Biology subjects

Oruganti, S.

Publications and source records attributed to Oruganti, S..

4 recordsLinked to original sources

bioRxiv2025

Relationship between SARC-F score and Peripheral Blood Lymphocytes in Juvenile Idiopathic Arthritis: An Observational Pilot Study

BackgroundGiven the relatively high prevalence of sarcopenia and immune profile abnormalities in inflammatory arthritis such as rheumatoid arthritis (RA), we investigated the relationship between exercise habits, SARC-F score and peripheral blood lymphocyte profiles in patients with Juvenile idiopathic arthritis (JIA). MethodsAll participants with JIA completed the SARC-F survey and self-reported exercise habits through online questionnaires. We defined two groups based on SARC-F scores as musculoskeletal function impaired (SARC-Fhi+) and musculoskeletal function not impaired (SARC-Fhi-). We used flow cytometry of peripheral blood mononuclear cells to define immune cell subpopulations. Statistical analyses were performed using GraphPad Prism software version10. ResultsOf the 18 participants with a median age of 24 years - five belonged to the SARC-Fhi+ group and 13 to the SARC-Fhi-group, of whom 80% and 38% were female, respectively. The SARC-Fhi + group had fewer CD45RA+CD27+ naive CD4+ T cells (26.60% vs. 45.30%, p=0.0264) and greater CD45RA-CD27-effector memory CD4+ T cells (11.90% vs. 7.00%, p=0.0350). The SARC-Fhi+ group also had fewer CD56-CD16+ NK cells compared to the SARC-Fhi-group (2.60% v. 4.28%, p = 0.0194). The moderate exercise group (n = 13) had increased numbers of total CD4+ T cells (54.06% vs. 37.30%, p=0.0140) and 3-fold fewer CD45RA+CD27-EMRA CD8+ T cells (3.17% vs. 10.40%, p=0.0350). There were no other significant differences for other immune cells / subpopulations including B cells. ConclusionsOur study findings suggest notable differences in immune profile relative to SARC-F score. Furthermore, the 3-fold lower frequency of CD8+ TEMRA subpopulation of T cells, reflective of immunosenescence, suggest a potential inverse relationship between moderate exercise and peripheral immune cell profile in JIA. Key messagesO_LISARC-F score was used as a clinically relevant tool to identify musculoskeletal function in JIA C_LIO_LISARC-Fhi+ group had fewer naive CD4+ T cells and greater effector memory CD4+ T cells C_LIO_LIModerate exercise group had 3-fold lower frequency of CD8+ TEMRA T cells C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=54 SRC="FIGDIR/small/681879v1_ufig1.gif" ALT="Figure 1"> View larger version (11K): org.highwire.dtl.DTLVardef@1eb9d4org.highwire.dtl.DTLVardef@13a18a4org.highwire.dtl.DTLVardef@127d55corg.highwire.dtl.DTLVardef@28bddf_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2025

Genetic enhancement of inbred lines through pre-breeding in maize

The improvement in the genetic yield potential of maize has led to the development of an extremely large number of maize cultivars across almost all maize-growing countries in the world. In the process, the genetic diversity in the modern maize cultivars has gradually narrowed down. To improve the genetic diversity, there is a need to undertake pre-breeding through wide-hybridization between inbred lines and their wild species, namely Zea mays ssp. Parvigluimis (WS-5) and Zea luxurians (WS-1). In the present study, 69 elite inbred lines were crossed with two wild relatives of maize, Z. mays ssp. Parviglumis and Z. luxurians. The resulting hybrids of wide hybridization showed typical wild species characters like tillering, prolificacy on main tiller and side tillers, and ear characters. This shows the introgression of characters from wild species. Combining ability analysis revealed the presence of a significant amount of variability among parents and crosses for most traits under study. Z. luxurians was a good general combiner for all the traits except tassel length, anthesis silking interval, and days to 75% dry husk based on the GCA effects. Whereas lines, IC0621049 and IC0621565, were good general combiners for all the traits except days to 75% dry husk. Among the crosses, highly significant SCA effects in the desired direction were shown by PFSR-3 x WS-5, EC618215 x WS-1, and IC213122 x WS-1 for plant height, ear diameter, no. of kernel rows per ear, no. of kernels per row, ear weight, and grain yield per ear. Molecular analysis also confirmed the genuine nature of hybrids. Cluster analysis classified all the parents involved in the crosses into two groups, with most of the inbred lines grouping with WS-5, revealing that most of the inbred lines were closely related to WS-5 as compared to WS-1. This may be the reason for the development of more successful crosses with WS-5 as compared to WS-1.

genetics↗

bioRxiv2025

ALOX12B overexpression in the skin drives inflammasome/Th17 signaling axis to promote inflammation in the mouse model and human patients

Inflammation plays a pivotal role in the etiopathogenesis of chronic inflammatory skin diseases. However, the underlying mechanism remains unclear. Here, we employed Gene expression meta-analysis and clinical validation strategy to dissect the global architecture of immune dysregulation responsible for inflammatory conditions in the skin. Using such approaches, we identified a gene signature comprising of ALOX12B, which is significantly upregulated in psoriatic and atopic dermatitis patient skin samples, and correlates with increased levels of pathological IL-1{beta} and Th17 responses. Surprisingly, ALOX12B is predominantly expressed in the skin. Furthermore, skin-specific overexpression of human ALOX12B in transgenic mice resulted in psoriasis-like inflammatory symptoms, including epidermal hyperplasia, immune cell infiltration, and elevated IL-1{beta}/Th17 responses. ALOX12B is a non-heme iron-containing enzyme that catalyses the production of 12R-HETE from polyunsaturated fatty acids such as arachidonic acid. Mechanistically, we found that ALOX12B/12R-HETE accumulation in the skin acts as an intrinsic danger signal that triggers enhanced IL-1{beta} processing and secretion via ROS generation and NLRP3 inflammasome activation. Increased IL-1{beta} levels in turn drive IL-17 producing T-cell polarization. We further designed a novel first-in-class, potent ALOX12B inhibitor, 6a, which exhibited favorable topical pharmacokinetic and safety profiles. The topical application of 6a reduced inflammation-associated pathologies in Tg-hALOX12B mice by suppressing 12R-HETE-induced IL-1{beta} production and ROS generation. These findings revealed a novel mechanism mediated by ALOX12B/12R-HETE overexpression that controls skin inflammation, thereby providing a promising therapeutic target for treating inflammatory skin diseases. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=138 SRC="FIGDIR/small/658245v1_ufig1.gif" ALT="Figure 1"> View larger version (61K): org.highwire.dtl.DTLVardef@13cdf3forg.highwire.dtl.DTLVardef@164cac3org.highwire.dtl.DTLVardef@3c0364org.highwire.dtl.DTLVardef@2ca91_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical Abstract.C_FLOATNO The proposed mechanism through which ALOX12B modulates the inflammatory pathway in psoriasiform-like inflammatory conditions in the skin. The study provides insight into the role of ALOX12B in skin inflammation. Increased levels of ALOX12B expression in the skin result in 12R-HETE accumulation, which subsequently triggers the IL-1/Th17 inflammatory cascade through ROS generation and inflammasome activation. IL-1 produced by the activated inflammasome leads to the polarization of naive T-cells to activated IL-17 producing CD4+ T-cells, which are involved in the skin-inflammation related pathologies such as keratinocyte proliferation, and cellular infiltration. Hence, we propose ALOX12B as a novel potential therapeutic target for psoriasis-like inflammatory skin disorders. Additionally, we designed a novel first-in-class ALOX12B inhibitor, 6a; which shows a substantial alleviation in ALOX12B enzymatic activity, thereby reducing cellular ROS, which in turn results in reduced levels of IL-1, as a result inhibiting IL-1/Th17 inflammatory pathway and subsequent reduction in pathological inflammatory skin conditions. A portion of the image was created using Biorender.com C_FIG HighlightsO_LIALOX12B is a key gene upregulated in the skin during psoriasis and atopic dermatitis. C_LIO_LITransgenic mice overexpressing ALOX12B in the skin developed Psoriasis-like inflammatory symptoms. C_LIO_LIMechanistically, ALOX12B, through 12R-HETE, enhanced IL-1{beta} production via ROS generation and NLRP3 inflammasome activation. Further elevated IL-1{beta} production promotes Th17 cell polarization. C_LIO_LINovel first-in-class ALOX12B inhibitor alleviates inflammatory symptoms in a transgenic mouse model. C_LIO_LIStudy reveals a crucial ALOX12B/12R-HETE-inflammasome-IL-17 axis involvement in inflammatory skin diseases. C_LI

immunology↗

bioRxiv2025

LEVERAGING TRANSFER LEARNING FOR HIGH-ACCURACY PHENOTYPIC SCREENING IN ZEBRAFISH IMAGE ANALYSIS

This paper presents a method for classifying zebrafish images captured before and after drug administration. Leveraging the power of transfer learning and fine-tuning, the approach effectively overcomes the challenges of limited datasets in biomedical imaging. By employing a pre-trained convolutional neural network (CNN) as the base model, transfer learning allows us to utilize learned features from large-scale image datasets, significantly reducing training time and computational resources. Fine-tuning specific layers of the model on our zebrafish dataset further enhances its ability to detect subtle visual differences induced by drug administration. The proposed approach achieves high accuracy in classifying zebrafish images, demonstrating its potential as a reliable tool for analysing phenotypic changes due to pharmacological interventions. This model could be instrumental in accelerating drug discovery and research in zebrafish-based assays, offering a scalable and efficient solution for image-based biomedical analysis.

bioinformatics↗