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1.
J Drug Target ; : 1-15, 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38980282

ABSTRACT

Cost-effective strategies for the treatment of chronic wounds must be developed. The green synthesis of gold nanoparticles (GNPs) it is possible to guarantee a lower toxicity in biological tissues and greater safety of applicability, in addition to adding the effects of nanoparticles (NPs) to those of extracts. The objective of this study was to evaluate the effects of treatment with biosynthesized GNPs in a chronic wound model. Wistar rats were distributed into 7 groups: Acute Wound (AW); Chronic wound (CW); CW + GNPs-Açaí; CW + GNPs-DB; CW + AV-GNPs; CW + SafGel®; CW + 660 nm laser. The chronic injury model was induced with topically applied Resiquimod for 6 days. Treatments were then initated on the fourteenth day after the last application of Resiquimod and carried out daily for ten days. The proposed therapies with GNPs were able to significantly reduce the inflammatory score and increase the rate of wound contraction. In histology, there was a reduction in the inflammatory infiltrate and increased gene expression of fibronectin and type III collagen, mainly in the CW + AV-GNPs group. The therapies were able to reduce pro-inflammatory cytokines, increase anti-inflammatory cytokines, and reduce oxidative stress. The results demonstrated that the effects of GNPs appear to complement those of the extracts, thereby enhancing the tissue repair process.

2.
Life (Basel) ; 14(6)2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38929764

ABSTRACT

BACKGROUND: Tracheal grafts have been investigated for over a century, aiming to replace various lesions. However, tracheal reconstruction surgery remains a challenge, primarily due to anatomical considerations, intraoperative airway management, the technical complexity of reconstruction, and the potential postoperative morbidity and mortality. Due to research development, the amniotic membrane (AM) and Wharton's Jelly (WJ) arise as alternatives within the new set of therapeutic alternatives. These structures hold significant therapeutic potential for tracheal defects. This study analyzed the capacity of tracheal tissue regeneration after 60 days of decellularized WJ and AM implantation in rabbits submitted to conventional tracheostomy. METHODS: An in vivo experimental study was carried out using thirty rabbits separated into three groups (Control, AM, and WJ) (n = 10). The analyses were performed 60 days after surgery through immunohistochemistry. RESULTS: Different immunomarkers related to scar regeneration, such as aggrecan, TGF-ß1, and α-SMA, were analyzed. However, they highlighted no significant difference between the groups. Collagen type I, III, and Aggrecan also showed no significant difference between the groups. CONCLUSIONS: Both scaffolds appeared to be excellent frameworks for tissue engineering, presenting biocompatibility and a desirable microenvironment for cell survival; however, they did not display histopathological benefits in trachea tissue regeneration.

3.
Immunol Res ; 2024 May 02.
Article in English | MEDLINE | ID: mdl-38698191

ABSTRACT

The pathological manifestation of the inflammatory process primarily stems from the heightened release of pro-inflammatory cytokines, with IL-1ß standing out as a pivotal cytokine. The excessive presence of IL-1ß disrupts immune signaling, thereby assuming a pathogenic and exacerbating role in the pathophysiology of numerous inflammatory diseases. Regulating IL-1ß levels becomes crucial, and the IL-1Ra molecule serves this purpose by binding to the IL-1R1 receptor, thereby impeding the binding of IL-1ß. Several pharmaceuticals have entered the market, aiming to neutralize IL-1ß's biological function through diverse mechanisms. However, the existing IL-1ß inhibitors are recombinant proteins, characterized by a high production cost and limited stability. Therefore, this study aimed to predict a peptide, named DAP1-2, based on the IL-1Ra molecule. DAP1-2 was designed to attenuate responses triggered by IL-1ß by blocking the IL-1R1 receptor. The selection of amino acids from the IL-1Ra molecule (PDB: I1RA) that interact with the three domains of the IL-1R1 receptor was performed using Swiss PDB Viewer. After prediction, chemical synthesis was made using the Fmoc-Synthesis technique. The efficacy of DAP1-2 was assessed using RAW 264.7 cells, which were exposed to LPS (5 µg/mL) for 24 h to induce IL-1ß expression and treated with the peptides in different concentrations. IL-1ß levels were assessed using ELISA, and the gene expression of IL-1ß was measured by RT-qPCR, additionally to the viability test. Results revealed a significant reduction in IL-1ß levels and gene expression in cells stimulated by LPS and treated with DAP1-2 in different concentrations. Furthermore, the MTT assay confirmed the nontoxic nature of the peptides on the cell lineage. This alternative approach shows promise as an IL-1 inhibitor, due to the stability, ease of production, and cost-effectiveness provided by the use of synthetic peptides.

4.
Article in English | MEDLINE | ID: mdl-38575248

ABSTRACT

Type 2 diabetes mellitus (T2D) is a metabolic disease, which occurs largely due to unhealthy lifestyle. As oxidative stress is believed to promote T2D, by inducing damage to lipids, proteins, and DNA, appropriate dietary interventions seem critical to prevent, manage, and even reverse this condition. Brazil nuts (Bertholletia excelsa, H.B.K.) are nature's richest source of selenium, a mineral that has shown several health benefits. Therefore, this study aims to assess the effects of selenium consumption, through Brazil nuts, on biochemical and oxidative stress parameters, and genomic instability in T2D patients. We recruited 133 patients with T2D, registered in the Integrated Clinics of the University of Southern Santa Catarina (Brazil). Participants consumed one Brazil nut a day for six months. Blood samples and exfoliated buccal cells were collected at the beginning and the end of the intervention. The glycemic profile, lipid profile, renal profile and hepatic profile, DNA damage and selenium content were evaluated. A total of 74 participants completed the intervention. Brazil nut consumption increased selenium and GSH levels, GPx, and CAT activity while DCF and nitrites levels decreased. Total thiols increased, and protein carbonyl and MDA levels decreased. Levels of baseline and oxidative DNA damage in T2D patients were significantly decreased, as well as the frequency of micronuclei and nuclear buds. The fasting glucose levels, HDL and LDL cholesterol, and GGT levels that increased significantly in patients with type 2 diabetes were significantly reduced with nut consumption. Our results show an increase in antioxidant activity, along with reductions of protein and lipid oxidation as well as DNA damage, suggesting that Brazil nut consumption could be an ally in reducing oxidative stress and modulating the genomic instability in T2D patients.


Subject(s)
Bertholletia , Diabetes Mellitus, Type 2 , Selenium , Humans , Bertholletia/chemistry , Selenium/pharmacology , Overweight , Diabetes Mellitus, Type 2/genetics , Mouth Mucosa , Lipids , DNA Damage , Genomic Instability
5.
Metab Brain Dis ; 39(4): 635-648, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38429463

ABSTRACT

Obesity results from an energy imbalance and has been considered an epidemic due to its increasing rates worldwide. It is classified as a low-grade chronic inflammatory disease and has associated comorbidities. Different nutritional strategies are used for the purpose of weight loss, highlighting low-carbohydrate (LC) diets, ketogenic diets, and intermittent fasting (IF). These strategies can lead to metabolic and behavioral changes as they stimulate different biochemical pathways. Therefore, this study evaluated memory, energy metabolism, neuroinflammation, oxidative stress, and antioxidant defense parameters in mice subjected to an LC diet, ketogenic diet (KD), or IF. Eighty male Swiss mice, 60 days old, were divided into 4 groups: control, LC, KD, or IF. Body weight was measured weekly, and food intake every 48 h. After 15 days of nutritional interventions, the animals were subjected to the behavioral object recognition test and subsequently euthanized. Then, visceral fat was removed and weighed, and the brain was isolated for inflammatory and biochemical analysis. We concluded from this study that the LC and KD strategies could damage memory, IF improves the production of adenosine triphosphate (ATP), and the LC, KD, and IF strategies do not lead to neuroinflammatory damage but present damage at the level of oxidative stress.


Subject(s)
Diet, Ketogenic , Oxidative Stress , Animals , Male , Mice , Oxidative Stress/physiology , Memory Disorders/metabolism , Memory Disorders/etiology , Neuroinflammatory Diseases/metabolism , Diet, Carbohydrate-Restricted , Fasting/metabolism , Energy Metabolism/physiology , Brain/metabolism
6.
Article in English | MEDLINE | ID: mdl-38552774

ABSTRACT

Alzheimer's disease (AD) and depression are inflammatory pathologies, leading to increased inflammatory response and neurotoxicity. Therefore, this study aimed to evaluate the effect of the treatment with fluoxetine and/or galantamine and/or donepezil on the levels of proinflammatory and anti-inflammatory cytokines in a mixed animal model of depression and dementia. Adult male Wistar rats underwent chronic mild stress (CMS) protocol for 40 days and were subjected to stereotaxic surgery for intra-hippocampal administration of amyloid-beta (Aꞵ) peptide or artificial cerebrospinal fluid (ACSF) to mimic the dementia animal model. On the 42nd day, animals were treated with water, galantamine, donepezil, and/or fluoxetine, orally for 17 days. On the 57th and 58th days, the Splash and Y-maze tests for behavior analysis were performed. The frontal cortex and hippocampus were used to analyze the tumor necrosis factor alfa (TNF-α), interleukin 1 beta (IL-1ꞵ), IL-6, and IL-10 levels. The results of this study show that animals subjected to CMS and administration of Aꞵ had anhedonia, cognitive impairment, increased TNF-α and IL-1ꞵ levels in the frontal cortex, and reduced IL-10 levels in the hippocampus. All treatment groups were able to reverse the cognitive impairment. Only donepezil did not decrease the TNF-α levels in the hippocampus. Fluoxetine + galantamine and fluoxetine + donepezil reversed the anhedonia. Fluoxetine reversed the anhedonia and IL-1ꞵ levels in the frontal cortex. In addition, fluoxetine + donepezil reversed the reduction of IL-10 levels in the hippocampus. The results indicate a pathophysiological interaction between AD and depression, and the association of medications in the future may be a possible therapeutic strategy to reduce inflammation, especially the fluoxetine-associated treatments.


Subject(s)
Dementia , Depression , Disease Models, Animal , Donepezil , Fluoxetine , Galantamine , Hippocampus , Rats, Wistar , Animals , Male , Fluoxetine/pharmacology , Fluoxetine/therapeutic use , Donepezil/pharmacology , Donepezil/therapeutic use , Rats , Hippocampus/drug effects , Hippocampus/metabolism , Dementia/drug therapy , Depression/drug therapy , Galantamine/pharmacology , Galantamine/therapeutic use , Cytokines/metabolism , Neuroinflammatory Diseases/drug therapy , Stress, Psychological/complications , Amyloid beta-Peptides/metabolism , Anhedonia/drug effects
7.
Arch Sex Behav ; 53(3): 981-1000, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38413532

ABSTRACT

Partner preferences are an important differential in relationship formation and evolutionary fitness, and vary according to individual, ecological, and social factors. In this study, we evaluated the variation in preference for intelligence, kindness, physical attractiveness, health, and socioeconomic level among individuals of different sexes and sexual orientations in a Brazilian sample. We analyzed the preference scores of 778 heterosexual, bisexual, and homosexual men and women in three budgeted mate design tasks (low vs. medium vs. high budget) and their association with sociosexuality, attachment styles, homogamy, and willingness to engage in short- and long-term relationships. Results indicated a global trait preference order, with intelligence ranking first, followed by kindness, physical attractiveness, health, and lastly by socioeconomic status. Typical sex differences were observed mostly within the heterosexual group, and specific combinations of sex and sexual orientation were linked to variation in preference for physical attractiveness, kindness, and socioeconomic status. We also found unique associations of the other variables with partner preferences and with willingness to engage in short- or long-term relationships. By exploring the partner preferences of non-heterosexual individuals from a Latin American country, an underrepresented group in evolutionary psychology research, our results help understand the universal and specific factors that guide partner preferences and human sexual behavior.


Subject(s)
Heterosexuality , Sexual Behavior , Female , Humans , Male , Sexual Behavior/psychology , Heterosexuality/psychology , Homosexuality , Reproduction , Bisexuality , Sexual Partners/psychology
8.
Rev Saude Publica ; 58: 01, 2024.
Article in English | MEDLINE | ID: mdl-38381891

ABSTRACT

OBJECTIVE: This study aims to propose a comprehensive alternative to the Bland-Altman plot method, addressing its limitations and providing a statistical framework for evaluating the equivalences of measurement techniques. This involves introducing an innovative three-step approach for assessing accuracy, precision, and agreement between techniques, which enhances objectivity in equivalence assessment. Additionally, the development of an R package that is easy to use enables researchers to efficiently analyze and interpret technique equivalences. METHODS: Inferential statistics support for equivalence between measurement techniques was proposed in three nested tests. These were based on structural regressions with the goal to assess the equivalence of structural means (accuracy), the equivalence of structural variances (precision), and concordance with the structural bisector line (agreement in measurements obtained from the same subject), using analytical methods and robust approach by bootstrapping. To promote better understanding, graphical outputs following Bland and Altman's principles were also implemented. RESULTS: The performance of this method was shown and confronted by five data sets from previously published articles that used Bland and Altman's method. One case demonstrated strict equivalence, three cases showed partial equivalence, and one showed poor equivalence. The developed R package containing open codes and data are available for free and with installation instructions at Harvard Dataverse at https://doi.org/10.7910/DVN/AGJPZH. CONCLUSION: Although easy to communicate, the widely cited and applied Bland and Altman plot method is often misinterpreted, since it lacks suitable inferential statistical support. Common alternatives, such as Pearson's correlation or ordinal least-square linear regression, also fail to locate the weakness of each measurement technique. It may be possible to test whether two techniques have full equivalence by preserving graphical communication, in accordance with Bland and Altman's principles, but also adding robust and suitable inferential statistics. Decomposing equivalence into three features (accuracy, precision, and agreement) helps to locate the sources of the problem when fixing a new technique.


Subject(s)
Linear Models , Humans , Brazil
9.
Inflammation ; 2024 Jan 18.
Article in English | MEDLINE | ID: mdl-38236386

ABSTRACT

Chronic hyperglycemia caused by diabetes mellitus (DM) slows down the healing process due to prolonged inflammation which impedes the regeneration progression. Photobiomodulation (PBM) is considered a non-pharmacological intervention and has anti-inflammatory and biostimulatory effects that accelerate the healing process. Currently found IL-1ß inhibitors are difficult to implement due to their cytotoxic potential, excessive amounts, and invasive administration, and therefore, the application of this peptide in diabetic wounds represents a promising intervention to help resolve the inflammatory response. This study aimed to investigate the effect of an IL-1ß inhibitor molecule associated with PBM irradiation in a model of epithelial injury in diabetic mice. After the induction of the DM model with streptozotocin (STZ), the skin lesion model was implemented through surgical excision. Sixty C57BL/6 mice divided into five experimental groups (n = 12) were used: excisional wound (EW), DM + EW, DM + EW + DAP 1-2 (inhibitor peptide), DM + EW + PBM, and DM + EW + PBM + DAP 1-2. Treatment started 12 h after wound induction and was performed daily for 5 days. Twenty-four hours after the last application, the animals were euthanized and the outer edge of the wound was removed. The results obtained demonstrate that the DM + EW + PBM + DAP 1-2 group caused a reduction in the levels of pro-inflammatory cytokines, an increase in anti-inflammatory cytokines, and an increase in TGF-ß and maintenance of the cellular redox state with a consequent reduction in levels of inflammatory infiltrate and concomitant stimulation of type III collagen gene expression, as well as a decrease in the size of the wound in square centimeter 6 days after the injury. Only the combination of therapies was able to favor the process of tissue regeneration due to the development of an approach capable of acting at different stages of the regenerative process, through the mechanisms of action of interventions on the inflammatory process by avoiding its stagnation and stimulating progression of regeneration.

10.
Mol Neurobiol ; 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38296901

ABSTRACT

Obesity causes inflammation in the adipose tissue and can affect the central nervous system, leading to oxidative stress and mitochondrial dysfunction. Therefore, it becomes necessary to seek new therapeutic alternatives. Gold nanoparticles (GNPs) could take carnitine to the adipose tissue, thus increasing fatty acid oxidation, reducing inflammation, and, consequently, restoring brain homeostasis. The objective of this study was to investigate the effects of GNPs associated with carnitine on the neurochemical parameters of obesity-induced mice. Eighty male Swiss mice that received a normal lipid diet (control group) or a high-fat diet (obese group) for 10 weeks were used. At the end of the sixth week, the groups were divided for daily treatment with saline, GNPs (70 µg/kg), carnitine (500 mg/kg), or GNPs associated with carnitine, respectively. Body weight was monitored weekly. At the end of the tenth week, the animals were euthanized and the mesenteric fat removed and weighed; the brain structures were separated for biochemical analysis. It was found that obesity caused oxidative damage and mitochondrial dysfunction in brain structures. Treatment with GNPs isolated reduced oxidative stress in the hippocampus. Carnitine isolated decreased the accumulation of mesenteric fat and oxidative stress in the hippocampus. The combination of treatments reduced the accumulation of mesenteric fat and mitochondrial dysfunction in the striatum. Therefore, these treatments in isolation, become a promising option for the treatment of obesity.

11.
Int J Environ Health Res ; 34(2): 826-838, 2024 Feb.
Article in English | MEDLINE | ID: mdl-36780534

ABSTRACT

The present study investigated the effects of aquatic exercise on parameters of functional autonomy, mental health, and oxidative dysfunction in elderly patients with DM2. A total of 130 elderly were included in the longitudinal clinical study and were attributed to the non-diabetic group (n = 27) and diabetes the group (n = 22). Both groups participated in 24 sessions of Hydro-HIIT, 48 h before and after Hydro-HIIT, the GDLAM index, depression, and anxiety scores and markers of oxidative dysfunction were quantified. After intervention, GI decreased in both groups (non-diabetes group = -24%; diabetes group = -22%) (p < 0.05), markers of depression (-46%), anxiety (-60%), DCFH-DA (-55%), SOD (+59%), TNF-α (-37%) and IL-1 (-48%) in diabetes group (p < 0.05). The intervention with Hydro-HIIT improves aspects related to functional autonomy, mental health, and exerts consequently, a modulating effect on oxidative stress and inflammatory response in elderly people diagnosed with DM2.


Subject(s)
Diabetes Mellitus, Type 2 , High-Intensity Interval Training , Humans , Aged , Diabetes Mellitus, Type 2/therapy , Mental Health , Exercise , Oxidative Stress
12.
J Drug Target ; 32(2): 172-185, 2024 12.
Article in English | MEDLINE | ID: mdl-38155427

ABSTRACT

Introduction: The search for fast and efficient treatment for dermonecrotic lesions caused by the venom of the spider from the Loxosceles simillis, is a demand in health. Prednisolone is one of the most used drugs, however it has side effects. In this context, addictionally gold nanoparticles (GNPs) have anti-inflammatory, antioxidant, and antibacterial properties. The use of photobiomodulation has show to be efficient in the process of tissue repair. Therefore, the purpose of this study was to investigate the anti-inflammatory effect of photobiomodulation and GNPs associated or not with a low concentration of prednisolone in animal models of dermonecrotic lesion.Methodology: For this, rabbits with venon-induced dermonecrotic lesion were subjected to topical treatment with prednisolone + laser or GNPs + laser or Pred-GNPs + laser. The area of edema, necrosis and erythema were measured. On the last day of treatment, the animals were euthanized to remove the organs for histopathological and biochemical analysis.Results: All treatments combinations were effective in promoting the reduction of necrotic tissue and erythema.Conclusion: With this results, we suggest that the use of laser and nanoparticles, associated or not with prednisolone, should be considered for the treatment of dermonecrotic injury.


Subject(s)
Low-Level Light Therapy , Metal Nanoparticles , Spider Venoms , Animals , Rabbits , Phosphoric Diester Hydrolases/chemistry , Gold , Spider Venoms/chemistry , Erythema , Prednisolone/pharmacology , Prednisolone/therapeutic use , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use
13.
Rev. saúde pública (Online) ; 58: 01, 2024. graf
Article in English | LILACS | ID: biblio-1536768

ABSTRACT

ABSTRACT OBJECTIVE This study aims to propose a comprehensive alternative to the Bland-Altman plot method, addressing its limitations and providing a statistical framework for evaluating the equivalences of measurement techniques. This involves introducing an innovative three-step approach for assessing accuracy, precision, and agreement between techniques, which enhances objectivity in equivalence assessment. Additionally, the development of an R package that is easy to use enables researchers to efficiently analyze and interpret technique equivalences. METHODS Inferential statistics support for equivalence between measurement techniques was proposed in three nested tests. These were based on structural regressions with the goal to assess the equivalence of structural means (accuracy), the equivalence of structural variances (precision), and concordance with the structural bisector line (agreement in measurements obtained from the same subject), using analytical methods and robust approach by bootstrapping. To promote better understanding, graphical outputs following Bland and Altman's principles were also implemented. RESULTS The performance of this method was shown and confronted by five data sets from previously published articles that used Bland and Altman's method. One case demonstrated strict equivalence, three cases showed partial equivalence, and one showed poor equivalence. The developed R package containing open codes and data are available for free and with installation instructions at Harvard Dataverse at https://doi.org/10.7910/DVN/AGJPZH. CONCLUSION Although easy to communicate, the widely cited and applied Bland and Altman plot method is often misinterpreted, since it lacks suitable inferential statistical support. Common alternatives, such as Pearson's correlation or ordinal least-square linear regression, also fail to locate the weakness of each measurement technique. It may be possible to test whether two techniques have full equivalence by preserving graphical communication, in accordance with Bland and Altman's principles, but also adding robust and suitable inferential statistics. Decomposing equivalence into three features (accuracy, precision, and agreement) helps to locate the sources of the problem when fixing a new technique.


Subject(s)
Confidence Intervals , Regression Analysis , Data Interpretation, Statistical , Statistical Inference , Data Accuracy
14.
Inflammopharmacology ; 31(6): 3153-3166, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37752305

ABSTRACT

Musculoskeletal pain is a widely experienced public healthcare issue, especially after traumatic muscle injury. Besides, it is a common cause of disability, but this pain remains poorly managed. However, the pathophysiology of traumatic muscle injury-associated pain and inflammation has not been fully elucidated. In this regard, the transient receptor potential ankyrin 1 (TRPA1) has been studied in inflammatory and painful conditions. Thus, this study aimed to evaluate the antinociceptive and anti-inflammatory effect of the topical application of a TRPA1 antagonist in a model of traumatic muscle injury in rats. The mechanical trauma model was developed by a single blunt trauma impact on the right gastrocnemius muscle of Wistar male rats (250-350 g). The animals were divided into four groups (Sham/Vehicle; Sham/HC-030031 0.05%; Injury/Vehicle, and Injury/HC-030031 0.05%) and topically treated with a Lanette® N cream base containing a TRPA1 antagonist (HC-030031, 0.05%; 200 mg/muscle) or vehicle (Lanette® N cream base; 200 mg/muscle), which was applied at 2, 6, 12, 24, and 46 h after muscle injury. Furthermore, we evaluated the contribution of the TRPA1 channel on nociceptive, inflammatory, and oxidative parameters. The topical application of TRPA1 antagonist reduced biomarkers of muscle injury (lactate/glucose ratio), spontaneous nociception (rat grimace scale), inflammatory (inflammatory cell infiltration, cytokine levels, myeloperoxidase, and N-acetyl-ß-D-glucosaminidase activities) and oxidative (nitrite levels and dichlorofluorescein fluorescence) parameters, and mRNA Trpa1 levels in the muscle tissue. Thus, these results demonstrate that TRPA1 may be a promising anti-inflammatory and antinociceptive target in treating muscle pain after traumatic muscle injury.


Subject(s)
Inflammation , Nociception , Rats , Male , Animals , Rats, Wistar , TRPA1 Cation Channel , Inflammation/drug therapy , Pain/drug therapy , Anti-Inflammatory Agents/pharmacology , Analgesics/pharmacology , Muscles
15.
J Neuroimmune Pharmacol ; 18(3): 235-247, 2023 09.
Article in English | MEDLINE | ID: mdl-37526817

ABSTRACT

Relapsing-remitting multiple sclerosis (RRMS) is an autoimmune neurological disease and is the most common subtype of MS. In addition, it is associated with the development of depression and anxiety. To date, depressive- and anxiety-like behaviours were only studied using models of progressive MS, which causes severe motor alterations. Thus, we sought to standardise the depressive and anxiety-like behaviours in an RRMS model induced by experimental autoimmune encephalomyelitis (RR-EAE) in mice. The RR-EAE model was induced in C57BL/6 female mice using myelin oligodendrocyte glycoprotein (MOG35-55) antigen and Quillaja saponin (Quil A) as an adjuvant. The immunisation of RR-EAE did not induce locomotor alteration but caused relapsing-remitting induction of clinical scores in mice until 35 post-immunization (p.i.). Also, increased levels of tumour necrosis factor alpha (TNF-α), astrocyte marker (GFAP), and microglial markers (IBA-1) were detected in the prefrontal cortex at 35 p.i. of RR-EAE. In the open field test, RR-EAE mice showed decreased time spent at the centre and sniffing behaviour (at days 21 and 34 p.i.). Also, on day 35 p.i. the RR-EAE group spent less time in the open arms and had decreased open-arm entries compared to control mice in the elevated plus maze (EPM) test, confirming the anxiety-like behaviour. At day 36° p.i. in the tail suspension test, mice showed depression-like behaviour with decreased latency time and increased immobility time. Thus, the RR-EAE model mimics the neuroinflammatory and behavioural features of the RRMS, including depression- and anxiety-like symptoms.


Subject(s)
Encephalomyelitis, Autoimmune, Experimental , Multiple Sclerosis, Relapsing-Remitting , Multiple Sclerosis , Mice , Female , Animals , Depression , Mice, Inbred C57BL , Myelin-Oligodendrocyte Glycoprotein/toxicity , Anxiety , Disease Models, Animal
16.
Int J Mol Sci ; 24(15)2023 Jul 28.
Article in English | MEDLINE | ID: mdl-37569463

ABSTRACT

Insulin resistance is the link between obesity and type 2 diabetes mellitus. The molecular mechanism by which obese individuals develop insulin resistance has not yet been fully elucidated; however, inconclusive and contradictory studies have shown that oxidative stress may be involved in the process. Thus, this study aimed to evaluate the effect of reactive species on the mechanism of insulin resistance in diet-induced obese mice. Obese insulin-resistant mice were treated with N-acetylcysteine (NAC; 50 mg/kg per day, for 15 days) by means of oral gavage. Twenty-four hours after the last NAC administration, the animals were euthanized and their tissues were extracted for biochemical and molecular analyses. NAC supplementation induced improved insulin resistance and fasting glycemia, without modifications in food intake, body weight, and adiposity. Obese mice showed increased dichlorofluorescein (DCF) oxidation, reduced catalase (CAT) activity, and reduced glutathione levels (GSH). However, treatment with NAC increased GSH and CAT activity and reduced DCF oxidation. The gastrocnemius muscle of obese mice showed an increase in nuclear factor kappa B (NFκB) and protein tyrosine phosphatase (PTP1B) levels, as well as c-Jun N-terminal kinase (JNK) phosphorylation compared to the control group; however, NAC treatment reversed these changes. Considering the molecules involved in insulin signaling, there was a reduction in insulin receptor substrate (IRS) and protein kinase B (Akt) phosphorylation. However, NAC administration increased IRS and Akt phosphorylation and IRS/PI3k (phosphoinositide 3-kinase) association. The results demonstrated that oxidative stress-associated obesity could be a mechanism involved in insulin resistance, at least in this animal model.

17.
Antioxidants (Basel) ; 12(8)2023 Aug 07.
Article in English | MEDLINE | ID: mdl-37627569

ABSTRACT

This study aimed to evaluate and compare the effects of treatment with gold nanoparticles (GNPs) reduced with Curcumin (Curcuma longa L.) or Açai (Euterpe oleracea) to a standard commercial treatment of the pharmacological type (Omcilon®) and an electrophysical agent (photobiomodulation) in the palatal wounds of rats. As for the in vitro assay, a cell viability test was performed to assess the toxicity of the synthesized nanoparticles. In vivo assay: 60 Wistar rats were divided into five groups (n = 12): I. Palatal Wound (PW); II. PW + Photobiomodulation (PBM); III. PW + Omcilon®; IV. PW + GNPs-Cur (0.025 mg/mL); V. PW + GNPs-Açai (0.025 mg/mL). Animals were first anesthetized, and circular lesions in the palatine mucosa were induced using a 4 mm-diameter punch. The first treatment session started 24 h after the injury and occurred daily for 5 days. The animals were euthanized, and the palatal mucosa tissue was removed for histological, biochemical, and molecular analysis. GNPs-Açai were able to significantly reduce pro-inflammatory cytokines and increase anti-inflammatory ones, reduce oxidant markers, and reduce inflammatory infiltrate while increasing the collagen area and contraction rate of the wound, along with an improved visual qualification. The present study demonstrated that the proposed therapies of GNPs synthesized greenly, thus associating their effects with those of plants, favor the tissue repair process in palatal wounds.

18.
Biomedicines ; 11(4)2023 Mar 24.
Article in English | MEDLINE | ID: mdl-37189621

ABSTRACT

Wound healing is a complex process of repair that involves the interaction between different cell types and involves coordinated interactions between intracellular and extracellular signaling. Bone Marrow Mesenchymal Stem Cells (BMSCs) based and acellular amniotic membrane (AM) therapeutic strategies with the potential for treatment and regeneration of tissue. We aimed to evaluate the involvement of paracrine effects in tissue repair after the flap skin lesion rat model. In the full-thickness flap skin experiment of forty Wistar rats: A total of 40 male Wistar rats were randomized into four groups: group I: control (C; n = 10), with full-thickness lesions on the back, without (BMSCs) or AM (n = 10); group II: injected (BMSCs; n = 10); group III: covered by AM; group IV-injected (AM + BMSCs; n = 10). Cytokine levels, IL-1, and IL-10 assay kits, superoxide dismutase (SOD), glutathione reductase (GRs) and carbonyl activity levels were measured by ELISA 28th day, and TGF-ß was evaluated by immunohistochemical, the expression collagen expression was evaluated by Picrosirius staining. Our results showed that the IL-1 interleukin was higher in the control group, and the IL-10 presented a higher mean when compared to the control group. The groups with BMSCs and AM showed the lowest expression levels of TGF-ß. SOD, GRs, and carbonyl activity analysis showed a predominance in groups that received treatment from 80%. The collagen fiber type I was predominant in all groups; however, the AM + BMSCs group obtained a higher average when compared to the control group. Our findings suggest that the AM+ BMSCs promote skin wound healing, probably owing to their paracrine effect attributed to the promotion of new collagen for tissue repair.

19.
Biochem Biophys Res Commun ; 654: 47-54, 2023 04 30.
Article in English | MEDLINE | ID: mdl-36889034

ABSTRACT

The bacterial cellulose membrane (CM) is a promising biomaterial due to its easy applicability and moist environment. Moreover, nanoscale silver compounds (AgNO3) are synthesized and incorporated into CMs to provide these biomaterials with antimicrobial activity for wound healing. This study aimed to evaluate the cell viability of CM incorporated with nanoscale silver compounds, determine the minimum inhibitory concentration (MIC) for Escherichia coli and Staphylococcus aureus, and its use on in vivo skin lesions. Wistar rats were divided according to treatment: untreated, CM (cellulose membrane), and AgCM (CM incorporated with silver nanoparticles). The euthanasia was performed on the 2nd, 7th, 14th, and 21st days to assess inflammation (myeloperoxidase-neutrophils, N-acetylglucosaminidase-macrophage, IL-1ß, IL-10), oxidative stress (NO-nitric oxide, DCF-H2O2), oxidative damage (carbonyl: membrane's damage; sulfhydryl: membrane's integrity), antioxidants (superoxide dismutase; glutathione), angiogenesis, tissue formation (collagen, TGF-ß1, smooth muscle α-actin, small decorin, and biglycan proteoglycans). The use of AgCM did not show toxicity, but antibacterial effect in vitro. Moreover, in vivo, AgCM provided balanced oxidative action, modulated the inflammatory profile due to the reduction of IL-1ß level and increase in IL-10 level, in addition to increased angiogenesis and collagen formation. The results suggest the use of silver nanoparticles (AgCM) enhanced the CM properties by providing antibacterial properties, modulation the inflammatory phase, and consequently promotes the healing of skin lesions, which can be used clinically to treat injuries.


Subject(s)
Interleukin-10 , Metal Nanoparticles , Rats , Animals , Interleukin-10/pharmacology , Silver/pharmacology , Cellulose , Hydrogen Peroxide/pharmacology , Rats, Wistar , Wound Healing , Anti-Bacterial Agents/pharmacology , Bacteria , Collagen/pharmacology , Models, Animal
20.
Basic Clin Pharmacol Toxicol ; 132(6): 473-485, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36882317

ABSTRACT

This study aimed to investigate the effect of intranasal treatment of gold nanoparticles (GNPs) and Curcumin (Cur) on the lipopolysaccharide (LPS)-induced acute pulmonary inflammatory response. A single intraperitoneal injection of LPS (0.5 mg/Kg) was performed, and the animals in the Sham group were injected with 0.9% saline. Treatment was daily intranasally with GNPs (2.5 mg/L), Cur (10 mg/kg) and GNP-Cur started 12 h after LPS administration and ended on the seventh day. The results show that the treatment performed with GNP-Cur was the most effective to attenuate the action of pro-inflammatory cytokines, and a lower leukocyte count in the bronchoalveolar lavage, in addition to positively regulating anti-inflammatory cytokines in relation to other groups. As a result, it promoted an oxirreductive balanced environment in the lung tissue, providing a histological outcome with a reduction in inflammatory cells and greater alveolar area. The group treated with GNPs-Cur was superior to the other groups, with better anti-inflammatory activity and reduced oxidative stress, resulting in less morphological damage to lung tissue. In conclusion, the use of reduced GNPs with curcumin demonstrates promising effects in the control of the acute inflammatory response, helping to protect the lung tissue at the biochemical and morphological levels.


Subject(s)
Curcumin , Metal Nanoparticles , Pneumonia , Rats , Animals , Lipopolysaccharides/toxicity , Rats, Wistar , Gold/pharmacology , Curcumin/pharmacology , Pneumonia/chemically induced , Pneumonia/drug therapy , Pneumonia/prevention & control , Lung/pathology , Cytokines , Inflammation/chemically induced , Inflammation/drug therapy , Inflammation/pathology , Anti-Inflammatory Agents/pharmacology
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