Biology subjects

Santos, A. A.

Publications and source records attributed to Santos, A. A..

7 recordsLinked to original sources

bioRxiv2025

Temporal Dynamics of Kidney Mitochondrial Dysfunction in Type 2 Diabetes: Analysis of the Goto-Kakizaki Model.

Type 2 diabetes mellitus (T2DM) is a major cause of diabetic kidney disease (DKD), a complication driven by chronic hyperglycemia, oxidative stress, and inflammation. Mitochondrial dysfunction has been recognized as a central feature of DKD, but the temporal relationship between mitochondrial alterations, mitophagy, and inflammatory responses remains unclear. Using the non-obese Goto-Kakizaki (GK) rat, a spontaneous model of T2DM, we examined renal mitochondrial changes at 21, 60, and 120 days. Histology revealed a trend toward increased glycation product deposition, more evident at 60 days. Cytochrome C and OPA-1 expression indicated early mitochondrial adaptation through enhanced respiratory activity and hyperfusion, while reduced PGC1- and PINK suggested impaired biogenesis and mitophagy. By 120 days, PGC1- and PINK increased, likely reflecting delayed, insufficient compensation, coinciding with mitochondrial depolarization. Cytokine analysis revealed a biphasic inflammatory profile: IL-18 and CXCL1 were sharply elevated at 21 days, IL-1{beta} remained stable, and IL-10 was elevated at 21 and 60 days, indicating early pro-inflammatory activation followed by anti-inflammatory modulation. These findings suggest that renal mitochondrial dysfunction in GK rats evolves from an adaptive state to late-stage failure, with inflammation occurring as transient peaks rather than a persistent process. The period between 21 and 60 days emerges as a critical therapeutic window in which strategies to preserve mitochondrial quality control and modulate inflammasome-related responses may be most effective.

cell biology↗

bioRxiv2025

Isoflavone treatment attenuates cardiovascular-kidney-metabolic (CKM) syndrome symptoms in an experimental model of ovariectomized rats.

Cardiovascular-kidney-metabolic (CKM) syndrome represents an integrated spectrum of obesity, type 2 diabetes mellitus, cardiovascular disease, and chronic kidney disease, driven by shared metabolic, inflammatory, and fibrotic mechanisms. Menopause-related estrogen deficiency exacerbates these disturbances, increasing susceptibility to metabolic syndrome and renal injury. This study investigated whether dietary supplementation with soy isoflavones attenuates obesity-associated kidney injury in ovariectomized rats exposed to a high-fat, high-caloric diet. Female Wistar rats underwent bilateral ovariectomy and were assigned to control diet, hipercaloric diet (DH), or DH supplemented with isoflavones (DH+ISO). Metabolic, biochemical, oxidative stress, histopathological, and inflammatory parameters were evaluated over 120 days. The DH diet induced weight gain, hypertension, dyslipidemia, hyperglycemia, impaired renal function, increased oxidative stress, and tubulointerstitial injury, consistent with a CKM phenotype. Isoflavone supplementation did not prevent diet-induced weight gain but attenuated systolic blood pressure elevation and improved lipid and glycemic profiles. Renal function was partially preserved in DH+ISO rats, as evidenced by lower plasma creatinine levels, improved creatinine clearance, reduced urea levels, and decreased urinary peroxide excretion compared with DH animals. Histopathological analysis revealed persistent tubular injury in both DH groups, although inflammatory and oxidative markers were attenuated in isoflavone-treated rats. Immunohistochemistry demonstrated reduced renal IL-6 expression in the DH+ISO group, accompanied by trends toward decreased macrophage infiltration and IL-1{beta} expression. Collectively, these findings indicate that soy isoflavones mitigate metabolic, inflammatory, and oxidative pathways implicated in obesity-related kidney injury in a postmenopausal experimental model. Isoflavone supplementation may represent a complementary therapeutic strategy for attenuating CKM-related renal damage associated with modern diets and estrogen deficiency.

pathology↗

bioRxiv2024

Physiological response of Microcystis aeruginosa exposed to aqueous extracts of Pistia stratiotes and Pontederia crassipes

Macrophyte extracts inhibit cyanobacteria growth, offering a sustainable solution for bloom control. The present study aimed to evaluate Microcystis aeruginosas response to aqueous extracts obtained from the dried biomass of Pistia stratiotes L. and Pontederia crassipes Mart. Solms. Physiological parameters analyzed included growth, photosynthesis, and antioxidative response. Reactive oxygen species generation and the chemical profile of the aqueous extracts were analyzed. At 4.0 g L-1, both extracts inhibited cyanobacterial growth in 6 days. P. stratiotes extract achieved 100% inhibition, while P. crassipes extract reached 60%. P. stratiotes extract showed higher photosynthetic inhibition (99% vs. 12% for P. crassipes). This was related to the downregulation of the psbA gene (coding for the photosystem II protein D1). Exposure to both extracts increased intracellular reactive oxygen species content in cyanobacterial cells and increased peroxiredoxin gene (prxA) transcripts. This response was not noted for sod (superoxide dismutase) transcripts, although SOD enzymatic activity increased in cultures exposed to P. stratiotes extracts. Upon incubation of the macrophyte extracts with M. aeruginosa cultures, phenol concentrations decreased, and their general metabolic profile changed. Thus, P. stratiotes extract outperformed P. crassipes, inhibiting M. aeruginosa growth, affecting photosystem II, and inducing oxidative stress. HighlightsO_LIAqueous extracts from dried biomass of P. stratiotes and P. crassipes inhibited M. aeruginosa growth. C_LIO_LIP. stratiotes extract suppressed photosystem II activity, while P. crassipes did not C_LIO_LIBoth extracts elicited ROS production in cells. C_LIO_LIPeroxiredoxin gene expression upregulated by extract exposure. C_LIO_LIP. stratiotes extract increased SOD activity in cells. C_LI

microbiology↗

bioRxiv2024

WHO WINS? COMPARISON BETWEEN EMERGENT MACROPHYTES AND PONTEDERIA CRASSIPES (WATER HYACINTH) AS NATURE-BASED SOLUTIONS FOR NUTRIENT PHYTOREMEDIATION AND CYANOBACTERIA MITIGATION

AO_SCPLOWBSTRACTC_SCPLOWEmergent macrophytes are commonly used to control eutrophication in Constructed Floating Wetlands (CFW) systems. However, tropical emergent macrophyte species, particularly from South America, are underrepresented in these applications. This study aims to investigate the potential of five emergent macrophytes, Alternanthera philoxeroides, Ludwigia leptocarpa, Polygonum ferrugineum, Typha domingensis, and Urochloa mutica in controlling eutrophication and inhibiting cyanobacterial growth, compared to the floating macrophyte Pontederia crassipes, the most studied macrophyte for this purpose. Phytoremediation experiments were performed ex-situ in mesocosms (50 L) with high soluble reactive phosphorus (SRP) concentration (400 {micro}g L-1). Allelopathic effects of the macrophytes root exudates on cyanobacteria were tested in vitro using a strain of Microcystis aeruginosa. While P. crassipes reduced SRP concentration by 86% in 14 days, the tested macrophytes reduced SRP concentration by > 94%, except for T. domingensis, which showed a reduction of 64%. NH4+ and NO3- removal in 14 days were 96% and 62%, respectively, for P. crassipes. These values corresponded to 96% and 63% for the five tested macrophytes. Root exudates of A. philoxeroides, L. leptocarpa, and P. ferrugineum caused inhibition of M. aeruginosa growth with no detection of Chl-a after 7 days. Thus, three emergent macrophytes were more efficient in removing nutrients than P. crassipes. and showed allelopathic potential against cyanobacteria, indicating that using local emergent macrophytes in CFW systems can be a valuable and sustainable tool to mitigate eutrophication and its consequences in aquatic environments. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=113 SRC="FIGDIR/small/603719v1_ufig1.gif" ALT="Figure 1"> View larger version (46K): org.highwire.dtl.DTLVardef@e09e31org.highwire.dtl.DTLVardef@b1d4a7org.highwire.dtl.DTLVardef@1003e0borg.highwire.dtl.DTLVardef@e97e22_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIEmergent macrophytes were similarly efficient to P. crassipes in nutrient removal C_LIO_LILudwigia leptocarpa was the most efficient in SRP removal in 7 days C_LIO_LIAllelopathy on cyanobacterium M. aeruginosa by A. philoxeroides, L. leptocarpa, and P. ferrugineum root exudates C_LIO_LIAdapting emergent macrophytes in CFW structures can be helpful in in situ phytoremediation. C_LI SO_SCPLOWTATEMENTC_SCPLOWO_SCPCAP C_SCPCAPO_SCPLOWOFC_SCPLOW NO_SCPLOWOVELTYC_SCPLOWThis study lies in its comparative analysis of underrepresented tropical emergent macrophytes from South America against the widely studied floating macrophyte, Pontederia crassipes (water hyacinth). By focusing on these local emergent macrophytes, the research addresses a significant knowledge gap. It provides insights into their potential application in Constructed Floating Wetlands (CFWs) for nutrient removal and cyanobacteria control. Key findings demonstrate that the selected emergent macrophytes outperform P. crassipes in reducing soluble reactive phosphorus (SRP) concentrations and exhibit substantial nitrogen removal efficiencies. Furthermore, the allelopathic potential of A. philoxeroides, L. leptocarpa, and P. ferrugineum against the harmful cyanobacterium Microcystis aeruginosa showcases their dual functionality in mitigating eutrophication and inhibiting harmful algal blooms.

ecology↗

bioRxiv2023

Impact of climate change on leafhopper vectors of phytoplasmas in North America

Climate change significantly contributes to shifts in the geographical range of pests and diseases. Leafhoppers (Hemiptera: Cicadellidae), known vectors of phytoplasmas pathogens, are linked to the transmission of more than 600 diseases affecting a thousand plant species worldwide. Despite this, the potential effects of climate change on leafhopper vectors of phytoplasmas remain a critical knowledge gap. To address this gap, our study investigated the potential impact of climate change on 14 species of Nearctic leafhoppers previously associated with phytoplasma-related diseases. Using the MaxEnt species distribution algorithm and other ecological niche modeling techniques, we assessed (i) the expected species richness under current climate conditions and four future scenarios and (ii) the environmental niche similarity among these species across these scenarios. Our projections suggest that the eastern region of North America holds the potential for the highest species richness, a trend expected to persist across all future scenarios, gradually expanding eastward. Notably, our findings indicate the increasing suitability of northern Canada for more species. Network analysis further revealed a remarkable similarity in environmental niches among most leafhopper species. Moreover, across the four future scenarios, there is a tendency for an increase in this similarity. Altogether, our study underscores the potential persistent presence of Nearctic leafhoppers in their current habitats while pointing to a shift toward northern North America in future scenarios. These findings have significant implications for sustainable pest management practices, prompting a necessary discussion on strategies to mitigate climate change and pest migrations impact on agricultural systems.

ecology↗

bioRxiv2020

Neuraminidase inhibitors rewire neutrophil function in murine sepsis and COVID-19 patient cells

Neutrophil overstimulation plays a crucial role in tissue damage during severe infections. Neuraminidase (NEU)-mediated cleavage of surface sialic acid has been demonstrated to regulate leukocyte responses. Here, we report that antiviral NEU inhibitors constrain host NEU activity, surface sialic acid release, ROS production, and NETs released by microbial-activated human neutrophils. In vivo, treatment with Oseltamivir results in infection control and host survival in peritonitis and pneumonia models of sepsis. Single-cell RNA sequencing re-analysis of publicly data sets of respiratory tract samples from critical COVID-19 patients revealed an overexpression of NEU1 in infiltrated neutrophils. Moreover, Oseltamivir or Zanamivir treatment of whole blood cells from severe COVID-19 patients reduces host NEU-mediated shedding of cell surface sialic acid and neutrophil overactivation. These findings suggest that neuraminidase inhibitors can serve as host-directed interventions to dampen neutrophil dysfunction in severe infections. At a GlanceIn a severe systemic inflammatory response, such as sepsis and COVID-19, neutrophils play a central role in organ damage. Thus, finding new ways to inhibit the exacerbated response of these cells is greatly needed. Here, we demonstrate that in vitro treatment of whole blood with the viral neuraminidase inhibitors Oseltamivir or Zanamivir, inhibits the activity of human neuraminidases as well as the exacerbated response of neutrophils. In experimental models of severe sepsis, oseltamivir decreased neutrophil activation and increased the survival rate of mice. Moreover, Oseltamivir or Zanamivir ex vivo treatment of whole blood cells from severe COVID-19 patients rewire neutrophil function.

immunology↗

bioRxiv2020

A new plant-specific syntaxin-6 protein may define an intracytoplasmic route for begomoviruses

Due to limited free diffusion in the cytoplasm, viruses must use active transport mechanisms to move intracellularly. Nevertheless, how the plant ssDNA begomoviruses hijacks the host intracytoplasmic transport machinery to move from the nucleus to the plasmodesmata remains enigmatic. Here, we identified nuclear shuttle protein (NSP)-interacting proteins from Arabidopsis by probing a protein microarray and demonstrated that the Cabbage leaf curl virus (CabLCV) NSP, a facilitator of the nucleocytoplasmic trafficking of viral (v)DNA, interacts with an endosomal vesicle-localized plant-specific syntaxin-6 protein, designated NSP-interacting syntaxin-6 domain-containing protein (NISP) in planta. NISP displays a pro-viral function, but not the syntaxin-6 paralog AT2G18860 that failed to interact with NSP. Consistent with these findings, nisp-1 mutant plants were less susceptible to begomovirus infection, a phenotype reversed by NISP complementation. NISP-overexpressing lines accumulated higher levels of viral DNA than wild-type. Furthermore, NISP interacted with NIG, an NSP-interacting GTPase involved in NSP-vDNA nucleocytoplasmic translocation. The NISP-NIG interaction was enhanced by NSP. We also showed that NISP associates with vDNA and might assemble a NISP-NIG-NSP-vDNA-complex. NISP may function as a docking site for recruiting NIG and NSP into endosomes, providing a mechanism for the intracytoplasmic translocation of the NSP-vDNA complex towards to and from the cell periphery.Author Summary As viruses must use an active and directed intracellular movement, they hijack the intracellular host transport system for their own benefits. Therefore, the identification of interactions between host proteins and begomovirus movement proteins should target the intracellular transport machinery. This work focused on the identification of these protein-protein interactions; it addressed the molecular bases for the intracellular transport of begomoviruses. We used a protein microarray to identify cellular partners for the movement protein (MP) and the viral nuclear shuttle protein (NSP), which is a facilitator of the nucleocytoplasmic trafficking of viral (v)DNA. We identified relevant protein-protein interaction (PPI) hubs connecting host and viral proteins. We revealed a novel NSP-interacting protein, which functions in the intracytoplasmic transport of proteins and DNA from begomoviruses and was designated NSP-interacting syntaxin domain-containing protein (NISP). Our data suggest an intracellular route connecting the release of newly synthesized begomoviral DNA in the cytosol with the cell surface. Resolving viral DNA-host protein complexes led to the identification of a novel class of components of the cell machinery and a representative member, NISP, that functions as a susceptibility gene against begomoviruses. As geminiviruses pose a severe threat to agriculture and food security, this recessive gene can now be exploited as a target for engineering resistance by gene editing in crops.Competing Interest StatementThe authors have declared no competing interest.View Full Text

plant biology↗