Analysis of the Physicochemical Properties of Acaricides Based on Lipinski's Rule of Five.

This study aimed to explore the similarity between the physical and chemical properties of different acaricides, determine whether Lipinski's Rule of Five (RO5) used in the design of drug molecules is suitable for screening acaricides, and provide methods for selection of new acaricides. We evaluated and predicted the molecular properties of >180 acaricides using Molinspiration. We calculated physicochemical property parameters, such as log p, molecular weight (MW), and number of hydrogen bond donors (HBDs), hydrogen bond acceptors (HBAs), and rotatable bonds (Rot B). We then conducted qualitative and quantitative analyses of the physicochemical properties of acaricides. The MW of all acaricides ranged from 141 to 663, with an average value of 337.8. The number of HBDs ranged from 0 to 5, with an average value of 0.46. The number of HBAs ranged from 0 to 9, with an average value of 4.07. The log p ranged from -0.79 to 8.74, with an average value of 4.61. The number of Rot B ranged from 0 to 14, with an average value of 5.62. Except for the microbial and plant-derived acaricides, the molecular properties of the remaining acaricides are in accordance with the Lipinski's RO5. Therefore, the Lipinski's RO5 can provide a basis for screening new acaricide drugs.

Fecal microbiota transplantation improves metabolism and gut microbiome composition in db/db mice.

Fecal microbiota transplantation (FMT) has become an effective strategy to treat metabolic diseases, including type 2 diabetes mellitus (T2DM). We previously reported that the intestinal microbiome had significant difference between individuals with normal glucose tolerance and T2DM in Chinese Kazak ethnic group. In this study, we investigated the effects of transplanted fecal bacteria from Kazaks with normal glucose tolerance (KNGT) in db/db mice. The mice were treated with 0.2 mL of fecal bacteria solution from KNGT daily for 10 weeks. We showed that the fecal bacteria from KNGT successfully colonized in the intestinal tract of db/db mice detected on day 14. In the FMT-treated db/db mice, the levels of fasting blood glucose, postprandial glucose, total cholesterol, triglyceride, and low-density lipoprotein-cholesterol were significantly downregulated, whereas high-density lipoprotein-cholesterol levels were upregulated. In the FMT-treated db/db mice, Desulfovibrio and Clostridium coccoides levels in gut were significantly decreased, but the fecal levels of Akkermansia muciniphila and colon histone deacetylase-3 (HDAC3) protein expression were increased. At 8 weeks, both intestinal target bacteria and HDAC3 were correlated with glycolipid levels; Akkermansia muciniphila level was positively correlated with HDAC3 protein expression (r = +0.620, P = 0.037). Our results suggest that fecal bacteria from KNGT could potentially be used to treat diabetic patients.

Antibiotic consumption in Shandong Province, China: an analysis of provincial pharmaceutical centralized bidding procurement data at public healthcare institutions, 2012-16.

Objectives: To explore the trends of antibiotic consumption in public healthcare institutions through analysing the provincial centralized bidding procurement (CBP) data in Shandong, China. Methods: The Shandong CBP system has been established since 2011, covering public healthcare institutions of 500 secondary and tertiary hospitals, 600 urban primary healthcare centres (PHCs) and 1600 rural PHCs. We collected all the antibiotic procurement records from the CBP system between 2012 and 2016. Antibiotic consumption data were calculated using Anatomical Therapeutic Chemical (ATC)/DDD methodology and normalized using DDD per 1000 inhabitants per day (DID). Results: Overall antibiotic consumption increased from 12.859 DID in 2012 to 15.802 DID in 2014, then decreased to 13.802 DID in 2016. The top three antibiotics consumed in 2016 were penicillins (4.251 DID), quinolones (2.957 DID) and macrolides (2.057 DID). PHCs consumed 80% of the total antibiotics, of which rural PHCs accounted for 88%. Antibiotic consumption peaked in 2014 for rural PHCs and in 2015 for hospitals, and declined thereafter. In urban PHCs, the consumption steadily increased from 2012 to 2016. Conclusions: Zero mark-up drug policies and national policies to improve rational use of antibiotic were associated with the reduction of antibiotic consumption in public healthcare institutions in Shandong Province. Regulations for antibiotic use in PHCs should be strengthened.

Direct Extraction of Tumor Response Based on Ensemble Empirical Mode Decomposition for Image Reconstruction of Early Breast Cancer Detection by UWB.

A direct extraction method of tumor response based on ensemble empirical mode decomposition (EEMD) is proposed for early breast cancer detection by ultra-wide band (UWB) microwave imaging. With this approach, the image reconstruction for the tumor detection can be realized with only extracted signals from as-detected waveforms. The calibration process executed in the previous research for obtaining reference waveforms which stand for signals detected from the tumor-free model is not required. The correctness of the method is testified by successfully detecting a 4 mm tumor located inside the glandular region in one breast model and by the model located at the interface between the gland and the fat, respectively. The reliability of the method is checked by distinguishing a tumor buried in the glandular tissue whose dielectric constant is 35. The feasibility of the method is confirmed by showing the correct tumor information in both simulation results and experimental results for the realistic 3-D printed breast phantom.

The miR-17-92 cluster regulates FOG-2 expression and inhibits proliferation of mouse embryonic cardiomyocytes

MicroRNAs (miRNAs) have gradually been recognized as regulators of embryonic development; however, relatively few miRNAs have been identified that regulate cardiac development. A series of recent papers have established an essential role for the miRNA-17-92 (miR-17-92) cluster of miRNAs in the development of the heart. Previous research has shown that the Friend of Gata-2 (FOG-2) is critical for cardiac development. To investigate the possibility that the miR-17-92 cluster regulates FOG-2 expression and inhibits proliferation in mouse embryonic cardiomyocytes we initially used bioinformatics to analyze 3’ untranslated regions (3’UTR) of FOG-2 to predict the potential of miR-17-92 to target it. We used luciferase assays to demonstrate that miR-17-5p and miR-20a of miR-17-92 interact with the predicted target sites in the 3’UTR of FOG-2. Furthermore, RT-PCR and Western blot were used to demonstrate the post-transcriptional regulation of FOG-2 by miR-17-92 in embryonic cardiomyocytes from E12.5-day pregnant C57BL/6J mice. Finally, EdU cell assays together with the FOG-2 rescue strategy were employed to evaluate the effect of proliferation on embryonic cardiomyocytes. We first found that the miR-17-5p and miR-20a of miR-17-92 directly target the 3’UTR of FOG-2 and post-transcriptionally repress the expression of FOG-2. Moreover, our findings demonstrated that over-expression of miR-17-92 may inhibit cell proliferation via post-transcriptional repression of FOG-2 in embryonic cardiomyocytes. These results indicate that the miR-17-92 cluster regulates the expression of FOG-2 protein and suggest that the miR-17-92 cluster might play an important role in heart development.

The miR-17-92 cluster regulates FOG-2 expression and inhibits proliferation of mouse embryonic cardiomyocytes.

MicroRNAs (miRNAs) have gradually been recognized as regulators of embryonic development; however, relatively few miRNAs have been identified that regulate cardiac development. A series of recent papers have established an essential role for the miRNA-17-92 (miR-17-92) cluster of miRNAs in the development of the heart. Previous research has shown that the Friend of Gata-2 (FOG-2) is critical for cardiac development. To investigate the possibility that the miR-17-92 cluster regulates FOG-2 expression and inhibits proliferation in mouse embryonic cardiomyocytes we initially used bioinformatics to analyze 3' untranslated regions (3'UTR) of FOG-2 to predict the potential of miR-17-92 to target it. We used luciferase assays to demonstrate that miR-17-5p and miR-20a of miR-17-92 interact with the predicted target sites in the 3'UTR of FOG-2. Furthermore, RT-PCR and Western blot were used to demonstrate the post-transcriptional regulation of FOG-2 by miR-17-92 in embryonic cardiomyocytes from E12.5-day pregnant C57BL/6J mice. Finally, EdU cell assays together with the FOG-2 rescue strategy were employed to evaluate the effect of proliferation on embryonic cardiomyocytes. We first found that the miR-17-5p and miR-20a of miR-17-92 directly target the 3'UTR of FOG-2 and post-transcriptionally repress the expression of FOG-2. Moreover, our findings demonstrated that over-expression of miR-17-92 may inhibit cell proliferation via post-transcriptional repression of FOG-2 in embryonic cardiomyocytes. These results indicate that the miR-17-92 cluster regulates the expression of FOG-2 protein and suggest that the miR-17-92 cluster might play an important role in heart development.

TC1 (C8orf4) is involved in ERK1/2 pathway-regulated G(1)- to S-phase transition.

Although previous studies have implicated a role for TC1 (C8orf4) in cancer cell proliferation, the molecular mechanism of its action is still largely unclear. In this study, we showed, for the first time, that the mRNA levels of TC1 were upregulated by mitogens (FBS/thrombin) and at least partially, through the ERK1/2 signaling pathway. Interestingly, the over-expression of TC1 promoted the G(1)- to S-phase transition of the cell cycle, which was delayed by the deficiency of ERK1/2 signaling in fibroblast cells. Furthermore, the luciferase reporter assay indicated that the over-expression of TC1 significantly increased Cyclin D1 promoter-driven luciferase activity. Taken together, our findings revealed that TC1 was involved in the mitogen-activated ERK1/2 signaling pathway and positively regulated G(1)- to S-phase transition of the cell cycle. Our results may provide a novel mechanism of the role of TC1 in the regulation of cell proliferation.

Expression of Pkd2l2 in testis is implicated in spermatogenesis.

Pkd2l2 is a novel member of the polycystic kidney disease (PKD) gene family in mammals. Prominently expressed in testis, this gene is still poorly understood. In this study, reverse transcription polymerase chain reaction (RT-PCR) results showed a time-dependent expression pattern of Pkd2l2 in postnatal mouse testis. Immunohistochemical analysis revealed that Pkd2l2 encoded a protein, polycystin-L2, which was predominantly detectable in the plasma membrane of spermatocytes and round spermatids, as well as in the head and tail of elongating spermatids within seminiferous tubules in mouse testis tissue sections of postnatal day 14 and adult mice. A green fluorescent fusion protein of Pkd2l2 resided in the plasma membrane of HEK 293 and MDCK cells, suggesting that it functions as a plasma membrane protein. Overexpression of Pkd2l2 increased the intracellular calcium concentration of MDCK cells, as detected by flow cytometry. Collectively, these data indicated that Pkd2l2 may be involved in the mid-late stage of spermatogenesis through modulation of the intracellular calcium concentration.

Characterization of a novel Xenopus SH3 domain binding protein 5 like (xSH3BP5L) gene.

SH3 domain binding protein 5 like (xSH3BP5L) gene encodes a protein that is a new found member of SH3 domain binding protein family which has been implicated at multiple levels of biological functions. Here, we have characterized Xenopus SH3 domain binding protein 5 like (xSH3BP5L) gene in the development of Xenopus laevis. Transcripts of xSH3BP5L were detected at all stages of development and in numerous adult tissues. Whole-mount in situ hybridization demonstrated that xSH3BP5L is expressed at the animal pole from stage-2 onward. Interestingly, translational inhibition of xSH3BP5L using antisense morpholino oligonucleotides (MOs) and overexpression of xSH3BP5L in Xenopus embryos resulted in failed or delayed blastopore closure. Taken together, these data suggested that xSH3BP5L is required for normal embryogenesis of blastopore closure in X. laevis.

[Sequencing the Rhesus boxes and determining the homozygosity of RHD gene in Han Chinese with RhD negative].

OBJECTIVE: To analyze the sequences of Rhesus boxes of RhD gene, and explore the genetic mechanism of RhD negative phenotype in Chinese Han population. Meanwhile the PCR product of Rhesus boxes is analyzed for determining RHD gene homozygosity. METHODS: DNA of 74 RhD negative samples were firstly analyzed with multiplex PCR-sequence specific primer(SSP). The further analysis was given to Rhesus boxes specific sequencing and RHD gene homozygosity determined by PCR-restriction fragment length polymorphism(RFLP) analysis to Rhesus boxes. RESULTS: In DNA samples of 74 RhD negative individuals, 46 samples(62%) showed the absence and homozygous negative of RHD gene; 22 samples(30%) all showed the existence of RHD specific exons, of which 19 were RHD gene heterozygous and 3 were homozygous; regardless of PCR-RFLP analysis showing no RHD specific exons, but further analysis of RHD specific PCR revealed one RHD gene, at least RHD gene exon 1 and 10 existing in 5 DNA samples(7%); 1 sample(1%) was lacking RHD exon 6 although the multiplex PCR showed the RHD gene to be positive. Analyzing the hybrid Rhesus box of 27 RhD negative samples revealed the Han Chinese population to have the same DNA sequence of hybrid Rhesus box as Caucasians. CONCLUSION: The RHD gene deletion is the main molecular mechanism of causing RhD negative formed in Han Chinese population, who have had the RHD gene deletion taken place within the defined breakpoint region as Caucasians.