Discovery of an ellipticine derivative as TLR3 inhibitor against influenza A virus and SARS-CoV-2.

Influenza and COVID-19 continue to pose global threats to public health. Classic antiviral drugs have certain limitations, coupled with frequent viral mutations leading to many drugs being ineffective, the development of new antiviral drugs is urgent. Meanwhile, the invasion of influenza virus can cause an immune response, and an excessive immune response can generate a large number of inflammatory storms, leading to tissue damage. Toll-like receptor 3 (TLR3) recognizes virus dsRNA to ignite the innate immune response, and inhibit TLR3 can block the excess immune response and protect the host tissues. Taking TLR3 as the target, SMU-CX1 was obtained as the specific TLR3 inhibitor by high-throughput screening of 15,700 compounds with IC50 value of 0.11 µM. Its anti-influenza A virus activity with IC50 ranged from 0.14 to 0.33 µM against multiple subtypes of influenza A virus and also showed promising anti-SARS-CoV-2 activity with IC50 at 0.43 µM. Primary antiviral mechanism study indicated that SMU-CX1 significantly inhibited PB2 and NP protein of viruses, it can also inhibit inflammatory factors in host cells including IFN-ß, IP-10 and CCL-5. In conclusion, this study demonstrates the potential of SMU-CX1 in inhibiting IAV and SARS-CoV-2 activity, thereby offering a novel approach for designing antiviral drugs against highly pathogenic viruses.

A small molecule compound targeting hemagglutinin inhibits influenza A virus and exhibits broad-spectrum antiviral activity.

Influenza A virus (IAV) is a widespread pathogen that poses a significant threat to human health, causing pandemics with high mortality and pathogenicity. Given the emergence of increasingly drug-resistant strains of IAV, currently available antiviral drugs have been reported to be inadequate to meet clinical demands. Therefore, continuous exploration of safe, effective and broad-spectrum antiviral medications is urgently required. Here, we found that the small molecule compound J1 exhibited low toxicity both in vitro and in vivo. Moreover, J1 exhibits broad-spectrum antiviral activity against enveloped viruses, including IAV, respiratory syncytial virus (RSV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human coronavirus OC43 (HCoV-OC43), herpes simplex virus type 1 (HSV-1) and HSV-2. In this study, we explored the inhibitory effects and mechanism of action of J1 on IAV in vivo and in vitro. The results showed that J1 inhibited infection by IAV strains, including H1N1, H7N9, H5N1 and H3N2, as well as by oseltamivir-resistant strains. Mechanistic studies have shown that J1 blocks IAV infection mainly through specific interactions with the influenza virus hemagglutinin HA2 subunit, thereby blocking membrane fusion. BALB/c mice were used to establish a model of acute lung injury (ALI) induced by IAV. Treatment with J1 increased survival rates and reduced viral titers, lung index and lung inflammatory damage in virus-infected mice. In conclusion, J1 possesses significant anti-IAV effects in vitro and in vivo, providing insights into the development of broad-spectrum antivirals against future pandemics.

Long non-coding RNA LSAMP-1 is down-regulated in non-small cell lung cancer and predicts a poor prognosis.

BACKGROUND: Long noncoding RNAs (lncRNAs) are emerging as master regulators for gene expression and thus play a vital role in human tumorigenesis and progression. But the involvement of novel lncRNAs in non-small cell lung cancer (NSCLC) remains largely unelucidated. METHODS: A total of 170 NSCLC and their adjacent non-tumor tissues were enrolled to detect the expression of Lnc-LSAMP-1 by RT-qPCR. The effects of Lnc-LSAMP-1 on cell proliferation, migration, invasion and drug-sensitivity were determined by in vitro and in vivo experiments. The proteins that interact with Lnc-LSAMP-1were confirmed by RNA pull-down assay. RNA-sequencing were used to identify the potential targets of Lnc-LSAMP-1 in NSCLC. RESULTS: We found that Lnc-LSAMP-1 was significantly down-regulated in 170 cases of NSCLC tissues when compared to their adjacent non-cancerous tissues. Loss expression of Lnc-LSAMP-1 was notably correlated with unfavorable prognosis of NSCLC patients. The ectopic expression of Lnc-LSAMP-1 drastically inhibited lung cancer cell proliferation, viability, invasion and migration ability, arrested cell cycle and facilitated apoptosis. Chemotherapy sensitization experiments showed that over-expressed Lnc-LSAMP-1 enhanced the inhibition of cell proliferation induced by TKI. Mechanistically, Lnc-LSAMP-1-LSAMP formed a complex which could protect the degradation of LSAMP gene, and thus exerted crucial roles in NSCLC progression and TKI targeted treatment. CONCLUSIONS: Consequently, our findings highlight the function and prognostic value of Lnc-LSAMP-1 in NSCLC and provide potential novel therapeutic targets and prognostic biomarkers for patients with NSCLC.

Copper-Mediated Cyclization of o-Hydroxyaryl Enaminones with 3-Indoleacetic Acids toward the Synthesis of 3-Indolmethyl-Chromones.

Here, we describe a copper-mediated tandem decarboxylative coupling/annulation protocol of o-hydroxyaryl enaminones with 3-indoleacetic acids. A series of 3-indolmethyl-chromones were afforded in up to 97% yield. A one-pot method for 3-indolmethyl-chromones from o-hydroxy acetophenones, N, N-dimethylformamide dimethyl acetal, and 3-indoleacetic acids was also developed. Derivatization of the products was conducted to provide various indolmethyl-substituted pyrimidines. Moreover, a biological evaluation revealed that some compounds had anti-influenza viral activities.

Overexpression miR-24-3p repressed Bim expression to confer tamoxifen resistance in breast cancer.

Endocrine therapy resistance represents a major challenge to the successful treatment of patients with breast cancer. The development of tamoxifen resistance commonly occurrs during the treatment of patients with breast cancer whereas its underlying mechanisms remain elusive. Here, we found that miR-24-3p regulated tamoxifen sensitivity in breast cancer cells. Forced overexpression of miR-24-3p augmented tamoxifen-induced cell viability inhibition in breast cancer cells, while knockdown of miR-24-3p partially attenuated the cytotoxicity effect of tamoxifen. Moreover, we discovered Bim as a target gene of miR-24-3p in breast cancer cells by RNA immunoprecipitation, quantitative reverse transcription polymerase chain reaction, Western blot, and dual luciferase reporter assay. In our established tamoxifen resistant MCF7 cell line (MCF7/TAM), there was a significant elevation of miR-24-3p and decrease of BIM expression compared with parental MCF7 cells. In addition, the inhibition of miR-24-3p could reverse the tamoxifen resistance of MCF7/TAM cells by the induction of cell apoptosis. Silencing of Bim expression blocked miR-24-3p inhibitor-induced elevation of tamoxifen sensitivity of MCF7/TAM cells. Using tumor tissues from patients with breast cancer, we also found that the expression of miR-24-3p was negatively correlated with Bim mRNA expression. Collectively, our study highlighted the pivotal role of miR-24-3p overexpression in mediating the development of tamoxifen resistance in breast cancer and suggested miR-24-3p might be a predictor or target for patients with breast cancer.

Long noncoding RNA HOXD-AS1 induces epithelial-mesenchymal transition in breast cancer by acting as a competing endogenous RNA of miR-421.

Breast cancer (BCa) is the most common malignant tumor in females. Long noncoding RNAs (lncRNAs) are deregulated in many types of human cancers, including BCa. The purpose of the present study was to examine the expression profile and biological role of HOXD cluster antisense RNA 1 (HOXD-AS1) in BCa. Our results revealed that HOXD-AS1 was upregulated in BCa tissues and cell lines, and high HOXD-AS1 expression was correlated with aggressive clinicopathological characteristics of BCa patients. Further gain-of-function and loss-of-function analysis showed that HOXD-AS1 overexpression promoted, whereas HOXD-AS1 knockdown inhibited BCa cell proliferation, cell cycle progression, migration, and invasion, indicating that HOXD-AS1 may function as a novel oncogene in BCa. Mechanistically, HOXD-AS1 could activate epithelial-mesenchymal transition (EMT) in BCa cells. We further proved that HOXD-AS1 might serve as a competing endogenous RNA of miR-421 in BCa cells, and miR-421 was downregulated and negatively correlated with HOXD-AS1 expression in BCa tissues. Besides, we confirmed that SOX4, a master regulator of EMT, was a direct target gene of miR-421. Further, rescue experiments suggested that miR-421 overexpression partly abrogated the oncogenic role of HOXD-AS1 in BCa cells. Therefore, we shed light on that HOXD-AS1/miR-421/SOX4 axis may be considered as a novel therapeutic target for the treatment of BCa patients.

Enhanced UC and IR luminescence properties regulated by tight network structure in multicomponent glasses.

Lanthanide-doped optical functional glasses have received substantial attention in recent years owing to their excellent upconversion (UC) and infrared (IR) performance pumping when used in a semiconductor laser. In this study, the luminescence properties of Ho3+ ions were improved through the design of components used to modulate the microenvironment of the glass. To the best of our knowledge, this is a novel approach to enhancing the UC and IR emissions, and results in up to more than 130% improvement by regulating a tight network glass structure. Herein, the specific preparation design and investigations into the thermal, structural and luminescence properties are described, the results of which indicate that such ZnO-modified germanosilicate (SG-Zn) multicomponent glasses are promising candidates in the fields of biological security marking, optical communication, and 3D volumetric displays.

Oxychloride glass with low phonon energy as a choice for infrared laser materials.

Recently, rare-earth-doped infrared (IR) luminescent glasses have drawn massive attention due to their potential applications in military, medical, and communications fields. In this Letter, we present a system of oxychloride Si-Ge-O-Cl glasses, suitable for rare-earth doping, which has been developed as a new, to the best of our knowledge, choice for IR luminescent materials. Raman spectra show a looser glass network because of the decreased phonon energy and density compared to the one in heavy-metal oxide glasses. The enhanced luminescence from the visible to the IR region has been obtained with a beneficial fluorescence decay time. The spectroscopy results indicate that the system of Si-Ge-O-Cl glasses may be a promising candidate for application in infrared laser materials with enhanced luminescence.

The Association of Occupational Stress and Depressive Symptoms among Employed Persons with Benign Breast Disease: The Mediating Role of Psychological Capital.

BACKGROUND: To evaluate the association between depressive symptoms and occupational stress, and the possibility of psychological capital (PsyCap) in alleviating depressive symptoms and occupational stress, we investigated the mediating role of PsyCap on the association between depressive symptoms and occupational stress among employed persons with benign breast disease (BBD) diagnosed by using ultrasonography. METHODS: A cross-sectional survey was conducted in 371 employed persons with BBD. Self-administered questionnaires, including the items of depressive symptoms, occupational stress, the 24-item Psychological Capital Questionnaire, as well as the age, education, marital status, occupation, monthly income, and weekly working hours, were obtained from all patients. The Center for Epidemiologic Studies Depression Scale (CES-D) was used to measure the depressive symptoms, an effort-reward imbalance model was used to assess occupational stress, while 24-item Psychological Capital Questionnaire measurements were used to measure the PsyCap. Baron and Kenny's technique was used to test the mediating effect of PsyCap. RESULTS: In total, 62% of employed persons with BBD had scores equal to or above the cutoff point (CES-D ≥16). Overcommitment was not significantly correlated with PsyCap (r = -0.096, p = 0.066). Depressive symptoms were positively correlated with the effort-reward ratio (ERR) (ß = 0.327, p < 0.001) in model 2, and it was negatively correlated with PsyCap (ß = -0.339, p < 0.001) in model 3. PsyCap associated with ERR mediated the depressive symptoms. CONCLUSIONS: Besides the medical intervention, the management of depressive symptoms and decrease in occupational stress should be considered to alleviate the depressive symptoms associated with employed persons with BBD. PsyCap is an active resource for relieving depressive symptoms and reducing occupational stress in persons with BBD.

A functional CNVR_3425.1 damping lincRNA FENDRR increases lifetime risk of lung cancer and COPD in Chinese.

Genomic imbalance referring to somatic variation in chromosome copies represents the most frequent event in tumorigenesis. Germline copy number variations (gCNVs) overlapping regions of genomic imbalance harbor similar structural characteristics and thus influence tumor susceptibility. We aimed to test effects of such gCNVs on the risk of lung cancer and chronic obstructive pulmonary disease (COPD). Genomic imbalance of lung cancer was determined by the array comparative genomic hybridization (aCGH), and common gCNVs at these imbalance regions were genotyped in lung cancer-based and COPD-based retrospective studies. Functional assays were conducted to assess function of promising CNVs. A total of 115 genomic imbalances were discovered occurring at a frequency of more than 25%. The CNVR_3425.1, overlapping the chr16q24.1 with genomic imbalance, was significantly associated with increased risks of lung cancer (OR = 1.76; 95% CI = 1.46-2.11) and COPD (OR = 1.98; 95% CI = 1.57-2.51). The increase copy of CNVR_3425.1 forms a new additional truncated FOXF1 adjacent non-coding developmental regulatory RNA (FENDRR) sequences comparing the gene promoter and perturbs the transcriptional factors (TFs) binding to the original FENDRR promoter and further downregulates FENDRR, a long intergenic non-coding RNA (lincRNA) that functions to inhibit lung cancer by affecting expressions of an abundant number of genes, including the tumor suppressor FOXF1. FENDRR can upregulate FOXF1 by competitively binding to miR-424. The TFs early growth response 1 (EGR1) and transcription factor AP-2 alpha (TFAP2A) were further found to involve the CNVR_3425.1-mediated FENDRR dysregulation. These findings suggested the CNVR_3425.1 to be a possibly predictive biomarker for the risk of lung cancer and COPD, and targeted molecular therapy pertaining to FENDRR upregulation may be a valuable pathway to fight two diseases.

Rare variant of MAP2K7 is associated with increased risk of COPD in southern and eastern Chinese.

BACKGROUND AND OBJECTIVE: A wide range of common loci have been extensively screened and evaluated for their associations with various complex diseases; however, the relevance of rare variants causing missense substitutions in the protein-coding genes in human diseases is still poorly understood. METHODS: In this study, we conducted a two-stage retrospective study of a total of 1791 patients with COPD and 1940 controls in southern and eastern Chinese to test relevancies of five rare variants (i.e. p.Glu116Lys, p.Asn118Ser, p.Arg138Cys, p.Ala195Thr and p.Leu259Phe) of human mitogen-activated protein kinase kinase 7 (MAP2K7) to COPD susceptibility. The effects of these loci on lung function were further estimated. RESULTS: The p.Glu116Lys rare variant had significant associations with COPD risk. Compared to individuals with Glu/Glu wild-genotype, those with 116Lys rare variants (Lys/Glu+Lys/Lys) had an increased risk of COPD (OR = 3.83, 95% CI: 2.64-5.56; P = 1.45 × 10-12 ). Meanwhile, the carriers with 116Lys rare variants (Lys/Glu+Lys/Lys) had lower pre-forced expiratory volume in 1 s (pre-FEV1 : 1.74 ± 0.70 vs 2.00 ± 0.68; P = 3.97 × 10-5 ) and lower pre-FEV1 to pre-forced vital capacity ratio (pre-FEV1 /FVC: 0.68 ± 0.14 vs 0.75 ± 0.12; P = 2.40 × 10-10 ) than those with Glu/Glu genotype. However, for other rare variants, no significant association with either COPD risk or lung function was observed. CONCLUSION: Our data strongly suggest that the p.Glu116Lys rare variant in MAP2K7 predisposes its carriers to develop COPD, which would provide a useful genetic biomarker for COPD susceptibility in Chinese.

Investigation and Analysis of Reference Intervals for Blood Cell Parameters in a Healthy Population from Daxingan Region Inner Mongolia.

BACKGROUND: Blood cell parameters in a healthy population of different ages and genders from the Daxingan region of Inner Mongolia were evaluated to establish reference intervals (RIs) for venous blood parameters for healthy individuals from this region. METHODS: Venous blood specimens were collected from 1757 healthy individuals aged 7-65 years and analyzed by an XE-5000 automated hematology analyzer. Results were statistically analyzed by gender and age group. RIs for venous blood parameters of children were compared to the National Clinical Laboratory Procedures and those of adults were compared to the Health Industry Standards of the People's Republic of China (WST405-2012). RESULTS: In the Daxingan region, WBC, RBC, MCV, and NEUT%, MONO%, and EO% of healthy children were significantly different between genders (p < 0.05). Other parameters were not significantly different (p > 0.05). All parameters of adults were significantly different between different genders (p < 0.05) except for LYMPH% and BASO%. Comparison of mean values between children and adults of the same gender revealed significant differences in each blood cell parameter (p < 0.05). RBC, MCV, MCH, MCHC, PLT, MONO%, and BASO% of adult men were significantly different between different age groups (p < 0.05), and HGB, HCT, and EO% of adult women were significantly different between different age groups (p < 0.05). For children, only the mean of MCHC and EO% were close to the National Clinical Laboratory Procedures. Mean of RBC, HGB, PLT, LYMPH%, and MONO% were higher and the remaining parameters were lower than the National Clinical Laboratory Procedures. Compared with WST405-2012 for adults, PLT of women aged 18-40 years and NEUT% of adults were higher, whereas the mean of EO% and BASO% were significantly lower. CONCLUSIONS: RIs for venous blood parameters change with age, geographic region, ethnic group, and gender. There is a great necessity to establish RIs for venous blood parameters among the healthy population in the Daxingan region.

A functional copy-number variation in MAPKAPK2 predicts risk and prognosis of lung cancer.

Mitogen-activated protein kinase-activated protein kinase 2 (MAPKAPK2) may promote cancer development and progression by inducing tumorigenesis and drug resistance. To assess whether the copy-number variation g.CNV-30450 located in the MAPKAPK2 promoter has any effect on lung cancer risk or prognosis, we investigated the association between g.CNV-30450 and cancer risk in three independent case-control studies of 2,332 individuals with lung cancer and 2,457 controls and the effects of g.CNV-30450 on cancer prognosis in 1,137 individuals with lung cancer with survival data in southern and eastern Chinese populations. We found that those subjects who had four copies of g.CNV-30450 had an increased cancer risk (odds ratio = 1.94, 95% confidence interval [CI] = 1.61-2.35) and a worse prognosis for individuals with lung cancer (with a median survival time of only 9 months) (hazard ratio = 1.47, 95% CI = 1.22-1.78) compared with those with two or three copies (with a median survival time of 14 months). Meanwhile, four copies of g.CNV-30450 significantly increased MAPKAPK2 expression, both in vitro and in vivo, compared with two or three copies. Our study establishes a robust association between the functional g.CNV-30450 in MAPKAPK2 and risk as well as prognosis of lung cancer, and it presents this functional copy-number variation as a potential biomarker for susceptibility to and prognosis for lung cancer.

Tissue Transglutaminase-Regulated Transformed Growth Factor-ß1 in the Parasite Links Schistosoma japonicum Infection with Liver Fibrosis.

Transforming growth factor (TGF-ß1) is among the strongest factors of liver fibrogenesis, but its association with Schistosoma-caused liver fibrosis is controversial. Tissue transglutaminase (tTG) is the principal enzyme controlling TGF-ß1 maturation and contributes to Sj-infected liver fibrosis. Here we aim to explore the consistency between tTG and TGF-ß1 and TGF-ß1 source and its correlation with liver fibrosis after Sj-infection. TGF-ß1 was upregulated at weeks 6 and 8 upon liver fibrosis induction. During tTG inhibition, TGF-ß1 level decreased in sera and liver of infected mice. TGF-ß1 showed positive staining in liver containing Sj adult worms and eggs. TGF-ß1 was also detected in Sj adult worm sections, soluble egg antigen and Sj adult worm antigen, and adult worms' culture medium. The TGF-ß1 mature peptide cDNA sequence and its extended sequence were amplified through RT-PCR and RACE-PCR using adult worms as template, and sequence is analyzed and loaded to NCBI GenBank (number GQ338152.1). TGF-ß1 transcript in Sj eggs was higher than in adult worms. In Sj-infected liver, transcriptional level of TGF-ß1 from Sj, but not mouse liver, correlated with liver fibrosis extent. This study provides evidence that tTG regulates TGF-ß1 and illustrates the importance of targeting tTG in treating Sj infection-induced fibrosis.

The effect of functional MAPKAPK2 copy number variation CNV-30450 on elevating nasopharyngeal carcinoma risk is modulated by EBV infection.

UNLABELLED: Mitogen-activated protein kinase-activated protein kinase 2 (MAPKAPK2) is recognized as oncogenic and simulative role on tumorigenesis by virtue of abnormal expression in cancer including nasopharyngeal carcinoma (NPC). We hypothesized that the copy number variation (CNV)-30450, which duplicates the MAPKAPK2 promoter, may affect MAPKAPK2 expression and be associated with NPC risk. In two independent case-control panels of southern and eastern Chinese with a total of 1590 NPC patients and 1979 cancer-free controls, we investigated the association between CNV-30450 and NPC risk by genotyping the CNV-30450 with the TaqMan assay, and tested its biological effect. Consistent findings were observed in the two populations, that the increased copy number of CNV-30450 was associated with increased risk of NPC (3/4-copy versus 2-copy: odds ratio = 1.28, 95% confidence interval = 1.10-1.49), in which lies a biological mechanism that the adverse genotypes enhanced the promoter activity of MAPKAPK2 and elevated MAPKAPK2 expression. Moreover, the CNV-30450 adverse genotypes significantly interacted with Epstein-Barr virus (EBV) infection on increasing NPC risk (P = 0.035), and the genotype-phenotype correlation was only significant in EBV-positive cases (P = 0.037) but not in EBV-negative ones (P = 0.366). These data suggest that the functional CNV-30450 in the MAPKAPK2 promoter elevates the NPC risk with a modulation by EBV infection, which may be an indicator of susceptibility to NPC. SUMMARY: This case-control study suggests that the functional CNV-30450 in the MAPKAPK2 promoter elevates the NPC risk with a modulation by EBV infection, which may be an indicator of susceptibility to NPC.

Nestin: predicting specific survival factors for breast cancer.

The purpose of this study is to investigate the relationship between nestin expression and clinicopathological characteristics, immunohistochemical markers and to determine the prognostic impact of nestin expression in breast cancer so as to lay a foundation for the treatment of breast cancer. A total of 109 patients who were histologically diagnosed with breast cancer and underwent radical operations from January 2006 to September 2007 in China Medical University were enrolled in the study. Nestin protein expression was evaluated by immunohistochemistry. The relationship between nestin and other parameters was analyzed by using chi-square test and Fisher's exact test. Nestin expression was observed in 37.6% (41/109) of cases. There were no significant differences between the age of >40 and ≤40 years group in terms of nestin expression (39.8 vs 18.2%; P = 0.161). The rate of nestin expression between those with and without lymph node metastasis was not significantly different (X (2) = 0.086; P = 0.769). The 5-year survival rates of the patients with nestin expression and those without were 34.1% (14/41) and 55.9% (38/68), respectively (P = 0.028). Overall, triple-negative breast cancers had higher expression rates than other cancers (54.1 vs 29.2%; P = 0.011). Nestin expression rate in ER- and PR-negative tumors was found to be significantly higher than cases that were ER- and PR-positive (P = 0.011 and P = 0.036, respectively). However, it was not found that HER2 expression was related to nestin expression (P = 0.120). These results suggest that the expression of nestin might play an important role in the prognosis of breast carcinoma, especially in the triple-negative subgroups.

Reference intervals for six lipid analytes in 8-14 year-old school children from three different ethnical groups in the Hulun Buir area of China.

BACKGROUND: Reference intervals vary according to gender, age, ethnicity, diet, and other factors. It is therefore recommended that population-specific reference intervals be established. This study investigated reference intervals of blood fat of healthy primary students (8 - 14 years) from Mongolian, Ewenki, and Han ethnicities in Hulun Buir area. METHODS: Blood samples were collected from 1,723 children aged 8 - 14 years: 805 boys (46%) and 918 girls (54%) were analyzed for cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (APOAI), and apolipoprotein B (APOB) levels. TC and LDL-C 90 and 75 percentiles were considered as the critical high lipoprotein level and the lipoprotein concentration standard, TG 90 percentiles as high blood triglycerides concentrations, 5 percentiles as HDL-C reference range lower level and 95 percentiles as reference range of APOAI and APOB, the normal lipid reference interval for three ethnic groups of pupils were set up. RESULTS: There were significant differences between Han and other ethnicities with respect to TC, TG, HDL-C, APOAI, APOB (p < 0.01), but not LDL-C (p > 0.05). There were significant differences in Mongolian and Ewenki ethnicities with respect to LDL-C, HDL-C, APOAI and APOB (p < 0.01), but not TC, TG (p > 0.05). There was significant difference between boys and girls of Han and Mongolian ethnicities in TG, HDL-C, LDL-C, APOAI, APOB lipid levels (p < 0.01); and there was significant difference between boys and girls of Ewenki ethnicity with respect to TG, HDL-C, APOAI, APOB lipid levels (p < 0.01). CONCLUSIONS: Reference intervals of serum lipid parameters blood fat for healthy Mongolian, Ewenki, and Han ethnicities of primary students in Hulun Buir are presented, which provide an important update for lipid markers and suggest earlier incidence of hypercholesterolemia when comparing to previous ranges.

Involvement of IL-13 and tissue transglutaminase in liver granuloma and fibrosis after schistosoma japonicum infection.

Schistosomiasis, one of the most devastating parasitic diseases, is caused by Schistosoma japonicum (Sj) infection resulting in serious liver fibrosis. Interleukin- (IL-) 13, which is produced by TH2 cells, is a critical profibrotic cytokine found in various organs, including the liver. Tissue transglutaminase (tTG), a group of multifunctional enzymes, serves a central function in the pathogenesis of chronic liver diseases. However, the relationship between IL-13, tTG, and liver fibrosis during Schistosoma infection has not been established. This study investigated the involvement of IL-13 and tTG in liver fibrogenesis during Sj infection in mice. Five weeks after Sj infection, granuloma and fibrosis development in the liver coincided with an increase in IL-13 and tTG in the liver and the upregulation of serum IL-13 in infected mice. Administration of cystamine, an inhibitor of tTG, abrogated the increase in both tTG and IL-13 in infected mice and ameliorated liver fibrogenesis and granuloma development. This result establishes a novel link among IL-13, tTG, and liver granuloma and fibrosis under Sj infection. Based on their important functions in liver fibrosis induced by Sj infection, IL-13 and tTG could be promising potential drug targets against schistosomiasis.

A functional polymorphism in the 3'-UTR of PXR interacts with smoking to increase lung cancer risk in southern and eastern Chinese smoker.

Pregnane X receptor (PXR) is an important member of the nuclear receptor superfamily that copes with various endobiotic and xenobiotic stimuli, such as carcinogens by regulating an array of environmental response genes. Low PXR expression has been shown to promote tumor initiation and metastasis. The aim of the current study was to investigate whether the single nucleotide polymorphisms (SNPs) of PXR could alter lung cancer susceptibility in Chinese by affecting the function or expression of PXR. We genotyped three putatively functional SNPs of PXR (i.e., rs3814055C>T, rs3732360C>T, and rs3814058C>T) and analyzed their associations with lung cancer risk in a two-stage case-control study with a total of 1559 lung cancer cases and 1679 controls in the southern and eastern Chinese population. We found that in comparison to the rs3814058CC common genotype, the rs3814058T variants (TC/TT) which is located in the 3'-untranslated region (3'-UTR) of PXR conferred a consistently increased risk of lung cancer in both the southern Chinese (odd ratios (OR)=1.24, 95% confidence interval (CI)=1.03-1.49) and the eastern Chinese (OR=1.33, 95% CI=1.02-1.75). The variants also significantly interacted with smoking on increasing cancer risk (p=0.023). Moreover, lung cancer tissues with the rs3814058T variants showed significantly lower PXR expression than those with rs3814058CC genotype in the smokers (p=0.041). These results suggested that the rs3814058C>T polymorphism of PXR interacts with smoking on increasing lung cancer risk in Chinese smokers, which might be a functional genetic biomarker for lung cancer.