Biology subjects

Sisnande, T.

Publications and source records attributed to Sisnande, T..

5 recordsLinked to original sources

bioRxiv2025

Interplay between Hyperglycemia and Chikungunya Virus Infection: Pathophysiological Insights from Murine Model

Chikungunya fever (CHIKF) is a re-emerging viral disease characterized by acute systemic manifestations and debilitating musculoskeletal symptoms that can persist after viral clearance. Although typically self-limiting in healthy individuals, clinical outcomes are significantly worsened in patients with pre-existing comorbidities, particularly diabetes mellitus (DM). Epidemiological data links DM to heightened CHIKF severity and a greater risk of developing chronic arthropathy, yet the mechanism underpinning this association remains poorly understood. In this study, we established an in vivo streptozotocin (STZ)-induced diabetic C57BL/6 mice as a model to investigate the impact of DM on CHIKV pathogenesis. STZ induces selective pancreatic {beta}-cell destruction and persistent hyperglycemia. Diabetic animals infected with CHIKV exhibited aggravated joint inflammation, increased nociceptive sensitivity, and elevated serum markers of muscle and hepatic injury, including creatine kinase (CK) and alanine aminotransferase (ALT). Histopathological analyses revealed that CHIKV infection alone disrupted joint architecture. However, in the diabetic context, these alterations were significantly exacerbated, with enhanced inflammatory infiltrates, chondrocyte loss, osteocyte necrosis, and fibrotic remodeling. These results demonstrate that the diabetic metabolic environment profoundly amplifies CHIKV-induced tissue damage and impairs resolution of inflammation, offering a plausible mechanistic explanation for the poorest CHIKF outcomes observed in diabetic patients. Thus, this model provides a valuable platform for exploring the molecular drivers of CHIKF severity and chronicity, especially among DM patients, as well as for development of pharmacological tools to mitigate CHIKV-associated complications in metabolically vulnerable populations. ImportanceChikungunya virus is responsible for a re-emerging disease that causes intense joint pain and long-lasting inflammation, especially in vulnerable individuals. People with diabetes are known to suffer more severe and persistent symptoms, but the biological reasons behind this have remained unclear. In this study, we used a diabetic mouse model to investigate how a high-glucose environment influences the course of Chikungunya virus infection. We found that diabetic mice experienced more intense joint damage, increased pain sensitivity, and signs of broader organ injury compared to non-diabetic animals. Microscopic analyses of tissues showed greater inflammation and structural damage in the joints of diabetic animals. These findings suggest that diabetes directly worsens the effects of Chikungunya virus infection by amplifying inflammation and delaying healing. This model helps explain why diabetic patients have worse outcomes and may assist in developing new treatments to protect high-risk populations from long-term complications of this infection.

immunology↗

bioRxiv2023

Oral delivery of the amylin receptor agonist pramlintide

AimThe aims of this study were to design and characterize polymeric microparticles for oral delivery of pramlintide, a triple proline human amylin analogue clinically proved efficient in diabetes therapy. MethodsThe microparticles were prepared with gastric-resistant polymer Eudragit S100 by double-emulsion and solvent evaporation technique. The study responses were repeatability, encapsulation efficiency, yield, morphology, particle size, response to acidic and alkaline milieu and pharmacokinetics. ResultsWe obtained spherical microcapsules, with particle size of 66 m {+/-} 11, with 83.2 % {+/-} 2.7 efficiency for pramlintide entrapment and 67.6 % {+/-} 2.1 yield. Intra-venous pramlintide free in solution showed a plasmatic half-life of 6.8 min in mice. In contrast, oral delivery of acid-resistant pramlintide-loaded microparticles in mice showed a protracted release for 120 min compared to 30 min obtained for pramlintide in solution. ConclusionsOral route is an alternative for therapeutic development of pramlintide formulations. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=126 SRC="FIGDIR/small/566408v1_ufig1.gif" ALT="Figure 1"> View larger version (45K): org.highwire.dtl.DTLVardef@d75002org.highwire.dtl.DTLVardef@1c5e914org.highwire.dtl.DTLVardef@492823org.highwire.dtl.DTLVardef@ea171b_HPS_FORMAT_FIGEXP M_FIG C_FIG

pharmacology and toxicology↗

bioRxiv2023

Spatially resolved distribution of pancreatic hormones proteoforms by MALDI-imaging mass spectrometry

Zinc plays crucial role in the immune system and endocrine processes. Dietary zinc restriction leads to the degeneration of the endocrine pancreas resulting in hormonal imbalance in {beta}-cell. Proteostasis may vary depending on the stage of a pathophysiological process, motivating the development of tools aimed at the direct analysis of biological status. Among proteomics methods, MALDI-ToF-MS can serve as a rapid peptidomics tool from analysis of extracts or by histological imaging. Here we report the optimization of MALDI imaging mass spectrometry analysis of thin histological sections from mouse pancreas, allowing the identification of major islet peptide hormones and major accumulated precursors and/or proteolytic products of peptide hormones. Cross-validation of the identified peptide hormones was performed by LC-ESI-MS from pancreatic islet extracts. Mice fed a zinc-restricted diet had a relatively lower amount of peptide intermediates in comparison with the control group. These data provide evidence for complex modulation of proteostasis by an imbalance of micronutrients, directly accessed by MALDI-MSI.

biochemistry↗

bioRxiv2020

Dietary zinc restriction induces nociceptive pain with reduced inflammation in mice

Zinc (Zn) is an essential micronutrient involved in a large diversity of cellular metabolism, included in the physiology of nervous system and pain modulation. There is little evidence for the role of Zn nutritional alternations to the onset and progression of neuropathic and inflammatory pain. We investigate the effects of a zinc restricted diet on the development of pain. Weaned mice were submitted to different diets: AIN-93 (38mg/kg of Zn) and Zn-deficient (AIN-93 with 11mg/kg of Zn), during four weeks. Mechanical allodynia was measured weekly using Von Frey hairs. Plantar assays for cold and heat allodynia, formalin-induced nociception and carrageenan-induced mechanical allodynia were performed at the 4th week. Plasma, DRG and livers samples were obtained for biochemical and metabolomics analysis. Zn deficient diet completely changed mice sensitivity pattern, inducing an intense allodynia evoked by mechanical, cold and heat stimulus since weaning and during four weeks. Showed also an increased sensitivity of neurogenic phase of formalin test but the inflammatory pain behavior was drastically reduced. Zn restriction increased the ATF-3 and SOD-1 levels at DRG and reduced that of GFAP, leading an increase of neuronal activation and oxidative stress, and reduced neuroimmune activity. Plasma TNF was also reduced and metabolomics analyses suggest a downregulation of lipid metabolism of arachidonic acid, reinforcing the impact of Zn restriction to the inflammatory response. Reduction of Zn intake interferes in pain circuits, reducing inflammatory pain, however enhancing nociceptive pain. Accordingly, Zn imbalance could be predisposing factor for NP development. Therefore, dietary zinc supplementation and its monitoring present clinical relevance.

biochemistry↗

bioRxiv2019

Zinc restriction promotes β-cell hyper-hormonemia and endocrine pancreas degeneration in mice

Zinc is a key component of proteins, including interaction with varying pancreatic hormones, including insulin and amylin. Zinc is key in insulin crystallinity in ZnT8 knock-out mice models, although the dietary role of zinc restriction over both energetic metabolism and {beta}-pancreatic hormonemia and morphology remained unexplored. We aimed to test whether dietary zinc restriction on swiss male mice would impact over endocrine pancreas and metabolic phenotype. We evaluated the role of dietary zinc restriction on {beta}-pancreatic hormonemia on non-transgenic Swiss male mice weaned onto a control or low-zinc diet for 4 weeks. Growth, glycemia, insulinemia, amylinemia and pancreatic islet were smaller in intervention group despite insulin crystallinity in secretory granules. We have found overlabelling for insulin, amylin and toxic oligomers in apoptotic pancreatic islet. High production of {beta}-pancreatic hormones in zinc-restricted animals counteract the decreasing islet size due to their apoptotic cells. We conclude that zinc deficiency is sufficient to promote islet {beta}-cell hormonal disruption and degeneration.

biochemistry↗