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1.
Molecules ; 26(17)2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34500838

RESUMO

Phenolic acids comprise a class of phytochemical compounds that can be extracted from various plant sources and are well known for their antioxidant and anti-inflammatory properties. A few of the most common naturally occurring phenolic acids (i.e., caffeic, carnosic, ferulic, gallic, p-coumaric, rosmarinic, vanillic) have been identified as ingredients of edible botanicals (thyme, oregano, rosemary, sage, mint, etc.). Over the last decade, clinical research has focused on a number of in vitro (in human cells) and in vivo (animal) studies aimed at exploring the health protective effects of phenolic acids against the most severe human diseases. In this review paper, the authors first report on the main structural features of phenolic acids, their most important natural sources and their extraction techniques. Subsequently, the main target of this analysis is to provide an overview of the most recent clinical studies on phenolic acids that investigate their health effects against a range of severe pathologic conditions (e.g., cancer, cardiovascular diseases, hepatotoxicity, neurotoxicity, and viral infections-including coronaviruses-based ones).


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Cinamatos/farmacologia , Hidroxibenzoatos/farmacologia , Extratos Vegetais/farmacologia , Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/tratamento farmacológico , Cinamatos/uso terapêutico , Ensaios Clínicos como Assunto , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Humanos , Hidroxibenzoatos/uso terapêutico , Hepatopatias/diagnóstico , Hepatopatias/tratamento farmacológico , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Índice de Gravidade de Doença , Resultado do Tratamento
2.
Int J Mol Sci ; 22(16)2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34445519

RESUMO

Cardiovascular disease is the leading cause of morbidity and mortality in diabetes. Recent clinical studies indicate that sodium-glucose co-transporter 2 (SGLT2) inhibitors improve cardiovascular outcomes in patients with diabetes. The mechanism underlying the beneficial effect of SGLT2 inhibitors is not completely clear but may involve direct actions on vascular cells. SGLT2 inhibitors increase the bioavailability of endothelium-derived nitric oxide and thereby restore endothelium-dependent vasodilation in diabetes. In addition, SGLT2 inhibitors favorably regulate the proliferation, migration, differentiation, survival, and senescence of endothelial cells (ECs). Moreover, they exert potent antioxidant and anti-inflammatory effects in ECs. SGLT2 inhibitors also inhibit the contraction of vascular smooth muscle cells and block the proliferation and migration of these cells. Furthermore, studies demonstrate that SGLT2 inhibitors prevent postangioplasty restenosis, maladaptive remodeling of the vasculature in pulmonary arterial hypertension, the formation of abdominal aortic aneurysms, and the acceleration of arterial stiffness in diabetes. However, the role of SGLT2 in mediating the vascular actions of these drugs remains to be established as important off-target effects of SGLT2 inhibitors have been identified. Future studies distinguishing drug- versus class-specific effects may optimize the selection of specific SGLT2 inhibitors in patients with distinct cardiovascular pathologies.


Assuntos
Complicações do Diabetes/prevenção & controle , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Remodelação Vascular/efeitos dos fármacos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Complicações do Diabetes/metabolismo , Células Endoteliais/citologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Humanos , Óxido Nítrico/metabolismo , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico
3.
Int J Mol Sci ; 22(15)2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34361003

RESUMO

Atopic dermatitis (AD) is a chronic and persistent inflammatory skin disease characterized by eczematous lesions and itching, and it has become a serious health problem. However, the common clinical treatments provide limited relief and are accompanied by adverse effects. Therefore, there is a need to develop novel and effective therapies to treat AD. Neferine is a small molecule compound isolated from the green embryo of the mature seeds of lotus (Nelumbo nucifera). It has a bisbenzylisoquinoline alkaloid structure. Relevant studies have shown that neferine has many pharmacological and biological activities, including anti-inflammatory, anti-thrombotic, and anti-diabetic activities. However, there are very few studies on neferine in the skin, especially the related effects on inflammatory skin diseases. In this study, we proved that it has the potential to be used in the treatment of atopic dermatitis. Through in vitro studies, we found that neferine inhibited the expression of cytokines and chemokines in TNF-α/IFN-γ-stimulated human keratinocyte (HaCaT) cells, and it reduced the phosphorylation of MAPK and the NF-κB signaling pathway. Through in vivo experiments, we used 2,4-dinitrochlorobenzene (DNCB) to induce atopic dermatitis-like skin inflammation in a mouse model. Our results show that neferine significantly decreased the skin barrier damage, scratching responses, and epidermal hyperplasia induced by DNCB. It significantly decreased transepidermal water loss (TEWL), erythema, blood flow, and ear thickness and increased surface skin hydration. Moreover, it also inhibited the expression of cytokines and the activation of signaling pathways. These results indicate that neferine has good potential as an alternative medicine for the treatment of atopic dermatitis or other skin-related inflammatory diseases.


Assuntos
Anti-Inflamatórios/farmacologia , Benzilisoquinolinas/farmacologia , Dermatite Atópica/tratamento farmacológico , Animais , Anti-Inflamatórios/uso terapêutico , Benzilisoquinolinas/uso terapêutico , Dermatite Atópica/etiologia , Dermatite Atópica/metabolismo , Dinitroclorobenzeno/toxicidade , Células HaCaT/efeitos dos fármacos , Células HaCaT/metabolismo , Humanos , Interferon gama/metabolismo , Sistema de Sinalização das MAP Quinases , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
4.
Cornea ; 40(9): 1204-1206, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34351874

RESUMO

PURPOSE: The purpose of this study was to report 2 patients with anterior scleritis manifesting after coronavirus disease 2019 (COVID-19). METHODS: The patients with confirmed COVID-19 developed anterior scleritis after their systemic symptoms were markedly improved. A thorough systemic workup identified no underlying autoimmune diseases. Ocular characteristics and safety and efficacy of systemic immunosuppressive therapy were evaluated. RESULTS: Case 1 was a 67-year-old woman who presented with necrotizing anterior scleritis in both eyes 3 weeks after the onset of COVID-19. One-week treatment with topical betamethasone and oral prednisolone (65 mg daily) did not result in improvement, so she was started on intravenous cyclophosphamide and subcutaneous adalimumab in addition to oral prednisolone. Necrotizing scleritis was gradually improved over 3 months. Case 2 was a 33-year-old man who presented with sectoral anterior scleritis in his right eye 2 weeks after the onset of COVID-19. He was started on topical betamethasone and oral prednisolone (85 mg daily). One week later, all signs and symptoms disappeared, and topical and oral corticosteroids were gradually tapered off over 2 weeks. There was no recurrence of respiratory symptoms or active scleritis in any cases after discontinuation of treatment. CONCLUSIONS: These cases suggest that COVID-19 can be associated with anterior scleritis, which responds to immunosuppressive and biologic agents. Ophthalmologists should consider anterior scleritis in patients with COVID-19 who present with ocular pain and redness during the convalescent phase of the illness.


Assuntos
COVID-19/diagnóstico , Infecções Oculares Virais/diagnóstico , SARS-CoV-2/isolamento & purificação , Esclerite/diagnóstico , Adalimumab/uso terapêutico , Adulto , Idoso , Anti-Inflamatórios/uso terapêutico , COVID-19/tratamento farmacológico , COVID-19/virologia , Teste de Ácido Nucleico para COVID-19 , Ciclofosfamida/uso terapêutico , Infecções Oculares Virais/tratamento farmacológico , Infecções Oculares Virais/virologia , Feminino , Humanos , Imunossupressores/uso terapêutico , Infusões Intravenosas , Infusões Subcutâneas , Masculino , Prednisolona/uso terapêutico , SARS-CoV-2/genética , Esclerite/tratamento farmacológico , Esclerite/virologia
5.
J Biomed Nanotechnol ; 17(7): 1417-1425, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34446144

RESUMO

A highly efficient method for constructing indomethacin-peptide conjugates was developed using the natural amino acid tyrosine (Y) as the anchor for indomethacin (Idm). With pH = 6, Idm-YEE conjugate self-assembled in a low critical micelle concentration (CMC, 0.037 mg/mL) and formed a transparent hydrogel (0.4 wt%). The formed Idm-YEE hydrogel presented sustained drug release of indomethacin with a maximum of 40% during first 24 hours, which was superior to the reported Idm-containing supramolecular hydrogel systems. As kept at 4 °C, the Idm-YEE hydrogel showed good storage stability up to 30 days without obvious hydrolysis. As shown by MTT assay, the Idm-YEE hydrogel exhibited good cell compatibility against retinal pigment epithelial cells (ARPE-19) and Human corneal epithelial cells (HCEC). Ocular irritation test (i.e., clinical observations, fluorescein staining and H&E histological analysis) results showed good integrity of corneal architecture and no edema after Idm-YEE hydrogel treatment, which proved its good ocular biocompatibility. Besides, the LPS-stimulated levels of key inflammatory mediators, including NO, PGE2 and IL-6, were greatly reduced by Idm-YEE hydrogel even in a low concentration (50 µM) in Raw264.7 cells, which indicated its comparable in vitro anti-inflammatory activity to indomethacin. Furthermore, the therapeutic efficacy of Idm-YEE hydrogel was evaluated in endotoxin-induced uveitis (EIU) rabbit model. By treating with dm-YEE hydrogel, the rabbit eyes had significantly lowered inflammation and exudation in the anterior chamber. The results of histological analysis, clinical score, inflammatory cell counts, aqueous protein concentration and immunohistochemical staining also demonstrated its good in vivo therapeutic activity towards ocular inflammation. Therefore, with good ocular biocompatibility and comparable anti-inflammatory effect towards ocular inflammation, the novel indomethacin-tripeptide hydrogel (Idm-YEE) developed in this work provides a potential treatment for anterior uveitis.


Assuntos
Hidrogéis , Uveíte , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Hidrogéis/uso terapêutico , Indometacina , Inflamação/tratamento farmacológico , Coelhos , Uveíte/tratamento farmacológico
6.
Int J Mol Sci ; 22(15)2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34360988

RESUMO

Replacement and inflammatory resorption are serious complications associated with the delayed replantation of avulsed teeth. In this study, we aimed to assess whether deferoxamine (DFO) can suppress inflammation and osteoclastogenesis in vitro and attenuate inflammation and bone resorption in a replanted rat tooth model. Cell viability and inflammation were evaluated in RAW264.7 cells. Osteoclastogenesis was confirmed by tartrate-resistant acid phosphatase staining, reactive oxygen species (ROS) measurement, and quantitative reverse transcriptase-polymerase chain reaction in teeth exposed to different concentrations of DFO. In vivo, molars of 31 six-week-old male Sprague-Dawley rats were extracted and stored in saline (n = 10) or DFO solution (n = 21) before replantation. Micro-computed tomography (micro-CT) imaging and histological analysis were performed to evaluate inflammation and root and alveolar bone resorption. DFO downregulated the genes related to inflammation and osteoclastogenesis. DFO also reduced ROS production and regulated specific pathways. Furthermore, the results of the micro-CT and histological analyses provided evidence of the decrease in inflammation and hard tissue resorption in the DFO group. Overall, these results suggest that DFO reduces inflammation and osteoclastogenesis in a tooth replantation model, and thus, it has to be further investigated as a root surface treatment option for an avulsed tooth.


Assuntos
Perda do Osso Alveolar/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Desferroxamina/uso terapêutico , Osteogênese , Avulsão Dentária/tratamento farmacológico , Perda do Osso Alveolar/etiologia , Animais , Anti-Inflamatórios/farmacologia , Regeneração Óssea , Desferroxamina/farmacologia , Masculino , Camundongos , Osteoclastos/citologia , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo , Células RAW 264.7 , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Avulsão Dentária/complicações
7.
Int J Mol Sci ; 22(15)2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34360990

RESUMO

Nrf2 (nuclear factor erythroid 2-related factor 2) and NF-κB (nuclear factor-kappa B) signaling pathways play a central role in suppressing or inducing inflammation and angiogenesis processes. Therefore, they are involved in many steps of carcinogenesis through cooperation with multiple signaling molecules and pathways. Targeting both transcription factors simultaneously may be considered an equally important strategy for cancer chemoprevention and therapy. Several hundreds of phytochemicals, mainly edible plant and vegetable components, were shown to activate Nrf2 and mediate antioxidant response. A similar number of phytochemicals was revealed to affect NF-κB. While activation of Nrf2 and inhibition of NF-κB may protect normal cells against cancer initiation and promotion, enhanced expression and activation in cancer cells may lead to resistance to conventional chemo- or radiotherapy. Most phytochemicals, through different mechanisms, activate Nrf2, but others, such as luteolin, can act as inhibitors of both Nrf2 and NF-κB. Despite many experimental data confirming the above mechanisms currently, limited evidence exists demonstrating such activity in humans. Combinations of phytochemicals resembling that in a natural food matrix but allowing higher concentrations may improve their modulating effect on Nrf2 and NF-κB and ultimately cancer prevention and therapy. This review presents the current knowledge on the effect of selected phytochemicals and their combinations on Nrf2 and NF-κB activities in the above context.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antineoplásicos Fitogênicos/uso terapêutico , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Neoplasias/tratamento farmacológico , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/farmacologia , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica , Humanos , Neoplasias/metabolismo , Neoplasias/prevenção & controle , Transdução de Sinais/efeitos dos fármacos
8.
Int Immunopharmacol ; 98: 107806, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34352471

RESUMO

Coronavirus Disease 2019 (COVID-19), caused by the novel virus SARS-CoV-2, is often more severe in older adults. Besides age, other underlying conditions such as obesity, diabetes, high blood pressure, and malignancies, which are also associated with aging, have been considered risk factors for COVID-19 mortality. A rapidly expanding body of evidence has brought up various scenarios for these observations and hyperinflammatory reactions associated with COVID-19 pathogenesis. Advanced glycation end products (AGEs) generated upon glycation of proteins, DNA, or lipids play a crucial role in the pathogenesis of age-related diseases and all of the above-mentioned COVID-19 risk factors. Interestingly, the receptor for AGEs (RAGE) is mainly expressed by type 2 epithelial cells in the alveolar sac, which has a critical role in SARS-CoV-2-associated hyper inflammation and lung injury. Here we discuss our hypothesis that AGEs, through their interaction with RAGE amongst other molecules, modulates COVID-19 pathogenesis and related comorbidities, especially in the elderly.


Assuntos
COVID-19/metabolismo , Produtos Finais de Glicação Avançada , Mediadores da Inflamação/metabolismo , Receptor para Produtos Finais de Glicação Avançada/metabolismo , SARS-CoV-2/patogenicidade , Fatores Etários , Animais , Anti-Inflamatórios/uso terapêutico , COVID-19/tratamento farmacológico , COVID-19/mortalidade , COVID-19/virologia , Senescência Celular , Comorbidade , Interações Hospedeiro-Patógeno , Humanos , Estresse Oxidativo , Prognóstico , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Transdução de Sinais
10.
Int J Mol Sci ; 22(15)2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34361019

RESUMO

Cholestatic liver diseases can progress to end-stage liver disease and reduce patients' quality of life. Although their underlying mechanisms are still incompletely elucidated, oxidative stress is considered to be a key contributor to these diseases. Heme oxygenase-1 (HO-1) is a cytoprotective enzyme that displays antioxidant action. It has been found that this enzyme plays a protective role against various inflammatory diseases. However, the role of HO-1 in cholestatic liver diseases has not yet been investigated. Here, we examined whether pharmacological induction of HO-1 by cobalt protoporphyrin (CoPP) ameliorates cholestatic liver injury. To this end, a murine model of 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet feeding was used. Administration of CoPP ameliorated liver damage and cholestasis with HO-1 upregulation in DDC diet-fed mice. Induction of HO-1 by CoPP suppressed the DDC diet-induced oxidative stress and hepatocyte apoptosis. In addition, CoPP attenuated cytokine production and inflammatory cell infiltration. Furthermore, deposition of the extracellular matrix and expression of fibrosis-related genes after DDC feeding were also decreased by CoPP. HO-1 induction decreased the number of myofibroblasts and inhibited the transforming growth factor-ß pathway. Altogether, these data suggest that the pharmacological induction of HO-1 ameliorates cholestatic liver disease by suppressing oxidative stress, hepatocyte apoptosis, and inflammation.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Colestase Intra-Hepática/tratamento farmacológico , Heme Oxigenase-1/metabolismo , Protoporfirinas/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Apoptose , Colestase Intra-Hepática/etiologia , Colestase Intra-Hepática/metabolismo , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo , Protoporfirinas/farmacologia , Piridinas/toxicidade , Xenobióticos/toxicidade
11.
Int J Mol Sci ; 22(15)2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34360973

RESUMO

Alzheimer's disease (AD) is a progressive neurodegenerative disease and accounts for most cases of dementia. The prevalence of AD has increased in the current rapidly aging society and contributes to a heavy burden on families and society. Despite the profound impact of AD, current treatments are unable to achieve satisfactory therapeutic effects or stop the progression of the disease. Finding novel treatments for AD has become urgent. In this paper, we reviewed novel therapeutic approaches in five categories: anti-amyloid therapy, anti-tau therapy, anti-neuroinflammatory therapy, neuroprotective agents including N-methyl-D-aspartate (NMDA) receptor modulators, and brain stimulation. The trend of therapeutic development is shifting from a single pathological target to a more complex mechanism, such as the neuroinflammatory and neurodegenerative processes. While drug repositioning may accelerate pharmacological development, non-pharmacological interventions, especially repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), also have the potential for clinical application. In the future, it is possible for physicians to choose appropriate interventions individually on the basis of precision medicine.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Estimulação Magnética Transcraniana/métodos , Doença de Alzheimer/terapia , Animais , Humanos , Medicina de Precisão/métodos
12.
Molecules ; 26(16)2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34443483

RESUMO

Skeletal muscle atrophy is the decrease in muscle mass and strength caused by reduced protein synthesis/accelerated protein degradation. Various conditions, such as denervation, disuse, aging, chronic diseases, heart disease, obstructive lung disease, diabetes, renal failure, AIDS, sepsis, cancer, and steroidal medications, can cause muscle atrophy. Mechanistically, inflammation, oxidative stress, and mitochondrial dysfunction are among the major contributors to muscle atrophy, by modulating signaling pathways that regulate muscle homeostasis. To prevent muscle catabolism and enhance muscle anabolism, several natural and synthetic compounds have been investigated. Recently, polyphenols (i.e., natural phytochemicals) have received extensive attention regarding their effect on muscle atrophy because of their potent antioxidant and anti-inflammatory properties. Numerous in vitro and in vivo studies have reported polyphenols as strongly effective bioactive molecules that attenuate muscle atrophy and enhance muscle health. This review describes polyphenols as promising bioactive molecules that impede muscle atrophy induced by various proatrophic factors. The effects of each class/subclass of polyphenolic compounds regarding protection against the muscle disorders induced by various pathological/physiological factors are summarized in tabular form and discussed. Although considerable variations in antiatrophic potencies and mechanisms were observed among structurally diverse polyphenolic compounds, they are vital factors to be considered in muscle atrophy prevention strategies.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Músculo Esquelético/efeitos dos fármacos , Atrofia Muscular/tratamento farmacológico , Atrofia Muscular/metabolismo , Compostos Fitoquímicos/farmacologia , Polifenóis/farmacologia , Animais , Anti-Inflamatórios/efeitos adversos , Anti-Inflamatórios/química , Anti-Inflamatórios/uso terapêutico , Antioxidantes/efeitos adversos , Antioxidantes/química , Antioxidantes/uso terapêutico , Humanos , Compostos Fitoquímicos/efeitos adversos , Compostos Fitoquímicos/química , Compostos Fitoquímicos/uso terapêutico , Polifenóis/efeitos adversos , Polifenóis/química , Polifenóis/uso terapêutico , Transdução de Sinais/efeitos dos fármacos
13.
Int J Mol Sci ; 22(16)2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34445305

RESUMO

Pulmonary arterial hypertension (PAH) is characterized by pulmonary vascular remodeling. Recent evidence supports that inflammation plays a key role in triggering and maintaining pulmonary vascular remodeling. Recent studies have shown that garlic extract has protective effects in PAH, but the precise role of allicin, a compound derived from garlic, is unknown. Thus, we used allicin to evaluate its effects on inflammation and fibrosis in PAH. Male Wistar rats were divided into three groups: control (CON), monocrotaline (60 mg/kg) (MCT), and MCT plus allicin (16 mg/kg/oral gavage) (MCT + A). Right ventricle (RV) hypertrophy and pulmonary arterial medial wall thickness were determined. IL-1ß, IL-6, TNF-α, NFκB p65, Iκß, TGF-ß, and α-SMA were determined by Western blot analysis. In addition, TNF-α and TGF-ß were determined by immunohistochemistry, and miR-21-5p and mRNA expressions of Cd68, Bmpr2, and Smad5 were determined by RT-qPCR. Results: Allicin prevented increases in vessel wall thickness due to TNF-α, IL-6, IL-1ß, and Cd68 in the lung. In addition, TGF-ß, α-SMA, and fibrosis were lower in the MCT + A group compared with the MCT group. In the RV, allicin prevented increases in TNF-α, IL-6, and TGF-ß. These observations suggest that, through the modulation of proinflammatory and profibrotic markers in the lung and heart, allicin delays the progression of PAH.


Assuntos
Anti-Inflamatórios/uso terapêutico , Dissulfetos/uso terapêutico , Hipertensão Pulmonar/tratamento farmacológico , Ácidos Sulfínicos/uso terapêutico , Animais , Antígenos CD/genética , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/genética , Antígenos de Diferenciação Mielomonocítica/metabolismo , Receptores de Proteínas Morfogenéticas Ósseas Tipo II/genética , Receptores de Proteínas Morfogenéticas Ósseas Tipo II/metabolismo , Citocinas/genética , Citocinas/metabolismo , Fibrose , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/metabolismo , Ventrículos do Coração/patologia , Masculino , NF-kappa B/genética , NF-kappa B/metabolismo , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/metabolismo , Artéria Pulmonar/patologia , Ratos , Ratos Wistar , Proteína Smad5/genética , Proteína Smad5/metabolismo
14.
Int J Mol Sci ; 22(15)2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34360771

RESUMO

Inflammation plays a central role in the pathogenesis of knee PTOA after knee trauma. While a comprehensive therapy capable of preventing or delaying post-traumatic osteoarthritis (PTOA) progression after knee joint injury does not yet clinically exist, current literature suggests that certain aspects of early post-traumatic pathology of the knee joint may be prevented or delayed by anti-inflammatory therapeutic interventions. We discuss multifaceted therapeutic approaches that may be capable of effectively reducing the continuous cycle of inflammation and concomitant processes that lead to cartilage degradation as well as those that can simultaneously promote intrinsic repair processes. Within this context, we focus on early disease prevention, the optimal timeframe of treatment and possible long-lasting sustained delivery local modes of treatments that could prevent knee joint-associated PTOA symptoms. Specifically, we identify anti-inflammatory candidates that are not only anti-inflammatory but also anti-degenerative, anti-apoptotic and pro-regenerative.


Assuntos
Anti-Inflamatórios/uso terapêutico , Traumatismos do Joelho , Osteoartrite do Joelho , Animais , Cartilagem Articular/metabolismo , Cartilagem Articular/patologia , Humanos , Traumatismos do Joelho/complicações , Traumatismos do Joelho/tratamento farmacológico , Traumatismos do Joelho/metabolismo , Traumatismos do Joelho/patologia , Articulação do Joelho/metabolismo , Articulação do Joelho/patologia , Osteoartrite do Joelho/tratamento farmacológico , Osteoartrite do Joelho/etiologia , Osteoartrite do Joelho/metabolismo , Osteoartrite do Joelho/patologia
15.
BMC Cardiovasc Disord ; 21(1): 375, 2021 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-34348657

RESUMO

BACKGROUND: Half of U.S. adults have received at least one dose of the COVID-19 vaccines produced by either Pfizer, Moderna, or Johnson and Johnson, which represents a major milestone in the ongoing pandemic. Given the emergency use authorizations for these vaccines, their side effects and safety were assessed over a compressed time period. Hence, ongoing monitoring for vaccine-related adverse events is imperative for a full understanding and delineation of their safety profile. CASE PRESENTATION: An 22-year-old Caucasian male presented to our hospital center complaining of pleuritic chest pain. Six months prior he had a mild case of COVID-19, but was otherwise healthy. He had received his first dose of the Moderna vaccine three days prior to developing symptoms. Laboratory analysis revealed a markedly elevated troponin and multiple imaging modalities during his hospitalization found evidence of wall motion abnormalities consistent with a diagnosis of perimyocarditis. He was started on aspirin and colchicine with marked improvement of his symptoms prior to discharge. CONCLUSIONS: We present a case of perimyocarditis that was temporally related to COVID-19 mRNA vaccination in an young male with prior COVID-19 infection but otherwise healthy. Our case report highlights an albeit rare but important adverse event for clinicians to be aware of. It also suggests a possible mechanism for the development of myocardial injury in our patient.


Assuntos
Vacinas contra COVID-19/efeitos adversos , Miocardite/induzido quimicamente , Anti-Inflamatórios/uso terapêutico , Aspirina/uso terapêutico , Vacinas contra COVID-19/administração & dosagem , Colchicina/uso terapêutico , Humanos , Esquemas de Imunização , Masculino , Miocardite/diagnóstico por imagem , Miocardite/tratamento farmacológico , Miocardite/fisiopatologia , Recuperação de Função Fisiológica , Resultado do Tratamento , Adulto Jovem
16.
Curr Protoc ; 1(8): e183, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34370402

RESUMO

The subcutaneous air pouch is an in vivo model that can be used to study the components of acute and chronic inflammation, the resolution of the inflammatory response, the oxidative stress response, and potential therapeutic targets for treating inflammation. Injection of irritants into an air pouch in rats or mice induces an inflammatory response that can be quantified by the volume of exudate produced, the infiltration of cells, and the release of inflammatory mediators. The model presented in this article has been extensively used to identify potential anti-inflammatory drugs. © 2021 Wiley Periodicals LLC. Basic Protocol: Air pouch model in the rat Alternate Protocol: Air pouch model in the mouse.


Assuntos
Anti-Inflamatórios , Inflamação , Animais , Anti-Inflamatórios/uso terapêutico , Carragenina/uso terapêutico , Modelos Animais de Doenças , Inflamação/tratamento farmacológico , Mediadores da Inflamação/uso terapêutico , Camundongos , Ratos
17.
Nutrients ; 13(7)2021 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-34371873

RESUMO

Menopause, probably the most important natural change in a woman's life and a major component of female senescence, is characterized, inter alia, by cessation of ovarian estrogen and progesterone production, resulting in a gradual deterioration of the female immune system. Hormone replacement therapy (HRT) is used in postmenopausal women to relieve some of the peri- and postmenopausal symptoms, while there is also evidence that the therapy may additionally partially reverse menopausal immune senescence. Flavonoids, and especially isoflavones, are widely used for the treatment of menopausal symptoms, although it is not at present clear whether they can reverse or alleviate other menopausal changes. HRT reverses the menopausal CD4/CD8 ratio and also limits the general peri- and postmenopausal inflammatory state. Moreover, the increased levels of interleukins (IL)-1ß, IL-6, and IL-8, as well as of tumor necrosis factor-α (TNF-α) are decreased after the initiation of HRT. However, some reports show no effect of HRT on IL-4, IL-10, and IL-12. It is thus evident that the molecular pathways connecting HRT and female immune senescence need to be clarified. Interestingly, recent studies have suggested that the anti-inflammatory properties of isoflavones possibly interact with inflammatory cytokines when applied in menopause treatments, thereby potentially reversing immune senescence. This narrative review presents the latest data on the effect of menopausal therapies, including administration of flavonoid-rich products, on age-associated immune senescence reversal with the aim of revealing possible directions for future research and treatment development.


Assuntos
Anti-Inflamatórios/uso terapêutico , Flavonoides/uso terapêutico , Terapia de Reposição Hormonal , Sistema Imunitário/efeitos dos fármacos , Imunossenescência/efeitos dos fármacos , Menopausa/efeitos dos fármacos , Fitoestrógenos/uso terapêutico , Fatores Etários , Animais , Anti-Inflamatórios/efeitos adversos , Citocinas/metabolismo , Feminino , Flavonoides/efeitos adversos , Terapia de Reposição Hormonal/efeitos adversos , Humanos , Sistema Imunitário/imunologia , Sistema Imunitário/metabolismo , Mediadores da Inflamação/metabolismo , Menopausa/imunologia , Menopausa/metabolismo , Fitoestrógenos/efeitos adversos , Fatores Sexuais
18.
J Infect Dis ; 224(4): 565-574, 2021 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-34398242

RESUMO

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing coronavirus disease 2019 (COVID-19), has led to significant morbidity and mortality. While most suffer from mild symptoms, some patients progress to severe disease with acute respiratory distress syndrome (ARDS) and associated systemic hyperinflammation. METHODS: First, to characterize key cytokines and their dynamics in this hyperinflammatory condition, we assessed abundance and correlative expression of a panel of 48 cytokines in patients progressing to ARDS as compared to patients with mild disease. Then, in an ongoing randomized controlled trial of convalescent plasma therapy (CPT), we analyzed rapid effects of CPT on the systemic cytokine dynamics as a correlate for the level of hypoxia experienced by the patients. RESULTS: We identified an anti-inflammatory role of CPT independent of its neutralizing antibody content. CONCLUSIONS: Neutralizing antibodies, as well as reductions in circulating interleukin-6 and interferon-γ-inducible protein 10, contributed to marked rapid reductions in hypoxia in response to CPT. CLINICAL TRIAL REGISTRY OF INDIA: CTRI/2020/05/025209. http://www.ctri.nic.in/.


Assuntos
COVID-19/imunologia , COVID-19/terapia , SARS-CoV-2/imunologia , Adulto , Anti-Inflamatórios/uso terapêutico , Anticorpos Neutralizantes/imunologia , COVID-19/tratamento farmacológico , COVID-19/epidemiologia , COVID-19/virologia , Citocinas/sangue , Citocinas/imunologia , Feminino , Humanos , Imunização Passiva/métodos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Plasma , RNA Viral/isolamento & purificação , Síndrome do Desconforto Respiratório/tratamento farmacológico , Síndrome do Desconforto Respiratório/imunologia , SARS-CoV-2/isolamento & purificação , Carga Viral
19.
Eur Rev Med Pharmacol Sci ; 25(14): 4854-4867, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34337735

RESUMO

OBJECTIVE: The purpose of this narrative review is to discuss the available information regarding the currently utilized COVID-19 therapies (and the evidence level supporting them) and opioids for chronic pain with a focus on warnings of potential interactions between these two therapeutic approaches. MATERIALS AND METHODS: Papers were retrieved from a PubMed search, using different combinations of keywords [e.g., pain treatment AND COVID-19 AND drug-drug interaction (DDI)], without limitations in terms of publication date and language. RESULTS: Remdesivir is an inhibitor of CYP3A4 and may increase the plasma concentration of CYP3A4 substrates (e.g., fentanyl). Dexamethasone is an inducer of CYP3A4 and glycoprotein P, thus coadministration with drugs metabolized by this isoform will lead to their increased clearance. Dexamethasone may cause hypokalemia, thus potentiating the risk of ventricular arrhythmias if it is given with opioids able to prolong the QT interval, such as oxycodone and methadone. Finally, the existing differences among opioids with regard to their impact on immune responses should also be taken into account with only tapentadol and hydromorphone appearing neutral on both cytokine production and immune parameters. CONCLUSIONS: Clinicians should keep in mind the frequent DDIs with drugs extensively metabolized by the CYP450 system and prefer opioids undergoing a limited hepatic metabolism. Identification and management of DDIs and dissemination of the related knowledge should be a major goal in the delivery of chronic care to ensure optimized patient outcomes and facilitate updating recommendations for COVID-19 therapy in frail populations, namely comorbid, poly-medicated patients or individuals suffering from substance use disorder.


Assuntos
Analgésicos Opioides/uso terapêutico , COVID-19/tratamento farmacológico , Dor Crônica/tratamento farmacológico , SARS-CoV-2 , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Alanina/análogos & derivados , Alanina/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Antivirais/uso terapêutico , Dexametasona/uso terapêutico , Interações Medicamentosas , Humanos
20.
Arch. argent. pediatr ; 119(4): S198-S211, agosto 2021. tab, ilus
Artigo em Espanhol | LILACS, BINACIS | ID: biblio-1281043

RESUMO

La pandemia ocasionada por el nuevo coronavirus (SARS-CoV-2), declarada por la Organización Mundial de la Salud OMS) en marzo de 2020, afecta a un reducido número de pacientes pediátricos, quienes presentan, en su mayoría, compromiso respiratorio leve y evolución favorable. Sin embargo, en niños previamente sanos, comenzó a observarse un aumento de casos definidos como síndrome inflamatorio multisistémico (SIM-C) o similar a Kawasaki (Kawasaki-like) asociado a la enfermedad por el nuevo coronavirus (COVID-19) (KL-C) que evolucionan al shock y requieren internación en la unidad de cuidados intensivos.Los cuadros de SIM-C y los KL-C se caracterizan por fiebre, signos de inflamación, síntomas gastrointestinales y disfunción cardiovascular; las formas graves de presentación tienen mayor incidencia de hipotensión y/o shock. En el laboratorio se observan marcadores de inflamación, hipercoagulabilidad y daño miocárdico. El tratamiento farmacológico de primera línea consiste en la administración de inmunoglobulina por vía intravenosa más ácido acetilsalicílico por vía oral.Se recomienda un abordaje multidisciplinario para un diagnóstico certero y un tratamiento temprano y eficaz para disminuir la morbimortalidad.


The pandemic caused by the SARS-CoV-2 virus declared by the WHO in March 11th 2020, affects a small number of pediatric patients, who mostly present mild respiratory compromise and favorable evolution.However began to be observed in previously healthy children, an increase in cases defined as "Multisystemic Inflammatory Syndrome" (MIS-C) or "Kawasaki-like" post-COVID 19 (KL-C) that evolve to shock and require hospitalization in the Pediatric Intensive Care Unit.MIS-C and KL-C are characterized by fever; signs of inflammation, gastrointestinal symptoms, and cardiovascular dysfunction, associated with sever forms of presentation with higher incidence of hypotension and/or shock. In the laboratory, markers of inflammation, hypercoagulability and myocardial damage are observed. First-line drug treatment consists of intravenous immunoglobulin plus oral acetylsalicylic acid.A multidisciplinary approach is recommended for an accurate diagnosis and an early and effective treatment, in order to reduce morbidity and mortality.


Assuntos
Humanos , Masculino , Feminino , Recém-Nascido , Lactente , Pré-Escolar , Criança , Adolescente , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica/terapia , COVID-19/diagnóstico , COVID-19/terapia , Terapia Respiratória/métodos , Imunoglobulinas Intravenosas/uso terapêutico , Terapia Combinada , Síndrome de Resposta Inflamatória Sistêmica/fisiopatologia , Cuidados Críticos/métodos , Diagnóstico Precoce , Diagnóstico Diferencial , Teste para COVID-19 , COVID-19/fisiopatologia , Fatores Imunológicos/uso terapêutico , Anti-Inflamatórios/uso terapêutico
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