[Analysis of the prevalence of dyslipidemia and correlative factors in Tajik population in Pamir Plateau of Xinjiang].

Objective: To investigate the prevalence of dyslipidemia and the level of blood lipids among Tajik people in Pamir Plateau, Xinjiang, and explore the related factors of dyslipidemia. Methods: It is a retrospective cross-sectional study. A multi-stage cluster random sampling survey was conducted among 5 635 Tajiks over 18 years old in Tashkorgan Tajik Autonomous County, Xinjiang Province from May to October 2021. Data were collected through questionnaire survey (general information, medical history, and personal history), physical examination (height, weight, waist, and blood pressure) and blood test (total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density cholesterol (HDL-C)) to analyze the dyslipidemia and its risk factors among Tajiks. Results: The age of Tajik participants was (41.9±15.0) years, including 2 726 males (48.4%). The prevalence of borderline high TC, high LDL-C and high TG levels were 17.2%, 14.7% and 8.9%, respectively. The prevalence of high TC, high LDL-C, high TG and low HDL-C were 4.1%, 4.9%, 9.4% and 32.4%, respectively, and the prevalence of dyslipidemia was 37.0%. There is a positive correlation between male,higher education level, higher body mass index (BMI) value,waist circumference, living in town, smoking and dyslipidemia. Conclusions: The low prevalence of high TC, high LDL-C, high TG and high prevalence of low HDL-C was a major characteristic of Tajik people in Pamir Plateau of Xinjiang. The lower rates of overweight and obesity may be one of the reasons for the lower prevalence of dyslipidemia among Tajik.

Exosome-mediated transfer of MIF confers temozolomide resistance by regulating TIMP3/PI3K/AKT axis in gliomas.

Temozolomide (TMZ) resistance is an important cause of clinical treatment failure and poor prognosis in gliomas. Increasing evidence indicates that cancer-derived exosomes contribute to chemoresistance; however, the specific contribution of glioma-derived exosomes remains unclear. The aim of this study was to explore the role and underlying mechanisms of exosomal macrophage migration inhibitory factor (MIF) on TMZ resistance in gliomas. We first demonstrated that MIF was upregulated in the exosomes of TMZ-resistant cells, engendering the transfer of TMZ resistance to sensitive cells. Our results indicated that exosomal MIF conferred TMZ resistance to sensitive cells through the enhancement of cell proliferation and the repression of cell apoptosis upon TMZ exposure. MIF knockdown enhanced TMZ sensitivity in resistant glioma cells by upregulating Metalloproteinase Inhibitor 3 (TIMP3) and subsequently suppressing the PI3K/AKT signaling pathway. Additionally, exosomal MIF promoted tumor growth and TMZ resistance of glioma cells in vivo, while IOS-1 (MIF inhibitor) promotes glioma TMZ sensitive in vivo. Taken together, our study demonstrated that exosome-mediated transfer of MIF enhanced TMZ resistance in glioma through downregulating TIMP3 and further activating the PI3K/AKT signaling pathway, highlighting a prognostic biomarker and promising therapeutic target for TMZ treatment in gliomas.

Topologically protected beam splitters and logic gates based on two-dimensional silicon photonic crystal slabs.

The beam splitters are essential optical components that are widely used in various optical instruments. The robustness of beam splitters is very necessary to all-optical networks. Here we report the design of the topologically protected beam splitter, whose splitting ratio can change flexibly to an arbitrary ratio, such as 50:50, 33:67, 25:75, based on the two-dimensional silicon photonic crystal slab. By using the 50:50 beam splitter, all major logic gates (OR, AND, NOT, XOR, NAND, XNOR, and NOR) are suitably designed with the linear interference approach. Additionally, these devices exhibit robustness even though some disorders exist. It is expected that these robust and compact devices are potentially applicable in optical computing and signal processing.

Inflammation in lung after acute myocardial infarction is induced by dendritic cell-mediated immune response.

The present study was performed to describe the changes of lung tissues in mice with acute myocardial infarction (AMI) and also explain the cell mechanism involved in inflammation in lung. AMI was established by left coronary ligation in mice. Then mice were divided into three groups: control group, MW1 group (sampling after surgery for one week) and MW2 group (sampling after surgery for two weeks). Afterwards, measurement of lung weight and lung histology, cell sorting in bronchoalveolar lavage (BAL) fluid and detection of several adhesive molecules, inflammatory molecules as well as enzyme associated with inflammation were performed. Moreover, dendritic cells (DCs) were isolated from bone marrow of C57B/L6 mice. After incubating with necrotic myocardium, the expression of antigen presenting molecules, co-stimulatory molecules and inflammatory molecules were detected by flow cytometry or immunohistochemistry in DCs. We also detected T-cell proliferation after incubating with necrotic myocardium-treated DCs. AMI induced pathological changes of lung tissue and increased inflammatory cell amount in BAL fluid. AMI also increased the expression of several inflammatory factors, adhesive molecules and enzymes associated with inflammation. CD11c and TLR9, which are DC surface markers, showed a significantly increased expression in mice with AMI. Additionally, necrotic myocardium significantly increased the expression of co-stimulatory factors including CD83 and CD80, inflammatory cytokines including TNF-α, IFN-γ and NF-κB in DCs. Furthermore, DCs treated with necrotic myocardium also significantly promoted T-cell proliferation. AMI induced inflammation in lung and these pathological changes were mediated by DC-associated immune response.

A genome-wide association analysis for susceptibility of pigs to enterotoxigenic Escherichia coli F41.

Enterotoxigenic Escherichia coli (ETEC) is a type of pathogenic bacteria that cause diarrhea in piglets through colonizing pig small intestine epithelial cells by their surface fimbriae. Different fimbriae type of ETEC including F4, F18, K99 and F41 have been isolated from diarrheal pigs. In this study, we performed a genome-wide association study to map the loci associated with the susceptibility of pigs to ETEC F41 using 39454 single nucleotide polymorphisms (SNPs) in 667 F2 pigs from a White Duroc×Erhualian F2 cross. The most significant SNP (ALGA0022658, P=5.59×10-13) located at 6.95 Mb on chromosome 4. ALGA0022658 was in high linkage disequilibrium (r 2>0.5) with surrounding SNPs that span a 1.21 Mb interval. Within this 1.21 Mb region, we investigated ZFAT as a positional candidate gene. We re-sequenced cDNA of ZFAT in four pigs with different susceptibility phenotypes, and identified seven coding variants. We genotyped these seven variants in 287 unrelated pigs from 15 diverse breeds that were measured with ETEC F41 susceptibility phenotype. Five variants showed nominal significant association (P<0.05) with ETEC F41 susceptibility phenotype in International commercial pigs. This study provided refined region associated with susceptibility of pigs to ETEC F41 than that reported previously. Further works are needed to uncover the underlying causal mutation(s).

Phylogeography and origin of Chinese domestic chicken.

The loss of local chicken breeds as result of replacement with cosmopolitan breeds indicates the need for conservation measures to protect the future of local genetic stocks. The aim of this study is to describe the patterns of polymorphism of the hypervariable control region of mitochondrial DNA (HVR1) in domestic chicken in China's Jiangxi province to investigate genetic diversity, genetic structure and phylo-dynamics. To this end, we sequenced the mtDNA HVR1 in 231 chickens including 22 individuals which belonged to previously published sequences. A neighbor-joining tree revealed that these samples clustered into five lineages (Lineages A, B, C, E and G). The highest haplotype diversity and nucleotide diversity were both found in Anyi tile-liked gray breed. We estimated that the most recent common ancestor of the local chicken existed approximately 16 million years ago. The mismatch distribution analysis showed two major peaks at positions 4 and 9, while the neutrality test (Tajima's D = -2.19, p < 0.05) and Fu's F-statistics (-8.59, p < 0.05) revealed a significant departure from the neutrality assumption. These results support the idea that domestication of chickens facilitated population increases. Results of a global AMOVA indicated that there was no obvious geographic structure among the local chicken breeds analyzed in this study. The data obtained in this study will assist future conservation management of local breeds and also reveals intriguing implications for the history of human population movements and commerce.

Pharmacokinetics of oxytetracycline in hemolymph from the Chinese mitten crab, Eriocheir sinensis.

The purpose of this study was to investigate the hemolymph kinetics and depuration time of oxytetracycline following intramuscular administration at doses of 2, 8 and 40 mg/kg body weight, respectively. The concentration of OTC in hemolymph was assayed using solid phase extraction and high performance liquid chromatography. The elimination half-life of the terminal part of the elimination phase (t(1/2ß) ) ranged from 87.9 to 114.3 h. The total body clearance (CL(b) ) was 0.0430 L/kg/h at the lower dose, 0.0123 L/kg/h at the medium dose and 0.0013 L/kg/h at the higher dose. The apparent volume of the central compartment (V(c) ) was found to be 1.383, 0.699 and 0.143 L/kg respectively. The depuration time for each dose was 13.6, 29.6 and 57.6 days, respectively. Results from the present study suggest that the 40 mg/kg dose might have the best therapeutic efficacy following intramuscular administration.

Identification of cytochrome P450 enzymes responsible for N -dealkylation of a new oral erectogenic, mirodenafil.

The purpose of this paper is to characterize the cytochrome P450 (CYP) enzymes involved in the metabolism of a new oral erectogenic, mirodenafil, to a major circulating active metabolite, N-dehydroxyethyl-mirodenafil, and to investigate the inhibitory potential of mirodenafil on seven CYP enzymes in human liver microsomes. CYP3A4 was identified as the major enzyme and CYP2C8 as a minor enzyme responsible for mirodenafil N-dealkylation based on correlation analysis, inhibition studies, and cDNA-expressed CYP enzyme activities. Plasma concentrations of mirodenafil and its N-dealkylated metabolite could therefore change with co-administration of known CYP3A4 inducers or inhibitors. Mirodenafil inhibited CYP3A4, CYP2C19 and CYP2D6 activities with IC50 values of 15.6, 38.2 and 77.0 microM, respectively, in human liver microsomes. However, it is very unlikely that mirodenafil will significantly alter the clearance of other compounds metabolized by CYPs 1A2, 2A6, 2C8, 2C9, 2C19, 2D6 and 3A4 because the maximum plasma concentration of mirodenafil is 0.55 microM after oral dosing of mirodenafil (100 mg) in male volunteers.

In vitro metabolism of eupatilin by multiple cytochrome P450 and UDP-glucuronosyltransferase enzymes.

Eupatilin, a pharmacologically active flavone derived from Artemisia plants, is extensively metabolized to eupatilin glucuronide, 4-O-desmethyleupatilin and 4-O-desmethyleupatilin glucuronide in human liver microsomes. This study characterized the human liver cytochrome P450 (CYP) and UDP-glucuronosyltransferase (UGT) enzymes responsible for the metabolism of eupatilin. The specific CYPs responsible for O-demethylation of eupatilin to the major metabolite, 4-O-desmethyleupatilin were identified using a combination of correlation analysis, immuno-inhibition, chemical inhibition in human liver microsomes and metabolism by human cDNA-expressed CYP enzymes. UGT enzymes involved in the eupatilin glucuronidation were identified using pooled human liver microsomes and human cDNA-expressed UGT enzymes. Eupatilin was predominantly metabolized by CYP1A2 and, to a lesser extent, CYP2C8 mediated O-demethylation of eupatilin to 4-O-desmethyleupatilin. Eupatilin glucuronidation was catalysed by UGT1A1, UGT1A3, UGT1A7, UGT1A8, UGT1A9, and UGT1A10.

Characterization of cytochrome P450s mediating ipriflavone metabolism in human liver microsomes.

Ipriflavone, a synthetic flavonoid for the prevention and treatment of osteoporosis, has been reported to be extensively metabolized in man to seven metabolites (M1-M7). This study was performed to characterize the human liver cytochrome P450s (CYP) responsible for the metabolism of ipriflavone. Hydroxylation at the beta-ring to M3, O-dealkylation to M1 and oxidation at isopropyl group to M4 and M5 are major pathways for ipriflavone metabolism in three different human liver microsome preparations. The specific CYPs responsible for ipriflavone oxidation to the active metabolites, M1, M3, M4 and M5 were identified using a combination of correlation analysis, immuno-inhibition, chemical inhibition in human liver microsomes and metabolism by expressed recombinant CYP enzymes. The inhibitory potencies of ipriflavone and its five metabolites, M1-M5 on seven clinically important CYPs were investigated in human liver microsomes. Our results demonstrate that CYP3A4 plays the major role in O-dealkylation of ipriflavone to M1 and CYP1A2 plays a dominant role in the formation of M3, M4 and M5. Ipriflavone and/or its five metabolites were found to inhibit potently the metabolism of CYPs 1A2, 2C8, 2C9 and 2C19 substrates.

Role of human cytochrome P450 3A4 in the metabolism of DA-8159, a new erectogenic.

The purpose of this paper was to characterize cytochrome P450 (CYP) enzymes involved in N-dealkylation of a new oral erectogenic, DA-8159 to DA-8164, a major circulating active metabolite, in human liver microsomes and to investigate the inhibitory potential of DA-8159 on CYP enzymes. CYP3A4 was identified as the major enzyme responsible for DA-8159 N-dealkylation to DA-8164 based on correlation analysis and specific CYP inhibitor and antibody-mediated inhibition study in human liver microsomes, and DA-8159 metabolism in cDNA expressed CYP enzymes. There is the possibility of drug-drug interactions when prescribing DA-8159 concomitantly with known inhibitors or inducers of CYP3A4. DA-8159 was found to be only a very weak inhibitor of eight major CYPs (1A2, 2A6, 2C8, 2C9, 2C19, 2D6, 2E1 and 3A4), the largest inhibition occurring against CYP2D6 (IC5o 67.7 microM) in human liver microsomes. Drug-drug interactions would not be predicted on the basis of DA-8159 inhibiting the metabolism of coadministered drugs.

In vitro metabolism of a new H(+)/K(+) ATPase inhibitor DBM-819 in liver microsomes using HPLC and electrospray mass spectrometry.

The metabolism of 1-(2-methyl-4-methoxyphenyl)-4-[(3-hydroxypropyl)amino]-6-methyl-2,3-dihydropyrrolo[3,2c]quinoline (DBM-819), a new H(+)/K(+) ATPase inhibitor, has been studied by HPLC with spectrometric detection and on-line LC-electrospray mass spectrometry. In vitro incubation of DBM-819 with rat liver microsomes in the presence of NADPH resulted in the production of four metabolites (M1-4), whereas DBM-819 was oxidized to two metabolites, M2 and M4, by human liver microsomes. M2, M3 and M4 were identified as O-demethyl-DBM-819, 8-hydroxy-DBM-819 and N-dehydroxypropyl-DBM-819, respectively, based on LC/MS/MS analysis with authentic standards. M1 was tentatively identified as 1-(hydroxy-2-methyl-4-methoxyphenyl)-4-[(3-hydroxypropyl)amino]-6-methyl-2,3-dihydropyrrolo[3,2c]quinoline. Rat liver CYP1A1/2 catalyzed the oxidation of DBM-819 to 8-hydroxy-DBM-819 and N-dehydroxypropyl-DBM-819. Human CYP3A4 was a major isozyme for the formation of O-demethyl-DBM-819 as well as N-dehydroxypropyl-DBM-819.