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1.
ACS Pharmacol Transl Sci ; 6(8): 1232, 2023 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-37588761

RESUMO

[This corrects the article DOI: 10.1021/acsptsci.2c00035.].

2.
ACS Pharmacol Transl Sci ; 5(8): 562-572, 2022 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-35983273

RESUMO

Crohn's disease (CD) is a chronic intestinal disturbance mediated by mucosal immune hyperactivity that is often associated with the formation of stenosis. No reliable solution to stenosis CD exists so far. Therefore, we generated carboxymethyl chitosan oligosaccharide (CMCOS) as a new promising therapy and investigate its efficacy in an improved rat CD model. CMCOS was synthesized by enzymatic hydrolysis, and its biosafety was evaluated in vivo. The rat model of stenosis CD was optimized by an orthogonal experiment of 75 or 100 mg/kg trinitrobenzenesulfonic acid (TNBS) in a 50 or 75% ethanol enema. The therapeutic efficacy of CMCOS on the rat model of stenosis CD was investigated and compared with the commercial drug 5-aminosalicylic acid over a 28 day period of disease progression. The rat model of stenosis CD was well established by intracolonic administration of 75 mg/kg TNBS in 75% ethanol. CMCOS significantly alleviated CD symptoms morphologically, hematologically, and pathologically, promoting functional recovery of intestinal epithelium in a dose-dependent manner. CMCOS reduced infiltrations of inflammatory cells by regulating the IL-17A/PPAR-γ pathway and reduced fibro-proliferation and fibro-degeneration of the colon tissue by downregulating the TGF-ß1/WT1 pathway. 75 mg/kg TNBS in a 75% ethanol enema induces a rat model of stenosis CD suitable for preclinical pathology and pharmacological studies. The safety, antifibrosis, and functional repair performance of CMCOS make it a promising candidate for the treatment of stenosis CD.

3.
Biomed Pharmacother ; 150: 112988, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35468583

RESUMO

Although extensive development has been made in the treatment of inflammatory bowel disease (IBD), adverse effects and incomplete efficacy of currently used medications are continuous challenge. Accumulated reports on the benefits of chitosan oligosaccharides in intestinal disorders make chitotriose (COS) a breakthrough in the development of new IBD drugs. This study aimed to investigate the biosafety, efficacy and pharmacological mechanisms of COS in the treatment of experimental IBD in compare with the commercial 5-Aminosalicylic acid (5-ASA). In this study, COS effectively relieved active inflammation, restored epithelial function, and reduced intestinal fibrosis. Further investigation demonstrated that COS treatment regulated redox state of the colon tissue by stimulating the transcription factor nuclear factor E2-related factor 2 (Nrf2), increasing production of endogenous antioxidants, and alleviating oxidative stress. The offset of oxidative stress shut down the nuclear factor kappa-B (NF-ĸB) inflammatory pathway, mitophagy of epithelial cells, M2 macrophage polarization in pre-fibrotic inflammation, and myofibroblast activation in intestinal fibrogenesis. In conclusion, COS is a safe and effective therapeutic agent for experimental IBD as a redox regulator. Our results expand the current understanding of the pharmacology of chitosan oligosaccharides for IBD treatment and provides experimental basis for the medicinal development of small molecule carbohydrates.


Assuntos
Quitosana , Doenças Inflamatórias Intestinais , Animais , Quitosana/farmacologia , Quitosana/uso terapêutico , Inflamação/metabolismo , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/metabolismo , Oxirredução , Estresse Oxidativo , Ratos , Transdução de Sinais , Trissacarídeos/farmacologia , Trissacarídeos/uso terapêutico
4.
Cell Tissue Bank ; 21(4): 667-673, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32870439

RESUMO

Rapid freezing and vitrification using sucrose are two simple and cost-effective sperm cryopreservation methods. However, it is still unclear which method is better and what the optimal concentration of sucrose is. This study aimed to determine the optimal sucrose concentration for human sperm cryopreservation and compare the cryoprotective effects of rapid freezing versus vitrification using different closed straw systems in terms of sperm motility and DNA integrity. Our data showed that: (1) The optimal sucrose concentration for vitrification was 0.25 mol/l among the tested 0, 0.125, 0.25 and 0.5 mol/l concentrations; (2) Sperm total motility and progressive motility were cryopreserved significantly better by rapid freezing than vitrification in standard 0.5 ml cryostraws (P < 0.05); and (3) Sperm total motility and progressive motility were cryopreserved significantly better by vitrification in the straw-in-straw system than rapid freezing in the standard 0.5 cryostraw (P < 0.05), but no difference was found in sperm nuclear DNA fragmentation level between the two cryopreservation methods (P > 0.05). It was concluded that sucrose at 0.25 mol/l concentration is suitable for human sperm rapid freezing and vitrification, and sperm cryopreservation can be achieved by rapid freezing using closed standard 0.5 ml straws or by vitrification using the novel straw-in-straw system made of standard 0.25 and 0.5 ml straws.


Assuntos
Criopreservação , Congelamento , Espermatozoides/fisiologia , Sacarose/farmacologia , Vitrificação , Adulto , Cromatina/metabolismo , Dano ao DNA , Humanos , Masculino , Espermatozoides/efeitos dos fármacos , Adulto Jovem
5.
Med Princ Pract ; 29(5): 451-457, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32126568

RESUMO

OBJECTIVES: We aimed to observe the relationship between serum 25-hydroxyvitamin D (25-[OH] D) and different cognitive domains, and to evaluate the predictive value of 25-(OH) D level for cognitive impairment in patients with white matter lesions (WML). METHODS: The differences in clinical data including 25-(OH) D were analyzed between cognitive normality (n = 87) and impairment (n = 139) groups, and variant cognitive domains were analyzed between groups of different levels of serum 25-(OH) D. Risk factors for cognitive impairments were evaluated with multivariate logistic regression analysis; a receiver operating characteristic (ROC) curve of 25-(OH) D levels was used to examine the association between 25-(OH) D and WML with cognitive dysfunction. RESULTS: As the severity of WML increased, the proportion of patients with a low level of serum 25-(OH) D increased (p < 0.05). The total MoCA (Montreal Cognitive Assessment) scores and all domain scores except naming were significantly lower in patients with low levels of serum 25-(OH) D than in patients with high levels of serum 25-(OH) D (p < 0.05). Multivariate logistic regression analyses showed that serum 25-(OH) D levels were independently correlated with cognitive impairment. In the ROC analysis, the optimal cut-off value for 25-(OH) D was 17.53 with 76% sensitivity and 70% specificity (AUC =0.751, 95% CI: 0.674-0.819, p < 0.05). CONCLUSION: We observed that vitamin D deficiency is associated with multiple areas of cognitive impairment and that it is an independent risk factor for cognitive impairment in WML.


Assuntos
Disfunção Cognitiva/epidemiologia , Leucoencefalopatias/epidemiologia , Deficiência de Vitamina D/epidemiologia , Vitamina D/análogos & derivados , Adulto , Idoso , Disfunção Cognitiva/sangue , Disfunção Cognitiva/etiologia , Estudos Transversais , Feminino , Humanos , Leucoencefalopatias/sangue , Leucoencefalopatias/complicações , Modelos Logísticos , Masculino , Testes de Estado Mental e Demência , Pessoa de Meia-Idade , Curva ROC , Fatores de Risco , Índice de Gravidade de Doença , Vitamina D/sangue , Substância Branca/patologia
6.
Medicine (Baltimore) ; 97(49): e13538, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30544461

RESUMO

RATIONALE: Autonomic symptoms are not uncommon in chronic inflammatory demyelinating polyneuropathy (CIDP), but they are mostly mild and transient and are overshadowed by somatic manifestations. Here, we report a very unusual case of CIDP with severe autonomic symptom, intestinal obstruction, as initial and persistent symptom which responded well to high-dose glucocorticoid and intravenous immunoglobulin treatment. PATIENT CONCERNS: We described a patient with CIDP with precedent and long-lasting incomplete intestinal obstruction. Clinical manifestations were precedent and chronic abdominal pain, distension and constipation, and later numbness and weakness of lower and upper limbs. Radiograph showed incomplete intestinal obstruction, cerebrospinal fluid (CSF) showed albuminocytological dissociation and electromyography indicated neurogenic lesion. DIAGNOSES: CIDP with incomplete intestinal obstruction was diagnosed based on the history, related symptoms, typical abdominal radiograph, CSF albuminocytological dissociation, and electromyographic findings. INTERVENTIONS: The patient was treated with intravenous methylprednisolone and immunoglobulin. OUTCOMES: After treatment, the intestinal obstruction disappeared and the somato-symptoms improved greatly and gradually. LESSONS: This case highlights the need for diagnostic vigilance in cases of incomplete intestinal obstruction of unknown cause. We recommend CSF and electromyography examination in view of rare but possibility of CIDP.


Assuntos
Obstrução Intestinal/diagnóstico , Obstrução Intestinal/etiologia , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/complicações , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/diagnóstico , Diagnóstico Diferencial , Feminino , Humanos , Obstrução Intestinal/terapia , Pessoa de Meia-Idade , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/terapia
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