the effectiveness of aromatherapy for alleviating psychiatric disorders was examined using data collected from previously published studies and our unpublished data. A possible signaling pathway from olfactory system to the central nerve system and the associated key molecular elements of aromatherapy are also proposed.

Supplemental Digital Content is available in the text, Background: During development, methylation permanently changes gene activity, while aberrant gene methylation is key to human tumorigenesis. Gene methylation is an epigenetic event leading to gene silencing and some tumor suppressor genes that are aberrantly methylated in both thyroid cancer and benign thyroid tumor, suggesting a role for methylation in early thyroid tumorigenesis. Specific gene methylation occurs in certain types of thyroid cancer and depends on particular signaling pathways. Most reports rely on data from varied samples that vary tremendously with respect to methylation. Results: We observed that hyperplastic/malignant (H/M) thyroid tissue and benign/manligant (B/M) tissue had the most profoundly methylated loci compared to hyperplastic/benign (H/B) tissue. These loci are mapped to 863 genes (|Δβ value| > 0.15) in B/M and 1082 genes (|Δβ value| > 0.15) in H/M. After bioinformatic analysis, these genes were found to be involved in T-cell receptor signaling pathway (B/M) and Jak–Stat signaling pathways (H/M). Conclusion: Our study offers the most comprehensive DNA methylation data for thyroid disease to date, using 1 patient with 3 tissue types and high-resolution 450K arrays. Our data may lay the foundation for future identification of novel epigenetic targets or diagnosis of thyroid cancer.

Increasing number of genetic studies suggest that the pathogenesis of Parkinson’s disease (PD) and cancer may involve similar genes, pathways, and mechanisms. The differen‐ ces in the pathological and cellular mechanisms, and the associated genetic mutations, may result in two such divergent diseases. However, the links between the molecular mechanisms that cause PD and cancer remain to be elucidated. This article appraises the overlapping molecular features of these diseases and discusses the implications for prevention and treatment. We propose that chronic inflammation (CI) in neurons and tumors contributes to a microenvironment that favors the amassing of DNA mutations and facilitating disease formation. CI may therefore play a key role in the development of PD and cancer, and provide a link between these two diseases.

// Zhiming Li 1,2 , Zaozao Zheng 1,2 , Jun Ruan 1,2 , Zhi Li 1,2 , Xuan Zhuang 4 and Chi-Meng Tzeng 1,2,3 1 Translational Medicine Research Center (TMRC), School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian, China 2 Key Laboratory for Cancer T-Cell Theranostics and Clinical Translation (CTCTCT), Xiamen University, Xiamen, Fujian, China 3 INNOVA Cell Theranostics/Clinics and TRANSLA Health Group, Xiamen University, Xiamen, Fujian, China 4 Department of Urology, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China Correspondence to: Xuan Zhuang, email: // Chi-Meng Tzeng, email: // Keywords : global miRNA and mRNA profile; integrated analysis; miR-34c-3p; PLCXD3; spermatogenesis; Pathology Section Received : June 06, 2016 Accepted : July 20, 2016 Published : July 29, 2016 Abstract Our previous research suggested that an integrated analysis of microRNA (miRNA) and messenger RNA (mRNA) expression is helpful to explore miRNA-mRNA interactions and to uncover the molecular mechanisms of male infertility. In this study, microarrays were used to compare the differences in the miRNA and mRNA expression profiles in the testicular tissues of severe oligozoospermia (SO) patients with obstructive azoospermia (OA) controls with normal spermatogenesis. Four miRNAs (miR-1246, miR-375, miR-410, and miR-758) and six mRNAs (SLC1A3, PRKAR2B, HYDIN, WDR65, PRDX1, and ADATMS5) were selected to validate the microarray data using quantitative real-time PCR. Using statistical calculations and bioinformatics predictions, we identified 33 differentially expressed miRNAs and 1,239 differentially expressed mRNAs, among which one potential miRNA-target gene pair, miR-34c-3p and PLCXD3 (Phosphatidylinositol-Specific Phospholipase C, X Domain Containing 3), was identified. Immunohistochemical analysis indicated that PLCXD3 was located within the germ cells of the mouse and human testis. Moreover, we found that miR-34c-3p was able to decrease PLCXD3 expression in mouse (GC-1 and TM4) and human (NCM460) cell lines, presumably indicating the possibility that miR-34c-3p acts as an intracellular mediator in germinal lineage differentiation. Notably, we reported the expression of the PLCXD3 protein in a man with normal spermatogenesis and the lack of the PLCXD3 protein in a man with SO. Therefore, the identified miRNA and mRNA may represent a potentially novel molecular regulatory network and therapeutic targets for the study or treatment of SO, which might provide a better understanding of the molecular basis of spermatogenesis dysfunction.

Objectives The previously reported functional mutation rs75932628-T (p.R47H) in the triggering receptor expressed on myeloid cells 2 (TREM2) is a genetic risk factor for Alzheimer9s disease, Parkinson9s disease (PD) and frontotemporal dementia, in European populations. This study aims to assess the genetic association of the variant rs75932628-T with PD and leucoaraiosis (LA) in a Han Chinese population. Setting This population-based study was conducted in China by Xiamen University and its affiliated hospital. Participants 308 patients with LA, 342 patients with PD and 198 healthy blood donors were recruited from the First Affiliated Hospital of Xiamen University. Outcome measures Genotyping was performed by molecular beacon real-time PCR and Sanger sequencing. Results None of our participants carried the rs75932628-T mutation. Conclusions Our results corroborate and extend previous findings, concluding that the variant rs75932628-T (p.R47H) in TREM2 is not a risk factor for LA or PD in the Han Chinese population.

A single-nucleotide polymorphism (SNP) is a variation in the DNA sequence that occurs when a single nucleotide in the genome differs across members of the same species. Variations in the DNA sequences of humans are associated with human diseases. This makes SNPs as a key to open up the door of personalized medicine. SNP(s) can also be used for human identification and forensic applications. Compared to short tandem repeat (STR) loci, SNPs have much lower statistical testing power for individual recognition due to the fact that there are only 3 possible genotypes for each SNP marker, but it may provide sufficient information to identify the population to which a certain samples may belong. In this report, using eight SNP markers for 641 samples, we performed a standard statistical classification procedure and found that 86% of the samples could be classified accurately under a two-population model. This study suggests the potential use of SNP(s) in population classification with a small number (n ≤ 8) of genetic markers for forensic screening, biodiversity and disaster victim controlling.