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1.
Life (Basel) ; 14(6)2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38929646

RESUMO

The secondary sex ratio (SSR), indicating the ratio of male to female live births, has garnered considerable attention within the realms of reproductive biology and public health. Numerous factors have been posited as potential trendsetters of the SSR. Given the extensive research on the impact of daily behaviors and habits on individuals' reproductive health, there is a plausible suggestion that lifestyle choices may also influence the SSR. By synthesizing the existing literature on the current research field, this comprehensive review indicates that an elevated SSR has been associated with an increased intake of fatty acids and monosaccharides, proper nutrition, higher educational levels, financial prosperity, and favorable housing conditions. On the other hand, a decreased SSR may be linked to undernutrition, socioeconomic disparities, and psychological distress, aligning with the Trivers-Willard hypothesis. Occupational factors, smoking habits, and cultural beliefs could also contribute to trends in the SSR. Our review underscores the significance of considering the aforementioned factors in studies examining the SSR and emphasizes the necessity for further research to unravel the mechanisms underpinning these connections. A more profound comprehension of SSR alterations due to lifestyle holds the potential to adequately develop public health interventions and healthcare strategies to enhance reproductive health and overall well-being.

2.
Chemosphere ; 361: 142467, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38810798

RESUMO

The secondary sex ratio (SSR), defined as the ratio of male to female offspring at birth, has garnered significant scientific interest due to its potential impact on population dynamics and evolution. In recent years, there has been a growing concern regarding the potential consequences of environmental chemicals on the SSR, given their widespread exposure and potential enduring ramifications on the reproductive system. While SSR serves as an indicator of health, ongoing research and scientific inquiry are being conducted to explore the potential relationship between chemicals and offspring ratio. Although some studies have suggested a possible correlation, others have yielded inconclusive results, indicating that the topic is intricate and still needs to be elucidated. The precise mechanism by which chemical agents exert their influence on the SSR remains ambiguous, with disruption of the endocrine system being a prominent justification. In light of the complex interplay between chemical exposure and SSR, the present review aims to comprehensively examine and synthesize existing scientific literature to gain a deeper understanding of how specific chemical exposures may impact SSR. Insights into chemical hazards that shift SSR patterns or trends could guide prevention strategies, including legislative bans of certain chemicals, to minimize environmental and public health risks.


Assuntos
Substâncias Perigosas , Razão de Masculinidade , Substâncias Perigosas/toxicidade , Substâncias Perigosas/análise , Feminino , Animais , Masculino , Disruptores Endócrinos/análise , Disruptores Endócrinos/toxicidade , Poluentes Ambientais/análise , Poluentes Ambientais/toxicidade , Exposição Ambiental/estatística & dados numéricos , Humanos
3.
J Clin Med ; 13(8)2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38673496

RESUMO

Neurocristopathies (NCPs) encompass a spectrum of disorders arising from issues during the formation and migration of neural crest cells (NCCs). NCCs undergo epithelial-mesenchymal transition (EMT) and upon key developmental gene deregulation, fetuses and neonates are prone to exhibit diverse manifestations depending on the affected area. These conditions are generally rare and often have a genetic basis, with many following Mendelian inheritance patterns, thus making them perfect candidates for precision medicine. Examples include cranial NCPs, like Goldenhar syndrome and Axenfeld-Rieger syndrome; cardiac-vagal NCPs, such as DiGeorge syndrome; truncal NCPs, like congenital central hypoventilation syndrome and Waardenburg syndrome; and enteric NCPs, such as Hirschsprung disease. Additionally, NCCs' migratory and differentiating nature makes their derivatives prone to tumors, with various cancer types categorized based on their NCC origin. Representative examples include schwannomas and pheochromocytomas. This review summarizes current knowledge of diseases arising from defects in NCCs' specification and highlights the potential of precision medicine to remedy a clinical phenotype by targeting the genotype, particularly important given that those affected are primarily infants and young children.

4.
Cureus ; 15(9): e45916, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37885524

RESUMO

Introduction Cataract formation is a prevalent issue worldwide, and understanding the cellular processes involved is crucial to advancing treatment options. The scope of the study was to explore the presence of apoptotic cells in the lens epithelium of Greek patients with senile cataracts using transmission electron microscopy (TEM). Methods Twenty-one patients with senile cataracts were included in this cross-sectional study, and their anterior lens capsules were thoroughly examined. The presence of apoptosis was ultrastructurally investigated, and its association with age, gender, biomicroscopic type of cataract, the coexistence of exfoliation syndrome (XFS), diabetes mellitus, and glaucoma was statistically correlated. Results We detected apoptotic cells in nine of the 21 patients. Morphological features indicative of apoptosis in the nuclei included degradation, nuclear membrane irregularity, reduction of nuclear volume, condensation, and margination of chromatin. The cytoplasm either appeared denser or contained vacuoles. Budding with membrane blebbing and pinopode-like projections were frequently observed. Apoptotic cells appeared smaller, exhibiting loose connections with neighboring cells and the basement membrane (BM). Interestingly, apoptotic bodies were also detected. Conclusions None of the examined risk factors showed a connection to apoptosis, whereas neighboring lens epithelial cells (LECs) phagocytose apoptotic bodies, seemingly assumed the role of macrophages. Comparing apoptosis rates between populations with different sun exposure levels could help reveal the relationship between ultraviolet B radiation exposure, apoptosis, and cataract formation.

5.
Medicines (Basel) ; 10(9)2023 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-37755241

RESUMO

BACKGROUND: Hashimoto's thyroiditis (HT) is an autoimmune disease exhibiting stromal fibrosis and follicular cell destruction due to lymphoplasmacytic infiltration. Besides deprecated analyses, histopathological approaches have not employed the use of electron microscopy adequately toward delineating subcellular-level interactions. METHODS: Biopsies for ultrastructural investigations were obtained from the thyroids of five patients with HT after a thyroidectomy. Transmission electron microscopy (TEM) was utilized to study representative tissue specimens. RESULTS: Examination indicated interstitial extravasated blood cells and a plethora of plasma cells, based on their subcellular identity landmarks. These antibody-secreting cells were profoundly spotted near follicular cells, fibroblasts, and cell debris entrenched in collagenous areas. Pathological changes persistently affected subcellular components of the thyrocytes, including the nucleus, endoplasmic reticulum (ER), Golgi apparatus, mitochondria, lysosomes, and other intracellular vesicles. Interestingly, significant endothelial destruction was observed, specifically in the larger blood vessels, while the smaller vessels appeared comparatively unaffected. CONCLUSIONS: Our TEM findings highlight the immune-related alterations occurring within the thyroid stroma. The impaired vasculature component and remodeling have not been described ultrastructurally before; thus, further exploration is needed with regards to angiogenesis in HT in order to achieve successful prognostic, diagnostic, and treatment-monitoring strategies.

6.
Curr Issues Mol Biol ; 45(5): 4285-4300, 2023 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-37232741

RESUMO

Being immune privileged, the central nervous system (CNS) is constituted by unique parenchymal and non-parenchymal tissue-resident macrophages, namely, microglia and border-associated macrophages (BAMs), respectively. BAMs are found in the choroid plexus, meningeal and perivascular spaces, playing critical roles in maintaining CNS homeostasis while being phenotypically and functionally distinct from microglial cells. Although the ontogeny of microglia has been largely determined, BAMs need comparable scrutiny as they have been recently discovered and have not been thoroughly explored. Newly developed techniques have transformed our understanding of BAMs, revealing their cellular heterogeneity and diversity. Recent data showed that BAMs also originate from yolk sac progenitors instead of bone marrow-derived monocytes, highlighting the absolute need to further investigate their repopulation pattern in adult CNS. Shedding light on the molecular cues and drivers orchestrating BAM generation is essential for delineating their cellular identity. BAMs are receiving more attention since they are gradually incorporated into neurodegenerative and neuroinflammatory disease evaluations. The present review provides insights towards the current understanding regarding the ontogeny of BAMs and their involvement in CNS diseases, paving their way into targeted therapeutic strategies and precision medicine.

7.
Curr Issues Mol Biol ; 45(4): 3238-3254, 2023 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-37185735

RESUMO

Microglial cells play an important role in neuroinflammation and secondary damages after spinal cord injury (SCI). Progressive microglia/macrophage inflammation along the entire spinal axis follows SCI, and various factors may determine the microglial activation profile. Neurotrophin-3 (NT-3) is known to control the survival of neurons, the function of synapses, and the release of neurotransmitters, while also stimulating axon plasticity and growth. We examined the effects of whole-body vibration (WBV) and forms of assisted locomotor therapy, such as passive flexion-extension (PFE) therapy, at the neuronal level after SCI, with a focus on changes in NT-3 expression and on microglia/macrophage reaction, as they play a major role in the reconstitution of CNS integrity after injury and they may critically account for the observed structural and functional benefits of physical therapy. More specifically, the WBV therapy resulted in the best overall functional recovery when initiated at day 14, while inducing a decrease in Iba1 and the highest increase in NT-3. Therefore, the WBV therapy at the 14th day appeared to be superior to the PFE therapy in terms of recovery. Functional deficits and subsequent rehabilitation depend heavily upon the inflammatory processes occurring caudally to the injury site; thus, we propose that increased expression of NT-3, especially in the dorsal horn, could potentially be the mediator of this favorable outcome.

8.
Int J Mol Sci ; 24(7)2023 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-37047021

RESUMO

In this study, we investigated the effect of oxygen tension on the expansion of ADMSCs and on their differentiation toward their chondrocytic phenotype, regenerating a lab-based cartilaginous tissue with superior characteristics. Controversial results with reference to MSCs that were cultured under different hypoxic levels, mainly in 2D culturing settings combined with or without other biochemical stimulus factors, prompted our team to study the role of hypoxia on MSCs chondrogenic differentiation within an absolute 3D environment. Specifically, we used 3D-printed honeycomb-like PCL matrices seeded with ADMSCs in the presence or absence of TGF and cultured with a prototype 3D cell culture device, which was previously shown to favor nutrient/oxygen supply, cell adhesion, and infiltration within scaffolds. These conditions resulted in high-quality hyaline cartilage that was distributed uniformly within scaffolds. The presence of the TGF medium was necessary to successfully produce cartilaginous tissues with superior molecular and increased biomechanical properties. Despite hypoxia's beneficial effect, it was overall not enough to fully differentiate ADMSCs or even promote cell expansion within 3D scaffolds alone.


Assuntos
Células-Tronco Mesenquimais , Humanos , Células-Tronco Mesenquimais/metabolismo , Cartilagem Hialina , Hipóxia/metabolismo , Impressão Tridimensional , Oxigênio/metabolismo , Alicerces Teciduais/química , Diferenciação Celular , Células Cultivadas , Engenharia Tecidual/métodos , Condrogênese
9.
Curr Issues Mol Biol ; 45(3): 2609-2628, 2023 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-36975541

RESUMO

Microglia belong to tissue-resident macrophages of the central nervous system (CNS), representing the primary innate immune cells. This cell type constitutes ~7% of non-neuronal cells in the mammalian brain and has a variety of biological roles integral to homeostasis and pathophysiology from the late embryonic to adult brain. Its unique identity that distinguishes its "glial" features from tissue-resident macrophages resides in the fact that once entering the CNS, it is perennially exposed to a unique environment following the formation of the blood-brain barrier. Additionally, tissue-resident macrophage progenies derive from various peripheral sites that exhibit hematopoietic potential, and this has resulted in interpretation issues surrounding their origin. Intensive research endeavors have intended to track microglial progenitors during development and disease. The current review provides a corpus of recent evidence in an attempt to disentangle the birthplace of microglia from the progenitor state and underlies the molecular elements that drive microgliogenesis. Furthermore, it caters towards tracking the lineage spatiotemporally during embryonic development and outlining microglial repopulation in the mature CNS. This collection of data can potentially shed light on the therapeutic potential of microglia for CNS perturbations across various levels of severity.

10.
Life (Basel) ; 13(2)2023 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-36836946

RESUMO

Embryogenesis and fetal development are highly delicate and error-prone processes in their core physiology, let alone if stress-associated factors and conditions are involved. Space radiation and altered gravity are factors that could radically affect fertility and pregnancy and compromise a physiological organogenesis. Unfortunately, there is a dearth of information examining the effects of cosmic exposures on reproductive and proliferating outcomes with regard to mammalian embryonic development. However, explicit attention has been given to investigations exploring discrete structures and neural networks such as the vestibular system, an entity that is viewed as the sixth sense and organically controls gravity beginning with the prenatal period. The role of the gut microbiome, a newly acknowledged field of research in the space community, is also being challenged to be added in forthcoming experimental protocols. This review discusses the data that have surfaced from simulations or actual space expeditions and addresses developmental adaptations at the histological level induced by an extraterrestrial milieu.

11.
Birth Defects Res ; 114(19): 1257-1265, 2022 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-36321666

RESUMO

BACKGROUND: Valproic acid (VPA), a prescribed drug commonly used for various neurological perturbations, has been implicated in teratogenic inflictions on developing fetuses during pregnancy. The purpose of this research was to delineate the gross morphological and histological effects of VPA in the developing eye tunics and lens. METHODS: A time-dependent administration of 500 mg/kg VPA to BALB/c groups of female mice was coordinated during organogenesis (gestational days 7, 8, and 9) and compared to controls that received normal saline. Seized fetuses were checked for macroscopic eye anomalies, histological malformations with Azan trichrome staining, and levels of apoptotic activity with the terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assay. RESULTS: Histochemical analysis showed that VPA-treated groups exhibited collagen deficiency (2.5-50% decrease in aniline blue intensity) and a marked increase in TUNEL-positive cells (p < .05) in corneal stroma and sclera/choroid layers while less was detected in retina and lens, when compared to controls. CONCLUSIONS: Since the evaluation of the inner structures did not manifest major differences, we conclude that VPA teratogenic influence display eclectic toxicity, as seen by increased apoptosis to eye layers with high degree fibrous context, particularly the outer tunics.


Assuntos
Teratogênese , Ácido Valproico , Gravidez , Camundongos , Feminino , Animais , Ácido Valproico/farmacologia , Marcação In Situ das Extremidades Cortadas , Apoptose , Teratogênicos/farmacologia , Feto , Camundongos Endogâmicos BALB C
12.
Cureus ; 14(9): e29101, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36249599

RESUMO

Congenital Herpes simplex virus (HSV) infection is considered a common pregnancy pathology that is not always easy to diagnose. This study aimed to present the spectrum of placental histopathological lesions in pregnancies complicated by HSV infection. MEDLINE and Google Scholar databases were searched using the keywords "HSV" and "placental histopathology" up to June 20, 2022. Study inclusion required presenting placental histopathological anomalies in pregnant women diagnosed with HSV infection antenatally, during labor, or postnatally. Herein, we briefly present placental pathogenesis conditions, which have been correlated with congenital HSV infection, providing clinicians with a short review describing herpetic placental pathology.

13.
Curr Issues Mol Biol ; 44(7): 3208-3237, 2022 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-35877446

RESUMO

The mammalian central nervous system (CNS) coordinates its communication through saltatory conduction, facilitated by myelin-forming oligodendrocytes (OLs). Despite the fact that neurogenesis from stem cell niches has caught the majority of attention in recent years, oligodendrogenesis and, more specifically, the molecular underpinnings behind OL-dependent myelinogenesis, remain largely unknown. In this comprehensive review, we determine the developmental cues and molecular drivers which regulate normal myelination both at the prenatal and postnatal periods. We have indexed the individual stages of myelinogenesis sequentially; from the initiation of oligodendrocyte precursor cells, including migration and proliferation, to first contact with the axon that enlists positive and negative regulators for myelination, until the ultimate maintenance of the axon ensheathment and myelin growth. Here, we highlight multiple developmental pathways that are key to successful myelin formation and define the molecular pathways that can potentially be targets for pharmacological interventions in a variety of neurological disorders that exhibit demyelination.

14.
Connect Tissue Res ; 63(6): 577-589, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35175165

RESUMO

PURPOSE OF THE STUDY: Reduced Bone Mineral Density (BMD) is a prevalent comorbidity in Juvenile Idiopathic Arthritis (JIA). Enthesitis and other tendon abnormalities, such as tenosynovitis, tendinitis and tendon ruptures are, also, common extra-articular manifestations of the disease. The aim of the present study was to investigate the effect of tocilizumab, an antibody that binds the Interleukin-6 (IL-6) Receptor, on inflammation-related bone loss and tendon inflammation in an animal model of JIA. MATERIALS AND METHODS: The Collagen-Induced Arthritis (CIA) model was induced in male rats followed by intraperitoneal administration of tocilizumab for 8 weeks. Methotrexate, the most widely used Disease-Modifying Antirheumatic Drug in the management of JIA, was, also, administered, either as a monotherapy or as an add-on therapy to tocilizumab. BMD was evaluated with Micro-Computed Tomography (Micro-CT) and histopathological examination. Tendon damage was, also, assessed histologically. Finally, two pro-inflammatory cytokines, Tumor Necrosis Factor-alpha (TNF-a) and Interleukin-23 (IL-23) were quantified in tendon tissues by ELISA analysis. RESULTS: Tocilizumab-treated animals exhibited a significantly improved trabecular microarchitecture on micro-CT analysis and histological examination. Tendon morphology was also improved. Anti-IL-6 treatment led to a significant decrease in TNF-a and IL-23 expression in tendon tissue. CONCLUSIONS: The results of the present study provide evidence that tocilizumab reduces inflammation-related bone loss and suppresses tendon inflammation in a juvenile CIA rat model. These findings offer perspectives for the management of osteoporosis and enthesitis in JIA.


Assuntos
Antirreumáticos , Artrite Experimental , Artrite Juvenil , Animais , Anticorpos Monoclonais Humanizados , Antirreumáticos/uso terapêutico , Artrite Experimental/tratamento farmacológico , Artrite Experimental/patologia , Artrite Juvenil/tratamento farmacológico , Citocinas , Inflamação/tratamento farmacológico , Interleucina-23/uso terapêutico , Interleucina-6 , Masculino , Metotrexato/uso terapêutico , Ratos , Tendões/patologia , Fator de Necrose Tumoral alfa , Microtomografia por Raio-X
15.
Tissue Eng Part B Rev ; 28(1): 206-245, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-33470169

RESUMO

Articular cartilage can be easily damaged from human's daily activities, leading to inflammation and to osteoarthritis, a situation that can diminish the patients' quality of life. For larger cartilage defects, scaffolds are employed to provide cells the appropriate three-dimensional environment to proliferate and differentiate into healthy cartilage tissue. Natural biomaterials used as scaffolds, attract researchers' interest because of their relative nontoxic nature, their abundance as natural products, their easy combination with other materials, and the relative easiness to establish Marketing Authorization. The last 15 years were chosen to review, document, and elucidate the developments on cell-seeded natural biomaterials for articular cartilage treatment in vivo. The parameters of the experimental designs and their results were all documented and presented. Considerations about the newly formed cartilage and the treatment of cartilage defects were discussed, along with difficulties arising when applying natural materials, research limitations, and tissue engineering approaches for hyaline cartilage regeneration. Impact statement This review includes information from the literature and has never been complied before. The last 15 years were chosen to document and elucidate the developments on in vivo, articular cartilage treatment with cell-seeded natural biomaterials. The parameters of the experimental designs and their results were all documented and presented thoroughly. Natural materials overall seem to have a positive role in the recovery of cartilage defects. We expect that the knowledge from this review will be very useful to researchers organizing experimental protocols on critical analysis of advanced therapy medicinal products for human use.


Assuntos
Materiais Biocompatíveis , Cartilagem Articular , Condrócitos , Humanos , Qualidade de Vida , Regeneração , Engenharia Tecidual/métodos , Alicerces Teciduais
16.
Inflammation ; 45(1): 445-459, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34515956

RESUMO

Anxiety disorders and cognitive decline are highly prevalent in rheumatic diseases, including Juvenile Idiopathic Arthritis (JIA). In this study, we investigated the effect of long-term treatment with infliximab and tocilizumab on anxiety-like behaviour and cognitive performance in a juvenile collagen-induced arthritis (CIA) rat model. Forty-nine rats with established moderate arthritis were randomly allocated into 7 equal groups: negative control, vehicle, methotrexate, infliximab, tocilizumab, methotrexate + infliximab and methotrexate + tocilizumab groups. Behavioural tests were performed to evaluate anxiety-like behaviour and cognitive function. Neuropathological changes were investigated by histological examination at the level of the hippocampus, the amygdala and the prefrontal cortex. Also, the expression of Brain-Derived Neurotrophic Factor (BDNF), a biomarker associated with neuronal survival and plasticity, was determined in the hippocampus and the amygdala by RT-qPCR. We found that both infliximab and tocilizumab reduced anxiety-like behaviour in the elevated-plus and elevated-zero maze tests. Tocilizumab, also, improved cognitive function in the olfactory social memory and passive avoidance tests. Anti-cytokine treatment reversed the histopathological changes in the brain induced by CIA. BDNF expression was higher in all treatment groups and especially those receiving monoclonal antibodies combined with methotrexate. Our data provide evidence that chronic infliximab and tocilizumab treatment reduces anxiety-like behaviour, improves cognitive function, reverses neuropathological changes and increases central BDNF expression in a juvenile arthritis rat model. These findings may be translated to humans to address behavioural comorbidities associated with JIA.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/uso terapêutico , Ansiedade/prevenção & controle , Artrite Juvenil/tratamento farmacológico , Transtornos Cognitivos/prevenção & controle , Infliximab/uso terapêutico , Animais , Ansiedade/etiologia , Artrite Juvenil/psicologia , Transtornos Cognitivos/etiologia , Quimioterapia Combinada , Masculino , Ratos , Ratos Wistar , Resultado do Tratamento
17.
Pharmacol Rep ; 74(1): 84-95, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34569017

RESUMO

BACKGROUND: Circulating cytokines have been proposed to be implicated in the development of mood disorders and cognitive impairment. This study aims to examine the effect of chronic treatment with infliximab, a tumor necrosis factor-alpha (TNF-alpha) inhibitor, and tocilizumab, an antibody against interleukin-6 (IL-6) receptor on anxiety-like behavior and cognitive function. METHODS: Twenty-eight male, Wistar rats were randomly allocated into negative control, vehicle, infliximab and tocilizumab groups. After 8 weeks of intraperitoneal drug administration, rats performed the elevated-plus maze, the elevated-zero maze, the olfactory social memory and the passive avoidance tests. Brain sections at the level of the hippocampus, the amygdala and the prefrontal cortex were histologically examined. Finally, hippocampal and amygdaloid brain-derived neurotrophic factor (BDNF) expression was determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). RESULTS: Infliximab group exhibited a significantly higher number of entries and time spent into the open arms of the mazes, showing a lower level of anxiety. In the olfactory social memory test, tocilizumab significantly increased the ratio of interaction. Both infliximab- and tocilizumab-treated animals had a significantly lower latency time in the passive avoidance test that suggests an improved memory. Histological examination revealed similar morphology and neuronal density between groups. BDNF expression levels were significantly increased in the groups receiving anti-cytokine treatment. CONCLUSIONS: Our findings suggest that long-term peripheral TNF-alpha and IL-6 inhibition improves anxiety and cognitive function in rats and leads to an increased BDNF expression in the brain.


Assuntos
Anticorpos Monoclonais Humanizados/farmacologia , Ansiedade , Comportamento Animal/efeitos dos fármacos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Cognição/efeitos dos fármacos , Infliximab/farmacologia , Animais , Ansiedade/tratamento farmacológico , Ansiedade/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Interleucina-6/antagonistas & inibidores , Ratos , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidores
18.
Int Immunopharmacol ; 99: 107917, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34217991

RESUMO

Several studies have demonstrated that rheumatic diseases, including Juvenile Idiopathic Arthritis (JIA), are associated with anxiety-like behavior and a cognitive decline. Infliximab, a Tumor Necrosis Factor-alpha (TNF-a) inhibitor, and tocilizumab, an antibody against Interleukin-6 (IL-6) receptor, are commonly used in the treatment of JIA. Here, we aimed to evaluate the effects of infliximab and tocilizumab on anxiety symptoms and cognitive function in a juvenile model of severe autoimmune arthritis. We found that both infliximab and tocilizumab improved anxiety-like behavior in the elevated-plus and elevated-zero maze tests. Tocilizumab, also, improved cognitive performance in the passive avoidance and olfactory social memory tests. Histological examination showed that anti-cytokine treatment reversed the histopathological alterations in the brain induced by arthritis. Further, infliximab and tocilizumab treatment increased Brain-Derived Neurotrophic Factor (BDNF) expression in the hippocampal and amygdaloid area of rat brain. In summary, our findings provide evidence that infliximab and tocilizumab have a beneficial effect on anxiety-like behavior and cognitive function and alleviate neuropathological alterations in a juvenile rat model of severe arthritis, suggesting that inhibition of TNF-a and IL-6 in the periphery, may be associated with a mood and memory enhancement in JIA patients.


Assuntos
Ansiolíticos/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/uso terapêutico , Ansiedade/tratamento farmacológico , Artrite Experimental/tratamento farmacológico , Doenças Autoimunes/tratamento farmacológico , Cognição/efeitos dos fármacos , Infliximab/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Animais , Ansiolíticos/farmacologia , Anticorpos Monoclonais Humanizados/farmacologia , Antirreumáticos/farmacologia , Ansiedade/genética , Ansiedade/patologia , Ansiedade/psicologia , Artrite Experimental/genética , Artrite Experimental/patologia , Artrite Experimental/psicologia , Doenças Autoimunes/genética , Doenças Autoimunes/patologia , Doenças Autoimunes/psicologia , Fator Neurotrófico Derivado do Encéfalo/genética , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/patologia , Infliximab/farmacologia , Masculino , Fármacos Neuroprotetores/farmacologia , Ratos Wistar
19.
Cureus ; 13(4): e14696, 2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-34055540

RESUMO

Objective Rheumatic diseases are associated with bone loss, both systemic and periarticular, and tendon abnormalities. The aim of this study is to examine the effect of three antiarthritic drugs, methotrexate, an anti-folate metabolite; infliximab, a Tumor Necrosis Factor-alpha (TNF-α) inhibitor; and tocilizumab, an antibody against Interleukin-6 (IL-6) receptor, on bone microarchitecture and tendon morphology in the absence of an inflammatory state. Materials and methods Thirty-five, 8- to 9-week-old, male, Wistar rats were randomly allocated into five groups: negative control (CTRL), vehicle (VEH), methotrexate (MTX), infliximab (INFX), and tocilizumab (TCZ). After 8 weeks of antiarthritic drug intraperitoneal administration, animals were euthanized and rat tibiae and patellar tendons were histologically examined. Results All sections exhibited normal bone microarchitecture. Histological scores in all groups corresponded to normal bone mineral density. No no apparent differences in tenocyte morphology and architecture of collagen fibers were observed. Conclusions The results of this study indicate that long-term administration of methotrexate, infliximab, and tocilizumab had no effect on bone microarchitecture and tendon morphology in rats in the absence of an inflammatory condition.

20.
Inflammopharmacology ; 29(3): 661-672, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33982199

RESUMO

Reduced Bone Mineral Density (BMD) and tendon abnormalities, such as tenosynovitis and enthesitis, are prevalent comorbidities in patients with rheumatoid arthritis (RA). The aim of the present study was to investigate the effect of chronic treatment with infliximab on BMD and tendon inflammation in an animal model of inflammatory arthritis. Collagen-Induced Arthritis (CIA) was induced in rats, followed by long-term intraperitoneal administration of infliximab. Two additional groups of animals received methotrexate either as a monotherapy or as a co-treatment to infliximab. BMD was evaluated by Micro-Computed Tomography (Micro-CT) and bone histological examination. Tendon inflammation was assessed histologically and by quantitative ELISA analysis of pro-inflammatory cytokines in tendon tissues. Both methotrexate and infliximab treatment alleviated joint inflammation and reduced paw edema. Infliximab-treated animals exhibited an improved trabecular microarchitecture on micro-CT and histological analysis compared to both non-treated and methotrexate-treated animals. Infliximab almost reversed the pathological changes in tendons induced by CIA. Finally, we observed statistically significant declines in tendon TNF-a and IL-23 levels after infliximab treatment. Our study provides evidence that infliximab prevents arthritis-related osteoporosis and suppresses tendon inflammation in an animal model of inflammatory arthritis, in addition to controlling disease activity. These findings offer perspectives for the management of osteoporosis and enthesitis in RA.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Experimental/tratamento farmacológico , Densidade Óssea/efeitos dos fármacos , Inflamação/tratamento farmacológico , Infliximab/uso terapêutico , Tendões/efeitos dos fármacos , Animais , Antirreumáticos/farmacologia , Artrite Experimental/diagnóstico por imagem , Densidade Óssea/fisiologia , Inflamação/diagnóstico por imagem , Infliximab/farmacologia , Masculino , Ratos , Ratos Wistar , Tendões/diagnóstico por imagem , Microtomografia por Raio-X/métodos
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