Hemolysis-associated anemia is characteristic of diseases such as atherosclerosis, lupus, malaria, and leishmaniasis; the toxic effects of free hemoglobin (Hb) have been extensively described. This study was based on the premise that release of this sequestered, inflammatory molecule can result in deleterious immunological consequences, particularly in the context of pre-existing lupus. IgG anti-Hb responses were detected in the sera of lupus patients. Lupus-prone mice exhibited heightened plasma Hb levels, and ferric (Fe3+) Hb triggered preferential release of lupus-associated cytokines from splenocytes derived from aging lupus-prone mice. Anti-Hb B cell precursor frequencies were heightened in such mice, which also expressed increased titers of anti-Hb antibodies in serum and in kidney eluates. Fe3+ Hb preferentially increased the functional maturation of bone marrow-derived dendritic cells (BMDCs) from lupus-prone mice, effects abrogated upon the inhibition of Stat3. Hb interacted with lupus-associated autoantigens extruded during apoptosis and coincubation of Hb and apoptotic blebs had additional maturation-inducing effects on lupus BMDCs. Immunization with Hb in lupus-prone mice induced antigen spreading to lupus-associated moieties; Hb-interacting autoantigens were preferentially targeted and increased complement deposition and glomerulosclerosis were observed. Hb therefore demonstrates both antigenicity and immunogenicity and triggers specific immuno-pathological effects in a lupus milieu.

Psoriasis is a common chronic inflammatory skin disease affecting >125 million individuals worldwide. The therapeutic course for the disease is generally designed upon the severity of the disease. In the present study, the gene expression profile GSE78097, was retrieved from the National Centre of Biotechnology (NCBI)-Gene Expression Omnibus (GEO) database to explore the differentially expressed genes (DEGs) in mild and severe psoriasis using the Affy package in R software. The Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathways of the DEGs were analysed using clusterProfiler, Bioconductor, version 3.8. In addition, the STRING database was used to develop DEG-encoded proteins and a protein-protein interaction network (PPI). Cytoscape software, version 3.7.1 was utilized to construct a protein interaction association network and analyse the interaction of the candidate DEGs encoding proteins in psoriasis. The top 2 hub genes in Cytohubba plugin parameters were validated using immunohistochemical analysis in psoriasis tissues. A total of 382 and 3,001 dysregulated mild and severe psoriasis DEGs were reported, respectively. The dysregulated mild psoriasis genes were enriched in pathways involving cytokine-cytokine receptor interaction and rheumatoid arthritis, whereas cytokine-cytokine receptor interaction, cell cycle and cell adhesion molecules were the most enriched pathways in severe psoriasis group. PL1N1, TLR4, ADIPOQ, CXCL8, PDK4, CXCL1, CXCL5, LPL, AGT, LEP were hub genes in mild psoriasis, whereas BUB1, CCNB1, CCNA2, CDK1, CDH1, VEGFA, PLK1, CDC42, CCND1 and CXCL8 were reported hub genes in severe psoriasis. Among these, CDC42, for the first time (to the best of our knowledge), has been reported in the psoriasis transcriptome, with its involvement in the adaptive immune pathway. Furthermore, the immunoexpression of CDK1 and CDH1 proteins in psoriasis skin lesions were demonstrated using immunohistochemical analysis. On the whole, the findings of the present integrated bioinformatics and immunohistochemical study, may enhance our under-standing of the molecular events occurring in psoriasis, and these candidate genes and pathways together may prove to be therapeutic targets for psoriasis vulgaris.

Aim: This study was aimed to evaluate the association of maternal determinants with birth weight (BW) of babies in tea garden workers (TGW) and housewives (HW). Methods: A total of 175 subjects were recruited from Assam Medical College, Dibrugarh, India. In this cross-sectional study, maternal determinants, BW of babies and placental weight were explored in TGW (n = 102) and HW (n = 73). These factors were assessed and correlated by logistic regression models. Results: A higher incidence of low birth weight (LBW) was found in mothers working in the tea garden (48.04%) as compared to HW (10.96%). Activity of plucking of leaves in tea garden by women had a higher risk for LBW babies (adjusted odd ratio [AOR] 4.33, 95% confidence interval [CI] 1.38-13.57, P = 0.012) and decreased placental weight (AOR 11.42, 95% CI 1.18-126.02, P = 0.036) as compared to HW considered as reference group. Women who worked continuously in the tea garden during 9 months of pregnancy also revealed an elevated risk for LBW (AOR 5.32, 95% CI 1.34-21.09, P = 0.017). Conclusion: This study suggests the activity of plucking of tea leaves by women is associated with LBW of babies and decreased placental weight. Particularly, if mothers worked continuously in the tea garden during 9 months of pregnancy, it also increased the risk of delivering LBW babies. This exploratory study provides an important platform for further prospective studies, which could be focused on the potential consequences of maternal occupational exposures during pregnancy on fetal development.

Angiogenesis, the formation of new capillaries from pre-existing vessels, is essential for tumor progression. Synthetic derivatives of anti-cancer compound, noscapine (an opium alkaloid) such as Cl-noscapine, Br-noscapine and Folate-noscapine along with two of the reference compounds, TNP-470 and paclitaxel were examined for anti-angiogenic activities by using human umbilical vein endothelial cells (HUVECs). The noscapine derivatives showed anti-angiogenic activity albeit at high concentration compared to the reference compounds. All the tested compounds inhibited angiogenesis in a dose-dependent manner; the drug concentration causing 50% inhibition of cell survival was 11.87 μM for Cl-noscapine, 6.9 μM for Br-noscapine and 6.79 μM for folate-noscapine. Besides, all the noscapine derivatives significantly inhibited cord formation (IC50 for Cl-noscapine is 50.76 μM, for Br-noscapine is 90.08 μM and for folate-noscapine is 18.44 μM) as well as migration and invasion (IC50 value of Cl-noscapine is 28.01 μM, for Br-noscapine is 19.78 μM and for folate-noscapine is 10.76 μM) of endothelial cells. Based on these results, we speculated that the inhibitory effects on human endothelial cell proliferation of noscapine derivatives might be important for anti-angiogenesis.

The aim of this study was to examine and compare the toxic effects of endosulfan and ochratoxin-A (OTA), individually and in combination, in adult male rats with respect to histopathological changes over 30 days of treatment. Adult male Wistar rats were randomly allotted to four groups (individual treatments, combination and control) of 10 rats each and fed OTA @ 4 ppm in feed (Group-I), endosulfan @ 5 mg/kg BW in corn oil by oral gavage (Group-II), and endosulfan with OTA in combination (Group-III) daily for 30 days. Group IV was kept as control and fed toxin free feed. After 30 days of treatment, tissues were collected in 10% buffered formalin for histopathological studies. The hematoxylin and eosin stained paraffin sections showed varying degree of degenerative and necrotic changes in kidneys and liver which were more severe in OTA treated rats in comparison to endosulfan fed group. However, the changes observed in group III rats, which received both OTA and endosulfan were even more pronounced than those observed in rats fed OTA or endosulfan alone. The present findings suggest that OTA and endosulfan had additive effects which may play an important role in pathogenesis.