Paraoxonase 2 protein is spatially expressed in the human placenta and selectively reduced in labour

Humans parturition involves interaction of hormonal, neurological, mechanical stretch and inflammatory pathways and the placenta plays a crucial role. The paraoxonases (PONs 1–3) protect against oxidative damage and lipid peroxidation, modulation of endoplasmic reticulum stress and regulation of apoptosis. Nothing is known about the role of PON2 in the placenta and labour. Since PON2 plays a role in oxidative stress and inflammation, both features of labour, we hypothesised that placental PON2 expression would alter during labour. PON2 was examined in placentas obtained from women who delivered by cesarean section and were not in labour and compared to the equivalent zone of placentas obtained from women who delivered vaginally following an uncomplicated labour. Samples were obtained from 12 sites within each placenta: 4 equally spaced apart pieces were sampled from the inner, middle and outer placental regions. PON2 expression was investigated by Western blotting and real time PCR. Two PON2 forms, one at 62 kDa and one at 43 kDa were found in all samples. No difference in protein expression of either isoform was found between the three sites in either the labour or non-labour group. At the middle site there was a highly significant decrease in PON2 expression in the labour group when compared to the non-labour group for both the 62 kDa form (p = 0.02) and the 43 kDa form (p = 0.006). No spatial differences were found within placentas at the mRNA level in either labour or non-labour. There was, paradoxically, an increase in PON2 mRNA in the labour group at the middle site only. This is the first report to describe changes in PON2 in the placenta in labour. The physiological and pathological significance of these remains to be elucidated but since PON2 is anti-inflammatory further studies are warranted to understand its role

THE SIGNIFICANCE OF MINIMAL RESIDUAL DISEASE IN ACUTE LYMPHOBLASTIC LEUKAEMIA: A SINGLE CENTRE STUDY

In Acute lymphoblastic Leukemia (ALL) assessment of molecular response to treatment, assessing minimal residual disease (MRD) is a major independent predictor of treatment outcome. Consequently, MRD is implemented in all ALL-treatment protocols to fill up or to redefine stratification of multifactorial risk with optional intensity of customized treatment. Aim: to specify the significance of MRD in the assessment of remission in children with ALL with results discordant between morphology and flow cytometry at the end of induction phase of therapy. Materials and Methods: A descriptive cross-sectional study was conducted at Jin Oncology Center from March 2019 through November 2023. Data were taken out of the records of 58 patients who had ALL less than 16 years old. All patients were less than 16 years old and treated by ukall. They were diagnosed using peripheral blood morphology, bone marrow study and/or flow cytometry when lymphoblasts in peripheral blood or bone marrow aspirate are ≥20% and was confirmed by flow cytometry. On 29th day of induction therapy, bone marrow was examined for morphology and flow cytometry. The presence or absence of MRD was determined, and CD19, CD10 and tdt were tested. By morphologic assessment they were divided patients into: Category 1, C1 (20% blasts). Statistical analysis was made using SPSS version 25. P value of less than 0.05 was considered significant. Results: The study involved 58 patients who had ALL. with a median age of 6.5 years, male to females ratio of 1.76:1, mean platelet count of 96.6 x 10⁹/L ,mean hemoglobin of 8.6 g/dL, mean leucocyte count of 74.3 x 10⁹/L), 48 cases (82.7%) of B-cell lineage and 10 cases (17.3%) of T-cell lineage, 94.6% of the B-cell cases were of the common B-ALL and the rest Pro-BALL type, 54.6% of the T-cell ALL was cortical T-ALL  and 44.4% Early T-cell ALL.  They were tested for MRD by morphology and flow cytometry on day 29. By morphology, 46 patients had remission but by flow only 24 cases. Seventeen cases had residual blasts >5%. In 19 cases there was a discrepancy between the results of morphology and flow. Twenty-five cases (52.08% of B-cell cases) were positive for MRD by flow results. Eight of the ten cases of T-ALL (80%), were positive for MRD by flow cytometry. Among 48 cases of B-ALL, 36 were in C1 category (morphologically in remission), 11 cases were in C2 category and one case in the C3 category. Of cases in C1 category, 17 were MRD +ve and 19 were MRD –ve by flow cytometry. In the C2 category, only 2 out of the 11 cases (18.18%) had discordant results between morphology and flow results. The correlation between morphology and flow results was 100% in the C3 category. Conclusion: MRD should not be the surrogate of morphology but to be used in conjunction in order to give us a more accurate representation of status of remission

High-Resolution Mass Spectrometry for Human Exposomics: Expanding Chemical Space Coverage

In the modern "omics" era, measurement of the human exposome is a critical missing link between genetic drivers and disease outcomes. High-resolution mass spectrometry (HRMS), routinely used in proteomics and metabolomics, has emerged as a leading technology to broadly profile chemical exposure agents and related biomolecules for accurate mass measurement, high sensitivity, rapid data acquisition, and increased resolution of chemical space. Non-targeted approaches are increasingly accessible, supporting a shift from conventional hypothesis-driven, quantitation-centric targeted analyses toward data-driven, hypothesis-generating chemical exposome-wide profiling. However, HRMS-based exposomics encounters unique challenges. New analytical and computational infrastructures are needed to expand the analysis coverage through streamlined, scalable, and harmonized workflows and data pipelines that permit longitudinal chemical exposome tracking, retrospective validation, and multi-omics integration for meaningful health-oriented inferences. In this article, we survey the literature on state-of-the-art HRMS-based technologies, review current analytical workflows and informatic pipelines, and provide an up-to-date reference on exposomic approaches for chemists, toxicologists, epidemiologists, care providers, and stakeholders in health sciences and medicine. We propose efforts to benchmark fit-for-purpose platforms for expanding coverage of chemical space, including gas/liquid chromatography-HRMS (GC-HRMS and LC-HRMS), and discuss opportunities, challenges, and strategies to advance the burgeoning field of the exposome

Molecular model of cytotoxin-1 from Naja mossambica mossambica venom in complex with chymotrypsin

Snake venom is a myriad of biologically active proteins and peptides. Three finger toxins are highly conserved in their molecular structure, but interestingly possess diverse biological functions. During the course of evolution the introduction of subtle mutations in loop regions and slight variations in the three dimensional structure, has resulted in their functional versatility. Cytotoxin-1(UniProt ID: P01467), isolated from Naja mossambica mossambica, showed the potential to inhibit chymotrypsin and the chymotryptic activity of the 20S proteasome. In the present work we describe a molec-ular model of cytotoxin-1 in complex with chymotrypsin, pre- pared by the online server ClusPro. Analysis of the molecular model shows that Cytotoxin-1(P01467) binds to chymotrypsin through its loop I located near the N -terminus. The concave side of loop I of the toxin fits well in the substrate binding pocket of the protease. We propose Phe" as the dedicated P1 site of the ligand. Being a potent inhibitor of the 20S proteasome, cytotoxin-1 (P01467) can serve as a potential antitumor agent. Already snake venom cytotoxins have been investigated for their ability as an anticancer agent. The molecular model of cytotoxin-1in complex with chymotrypsin provides important information towards understanding the complex formation