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Context: Collagen V (COLV) is normally sequestered within the lung interstitium and therefore hidden from the immune system, being considered an autoantigen involved in experimental and human pulmonary fibrosis. Previous studies have suggested a possible contribution of IL-17 in the development and progression of pulmonary inflammation and fibrosis. Our aim was to correlate IL-17+ cells and pulmonary fibrosis in C57BL/6 mice immunized with COLV. Design: C57BL/6 female mice (n = 6) were subcutaneously immunized (IM) with 150 ig/200 iL of COLV in complete Freund adjuvant. Control mice (n = 6) were immunized with adjuvant. Collagen deposition was evaluated by picrosirius, immunofluorescence, and quantified by image analysis. TGF, CTGF, CD4+, and IL-17+ cells were evaluated by immunohistochemistry and point counting method. Results: C57BL/6 IM mice presented with intense pulmonary inflammation with significant numbers of CD4+ (P = .002) and IL17+ (P = .001) cells in the pulmonary interstitium, prominent thickness of the septal and bronchovascular interstitium with thick collagen fibers and higher amounts of type I (P < .005) collagen, compared to controls. In addition, C57BL/6 IM mice showed high expression of COLV thick fibers along the bronchovascular and septal interstitium (P = .002), compared to controls. Higher expression of TGF (P < .002) and CTGF (P < .001) were observed in C57BL/6 IM mice than in the control group. Conclusions: COLV-induced pulmonary remodeling was seen in healthy C57BL/6 mice, suggesting a promising pulmonary fibrosis model important for study of this pathogenesis. Higher expression of IL-17+ cells correlated with pulmonary fibrosis and COLV overexpression, suggesting that this cytokine can play a role in pulmonary remodeling. Strategies to block IL-17+ cells may represent a promising therapeutic target for the pulmonary fibrosis process., W. R. Teodoro (1); A. P. P. Velosa (1); A. Santos Filho (1); P. C. Andrade (1); V. Martins (2); E. M. Eher (2); S. M. Fernezlian (2); S. Catanozi [...]

We hypothesized that after synovial injury, collagen V (Col V) expose occult antigens, and Col V autoantibodies develop, indicating the loss of immune tolerance against this molecule, thus leading to damage to mesenchymal-derived cells as well as the extracellular matrix in experimental arthritis. Thus, the present study investigated the effects of oral administration of Col V on the synovium after the development of inflammation in mBSA/CFA-induced arthritis. After fourteen days of intraarticular administration of mBSA, 10 male Lewis rats were orally administered Col V (500 μg/300 μL) diluted in 0.01 N acetic acid (IA-Col V group). The arthritic group (IA group, n = 10) received only intraarticular mBSA. An intra-articular saline injection (20 μL) was given to the control group (CT-Col V, n = 5). IA group presented damaged synovia, the expansion of the extracellular matrix by cellular infiltrate, which was characterized by T and B lymphocytes, and fibroblastic infiltration. In contrast, after Col V oral immunotherapy IA-Col V group showed a significant reduction in synovial inflammation and intense expression of IL-10+ and FoxP3+ cells, in addition to a reduction in Col V and an increase in Col I in the synovia compared to those in the IA group. Furthermore, an increase in IL-10 production was detected after IA-Col V group spleen cell stimulation with Col V in vitro. PET imaging did not differ between the groups. The evaluation of oral treatment with Col V, after mBSA/CFA-induced arthritis in rats, protects against inflammation and reduces synovial tissue damage, through modulation of the synovial matrix, showing an immunotherapeutic potential in inhibiting synovitis., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ramos da Silveira et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Dietary sodium restriction increases plasma triglycerides (TG) and total cholesterol (TC) concentrations as well as causing insulin resistance and stimulation of the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system. Stimulation of the angiotensin II type-1 receptor (AT1) is associated with insulin resistance, inflammation, and the inhibition of adipogenesis. The current study investigated whether aerobic exercise training (AET) mitigates or inhibits the adverse effects of dietary sodium restriction on adiposity, inflammation, and insulin sensitivity in periepididymal adipose tissue. LDL receptor knockout mice were fed either a normal-sodium (NS; 1.27% NaCl) or a low-sodium (LS; 0.15% NaCl) diet and were either subjected to AET for 90 days or kept sedentary. Body mass, blood pressure (BP), hematocrit, plasma TC, TG, glucose and 24-hour urinary sodium (U Na ) concentrations, insulin sensitivity, lipoprotein profile, histopathological analyses, and gene and protein expression were determined. The results were evaluated using two-way ANOVA. Differences were not observed in BP, hematocrit, diet consumption, and TC. The LS diet was found to enhance body mass, insulin resistance, plasma glucose, TG, LDL-C, and VLDL-TG and reduce U Na , HDL-C, and HDL-TG, showing a pro-atherogenic lipid profile. In periepididymal adipose tissue, the LS diet increased tissue mass, TG, TC, AT1 receptor, pro-inflammatory macro-phages contents, and the area of adipocytes; contrarily, the LS diet decreased anti-inflammatory macrophages, protein contents and the transcription of genes related to insulin sensitivity. The AET prevented insulin resistance, but did not protect against dyslipidemia, adipose tissue pro-inflammatory profile, increased tissue mass, AT1 receptor expression, TG, and TC induced by the LS diet.

Cardiovascular risk increases during the aging process in women with atherosclerosis and exercise training is a strategy for management of cardiac risks in at-risk populations. Therefore, the aims of this study were to evaluate: (1) the influence of the aging process on cardiac function, hemodynamics, cardiovascular autonomic modulation, and baroreflex sensitivity in females with atherosclerosis at the onset of reproductive senescence; and (2) the impact of exercise training on age-related dysfunctions in this model. Eighteen Apolipoprotein-E knockout female mice were divided equally into young (Y), middle-aged (MA), and trained middle-aged (MAT). Echocardiographic exams were performed to verify cardiac morphology and function. Cannulation for direct recording of blood pressure and heart rate, and analysis of cardiovascular autonomic modulation, baroreflex sensitivity were performed. The MA had lower cardiac diastolic function (E'/A' ratio), and higher aortic thickness, heart rate and mean arterial pressure, lower heart rate variability and baroreflex sensitivity compared with Y. There were no differences between Y and MAT in these parameters. Positive correlation coefficients were found between aortic wall thickness with hemodynamics data. The aging process causes a series of deleterious effects such as hemodynamic overload and dysautonomia in female with atherosclerosis. Exercise training was effective in mitigating aged-related dysfunctions., (© 2024. The Author(s).)

(1) Introduction: Restriction in sodium intake is an important strategy for reducing cardiovascular morbidity and mortality, considering the direct influence of high-sodium diet consumption on the development of hypertension and cardiovascular diseases. There are only a few studies dealing with the influence of dietary sodium on the development of nonalcoholic fatty liver disease (NAFLD). In this systematic review, evidence in humans and animal models was compiled in a critical view of the influence of dietary sodium intake patterns on NAFLD markers; (2) Methods: Systematic review of PubMed data. Clinical outcomes included the prevalence/incidence of NAFLD for human studies, and NAFLD markers (hepatic lipogenesis, and markers of steatosis, fibrosis, and inflammation) for animal studies. The protocol was registered at the International Prospective Register of Systematic Review (PROSPERO; CRD42023390447); (3) Results and Conclusion: Seven studies in humans and eight in animals were included. All studies in humans were observational and associated high-sodium intake with NAFLD. However, in animals, both the increased and reduced consumption of sodium negatively influenced markers of liver steatosis, inflammation, and fibrosis.

This study investigated the efficacy of aerobic exercise training (AET) in the prevention of dyslipidemia, insulin resistance (IR), and atherogenesis induced by severe low-sodium (LS) diet. LDL receptor knockout (LDLR KO) mice were fed a low-sodium (LS) (0.15% NaCl) or normal-sodium (NS; 1.27% NaCl) diet, submitted to AET in a treadmill, 5 times/week, 60 min/day, 15 m/min, for 90 days, or kept sedentary. Blood pressure (BP), plasma total cholesterol (TC) and triglyceride (TG) concentrations, lipoprotein profile, and insulin sensitivity were evaluated at the end of the AET protocol. Lipid infiltration, angiotensin II type 1 receptor (AT1), receptor for advanced glycation end products (RAGE), carboxymethyllysine (CML), and 4-hydroxynonenal (4-HNE) contents as well as gene expression were determined in the brachiocephalic trunk. BP and TC and gene expression were similar among groups. Compared to the NS diet, the LS diet increased vascular lipid infiltration, CML, RAGE, 4-HNE, plasma TG, LDL-cholesterol, and VLDL-TG. Conversely, the LS diet reduced vascular AT1 receptor, insulin sensitivity, HDL-cholesterol, and HDL-TG. AET prevented arterial lipid infiltration; increases in CML, RAGE, and 4-HNE contents; and reduced AT1 levels and improved LS-induced peripheral IR. The current study showed that AET counteracted the deleterious effects of chronic LS diet in an atherogenesis-prone model by ameliorating peripheral IR, lipid infiltration, CML, RAGE, 4-HNE, and AT1 receptor in the intima-media of the brachiocephalic trunk. These events occurred independently of the amelioration of plasma-lipid profile, which was negatively affected by the severe dietary-sodium restriction.

The SARS-CoV-2 pandemic have been affecting millions of people worldwide, since the beginning of 2020. COVID-19 can cause a wide range of clinical symptoms, which varies from asymptomatic presentation to severe respiratory insufficiency, exacerbation of immune response, disseminated microthrombosis and multiple organ failure, which may lead to dead. Due to the rapid spread of SARS-CoV-2, the development of vaccines to minimize COVID-19 severity in the world population is imperious. One of the employed techniques to produce vaccines against emerging viruses is the synthesis of recombinant proteins, which can be used as immunizing agents. Based on the exposed, the aim of the present study was to verify the systemic and immunological effects of IM administration of recombinant Nucleocapsid protein (NP), derived from SARS-CoV-2 and produced by this research group, in 2 different strains of rats (Rattus norvegicus); Wistar and Lewis. For this purpose, experimental animals received 4 injections of NP, once a week, and were submitted to biochemical and histological analysis. Our results showed that NP inoculations were safe for the animals, which presented no clinical symptoms of worrying side effects, nor laboratorial alterations in the main biochemical and histological parameters, suggesting the absence of toxicity induced by NP. Moreover, NP injections successfully triggered the production of specific anti-SARS-CoV-2 IgG antibodies by both Wistar and Lewis rats, showing the sensitization to have been well sufficient for the immunization of these strains of rats. Additionally, we observed the local lung activation of the Bronchus-Associated Lymphoid Tissue (BALT) of rats in the NP groups, suggesting that NP elicits specific lung immune response. Although pre-clinical and clinical studies are still required, our data support the recombinant NP produced by this research group as a potential immunizing agent for massive vaccination, and may represent advantages upon other recombinant proteins, since it seems to induce specific pulmonary protection., Competing Interests: The authors declare that no competing interests exist.

Primary hyperlipidaemia in Schnauzer is characterized by increased plasma triglycerides (TG) and/or total cholesterol (TC) concentration and is associated with an increased risk of developing pancreatitis, insulin resistance and seizures. In humans, omega-3 fatty acids in addition to a low-fat diet can be used to reduce TG and TC. This study evaluated the therapeutic efficacy of omega-3 fatty acids associated to a diet management with two different fat content in Schnauzer with primary hyperlipidaemia. Eighteen dogs with primary hyperlipidaemia were divided into two groups: group 1, n = 10, 8 females, 2 males, age (mean ± standard deviation) of 7.13 ± 2.70 years and body weight (BW) (mean ± standard deviation) of 7.25 ± 1.22 kg were treated with fish oil (approximately 730 mg/day of omega-3) associated with a low-fat and low-calorie diet (approximately 24g of fat/1000 kcal) for 90 days (T90); and group 2, n = 8 dogs, 6 females, 2 males, with 7.0 ± 1.77 years old and average BW of 8.36 ± 1.51 kg, treated with fish oil (approximately 730 mg/day of omega-3) and maintenance diet with moderate amount of fat (approximately 33g of fat/1000 kcal) for 90 days. Plasma TG and TC concentrations and lipoprotein (LP) profile (VLDL, LDL, HDL) were evaluated before and after treatment. TG and TC serum concentrations, expressed in mg/dL (mean ± standard deviation), before and after treatment in group 1 were: TG = 391.30 ± 487.86 (T0) and 118.7 ± 135.21 (T90); TC = 308.2 ± 63.06 (T0) and 139 ± 36.91 (T90). As for group 2, TG = 391.63 ± 336.89 (T0) and 250.75 ± 211.56 (T90); TC = 257.25 ± 92.88 (T0) and 207.25 ± 63.79 (T90). A reduction (p<0.05) of TG and TC was observed in both groups. The distribution of TG and TC among LP was not different between the pre (T0) and post treatment (T90) periods. After 90 days of treatment, the administration of omega-3 fatty acids, associated with a low-fat or maintenance diet reduced triglyceridemia and cholesterolemia without altering LP profile. The current investigation shows that both therapies were effective in reducing plasma TC and TG concentrations without altering LP profile., Competing Interests: The funder [Avert and Archer Daniels Midland Company (ADM)] provided support in the form of products and food for carrying out the study, however, this does not alter our adherence to PLOS ONE policies on sharing data and materials. The authors have declared that no competing interests exist.