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1.
Int J Mol Sci ; 25(13)2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-39000140

RESUMO

Renal involvement is an important cause of morbidity and mortality in systemic lupus erythematosus (SLE). The present study included patients with recently diagnosed Class III and Class IV lupus nephritis (LN) treated by Rheumatology who, upon the detection of alterations in their kidney function, were referred to Nephrology for the joint management of both medical specialties. The purpose of this study was to compare the plasma expression of Toll-Like Receptor 7 (TLR7) and TLR9 in healthy control (HC) subjects and newly diagnosed Class III and Class IV LN patients with 12-month follow-ups. The plasma expression of TLR7 and TLR9 proteins was determined by the ELISA method. A significant increase in the expression of TLR7 protein was found in Class III LN in the basal determination compared to the expression in the HC (p = 0.002) and at 12 months of follow-up (p = 0.03) vs. HC. The expression of TLR9 showed a behavior opposite to that of TLR7. TLR9 showed decreased protein expression in LN Class III patients' baseline and final measurements. The result was similar in the basal and final determinations of LN Class IV compared to the expression in HC. A significant decrease in SLEDAI -2K was observed at 12 months of follow-up in patients in Class III (p = 0.01) and Class IV (p = 0.0001) of LN. Complement C3 levels improved significantly at 12-month follow-up in Class IV patients (p = 0.0001). Complement C4 levels decreased significantly at 12-month follow-up in LN Class III compared to baseline (p = 0.01). Anti-DNA antibodies decreased significantly at 12 months of follow-up in Class IV LN (p = 0.01). A significant increase in proteinuria was found at 12 months of follow-up in Class III LN, compared to the baseline determination (p = 0.02). In LN Class IV, proteinuria decreased at 12 months of follow-up compared to baseline (p = 0.0001). Albuminuria decreased at 12 months of follow-up in LN Class IV (p = 0.006). Class IV LN, albuminuria also decreased at 12 months of follow-up (p = 0.009). Hematuria persisted in all patients and the glomerular filtration rate did not change. Three Class IV patients died before 12 months of follow-up from various causes. In conclusion, although the rheumatologic data appeared to improve, the renal function data remained inconsistent. Decreased expression of TLR9 and increased expression of TLR7 could be useful in the early diagnosis of Class III and Class IV LN is correct.


Assuntos
Nefrite Lúpica , Receptor 7 Toll-Like , Receptor Toll-Like 9 , Humanos , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/sangue , Nefrite Lúpica/metabolismo , Receptor 7 Toll-Like/metabolismo , Receptor 7 Toll-Like/genética , Receptor Toll-Like 9/metabolismo , Feminino , Adulto , Masculino , Seguimentos , Pessoa de Meia-Idade , Estudos de Casos e Controles , Adulto Jovem
2.
Biol Res ; 57(1): 49, 2024 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-39068496

RESUMO

BACKGROUND: The significant role of embryonic cerebrospinal fluid (eCSF) in the initial stages of brain development has been thoroughly studied. This fluid contains crucial molecules for proper brain development such as members of the Wnt and FGF families, apolipoproteins, and retinol binding protein. Nevertheless, the source of these molecules remains uncertain since they are present before the formation of the choroid plexus, which is conventionally known as the primary producer of cerebrospinal fluid. The subcommissural organ (SCO) is a highly conserved gland located in the diencephalon and is one of the earliest differentiating brain structures. The SCO secretes molecules into the eCSF, prior to the differentiation of the choroid plexus, playing a pivotal role in the homeostasis and dynamics of this fluid. One of the key molecules secreted by the SCO is SCO-spondin, a protein involved in maintenance of the normal ventricle size, straight spinal axis, neurogenesis, and axonal guidance. Furthermore, SCO secretes transthyretin and basic fibroblast growth factor 2, while other identified molecules in the eCSF could potentially be secreted by the SCO. Additionally, various transcription factors have been identified in the SCO. However, the precise mechanisms involved in the early SCO development are not fully understood. RESULTS: To uncover key molecular players and signaling pathways involved in the role of the SCO during brain development, we conducted a transcriptomic analysis comparing the embryonic chick SCO at HH23 and HH30 stages (4 and 7 days respectively). Additionally, a public transcriptomic data from HH30 entire chick brain was used to compare expression levels between SCO and whole brain transcriptome. These analyses revealed that, at both stages, the SCO differentially expresses several members of bone morphogenic proteins, Wnt and fibroblast growth factors families, diverse proteins involved in axonal guidance, neurogenic and differentiative molecules, cell receptors and transcription factors. The secretory pathway is particularly upregulated at stage HH30 while the proliferative pathway is increased at stage HH23. CONCLUSION: The results suggest that the SCO has the capacity to secrete several morphogenic molecules to the eCSF prior to the development of other structures, such as the choroid plexus.


Assuntos
Encéfalo , Perfilação da Expressão Gênica , Órgão Subcomissural , Animais , Encéfalo/metabolismo , Encéfalo/embriologia , Encéfalo/crescimento & desenvolvimento , Órgão Subcomissural/metabolismo , Órgão Subcomissural/embriologia , Embrião de Galinha , Regulação da Expressão Gênica no Desenvolvimento
3.
Biol Res ; 57(1): 22, 2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38704609

RESUMO

BACKGROUND: Chromatin dynamics is deeply involved in processes that require access to DNA, such as transcriptional regulation. Among the factors involved in chromatin dynamics at gene regulatory regions are general regulatory factors (GRFs). These factors contribute to establishment and maintenance of nucleosome-depleted regions (NDRs). These regions are populated by nucleosomes through histone deposition and nucleosome sliding, the latter catalyzed by a number of ATP-dependent chromatin remodeling complexes, including ISW1a. It has been observed that GRFs can act as barriers against nucleosome sliding towards NDRs. However, the relative ability of the different GRFs to hinder sliding activity is currently unknown. RESULTS: Considering this, we performed a comparative analysis for the main GRFs, with focus in their ability to modulate nucleosome sliding mediated by ISW1a. Among the GRFs tested in nucleosome remodeling assays, Rap1 was the only factor displaying the ability to hinder the activity of ISW1a. This effect requires location of the Rap1 cognate sequence on linker that becomes entry DNA in the nucleosome remodeling process. In addition, Rap1 was able to hinder nucleosome assembly in octamer transfer assays. Concurrently, Rap1 displayed the highest affinity for and longest dwell time from its target sequence, compared to the other GRFs tested. Consistently, through bioinformatics analyses of publicly available genome-wide data, we found that nucleosome occupancy and histone deposition in vivo are inversely correlated with the affinity of Rap1 for its target sequences in the genome. CONCLUSIONS: Our findings point to DNA binding affinity, residence time and location at particular translational positions relative to the nucleosome core as the key features of GRFs underlying their roles played in nucleosome sliding and assembly.


Assuntos
Montagem e Desmontagem da Cromatina , Proteínas de Ligação a DNA , Nucleossomos , Nucleossomos/metabolismo , Nucleossomos/genética , Montagem e Desmontagem da Cromatina/fisiologia , Adenosina Trifosfatases/metabolismo , Adenosina Trifosfatases/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Histonas/metabolismo
4.
PLoS Negl Trop Dis ; 18(5): e0012187, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38809847

RESUMO

BACKGROUND: Snakebite envenomation inflicts a high burden of mortality and morbidity in sub-Saharan Africa. Antivenoms are the mainstay in the therapy of envenomation, and there is an urgent need to develop antivenoms of broad neutralizing efficacy for this region. The venoms used as immunogens to manufacture snake antivenoms are normally selected considering their medical importance and availability. Additionally, their ability to induce antibody responses with high neutralizing capability should be considered, an issue that involves the immunization scheme and the animal species being immunized. METHODOLOGY/PRINCIPAL FINDINGS: Using the lethality neutralization assay in mice, we compared the intrageneric neutralization scope of antisera generated by immunization of horses with monospecific, bispecific/monogeneric, and polyspecific/monogeneric immunogens formulated with venoms of Bitis spp., Echis spp., Dendroaspis spp., spitting Naja spp. or non-spitting Naja spp. It was found that the antisera raised by all the immunogens were able to neutralize the homologous venoms and, with a single exception, the heterologous congeneric venoms (considering spitting and non-spitting Naja separately). In general, the polyspecific antisera of Bitis spp, Echis spp, and Dendroaspis spp gave the best neutralization profile against venoms of these genera. For spitting Naja venoms, there were no significant differences in the neutralizing ability between monospecific, bispecific and polyspecific antisera. A similar result was obtained in the case of non-spitting Naja venoms, except that polyspecific antiserum was more effective against the venoms of N. melanoleuca and N. nivea as compared to the monospecific antiserum. CONCLUSIONS/SIGNIFICANCE: The use of polyspecific immunogens is the best alternative to produce monogeneric antivenoms with wide neutralizing coverage against venoms of sub-Saharan African snakes of the Bitis, Echis, Naja (non-spitting) and Dendroaspis genera. On the other hand, a monospecific immunogen composed of venom of Naja nigricollis is suitable to produce a monogeneric antivenom with wide neutralizing coverage against venoms of spitting Naja spp. These findings can be used in the design of antivenoms of wide neutralizing scope for sub-Saharan Africa.


Assuntos
Antivenenos , Testes de Neutralização , Animais , Cavalos/imunologia , Antivenenos/imunologia , Antivenenos/administração & dosagem , Camundongos , África Subsaariana , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/sangue , Venenos de Serpentes/imunologia , Soros Imunes/imunologia , Venenos Elapídicos/imunologia , Mordeduras de Serpentes/imunologia
5.
Proc Biol Sci ; 291(2021): 20240262, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38654646

RESUMO

The fossil fish Ptychodus Agassiz, 1834, characterized by a highly distinctive grinding dentition and an estimated gigantic body size (up to around 10 m), has remained one of the most enigmatic extinct elasmobranchs (i.e. sharks, skates and rays) for nearly two centuries. This widespread Cretaceous taxon is common in Albian to Campanian deposits from almost all continents. However, specimens mostly consist of isolated teeth or more or less complete dentitions, whereas cranial and post-cranial skeletal elements are very rare. Here we describe newly discovered material from the early Late Cretaceous of Mexico, including complete articulated specimens with preserved body outline, which reveals crucial information on the anatomy and systematic position of Ptychodus. Our phylogenetic and ecomorphological analyses indicate that ptychodontids were high-speed (tachypelagic) durophagous lamniforms (mackerel sharks), which occupied a specialized predatory niche previously unknown in fossil and extant elasmobranchs. Our results support the view that lamniforms were ecomorphologically highly diverse and represented the dominant group of sharks in Cretaceous marine ecosystems. Ptychodus may have fed predominantly on nektonic hard-shelled prey items such as ammonites and sea turtles rather than on benthic invertebrates, and its extinction during the Campanian, well before the end-Cretaceous crisis, might have been related to competition with emerging blunt-toothed globidensine and prognathodontine mosasaurs.


Assuntos
Fósseis , Filogenia , Tubarões , Animais , Fósseis/anatomia & histologia , México , Tubarões/anatomia & histologia , Tubarões/classificação , Tubarões/fisiologia , Evolução Biológica , Dente/anatomia & histologia
6.
Toxicon X ; 22: 100195, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38606385

RESUMO

Mice are routinely used in snake venom research but are costly and subject to pain and suffering. The crustacean Artemia salina could be an alternative to mice, but data to support its adoption in snake venom research is limited. The aim of the present study was to evaluate the suitability of A. salina as a surrogate of mice in assessing the toxicity of venoms and the preclinical efficacy of antivenoms. The toxicity of venoms from 22 snakes of medical importance in sub-Saharan Africa was evaluated in mice (intraperitoneally; i.p. and intravenously; i.v.) and in A. salina. Subsequently, the capacity of a commercial antivenom to neutralize the toxicity of these venoms in mice and A. salina was investigated. There was a positive correlation between the i.v. median lethal doses (LD50s) and the i.p. LD50s in mice (r = 0.804; p < 0.0001), a moderate correlation between the i.v. LD50s in mice and the median lethal concentrations (LC50s) in A. salina (r = 0.606; p = 0.003), and a moderate correlation between the i.p. LD50s in mice and the LC50s in A. salina (r = 0.426; p = 0.048). Moreover, there was a strong correlation between the i.p. median effective doses (ED50s) and the i.v. ED50s in mice (r = 0.941, p < 0.0001), between the i.p. ED50s in mice and the ED50s in A. salina (r = 0.818, p < 0.0001), and between the i.v. ED50s in mice and the ED50s in A. salina (r = 0.972, p < 0.0001). These findings present A. salina as a promising candidate for reducing reliance on mice in snake venom research. Future investigations should build upon these findings, addressing potential limitations and expanding the scope of A. salina in venom research and antivenom development.

8.
Sensors (Basel) ; 24(6)2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38543996

RESUMO

This paper presents the design, implementation, and validation of an on-blade sensor system for remote vibration measurement for low-capacity wind turbines. The autonomous sensor system was deployed on three wind turbines, with one of them operating in harsh weather conditions in the far south of Chile. The system recorded the acceleration response of the blades in the flapwise and edgewise directions, data that could be used for extracting the dynamic characteristics of the blades, information useful for damage diagnosis and prognosis. The proposed sensor system demonstrated reliable data acquisition and transmission from wind turbines in remote locations, proving the ability to create a fully autonomous system capable of recording data for monitoring and evaluating the state of health of wind turbine blades for extended periods without human intervention. The data collected by the sensor system presented in this study can serve as a foundation for developing vibration-based strategies for real-time structural health monitoring.

9.
Toxicon X ; 21: 100187, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38404947

RESUMO

As injectable therapeutics, snake antivenoms must meet specifications for endotoxin content. The Limulus amebocyte lysate (LAL) test was used to evaluate the endotoxin content in several commercially available antivenoms released for clinical use. It was found that some products have endotoxin concentrations higher than the accepted limit for these contaminants. These results emphasize the need to include endotoxin determination as part of the routine evaluation of antivenoms by manufacturers and regulatory agencies.

10.
Atherosclerosis ; 390: 117456, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38262274

RESUMO

BACKGROUND AND AIMS: Information on the association between dietary oily fish intake and intracranial atherosclerosis is limited and contradictory. Inconsistencies might be in part related to heterogeneous designs and differences in race/ethnicity of study populations. We aim to assess whether oily fish intake is inversely associated with intracranial artery stenosis (ICAS) in frequent fish consumers of indigenous ancestry living in coastal Ecuador. METHODS: The study included 384 participants aged ≥60 years enrolled in the Atahualpa Project Cohort. Dietary oily fish intake was quantified systematically via validated surveys and all participants received a time-of-flight MRA of intracranial vessels. Poisson regression models, adjusted for demographics, level of education, traditional risk factors and severe tooth loss, were fitted to assess the association between amounts of oily fish intake and the number of intracranial arteries with moderate-to-severe (≥50 %) stenosis. RESULTS: Participants had a mean age of 67.7 ± 7 years, and 56 % were women. The mean oily fish intake was 8.9 ± 5.2 servings/week; 283 (74 %) participants consumed ≥5.2 servings/week (2nd to 4th quartiles of fish intake). Forty-three (11 %) participants had at least one major intracranial artery with moderate-to-severe stenosis. Both univariate and multivariate models showed a significant inverse association between consumption of oily fish in the 2nd to 4th quartiles and ≥50 % stenosis in at least one artery (ß: 0.46; 95 % C.I.: 0.27-077, and ß: 0.52; 95 % C.I.: 0.30-0.90, respectively). CONCLUSIONS: Consumption of more than five oily fish servings/week is associated with lower prevalence of moderate-to-severe ICAS in indigenous Ecuadorians.


Assuntos
Dieta , População da América do Sul , Animais , Humanos , Feminino , Idoso , Pessoa de Meia-Idade , Masculino , Equador/epidemiologia , Constrição Patológica , Fatores de Risco
11.
Heliyon ; 10(1): e23485, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38173536

RESUMO

This is a case report of a young adult who died of COVID-19 twelve days after admission, with coronavirus nucleocapsid protein and lipofuscin found in the heart and kidney tissues, providing further evidence of the role of SARS-CoV-2 in cellular senescence.

12.
Toxins (Basel) ; 16(1)2024 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-38251253

RESUMO

Even though there are guidelines for the management of snakebite envenoming (SBE), the use of antibiotics in this pathology remains controversial. The aim of this study is to provide a narrative review of the literature and recommendations based on the best available evidence regarding antibiotic use in SBE. We performed a narrative review of relevant literature regarding SBE and antibiotic use as prophylaxis or treatment. A total of 26 articles were included. There is wide use of antibiotics in SBE; nevertheless, infection was not necessarily documented. The antibiotics used varied according to the study, from beta lactams to lincosamide and nitroimidazoles, and from monotherapy to combined antimicrobials. The most common recommendations were to manage skin and soft tissue infections and avoid infectious complications, but these suggestions are not necessarily based on bacteriological findings. Prophylactic use of antibiotics in SBE is discouraged in most studies. Antibiotic prescription in SBE should be based on the susceptibility of microorganisms isolated from the affected tissue or identified in snakes' oral cavities. Antibiotics should be reserved only for patients with a demonstrated infection, or those at a high risk of developing an infection, i.e., presenting severe local envenoming, local signs of infection, or those with incorrect manipulation of wounds. Prospective studies are needed to correlate microbiological findings at the wound site and the response to antibiotic use.


Assuntos
Gestão de Antimicrobianos , Nitroimidazóis , Mordeduras de Serpentes , Humanos , Antibacterianos/uso terapêutico , Mordeduras de Serpentes/tratamento farmacológico , Boca
13.
Toxicon X ; 21: 100183, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38274651

RESUMO

Snakebite envenomation is a neglected tropical disease posing a high toll of mortality and morbidity in sub-Saharan Africa. Polyspecific antivenoms of broad effectiveness and specially designed for this region require a detailed understanding of the immunological features of the mamba snake (Dendroaspis spp.) venoms for the selection of the most appropriate antigen combination to produce antivenoms of wide neutralizing scope. Monospecific antisera were generated in rabbits against the venoms of the four species of mambas. The toxic effects of the immunization scheme in the animals were evaluated, antibody titers were estimated using immunochemical assays, and neutralization of lethal activity was assessed. By the end of the immunization schedule, rabbits showed normal values of the majority of hematological parameters tested. No muscle tissue damage was noticed, and no alterations in most serum chemical parameters were observed. Immunological analyses revealed a variable extent of cross-reactivity of the monospecific antisera against the heterologous venoms. The venoms of D. jamesoni and D. viridis generated the antisera with broader cross-reactivity by immunochemical parameters. The venoms of D. polylepis and D. viridis generated the antisera with better cross-neutralization of lethality, although the neutralizing ability of all antisera was lower than 0.16 mg venom/mL antiserum against either homologous or heterologous venoms. These experimental results must be scaled to large animal models used in antivenom manufacture at industrial level to assess whether these predictions are reproducible.

14.
Biol. Res ; 572024.
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1564037

RESUMO

Background Chromatin dynamics is deeply involved in processes that require access to DNA, such as transcriptional regulation. Among the factors involved in chromatin dynamics at gene regulatory regions are general regulatory factors (GRFs). These factors contribute to establishment and maintenance of nucleosome-depleted regions (NDRs). These regions are populated by nucleosomes through histone deposition and nucleosome sliding, the latter catalyzed by a number of ATP-dependent chromatin remodeling complexes, including ISW1a. It has been observed that GRFs can act as barriers against nucleosome sliding towards NDRs. However, the relative ability of the different GRFs to hinder sliding activity is currently unknown. Results Considering this, we performed a comparative analysis for the main GRFs, with focus in their ability to modulate nucleosome sliding mediated by ISW1a. Among the GRFs tested in nucleosome remodeling assays, Rap1 was the only factor displaying the ability to hinder the activity of ISW1a. This effect requires location of the Rap1 cognate sequence on linker that becomes entry DNA in the nucleosome remodeling process. In addition, Rap1 was able to hinder nucleosome assembly in octamer transfer assays. Concurrently, Rap1 displayed the highest affinity for and longest dwell time from its target sequence, compared to the other GRFs tested. Consistently, through bioinformatics analyses of publicly available genome-wide data, we found that nucleosome occupancy and histone deposition in vivo are inversely correlated with the affinity of Rap1 for its target sequences in the genome. Conclusions Our findings point to DNA binding affinity, residence time and location at particular translational positions relative to the nucleosome core as the key features of GRFs underlying their roles played in nucleosome sliding and assembly.

15.
Cir. Urug ; 8(1): e403, 2024. ilus
Artigo em Espanhol | LILACS, UY-BNMED, BNUY | ID: biblio-1564270

RESUMO

Se trata de un paciente de sexo masculino de 89 años de edad, portador de prótesis mitral, intervenido hace 20 años, acude a urgencias por dolor abdominal y vómitos. Se realiza una tomografía computarizada (TC) toraco-abdominal que confirma la presencia de eventración subxifoidea con sufrimiento parietal, requiriendo resección intestinal y eventroplastia con malla intraperitoneal. La eventración subxifoidea constituye una patología infrecuente, que tiene lugar, de forma mayoritaria, en pacientes que han precisado intervenciones del área cardíaca, o hepatobiliopancreática. Su diagnóstico se basa en la clínica y examen físico. Esta patología supone un reto para el cirujano dada la complejidad quirúrgica de la región anatómica donde aparece, pues las estructuras condrocostales adyacentes dificultan la sutura y eventroplastia. En casi todas las series la reparación ha sido electiva, siendo la cirugía de urgencia por incarceración algo anecdótico. La técnica sugerida sería la eventroplastia preperitoneal con malla retroxifoidea irreabsorbible, sin embargo, ésta se encuentra condicionada a los hallazgos intraoperatorios, especialmente a la estrangulación.


Assuntos
Humanos , Masculino , Idoso de 80 Anos ou mais , Hérnia Incisional/diagnóstico por imagem , Hérnia Incisional/cirurgia , Octogenários
16.
Toxicon, v. 247, 107824, jun. 2024
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IBPROD, Sec. Est. Saúde SP | ID: bud-5435

RESUMO

Phagocytosis, an essential process for host defense, requires the coordination of a variety of signaling reactions. MT-II, an enzymatically inactive Lys49 phospholipase A2 (PLA2) homolog, and MT-III, a catalytically-active Asp49 PLA2, are known to activate phagocytosis in macrophages. In this study, the signaling pathways mediating phagocytosis, focusing on protein kinases, were investigated. Macrophages from male Swiss mice peritoneum were obtained 96 h after intraperitoneal thioglycolate injection. Phagocytosis was evaluated using nonopsonized zymosan particles in the presence or absence of specific inhibitors, as well as PKC and PKC-α localization by confocal microscopy. Moreover, protein kinase C (PKC) activity was assessed by γP32 ATP in macrophages stimulated by both PLA2s. Data showed that both sPLA2s increased phagocytosis. Cytochalasin D, staurosporine/H7, wortmannin, and herbimycin, inhibitors of actin polymerization, PKC, phosphoinositide 3-kinase (PI3K), and protein tyrosine kinase (PTK), respectively, significantly reduced phagocytosis induced by both PLA2s. PKC activity was increased in macrophages stimulated by both PLA2s. Actin polymerization and talin were evidenced by immunofluorescence and talin was recruited 5 min after both PLA2s stimulation. PKC and PKC-α localization within the cell were increased after 60 min of MT-II and MT-III stimulation. These data suggest that the effect of both PLA2s depends on actin cytoskeleton rearrangements and the activation of PKC, PI3K, and PTK signaling events required for phagocytosis.

17.
Toxicon, v. 243, 107716, mai. 2024
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IBPROD, Sec. Est. Saúde SP | ID: bud-5322

RESUMO

The phagocytic activity of macrophages activated with MT-II, a Lys-49 PLA2 homolog, and MT-III, an Asp-49 PLA2, from Bothrops asper snake venom, was investigated in this study using a pharmacological approach. Stimulating thioglycollate-elicited macrophages with both venom components enhanced their ability to phagocytose non-opsonized zymosan particles. MT-II and MT–III–induced phagocytosis was drastically inhibited by pretreating cells with L-NAME, aminoguanidine or L-NIL, cNOS or iNOS inhibitors, or with ODQ (sGC inhibitor) or Rp-cGMPS (PKG inhibitor). These results indicate that the NO/sGC/GMP/PKG pathway plays an essential role in the β-glucan-mediated phagocytosis induced in macrophages by these venom-secretory PLA2s.

18.
Cell Biosci ; 13(1): 232, 2023 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-38135881

RESUMO

BACKGROUND: mTORC2 is a critical regulator of cytoskeleton organization, cell proliferation, and cancer cell survival. Activated mTORC2 induces maximal activation of Akt by phosphorylation of Ser-473, but regulation of Akt activity and signaling crosstalk upon growth factor stimulation are still unclear. RESULTS: We identified that NUAK1 regulates growth factor-dependent activation of Akt by two mechanisms. NUAK1 interacts with mTORC2 components and regulates mTORC2-dependent activation of Akt by controlling lysosome positioning and mTOR association with this organelle. A second mechanism involves NUAK1 directly phosphorylating Akt at Ser-473. The effect of NUAK1 correlated with a growth factor-dependent activation of specific Akt substrates. NUAK1 induced the Akt-dependent phosphorylation of FOXO1/3a (Thr-24/Thr-32) but not of TSC2 (Thr-1462). According to a subcellular compartmentalization that could explain NUAK1's differential effect on the Akt substrates, we found that NUAK1 is associated with early endosomes but not with plasma membrane, late endosomes, or lysosomes. NUAK1 was required for the Akt/FOXO1/3a axis, regulating p21CIP1, p27KIP1, and FoxM1 expression and cancer cell survival upon EGFR stimulation. Pharmacological inhibition of NUAK1 potentiated the cell death effect induced by Akt or mTOR pharmacological blockage. Analysis of human tissue data revealed that NUAK1 expression positively correlates with EGFR expression and Akt Ser-473 phosphorylation in several human cancers. CONCLUSIONS: Our results showed that NUAK1 kinase controls mTOR subcellular localization and induces Akt phosphorylation, demonstrating that NUAK1 regulates the growth factor-dependent activation of Akt signaling. Therefore, targeting NUAK1, or co-targeting it with Akt or mTOR inhibitors, may be effective in cancers with hyperactivated Akt signaling.

19.
Antioxidants (Basel) ; 12(12)2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38136185

RESUMO

Lupus nephritis (LN) is the most frequent and severe complication of systemic lupus erythematosus (SLE). A prospective cohort with a six-month follow-up was performed. Twelve SLE patients diagnosed with LN Class III, twelve NL Class IV patients, and twelve healthy control subjects (HC) were included. SLE data, renal function, oxidants, antioxidants, and inflammation were determined at baseline and six-month follow-up. During the six-month follow-up, the SLE Disease Activity Index (SLEDAI-2K) decreased in both LN Class III (20.08 ± 6.92 vs. 11.92 ± 5.87, p < 0.001) and LN Class IV (25.33 ± 6.01 vs. 13.83 ± 5.52, p < 0.001) patients. Furthermore, the values of the C4 component also increased during follow-up for LN Class III (25.36 ± 6.34 vs. 30.91 ± 9.22, p = 0.027) and LN Class IV (12.18 ± 3.90 vs. 20.33 ± 8.95, p = 0.008) groups. Regarding inflammation markers, both groups presented decreased C-reactive protein (CRP), but this was only significant for patients with LN class III (7.93 ± 1.77 vs. 4.72 ± 3.23, p = 0.006). Renal function remained stable in both groups, with no changes in eGFR. Patients with LN Class III and Class IV showed higher baseline levels for lipoperoxides (Class III p < 0.01, Class IV p < 0.1) and carbonyl groups in proteins (Class III p < 0.01, Class IV p < 0.1) compared to HC. Moreover, both groups presented lower baseline values of total antioxidant capacity (Class III p < 0.01, Class IV p < 0.1) and catalase (Class III p < 0.01, Class IV p < 0.1) compared to HCs. However, antioxidant and oxidant markers did not show significant differences between baseline values and at six months for either of the two study groups. In conclusion, patients show an imbalance in the oxidative state characterized by the increase in the oxidants LPO and protein carbonyl groups and the decrease in the activity of the antioxidant enzymes TAC and CAT compared to HC. However, the patients did not present an increase in disease activity and renal function improvement. The glomerular filtration rate did not change during the length of the study, and SLEDAI -2K, C3, and C4 improved. The early co-management between Rheumatologists and Nephrologists is essential to prevent the rapid progression of LN. It would be interesting to administer antioxidant supplements to patients with a recent diagnosis of LN and evaluate its effect in a follow-up study.

20.
Horiz. enferm ; 34(3): 465-476, 20 dic. 2023. tab, ilus
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1525119

RESUMO

El envejecimiento global es uno de los grandes desafíos sanitarios del siglo XXI, el 2030 una de cada seis personas tendrá ≥ 60 años. En Chile se proyecta un 32,1% para el 2050. Esta realidad demográfica desafía a la enfermería en el abordaje multidimensional del envejecimiento. La espiritualidad como atributo de la autotrascendencia es un factor condicionante de acciones promotoras de salud en las personas mayores. Desde la perspectiva de la Dra. Reed, se presentan los resultados de validación de su Escala de Perspectiva Espiritual. La población fue de 202 personas mayores en promedio de 71 años (D.E.= 8,2338). El método utilizado fue diseño psicométrico y corte transversal. La escala general presentó; α de Cronbach=0,92; dimensiones prácticas espirituales α de Cronbach= 0,822; dimensión creencias espirituales α de Cronbach=0,914. El análisis de modelo de un factor (CFI=0,956, RMSEA=0,167 IC95% [0,147 - 0,188] y un c2=232,762; p=0,000), como de dos factores coherentes con la estructura teórica propuesta por Reed (CFI=0,984; RMSEA=0,102 IC95% [0,081 ­ 0,125] y c2=105,890; p=0,000), presentaron cargas factoriales altas y relativamente homogéneas. La escala general y las subescalas de creencias y prácticas espirituales mostraron adecuada confiabilidad. El análisis de modelos anidados mostró un mejor ajuste del modelo de dos factores. Los resultados suman para afirmar que la Escala de Perspectiva Espiritual, contribuye a la precisión empírica, potencial heurístico y verificabilidad de la Teoría de Transcendencia de Reed. Se vislumbra que la espiritualidad es un factor mediador en la relación entre la vulnerabilidad, autotrascendencia y bienestar de la persona mayor.


Global aging is one of the great health challenges of the 21st century. By 2030, one in six people will be ≥60 years of age, with 32.1% projected for Chile by 2050. This demographic reality challenges nursing in the multidimensional approach to aging. The dimension of spirituality as an attribute of self-transcendence is a conditioning factor of health promoting actions in the elderly. The validation results of Dr. Reed's Spiritual Perspective Scale are presented. The population included 202 people older than 71 years on average (SD= 8.2338). The method used was a psychometric and cross-sectional design. The general scale presented Cronbach's α=0.92; spiritual practical dimension, Cronbach's α=0.822; spiritual beliefs dimension, Cronbach's α=0.914. The analysis of a one-factor model (CFI=.956, RMSEA=0.167 IC95% [0.147-0.188] and c2=232.762; p=0.000), as two factors consistent with the theoretical structure proposed by Reed (CFI=0.984; RMSEA=0.102 IC95% [0.081-0.125] and c2=105.890; p=0.000), presented high and relatively homogeneous factorial loads. The general scale and the subscales of spiritual beliefs and practices showed adequate reliability. The analysis of nested models showed a better adjustment of the two-factor model. The results collectively affirm that the Spiritual Perspective Scale contributes to the empirical precision, heuristic potential, and verifiability of Reed's Theory of Transcendence. It is observed that spirituality is a mediating factor in the relationship between vulnerability, self-transcendence, and well-being of humans.

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