分子バイオマーカーと診断のジャーナル

Background: Chronic inflammation is considered as an emerging area of research interest because of its cognize association with different organ cancers. Recent advances in cancer research have substantiated that targeting cytokines have a strong therapeutic potential in reducing the mortality of inflammation-related cancers. Gallbladder cancer (GBC) has been consistently associated with inflammation mostly due to presence of gallstones which prelude inflammatory response. The Interleukin-1 (IL1) gene cluster serves an important function of immunomodulation, thereby regulating interplay between inflammation and cancer. Studies on the association of IL1 polymorphisms with GS and GBC have shown drastic variations in different populations. Since no such study has been carried out in ethnic Kashmiri population which is known for high incidence of GS disease, we aimed to evaluate the possible role of pro-inflammatory IL1 family in the pathogenesis of GBC and GS disease. Methods: A total of 370 individuals (120 GBC, 120 GS and 130 healthy controls) were prospectively recruited. The study analyzed various polymorphisms of IL1 gene family to predict their association with GBC and gallstone disease. PCR-Restriction Fragment Length Polymorphism (PCR-RFLP) was used for genotyping and SPSS 23.0 software was used to calculate odds ratios (ORs) and confidence intervals (CIs). Tissuespecific expression of IL-1α was done by Quantitative Real-time PCR (qRT-PCR) and the data was analyzed by Graph Pad Prism version 5. Results: IL1R2 T/G DraIII 'GG' genotype (OR: 2.65, 95% CI: 1.27-5.53, P=0.011) and 'G' allele (OR: 1.57, 95% CI: 1.10-2.24, P=0.014) indicated a positive association with GBC. Two polymorphisms in the IL1 gene family (IL-1α +4845G/T and IL1R1Pst1C/T) were observed to be insignificant towards GBC in our study cohort. IL-1α mRNA expression did not differ between tumor and adjacent normal GB tissues. Above all none of the studied polymorphisms was significant towards gallstone disease. Conclusion:  We conclude that IL1R2 DraIII T/G SNP bears a significant association with GBC and could be an important etiological factor for GBC in our population. 

The COVID-19 pandemic has played havoc on both the global health and economy. Permanent quarantine measures do not appear to be feasible due to obvious reasons. However, a molecular signature to differentiate between low-risk and high-risk individuals will be helpful to set better quarantine measures. Pathogens, including viruses of the upper respiratory tract utilize mucin proteins to enter into host cells. In this review, we highlight the importance of studying the glycome and mucin signature in predicting the susceptibility, progression and response to therapy in COVID-19 patients. Identifying the high-risk versus low-risk groups will help take better actions to save both the health system and economy. 

SUMOylation, as post-translational modifications, plays essential roles in various biological functions including cell growth and migration, stress response, and tumorigenesis. In SUMOylation, SENP1 catalyzes the SUMO protein maturation to combine with target proteins. Breast cancer is a common malignancy in women and also SENP1 progression is high in this cancer. Thymoquinone is a biologically active substance and a secondary metabolite found in the black seed, and recent researches indicate antioxidant, anti-inflammatory, anti-cancer and other important biological activities. The effects and mechanisms of Thymoquinone on SENP1 are not well studied. For this purpose, the first MCF-7 tumor cell line and normal MCF-10A cell line were cultured in normal conditions and then treated with specific doses of thymoquinone. The lethal activity was evaluated by MTT assay and exhibited that the toxicity of thymoquinone on MCF-7 cell line was higher than healthy cell and the intensity of its effect was different from MCF-10A cell. Then SENP1 gene expressions were measured. Gene expression changes in tumor cells were then compared with normal cells and it was found that thymoquinone was able to reduce SENP1 gene expression in the tumor cells. Then docking of Thymoquinone with SENP1 protein was performed. The amount of binding energy between Thymoquinone and protein SENP1 is -54 and with dimer of Thymoquinone is -80. Based on what researchers have concluded in this study, it is possible that the mentioned gene and SENP1 Protease can be considered as a candidate for breast cancer treatment and drug target. 

Objective: To compare the mean values of CSF parameters (lactate, protein, sugar, ADA) and thereby distinguish between cases of bacterial and non-bacterial meningitis. Materials and methods: A cross sectional study was conducted in which 60 adult patients were included and CSF parameters (differential counts, protein, sugar, ADA, lactate) were in analyzed in 22 patients of bacterial meningitis and 38 patients of aseptic meningitis. Data were analyzed using SPSS version 21.0. Descriptive statistics are represented using frequencies and percentages. Analytical statistics were represented using Chi-square test for the comparison of categorical variables. The mean values were compared using independent t- test. Results: Among the other CSF parameters, the mean value of CSF lactate and CSF sugars were found to have significant difference (p-value 0.01) in bacterial and non-bacterial meningitis. With a cut off value of 3 mmol/l, CSF lactate was useful in differentiating bacterial meningitis from aseptic meningitis. However other parameters including CSF protein and CSF ADA did not show significant difference between bacterial meningitis including TBM and non-bacterial meningitis, whereas CSF lactate also showed significant difference in TBM and viral meningitis. It was also found out that mortality is proportionately increased with the increasing lactate levels. Conclusion: This study concludes that CSF lactate is an important, independent and reliable biomarker with a cut off value of 3mmol/L, to differentiate bacterial meningitis including TBM from nonbacterial meningitis. TBM and viral meningitis are difficult to differentiate due to their similar clinical features and lab parameters. In such cases, CSF lactate can be taken as a reliable differentiating marker. CSF lactate can be used when CSF gram stain and cultures are inconclusive and time consuming. Thus, helps in initiating early treatment and achieving better outcomes. 

Peripheral blood mononuclear cells (PBMCs) were isolated from 3 groups of she-buffaloes (Tuberculosis, Metritis, and Healthy control) was sequenced by RNA-Seq (using Illumina Hiseq 2500 platform). The pre-processed reads, obtained from transcriptome sequencing, were aligned to the Bostaurus genome using the Hisat-2 program. Gene expression was studied using the String Tie program. A total of 31982 transcripts were identified. Comparisons of the entire 3 groups’ revealed 176 differentially expressed genes (DEGs) in TB vs. healthy groups and 162 DEGs in metritis vs. healthy groups. Analysis of gene ontology and pathways (molecular function and biological processes) identified certain pathways like cytokine activity, Wnt signaling, PI3K-Akt signaling, MAPK signalling (between TB and healthy groups) and cAMP signaling, Wnt signaling, TGFbeta signaling, MAPK signaling, PI3K-Akt signaling, etc. between metritis-positive and healthy buffaloes. Network analysis identified the immunerelated genes contributing to the system biology related to the disease-resistance in Nili Ravi buffalo. Besides, five differentially expressed genes have been validated using SYBR-green chemistry of qPCR. In the future, these key genes could be studied in detail to explore their potential to be promising biomarkers for selecting breeding animals with higher tolerance against these economically devastating diseases.