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1.
Ned Tijdschr Geneeskd ; 1672023 Jan 04.
Artigo em Holandês | MEDLINE | ID: mdl-36633087

RESUMO

A 45-year-old male developed symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) after receiving antibiotics from the penicillin group. He got symptomatic treatment with good result. SDRIFE is a self-limiting condition, however recurrences after re-exposure are described.


Assuntos
Erupção por Droga , Exantema , Masculino , Humanos , Pessoa de Meia-Idade , Penicilinas/efeitos adversos , Exantema/induzido quimicamente , Exantema/diagnóstico , Prurido
2.
BMC Palliat Care ; 22(1): 4, 2023 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-36609269

RESUMO

BACKGROUND: Limited efficacy has been observed when using opioids to treat neuropathic pain. Lidocaine patches reduce neuropathic pain in postherpetic neuralgia, but their benefits for cancer-related neuropathic pain remain unclear. This study aimed to investigate a treatment for cancer-related neuropathic pain. METHODS: We conducted a prospective, open-label, single-arm study to assess the efficacy and safety of lidocaine transdermal patches in patients experiencing localized, superficial, neuropathic cancer pain. Terminal cancer patients already receiving opioid treatment participated in the 3-day study. The primary endpoint was pain intensity evaluated by the numerical rating scale (NRS). The secondary endpoints were the pain relief score and the quality of analgesic treatment. RESULTS: The results showed a significant difference in the median NRS over 3 days (Kruskal-Wallis test, p < 0.0001). The median NRS pain intensity from Day 1 to Day 3 was 4.0 with 95% C.I. (3.3, 5.0), 3.0 (2.5, 3.5), and 2.6 (2.0, 3.0), respectively. The difference between the median NRS pain intensities of any 2 days was significant (Wilcoxon signed-rank test, p < 0.0001). The generalized estimating equation (GEE) estimation model showed significant differences between the NRS pain intensities on any 2 days. There was no significant difference in the pain relief score or the quality of analgesic treatment. CONCLUSIONS: In this study, the 5% lidocaine transdermal patch reduced the NRS pain intensity in neuropathic cancer patients already receiving opioid treatment. Treatment of localized and superficial neuropathic pain caused by cancer was well tolerated and effective.


Assuntos
Neoplasias , Neuralgia , Humanos , Lidocaína/uso terapêutico , Lidocaína/efeitos adversos , Analgésicos Opioides/uso terapêutico , Medição da Dor , Estudos Prospectivos , Adesivo Transdérmico , Neuralgia/etiologia , Neuralgia/induzido quimicamente , Analgésicos/uso terapêutico , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Resultado do Tratamento
3.
Eur J Med Res ; 28(1): 10, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36609359

RESUMO

BACKGROUND: Gouty arthritis (GA) is a chronic systemic disease with recurrent acute monoarthritis. In a previous study, a higher incidence of acute flares was observed during the initial marked decrease in serum urate level. Our study evaluated the effect of early urate-lowering therapy in patients with acute GA flares. METHODS: This study included 40 patients with acute GA; of them, 20 received colchicine 0.5 mg colchicine twice daily, while 20 received probenecid 500 mg and colchicine 0.5 mg twice daily. We evaluated GA severity and laboratory data for 2 weeks after the initial therapy. Medians and interquartile ranges (IQRs) were calculated to evaluate clinical presentations between these two groups. RESULTS: Rapidly decreasing median serum uric acid levels was found in the patients treated with probenecid and colchicine compared with the patients treated with colchicine alone on day 8 (- 1.9 [IQR, - 3.7 to 0] vs 0.8 [IQR, - 0.1-2.2]; P < 0.001). However, the median decrease in visual analog scale score did not differ significantly between the two groups (- 5.5 [IQR, - 8.0 to - 3.0] vs - 3.5 [IQR, - 5.9 to - 2.0]; P = 0.080). CONCLUSION: No significant increase was noted in acute gout flare severity or duration among GA patients treated with early aggressive control of hyperuricemia using probenecid plus colchicine.


Assuntos
Artrite Gotosa , Gota , Humanos , Artrite Gotosa/tratamento farmacológico , Artrite Gotosa/induzido quimicamente , Supressores da Gota/uso terapêutico , Supressores da Gota/efeitos adversos , Ácido Úrico , Probenecid/uso terapêutico , Exacerbação dos Sintomas , Colchicina/uso terapêutico , Colchicina/efeitos adversos , Doença Crônica
4.
Ultrastruct Pathol ; 47(1): 12-21, 2023 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-36588172

RESUMO

Calanus oil, an oil extracted from the marine crustacean Calanus finmarchicus, is one of the richest sources of omega-3 and poly-unsaturated fatty acids. Although calanus oil has been shown to have a significant anti-hypertensive, anti-inflammatory, anti-fibrotic and anti-obesity effects in various cardiovascular diseases, but little is known about its effect on pathological cardiac hypertrophy. Thus, the present study was carried out to evaluate the therapeutic effect of calanus oil on cardiac hypertrophy. Cardiac hypertrophy was induced by subcutaneous injections with isoproterenol (5 mg/kg b.w) for 14 consecutive days. Calanus oil (400 mg/kg) was given orally for 4 weeks. Cardiac pathological remodeling was evaluated by echocardiography, after which morphometric, biochemical, histological and ultrastructural analyses were performed. Calanus oil treatment significantly ameliorated isoproterenol-induced structural and functional alterations in echocardiography. Calanus oil also reduced the relative heart weight, significantly decreased the elevated cardiac enzymes (LDH and CK-MB) and the lipid peroxidation marker (MDA), augmented the myocardial antioxidant status (TAC), and ameliorated the histopathological and ultrastructural changes in cardiac tissues and prevented interstitial collagen deposition. The present study, for the first time, provided morphometric, biochemical, histological and ultrastructural evidences supporting the promising anti-hypertrophic effect of calanus oil against ISO-induced cardiac hypertrophy. This anti-hypertrophic effect of calanus oil is via regulating myocardial remodeling and oxidative stress. Therefore, it could be used as potential pharmacological intervention in the management of cardiac hypertrophy.


Assuntos
Miocárdio , Estresse Oxidativo , Humanos , Isoproterenol/toxicidade , Isoproterenol/metabolismo , Miocárdio/metabolismo , Cardiomegalia/induzido quimicamente , Cardiomegalia/prevenção & controle , Cardiomegalia/patologia , Antioxidantes/farmacologia , Anti-Inflamatórios/farmacologia
5.
Cancer Control ; 30: 10732748221144930, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36598023

RESUMO

INTRODUCTION: Plexiform neurofibromas (PN) represent the main cause of morbidity in patients affected by Neurofibromatosis Type 1 (NF1). Until recently, surgery has been the main treatment option in these patients, but it is burdened with a low efficacy rate and a high incidence of side effects as well as recurrence. In recent years, MEK inhibitors (MEKi) such as selumetinib and trametinib have shown great promise. METHODS: We retrospectively describe a single center cohort of NF1 patients affected by PN1 and treated with MEKi since 2019 to 2021. Patients recruited in the study were affected by PN that were not eligible to complete surgical excision, symptomatic or with major cosmetic deformation or functional neurological deficits. RESULTS: Most patients experienced improvement in clinical symptoms and quality of life, with reduction or stabilization of lesions. However, no complete response was achieved. The most common adverse effects involved the skin, affecting every patient. Importantly, no life-threatening adverse effects occurred. CONCLUSIONS: In our experience, MEKi treatment has been shown to be both safe and effective in improving symptomatology and quality of life.


Assuntos
Neurofibroma Plexiforme , Neurofibromatose 1 , Humanos , Neurofibroma Plexiforme/tratamento farmacológico , Neurofibroma Plexiforme/patologia , Neurofibroma Plexiforme/cirurgia , Estudos Retrospectivos , Qualidade de Vida , Neurofibromatose 1/tratamento farmacológico , Neurofibromatose 1/induzido quimicamente , Neurofibromatose 1/patologia , Inibidores de Proteínas Quinases/efeitos adversos , Quinases de Proteína Quinase Ativadas por Mitógeno/uso terapêutico
6.
Int J Immunopathol Pharmacol ; 37: 3946320221150720, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36600460

RESUMO

INTRODUCTION: Ulcerative colitis (UC) is a chronic non-specific inflammatory bowel disease, and until now therapeutic agents for UC still cannot exert satisfied effects. Therefore, this study aimed to investigate the ameliorative effect of boswellic acid coated zinc nanoparticles (BAs-ZnNPs) on dextran sodium sulphate (DSS) induced-UC in rats. METHODS: Rats were divided into five groups; control, BAs-ZnNPs, DSS, DSS+BAs, and DSS + BAs-ZnNPs. The activity of alkaline phosphatase (ALP) was determined colorimetrically, while the concentration of IgM, IgG, TNF-α, IL-1ß, and IL-8 were measured by ELISA. Levels of gene expression of NF-κB and COX-2 genes were evaluated by RT-qPCR, while the expression of protein levels of PI3K and STAT-3 were done by western blotting. Finally, histopathological examination of colon tissues of different groups of rats was done. RESULTS: The depicted ball-like structure of the BAs-ZnNPs in the TEM images ranging in size from 50 to 100 nm in diameter while their formation was confirmed by UV-visible spectroscopy with a sharp peak of maximum absorbance at 266 nm. Our results revealed that BAs-ZnNPs exerted an anti-inflammatory effect in the experimental model of colitis, demonstrated histologically and biochemically as shown by the improvement of ALP, IgM, IgG, and the gene expression levels of NF-κB and COX-2. Also, this beneficial effect was associated with the reduction in the expression of TNF-α, IL-1ß, IL-8, PI3K, and STAT-3. Thus, this effect improves the altered immune response associated with the colonic inflammation. CONCLUSION: BAs-ZnNPs can be proposed as a therapeutic candidate to attenuate UC. The potential underlying mechanism includes suppression of ALP, IgM, IgG, IL-1ß, and IL-8 levels via regulation of NF-κB and COX-2 gene expression and STAT-3 and PI3K protein expression in a UC rat model.


Assuntos
Colite Ulcerativa , Nanopartículas Metálicas , Zinco , Animais , Ratos , Doença Crônica , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Sulfato de Dextrana , Modelos Animais de Doenças , Imunoglobulina G , Imunoglobulina M , Inflamação , Interleucina-8 , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinases , Fator de Necrose Tumoral alfa/metabolismo , Zinco/uso terapêutico
7.
Int J Mol Sci ; 24(1)2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36614177

RESUMO

FROUNT is an intracellular protein that promotes pseudopodia formation by binding to the chemokine receptors CCR2 and CCR5 on macrophages. Recently, disulfiram (DSF), a drug treatment for alcoholism, was found to have FROUNT inhibitory activity. In this study, we investigated the effect of DSF eye drops in a rat corneal alkali burn model. After alkali burn, 0.5% DSF eye drops (DSF group) and vehicle eye drops (Vehicle group) were administered twice daily. Immunohistochemical observations and real-time reverse transcription-polymerase chain reaction (RT-PCR) analyses were performed at 6 h and 1, 4, and 7 days after alkali burn. Results showed a significant decrease in macrophage accumulation in the cornea in the DSF group, but no difference in neutrophils. RT-PCR showed decreased expression of macrophage-associated cytokines in the DSF group. Corneal scarring and neovascularization were also suppressed in the DSF group. Low-vacuum scanning electron microscopy imaging showed that macrophage length was significantly shorter in the DSF group, reflecting the reduced extension of pseudopodia. These results suggest that DSF inhibited macrophage infiltration by suppressing macrophage pseudopodia formation.


Assuntos
Queimaduras Químicas , Lesões da Córnea , Neovascularização da Córnea , Queimaduras Oculares , Ratos , Animais , Dissulfiram/farmacologia , Dissulfiram/uso terapêutico , Queimaduras Químicas/tratamento farmacológico , Queimaduras Químicas/metabolismo , Soluções Oftálmicas/farmacologia , Álcalis/farmacologia , Pseudópodes/metabolismo , Córnea/metabolismo , Macrófagos/metabolismo , Lesões da Córnea/tratamento farmacológico , Lesões da Córnea/metabolismo , Neovascularização da Córnea/tratamento farmacológico , Queimaduras Oculares/induzido quimicamente , Queimaduras Oculares/tratamento farmacológico , Queimaduras Oculares/metabolismo , Modelos Animais de Doenças
8.
Int J Mol Sci ; 24(1)2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36614217

RESUMO

Silicosis is a refractory disease. Previous studies indicate that damaged alveolar epithelial cells act as a driver in pulmonary fibrosis. Our results show that epithelial cells that acquire the mesenchymal phenotype are associated with the pathogenesis of silicosis. c-Src kinase, a non-receptor tyrosine kinase, has been shown to be a positive regulator of organ fibrosis, but specific mechanisms remain unclear and rarely researched in silicosis. The activated Phosphatidylinositol-3 kinases/AKT(PI3K/AKT) pathway promotes fibrosis. We aimed to determine whether c-Src regulates fibrosis via the PI3K/AKT signaling pathway in the development of silicosis. C57/BL mice were intratracheally perfused with 10 mg silica suspension to establish a model of silicosis. In vivo, silica particles induced lung fibrosis. The profibrotic cytokine transforming growth factor-ß1 (TGF-ß1) exhibited a high expression in pulmonary fibrosis. The phosphorylated c-Src protein was increased and the PI3K/AKT pathway was activated in model lung tissue. In vitro, silica increased the expression of TGF-ß1- and TGF-ß1-induced mesenchymal phenotype and fibrosis in a mouse epithelial cells line. siRNA-Src inhibited the c-Src, the phosphorylation of the PI3K/AKT pathway, and the mesenchymal phenotype induced by TGF-ß1. LY294002, a specific inhibitor of PI3K, suppressed the phosphorylation of PI3K/AKT but did not affect Src activation. SU6656, a selective Src inhibitor, attenuated fibrosis in silicosis model. In summary, c-Src promotes fibrosis via the PI3K/AKT pathway in silica-induced lung fibrosis, and Src kinase inhibitors are potentially effective for silicosis treatment.


Assuntos
Fibrose Pulmonar , Silicose , Camundongos , Animais , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/tratamento farmacológico , Fosfatidilinositol 3-Quinases/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Dióxido de Silício/toxicidade , Quinases da Família src/metabolismo , Silicose/tratamento farmacológico
9.
Int J Mol Sci ; 24(1)2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36614208

RESUMO

Methotrexate (MTX) is a widely used neurotoxic drug with broad antineoplastic and immunosuppressant spectra. However, the exact molecular mechanisms by which MTX inhibits hippocampal neurogenesis are yet unclear. Dexmedetomidine (Dex), an α2-adrenergic receptor agonist, has recently shown neuroprotective effects; however, its full mechanism is unexplored. This study investigated the potential of Dex to mitigate MTX-induced neurotoxicity and memory impairment in rats and the possible role of the miR-15a/ROCK-1/ERK1/2/CREB/BDNF pathway. Notably, no former studies have linked this pathway to MTX-induced neurotoxicity. Male Sprague Dawley rats were placed into four groups. Group 1 received saline i.p. daily and i.v. on days 8 and 15. Group 2 received Dex at 10 µg/kg/day i.p. for 30 days. Group 3 received MTX at 75 mg/kg i.v. on days 8 and 15, followed by four i.p. doses of leucovorin at 6 mg/kg after 18 h and 3 mg/kg after 26, 42, and 50 h. Group 4 received MTX and leucovorin as in group 3 and Dex daily dosages as in group 2. Bioinformatic analysis identified the association of miR-15a with ROCK-1/ERK1/2/CREB/BDNF and neurogenesis. MTX lowered hippocampal doublecortin and Ki-67, two markers of neurogenesis. This was associated with the downregulation of miR-15a, upregulation of its target ROCK-1, and reduction in the downstream ERK1/2/CREB/BDNF pathway, along with disturbed hippocampal redox state. Novel object recognition and Morris water maze tests demonstrated the MTX-induced memory deficiencies. Dex co-treatment reversed the MTX-induced behavioral, biochemical, and histological alterations in the rats. These neuroprotective actions could be partly mediated through modulating the miR-15a/ROCK-1/ERK1/2/CREB/BDNF pathway, which enhances hippocampal neurogenesis.


Assuntos
Dexmedetomidina , MicroRNAs , Ratos , Masculino , Animais , Metotrexato/toxicidade , Metotrexato/metabolismo , Ratos Sprague-Dawley , Dexmedetomidina/farmacologia , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Sistema de Sinalização das MAP Quinases , Leucovorina/farmacologia , Hipocampo/metabolismo , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/metabolismo , Neurogênese , MicroRNAs/metabolismo
10.
Int J Mol Sci ; 24(1)2023 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-36614242

RESUMO

Atractylodin is a major compound in the rhizome of Atractylodes&nbsp;lancea, an oriental herbal medicine used for the treatment of gastrointestinal diseases, including dyspepsia, nausea, and diarrhea. Recent studies have shown that atractylodin exerts anti-inflammatory effects in various inflammatory diseases. Herein, we investigated the anti-colitis effects of atractylodin and its molecular targets. We determined the non-cytotoxic concentration of atractylodin (50 µM) using a cell proliferation assay in colonic epithelial cells. We found that pretreatment with atractylodin significantly inhibits tumor necrosis factor-α-induced phosphorylation of nuclear factor-κ-light-chain-enhancer of activated B in HCT116 cells. Through docking simulation analysis, luciferase assays, and in vitro binding assays, we found that atractylodin has an affinity for peroxisome proliferator-activated receptor alpha (PPARα). Daily administration of atractylodin (40 mg/kg) increased the survival rate of mice in a dextran sodium sulfate-induced colitis mouse model. Thus, atractylodin can be a good strategy for colitis therapy through inducing PPARα-dependent pathways.


Assuntos
Colite , PPAR alfa , Animais , Camundongos , Colite/induzido quimicamente , Colite/tratamento farmacológico , Fosforilação , Furanos/química , Camundongos Endogâmicos C57BL , Sulfato de Dextrana
11.
Redox Rep ; 28(1): 2152607, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36692085

RESUMO

Renal proximal tubular cells are highly vulnerable to different types of assaults during filtration and reabsorption, leading to acute renal dysfunction and eventual chronic kidney diseases (CKD). The chemotherapeutic drug cisplatin elicits cytotoxicity causing renal tubular cell death, but its executing mechanisms of action are versatile and elusive. Here, we show that cisplatin induces renal tubular cell apoptosis and ferroptosis by disrupting glutathione (GSH) metabolism. Upon cisplatin treatment, GSH metabolism is impaired leading to GSH depletion as well as the execution of mitochondria-mediated apoptosis and lipid oxidation-related ferroptosis through activating IL6/JAK/STAT3 signaling. Inhibition of JAK/STAT3 signaling reversed cell apoptosis and ferroptosis in response to cisplatin induction. Using a cisplatin-induced acute kidney injury (CAKI) mouse model, we found that inhibition of JAK/STAT3 significantly mitigates cisplatin nephrotoxicity with a reduced level of serum BUN and creatinine as well as proximal tubular distortion. In addition, the GSH booster baicalein also reclaims cisplatin-induced renal tubular cell apoptosis and ferroptosis as well as the in vivo nephrotoxicity. In conclusion, cisplatin disrupts glutathione metabolism, leading to renal tubular cell apoptosis and ferroptosis. Rewiring glutathione metabolism represents a promising strategy for combating cisplatin nephrotoxicity.


Assuntos
Injúria Renal Aguda , Ferroptose , Camundongos , Animais , Cisplatino , Apoptose , Rim/metabolismo , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/metabolismo , Glutationa/metabolismo
12.
Oxid Med Cell Longev ; 2023: 3317307, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36686377

RESUMO

Activation of the nod-like receptor protein 3 (NLRP3) inflammasome by monosodium urate (MSU) crystals has been identified as the molecular basis for the acute inflammatory response in gouty arthritis. However, MSU crystals alone are not sufficient to induce acute gouty arthritis (AGA). Adenosine triphosphate (ATP) is an endogenous signaling molecule involved in the NLRP3 inflammasome activation. We aimed to explore the role of ATP in MSU crystal-induced AGA development. In peripheral blood mononuclear cell-derived macrophages obtained from gout patients, we observed a synergistic effect of ATP on MSU crystal-induced IL-1ß release. Furthermore, in a rat model of spontaneous gout, we demonstrated that a synergistic effect of ATP and MSU crystals, but not MSU crystals alone, is essential for triggering AGA. Mechanistically, this synergistic effect is achieved through the purinergic receptor P2X7 (P2X7R). Blockade of P2X7R prevented AGA induction in rats after local injection of MSU crystals, and carrying the mutant hP2X7R gene contributed to the inhibition of NLRP3 inflammasome activation induced by costimulation of MSU crystals and ATP in vitro. Taken together, these results support the synergistic effect of ATP on MSU crystal-induced NLRP3 inflammasome activation facilitating inflammatory episodes in AGA. In this process, P2X7R plays a key regulatory role, suggesting targeting P2X7R to be an attractive therapeutic strategy for the treatment of AGA.


Assuntos
Artrite Gotosa , Gota , Ratos , Animais , Artrite Gotosa/induzido quimicamente , Artrite Gotosa/tratamento farmacológico , Artrite Gotosa/metabolismo , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Trifosfato de Adenosina , Leucócitos Mononucleares/metabolismo , Ácido Úrico/toxicidade , Ácido Úrico/química , Gota/metabolismo
13.
Cardiovasc Toxicol ; 23(1): 46-60, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36650404

RESUMO

Cuprizone (CPZ) is a neurotoxic agent that is used to induce demyelination and neurotoxicity in rats. This study aimed to investigate the protective potential of sulforaphane (SF), nuclear factor E2 related factor (Nrf-2) activator, against CPZ-induced cardiotoxicity and hepatotoxicity. Male adult Wistar rats (n = 18) were fed with a regular diet or a CPZ-contained diet (0.2%) for four weeks. The rats were divided into three groups (n = 6): negative control rats, CPZ-exposed rats, and CPZ + SF treated rats. SF was intraperitoneally administrated (2 mg/kg/day) for two weeks. The anti-inflammatory and anti-oxidative functions of SF were investigated biochemically, histologically, and immunohistochemically. CPZ increased serum levels of cardiac troponin 1 (CTn1), aspartate amino transaminase (AST), alanine amino transaminase (ALT), and alkaline phosphatase (ALP). In addition, serum levels of inflammatory interferon-gamma (IFN-γ), and pro-inflammatory interleukin 1ß (IL-1ß) were significantly elevated. Moreover, CPZ administration provoked oxidative stress as manifested by declined serum levels of total antioxidant capacity (TAC), as well as, stimulated lipid peroxidation and decreased catalase activities in both cardiac and hepatic tissues. SF treatment reversed all these biochemical alterations through exerting anti-oxidative and anti-inflammatory activities, and this was supported by histopathological investigations in both cardiac and hepatic tissues. This SF-triggered modulation of oxidative stress and inflammation is strongly associated with Nrf-2 activation, as evidenced by activated immunoexpression in both cardiac and hepatic tissues. This highlights the cardioprotective and hepatoprotective activities of SF via Nrf-2 activation and enhancing catalase function.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Cuprizona , Ratos , Masculino , Animais , Ratos Wistar , Catalase/metabolismo , Cuprizona/metabolismo , Cuprizona/farmacologia , Cuprizona/uso terapêutico , Cardiotoxicidade/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Inflamação/induzido quimicamente , Inflamação/metabolismo , Estresse Oxidativo , Antioxidantes/metabolismo , Fígado/patologia , Anti-Inflamatórios/uso terapêutico
14.
Pharm Biol ; 61(1): 281-287, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36655287

RESUMO

CONTEXT: Vitiligo is a common skin disease with a complex pathogenesis, and so far, no effective treatment is available. Lycium barbarum L. (Solanaceae) polysaccharide (LBP), the main active ingredient of goji berries, has been demonstrated to protect keratinocytes and fibroblasts against oxidative stress. OBJECTIVE: This study explored the effects and mechanism of LBP on monobenzone-induced vitiligo in mice. MATERIALS AND METHODS: C57BL/6 mice were randomly divided into five groups (n = 6): negative control that received vaseline, vitiligo model group induced by monobenzone that treated with vaseline, positive control that received tacrolimus (TAC), LBP groups that received 0.3 and 0.6 g/kg LBP, respectively. We quantified the depigmentation by visual examination and scores, detected the expression of CD8+ T cells, pro-inflammatory cytokines and analysed the STAT3-Hsp70-CXCL9/CXCL10 pathway. RESULTS: LBP 0.3 and 0.6 g/kg groups can significantly reduce depigmentation scores and the infiltration of local inflammatory cells in the skin lesions. Moreover, the expression of CXCL9, CXCL3, CXCL10 and HSP70 decreased by 54.3, 20.3, 48.5 and 27.2% in 0.3 g/kg LBP group, which decreased by 62.1, 26.6, 58.2 and 34.5% in 0.6 g/kg LBP group. In addition, 0.3 and 0.6 g/kg LBP decreased the release of IL-8 (9.7%, 22.8%), IL-6 (40.8%, 42.5%), TNF-α (25.7%, 35%), IFN-γ (25.1%, 27.6%) and IL-1ß (23.7%, 33.7%) and inhibited the phosphorylation expression of STAT3 by 63.2 and 67.9%, respectively. CONCLUSION: These findings indicated LBP might be recommended as a new approach for vitiligo which provide a theoretical basis for the clinical application of LBP in treating vitiligo patients.


Assuntos
Medicamentos de Ervas Chinesas , Lycium , Vitiligo , Animais , Camundongos , Vitiligo/tratamento farmacológico , Vitiligo/prevenção & controle , Vitiligo/induzido quimicamente , Camundongos Endogâmicos C57BL , Hidroquinonas/efeitos adversos , Medicamentos de Ervas Chinesas/uso terapêutico
15.
Ann Med ; 55(1): 463-479, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36655629

RESUMO

BACKGROUND: The combination of Sofosbuvir (SOF), velpatasvir (VEL), and voxilaprevir (VOX) is an effective, safe rescue therapy for patients with previous treatment failure. Direct-acting antiviral (DAA) treatment for hepatitis C virus (HCV) infection in diabetics with a history of hypoglycemia could improve insulin resistance due to HCV clearance. However, some studies have shown that SOF/VEL/VOX causes grade 3 hyperglycemia and other adverse events, which contradicts the findings of other DAA studies. AIM: To analyze the incidence of grade 3 hyperglycemia of SOF/VEL/VOX for chronic HCV infection. METHODS: We searched electronic databases from the inception of each database until October 2021. A random-effects model was employed to pool data. The study was conducted according to the PRISMA guidelines, and quality assessment was performed by using the Cochrane risk-of-bias tool for randomized controlled trials (RCTs). The study protocol was registered on the INPLASY database (Registration No. 2021120109). RESULTS: Five RCTs were included in this review. Overall, 49 of 2315 patients had grade 3 hyperglycemia with a risk ratio of 0.015 (95% confidence interval, 0.010-0.020; p < .001), and the incidence risk ratio (IRR) for cirrhosis compared to without cirrhosis was 12.000 (95% confidence interval: 0.727-198.160), the HCV genotype 3-genotype 1 IRR was 4.13 (95% confidence interval: 1.52-11.22) in subgroup analysis. No significant differences were found within the other subgroups, in prior DAA treatment experience, and in treatment duration. CONCLUSION: Although the incidence of hyperglycemia was rare in diabetic patients with HCV, it is recommended that glucose levels be closely monitored during the first 3 months of therapy and that diabetes medication be modified if necessary.


Assuntos
Hepatite C , Hiperglicemia , Humanos , Sofosbuvir/efeitos adversos , Hepacivirus/genética , Resposta Viral Sustentada , Antivirais/efeitos adversos , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Hepatite C/induzido quimicamente , Quimioterapia Combinada , Hiperglicemia/epidemiologia , Genótipo , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como Assunto
16.
Pharm Biol ; 61(1): 228-240, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36655330

RESUMO

CONTEXT: Da-Yuan-Yin is a Chinese traditional prescription. OBJECTIVE: This study explores the therapeutic effects of the Da-Yuan-Yin decoction polyphenol fraction (DYY-4) on acute lung injury (ALI) in mice induced by lipopolysaccharide (LPS). MATERIALS AND METHODS: The mice (n = 10) were orally administrated with DYY-4 (15, 30, and 60 mg/kg) or DXM (5 mg/kg), half an hour after LPS (2 mg/kg) instilled intratracheally. The protein content and the levels of inflammatory factors, the levels of complements, the mRNA expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), the level of myeloperoxidase (MPO) and superoxide dismutase (SOD), the expression of the IkB kinase (IKK) and nuclear factor-kappa B (NF-κB), the lung wet-to-dry weight (W/D) ratio and lung tissue were evaluated, 24 h after LPS challenge. Network pharmacology predicted potential targets. RESULTS: DYY-4 (30, 60 mg/kg, p < 0.01, p < 0.01) decreased the lung W/D ratio, total protein concentration, the levels of C3, C3c and C5a, the levels of TNF-α, IL-6, and IL-1ß, while increased the levels of IL-4 and IL-10. DYY-4 (60 mg/kg) decreased the levels of C5aR1, C5b-9 and COX-2 mRNA (p < 0.05), the levels of MPO and iNOS mRNA, the activation of the IKK/NF-κB pathway (p < 0.01), and increased the levels of IL-13 and SOD (p < 0.01). DYY-4 (60 mg/kg) relieved the lung tissue pathological changes and reduced the C3c deposition. DISCUSSION AND CONCLUSIONS: Network pharmacology combined with animal experiments revealed the targets of DYY-4 alleviating ALI.


Assuntos
Lesão Pulmonar Aguda , NF-kappa B , Camundongos , Animais , NF-kappa B/metabolismo , Lipopolissacarídeos/toxicidade , Polifenóis/efeitos adversos , Ciclo-Oxigenase 2/genética , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/prevenção & controle , Pulmão , Superóxido Dismutase , RNA Mensageiro
17.
Artif Cells Nanomed Biotechnol ; 51(1): 33-40, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36656591

RESUMO

Sepsis is a devastating complication of infection and injury that, through widespread endothelial dysfunction, can cause perfusion deficits and multi-organ failure. To address the recognised need for therapeutics targetting the endothelial barrier, a topical formulation (CUR; VASCEPTOR™; Vascarta Inc, Summit, NJ) was developed to transdermally deliver bio-active concentrations of curcumin-an anti-inflammatory and nitric oxide promoter. Male, Sprague Dawley rats were treated daily with lipopolysaccharide (LPS, 10 mg/kg, IP) to induce endotoxemia, and topical applications of Vehicle Control (LPS + VC; N = 7) or Curcumin (LPS + CUR; N = 7). A third group received neither LPS nor treatment (No-LPS; N = 8). After 72 h, animals were surgically prepared for measurements of physiology and endothelial dysfunction in the exteriorised spinotrapezius muscle through the extravasation of 67 kDa TRITC-BSA (albumin) and 500 kDa FITC-dextran (dextran). At 72 h, LPS + VC saw weight loss, and increases to pulse pressure, lactate, pCO2, CXCL5 (vs No-LPS) and IL-6 (vs 0 h; p < 0.05). LPS + CUR was similar to No-LPS, but with hypotension. Phenylephrine response was increased in LPS + CUR. Regarding endothelial function, LPS + CUR albumin and dextran extravasation were significantly reduced versus LPS + VC suggesting that Curcumin mitigated endotoxemic endothelial dysfunction. The speculated mechanisms are nitric oxide modulation of the endothelium and/or an indirect anti-inflammatory effect.


Assuntos
Curcumina , Endotoxemia , Animais , Masculino , Ratos , Albuminas , Anti-Inflamatórios , Curcumina/farmacologia , Dextranos , Endotélio , Endotoxemia/induzido quimicamente , Endotoxemia/tratamento farmacológico , Lipopolissacarídeos , Óxido Nítrico , Ratos Sprague-Dawley
18.
Gut Microbes ; 15(1): 2163838, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36656595

RESUMO

Conflicting evidence exists on the association between consumption of non-steroidal anti-inflammatory drugs (NSAIDs) and symptomatic worsening of inflammatory bowel disease (IBD). We hypothesized that the heterogeneous prevalence of pathobionts [e.g., adherent-invasive Escherichia coli (AIEC)], might explain this inconsistent NSAIDs/IBD correlation. Using IL10-/- mice, we found that NSAID aggravated colitis in AIEC-colonized animals. This was accompanied by activation of the NLRP3 inflammasome, Caspase-8, apoptosis, and pyroptosis, features not seen in mice exposed to AIEC or NSAID alone, revealing an AIEC/NSAID synergistic effect. Inhibition of NLRP3 or Caspase-8 activity ameliorated colitis, with reduction in NLRP3 inflammasome activation, cell death markers, activated T-cells and macrophages, improved histology, and increased abundance of Clostridium cluster XIVa species. Our findings provide new insights into how NSAIDs and an opportunistic gut-pathobiont can synergize to worsen IBD symptoms. Targeting the NLRP3 inflammasome or Caspase-8 could be a potential therapeutic strategy in IBD patients with gut inflammation, which is worsened by NSAIDs.


Assuntos
Anti-Inflamatórios não Esteroides , Colite , Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Animais , Camundongos , Anti-Inflamatórios não Esteroides/efeitos adversos , Caspase 8/metabolismo , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/microbiologia , Inflamassomos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/microbiologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Inibidores de Caspase/farmacologia , Escherichia coli/patogenicidade
19.
BMJ Open ; 13(1): e064220, 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36657752

RESUMO

INTRODUCTION: Primary membranous nephropathy (PMN) is a major cause of nephrotic syndrome in adults. Rituximab has been recommended in the treatment of PMN by the updated Kidney Disease Improved Outcome guideline. However, the optimal dosing regimen of rituximab for the initial treatment of patients with PMN is unclear. METHODS AND ANALYSIS: A comprehensive screening will be performed by searching PubMed, Embase and the CENTRAL (Cochrane Central Register of Controlled Trials) without language restriction. Studies evaluating the efficacy of rituximab monotherapy using the following types of dosing regimens will be included: high-dose regimen; standard regimen and low-dose regimen. Studies with less than 10 participants will be excluded. The primary outcome is the remission rate at 12 months. The secondary outcomes are remission rate at 6 and 24 months, complete remission rate at 6, 12 and 24 months, relapse at 6, 12 and 24 months, and side effects. Risk of Bias In Non-randomised Studies of Interventions tool will be used to assess the risk of bias for non-randomised studies and the Cochrane risk of bias assessment tool will be used for randomised controlled trials. The pooled remission rate, complete remission rate, relapse rate and side effects will be estimated using the metaprop command. All analyses will be calculated using Stata software (V.15.0; StataCorp). ETHICS AND DISSEMINATION: Ethics approval is not required. The results of our study will be submitted to a peer-review journal. PROSPERO REGISTRATION NUMBER: CRD42022319401.


Assuntos
Glomerulonefrite Membranosa , Nefropatias , Síndrome Nefrótica , Adulto , Humanos , Glomerulonefrite Membranosa/tratamento farmacológico , Imunossupressores/uso terapêutico , Nefropatias/induzido quimicamente , Recidiva Local de Neoplasia/tratamento farmacológico , Síndrome Nefrótica/tratamento farmacológico , Rituximab/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Ensaios Clínicos Controlados não Aleatórios como Assunto
20.
J Immunother Cancer ; 11(1)2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36657813

RESUMO

BACKGROUND: Non-invasive biomarkers of immune checkpoint inhibitor-associated acute tubulointerstitial nephritis (ICI-nephritis) are urgently needed. Because ICIs block immune checkpoint pathways that include cytotoxic T lymphocyte antigen 4 (CTLA4), we hypothesized that biomarkers of immune dysregulationpreviously defined in patients with congenital CTLA4 deficiency, including elevated soluble interleukin-2 receptor alpha (sIL-2R) and flow cytometric cell-based markers of B and T cell dysregulation in peripheral blood may aid the diagnosis of ICI-nephritis. METHODS: A retrospective cohort of patients diagnosed with ICI-nephritis was compared with three prospectively enrolled control cohorts: ICI-treated controls without immune-related adverse events, patients not on ICIs with hemodynamic acute kidney injury (hemodynamic AKI), and patients not on ICIs with biopsy proven acute interstitial nephritis from other causes (non-ICI-nephritis). sIL-2R level and flow cytometric parameters were compared between groups using Wilcoxon rank sum test or Kruskal-Wallis test. Receiver operating characteristic curves were generated to define the accuracy of sIL-2R and flow cytometric biomarkers in diagnosing ICI-nephritis. The downstream impact of T cell activation in the affected kidney was investigated using archived biopsy samples to evaluate the gene expression of IL2RA, IL-2 signaling, and T cell receptor signaling in patients with ICI-nephritis compared with other causes of drug-induced nephritis, acute tubular injury, and histologically normal controls. RESULTS: sIL-2R level in peripheral blood was significantly higher in patients with ICI-nephritis (N=24) (median 2.5-fold upper limit of normal (ULN), IQR 1.9-3.3), compared with ICI-treated controls (N=10) (median 0.8-fold ULN, IQR 0.5-0.9, p<0.001) and hemodynamic AKI controls (N=6) (median 0.9-fold-ULN, IQR 0.7-1.1, p=0.008). A sIL-2R cut-off point of 1.75-fold ULN was highly diagnostic of ICI-nephritis (area under the curve >96%) when compared with either ICI-treated or hemodynamic AKI controls. By peripheral blood flow cytometry analysis, lower absolute CD8+T cells, CD45RA+CD8+ T cells, memory CD27+B cells, and expansion of plasmablasts were prominent features of ICI-nephritis compared with ICI-treated controls. Gene expressions for IL2RA, IL-2 signaling, and T cell receptor signaling in the kidney tissue with ICI-nephritis were significantly higher compared with controls. CONCLUSION: Elevated sIL-2R level and flow cytometric markers of both B and T cell dysregulation may aid the diagnosis of ICI-nephritis.


Assuntos
Injúria Renal Aguda , Inibidores de Checkpoint Imunológico , Nefrite Intersticial , Humanos , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/diagnóstico , Biomarcadores , Antígeno CTLA-4 , Inibidores de Checkpoint Imunológico/efeitos adversos , Interleucina-2 , Nefrite Intersticial/induzido quimicamente , Nefrite Intersticial/diagnóstico , Receptores de Antígenos de Linfócitos T , Estudos Retrospectivos
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