[Gender differences of genetic etiology in the incidence of major depressive disorder among Han freshmen].

Objective: To analyze the gender differences of genetic etiology in the incidence of major depression disorder among Han freshmen. Methods: A 1-year follow-up survey was carried out among 8 079 Han freshmen from Jining, Rizhao and Weifang without lifetime major depressive disorder (MDD) at baseline (April to October 2018) and 4 828 venous blood samples were also collected. After extracting DNA, Sequenom Mass Array time-of-flight mass spectrometry biochip technology was used to detect the genotypes of 17 single nucleotide polymorphisms (SNPs) MDD-related loci. Logistic regression was used for univariate analysis. Generalized multifactor dimension reduction was used to analyze gene-gene interactions. Composite International Diagnostic Interview (CIDI) 3.0 was used for MDD diagnosis. Results: The 1-year incidence of MDD among Han freshmen was 2.23% (95%CI: 1.91%-2.60%) and the gender difference of incidence between males (1.97%, 95%CI: 1.52%-2.56%) and females (2.39%, 95%CI: 1.98%-2.90%) was not statistically significant (P>0.05). AG genotype of rs768705 (nearby gene: TMEM161B) was a risk factor for MDD (OR=1.98, 95%CI: 1.24-2.83). The TC genotype of rs17727765 (nearby gene: CRYBA1) was only a risk factor for MDD in males (OR=9.61, 95%CI: 2.04-45.30). An 8-loci interaction model (PMFBP1, OLFM4, LHPP, ENOX1, TMEM161B, SPPL3, FBXL4 and L3MBTL2) could predict MDD in women with an accuracy rate of 60.05%. No effective prediction model was found for MDD in men. Conclusions: There might be gender differences in the genetic etiology of MDD. Further researches on the genetic causes of MDD in men should be explored.

In silico analysis and experimental validation of azelastine hydrochloride (N4) targeting sodium taurocholate co-transporting polypeptide (NTCP) in HBV therapy.

OBJECTIVES: The aim of this study was to explore sodium taurocholate co-transporting polypeptide (NTCP) exerting its function with hepatitis B virus (HBV) and its targeted candidate compounds, in HBV therapy. MATERIALS AND METHODS: Identification of NTCP as a novel HBV target for screening candidate small molecules, was used by phylogenetic analysis, network construction, molecular modelling, molecular docking and molecular dynamics (MD) simulation. In vitro virological examination, q-PCR, western blotting and cytotoxicity studies were used for validating efficacy of the candidate compound. RESULTS: We used the phylogenetic analysis of NTCP and constructed its protein-protein network. Also, we screened compounds from Drugbank and ZINC, among which five were validated for their authentication in HepG 2.2.15 cells. Then, we selected compound N4 (azelastine hydrochloride) as the most potent of them. This showed good inhibitory activity against HBsAg (IC50 = 7.5 µm) and HBeAg (IC50 = 3.7 µm), as well as high SI value (SI = 4.68). Further MD simulation results supported good interaction between compound N4 and NTCP. CONCLUSIONS: In silico analysis and experimental validation together demonstrated that compound N4 can target NTCP in HepG2.2.15 cells, which may shed light on exploring it as a potential anti-HBV drug.

Unravelling the multifaceted roles of Atg proteins to improve cancer therapy.

Autophagy follows a lysosomal degradation pathway in which a cell digests its own components. It is highly regulated by a limited number of autophagy-related genes (Atg) and the proteins they encode, that are crucial for cells to undergo the process via modulating autophagsome formation. Recently, accumulating evidence has revealed the core molecular machinery of autophagy; however, intricate relationships between autophagy and cancer remain an enigma. Several studies have shown that Atgs can play an important role in carcinogenesis, by which Atgs may modulate a series of oncogenic and tumour suppressive pathways, implicating microRNA (miRNA) involvement. In this review, we will present the key role of Atgs in deciding the fate of cancer cells, discuss some representative Atgs and their proteins such as ULK, Beclin-1, and Atg8/LC3-Atg4, which can also be regulated by miRNAs. Thus, Atgs can be considered to be targets for cancer treatment, which may illuminate the future of cancer therapy.

Programmed cell death pathways in cancer: a review of apoptosis, autophagy and programmed necrosis.

Programmed cell death (PCD), referring to apoptosis, autophagy and programmed necrosis, is proposed to be death of a cell in any pathological format, when mediated by an intracellular program. These three forms of PCD may jointly decide the fate of cells of malignant neoplasms; apoptosis and programmed necrosis invariably contribute to cell death, whereas autophagy can play either pro-survival or pro-death roles. Recent bulk of accumulating evidence has contributed to a wealth of knowledge facilitating better understanding of cancer initiation and progression with the three distinctive types of cell death. To be able to decipher PCD signalling pathways may aid development of new targeted anti-cancer therapeutic strategies. Thus in this review, we present a brief outline of apoptosis, autophagy and programmed necrosis pathways and apoptosis-related microRNA regulation, in cancer. Taken together, understanding PCD and the complex interplay between apoptosis, autophagy and programmed necrosis may ultimately allow scientists and clinicians to harness the three types of PCD for discovery of further novel drug targets, in the future cancer treatment.

Molecular cloning of a new wheat calreticulin gene TaCRT1 and expression analysis in plant defense responses and abiotic stress resistance.

Calreticulin proteins play essential roles in regulating various metabolic processes and in molecular signal transduction in animals and plants. Using homologous PCR, we screened a cDNA library of the wheat resistance gene Yr5 from a near-isogenic line in the susceptible common wheat variety Taichung 29, which was inoculated with an incompatible race CYR32 of Puccinia striiformis. We isolated a novel full-length cDNA encoding calreticulin protein, which we named TaCRT1. Sequence analyses indicated that TaCRT1 contains an open reading frame of 1287 bp in length; it was deduced to encode 428 amino acids. Clustering analysis showed that TaCRT1 belongs to group III of the calreticulin protein family. Semi-quantitative RT-PCR was used to analyze expression profiles of the isolated gene under biotic and abiotic stresses. Expression of TaCRT1 was suppressed by exogenous application of phytohormones, such as abscisic acid and methyl jasmonate, and by dehydration; but it was induced by CYR32 infection and cold treatment. Based on the expression patterns, we propose that TaCRT1 participates in regulatory processes involved in defense responses and stress resistance in wheat.

[Otoacoustic emission cochleogram evoked by bone conducted stimulation].

As bone conducted stimulation, tone bursts of different frequencies were applied through the forehead in 7 normal-hearing subjects. Binaural evoked otoacoustic emissions (EOAE) were then recorded simultaneously, which saved one half of the time required for conventional monaural recording. Analysed with autoregressive modeling, the main echo of EOAE was a narrow-band sound with a stimulus dependent central frequency. It was suggested that the generation site of EOAE was near to that cochlear portion stimulated by the corresponding frequency. The latency of EOAE, although independent of the stimulus intensity, tended to be shorter at higher stimulus frequencies. This was possibly due to the differences in the distances from the generation sites of the otoacoustic emissions to the tympanic membrane. Recordable otoacoustic emissions were evoked by tone bursts of 1.0, 2.0, 3.0 and 4.0 kHz in all the 14 normal ears except one at 4.0 kHz, and 10 and 7 ears by tone bursts of 0.5 and 6.0 kHz, respectively. Emission cochleogram was obtained when the means of EOAE detection thresholds were plotted in an audiogram format. The lowest threshold was found at 1.0 kHz. This might be related to the middle ear resonance frequency of 1100 +/- 230 Hz. The technique of simultaneous recording of binaural EOAE and plotting of emission cochleogram described in this paper is clinically useful as a means of objective evaluation of hearing.