Extracellular mitochondrial components as new biomarkers for lupus nephritis.

Major reason for mortality among systemic lupus erythematosus patients is renal failure due to the deposition of immune complexes in the glomeruli. Being a chronic disease with multiple relapses and remissions across the lifespan, it's important to know the degree of nephritis for diagnosis as well as the long-term clinical management of the patients. Currently, renal biopsy is being used as the gold standard to diagnose and define the stages of the disease. However, renal biopsy being invasive only provides a localized picture of nephritis, and has the risk of bleeding. Additionally, it is also cost-intensive. Hence, a reliable, non-invasive biomarker is required for lupus nephritis. This study has evaluated extracellular mitochondrial components, including cell-free mitochondria, and cell-free mitochondrial DNA as probable biomarkers of the degree of nephritis. Both showed a significant correlation with proteinuria and protein-creatinine ratio. Our study substantiates their usage as clinical biomarkers of nephritis upon their validation in a larger cohort of lupus nephritis patients and other forms of nephritis. Although the current data suggest using cell-free mitochondria as a biomarker of lupus nephritis is better than the cell-free mitochondrial DNA.

Morphological and Molecular Characterization of Two New and Two Already Known Species of the Genus Pallisentis (Acanthocephala: Quadrigyridae) from India with an Update in Key to the Species.

To date, 31 species assigned to the genus Pallisentis Van cleave, 1928 have been reported from India. The present study includes morphological and molecular descriptions of two new species of Pallisentis Van Cleave, 1928, namely P. himachalensis and P. longus from the fresh water fishes Channa punctata (Bloch, 1793) and C. marulius (Hamilton, 1822), respectively, procured from Himachal Pradesh and Chandigarh, India. Of total 35 fishes, 17 were found infected with acanthocephalan parasites. The prevalence of infection was 42.85 and 52.38% for C. punctata and C. marulius, respectively. The morphological characters of P. himachalensis n. sp. include proboscis with 4 circles of hooks with 810 hooks per circle, which gradually decline in size. The trunk in male comprises 1516 circles of collar spines and 2737 circles of trunk spines ending above the anterior testis with syncytial cement gland having 2629 nuclei. The trunk in female comprises of 1418 circles of collar spines and 5573 circles of trunk spines present till the anterior end of reproductive system with additional 34 circles at the posterior end. P. longus n. sp. is the longest species reported in the genus and the length of female reach up to 44 mm. The proboscis comprises 4 circles of proboscis hooks with 910 hooks per circle. In males 1316 circles of the collar spines and 2731 circles of trunk spines are present with syncytial cement gland containing 2025 nuclei. The females are much longer with 1516 circles of collar spines and 6469 circles of trunk spines present till the posterior end. The study also reports two already described species: P. gomtii Gupta and Verma, 1980 from C. punctata and P. nandai Sarkar, 1953 from C. marulius. Total 12 sequences for 4 species have been generated based on 18S, 28S and ITS15.8SITS2 molecular markers. The 18S and ITS15.8SITS2 Bayesian inference trees generated in the present study showed distinct identities of all 4 species. Moreover, the Bayesian inference tree generated in the present study based on 18S showed the clustering of Pallisentis species in three different clades compared to the previous studies in which only two clades within the genus were reported. The molecular analysis showed the monophyletic origin of the genus Pallisentis and does not support subgeneric classification within the genus.

DNA damage induces STING mediated IL-6-STAT3 survival pathway in triple-negative breast cancer cells and decreased survival of breast cancer patients.

Triple-negative breast cancer is aggressive and metastatic breast cancer type and shows immune evasion, drug resistance, relapse and poor survival. Anti-cancer therapy like ionizing radiation and chemotherapeutic drug majorly induces DNA damage hence, alteration in DNA damage repair and downstream pathways may contribute to tumor cell survival. DNA damage during chemotherapy is sensed by cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes (STING), which determines the anti-tumor immune response by modulating the expression of programmed cell death ligand-1 (PD-L1), immune suppressor, in the tumor microenvironment. Triple-negative breast cancer cells are cGAS-STING positive and modulation of this pathway during DNA damage response for survival and immune escape mechanism is not well understood. Here we demonstrate that doxorubicin-mediated DNA damage induces STING mediated NF-κB activation in triple-negative as compared to ER/PR positive breast cancer cells. STING-mediated NF-κB induces the expression of IL-6 in triple-negative breast cancer cells and activates pSTAT3, which enhances cell survival and PD-L1 expression. Doxorubicin and STAT3 inhibitor act synergistically and inhibit cell survival and clonogenicity in triple-negative breast cancer cells. Knockdown of STING in triple-negative breast cancer cells enhances CD8 mediated immune cell death of breast cancer cells. The combinatorial treatment of triple-negative breast cells with doxorubicin and STAT3 inhibitor reduces PD-L1 expression and activates immune cell-mediated cancer cell death. Further STING and IL-6 levels show a positive correlation in breast cancer patients and poor survival outcomes. The study here strongly suggests that STING mediated activation of NF-κB enhances IL-6 mediated STAT3 in triple-negative breast cancer cells which induces cell survival and immune-suppressive mechanism.

Morphological and molecular description of Pallisentis roparensis n. sp. (Acanthocephala: Quadrigyridae) infecting the freshwater cat fish Wallago attu from Ropar Wetland, Punjab, India.

The study describes a new species of Pallisentis Van Cleave, 1928 infecting the freshwater cat fish Wallago attu Bloch and Schneider, 1801 from Ropar wetland, Punjab, India. The morphological characters of Pallisentis roparensis include proboscis with 4 circles of 10 hooks each gradually declining in size, first circle of hooks <100 µm in length, 15-16 circles of Y-shaped collar spines and conical trunk spines present up to the posterior end in the females and the anterior region of cement gland in males. Saefftigen's pouch is present and cement gland nuclei are 22-25 in males. The sequences generated for 18S, 28S and ITS1-5.8S-ITS2 molecular markers of the newly described species are nested well among the other comparable sequences from the GenBank. The phylogenetic analyses show the monophyly of the genus Pallisentis but point towards the paraphyletic relationship among the three subgenera. The histopathology of fish intestine indicates that the parasite stimulates the inflammatory immune response causing serious injury to the mucosa and dilation of the lymphatic vessels of small intestine.

Phylogenetic analysis of Pallisentis nagpurensis (Acanthocephala: Quadrigyridae) infecting snakehead murrel Channa striata in Himachal Pradesh, India.

Till date 34 species of Pallisentis have been validated with almost negligible studies on its molecular phylogeny. The discovered species of the genus Pallisentis are confined only to the Asian continent. Many different species of Acanthocephala infecting commercially important freshwater as well as the marine fishes have been recorded from India mainly on the basis of morphology. The original record of morphological characteristics of Pallisentis nagpurensis (Bhalerao 1931) Baylis, 1933 can be traced back to the Bhalerao, 1931 from Channa striata (Ophiocephalus striatus) from the state of Uttar Pradesh, India without the separate documentation of male and female characteristics. Same species has also been reported to infect Channa striata from different parts of India as well as from the Indonesia and Ceylon (Baylis, 1933 and Fernando and Furtado, 1963). The present study compiles the morphological characteristics of male and female P. nagpurensis along with the comparison with similar species from same geographical region. This study also reports the first record of 18S, 28S rRNA and ITS1-5.8S-ITS2 gene sequences of P. nagpurensis generated for analyzing the phylogeny within this taxonomic group. P. nagpurensis together with the other species of Pallisentis reported from India distinctly formed a sub-clade separating it from the other members of same genus.