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1.
Artigo em Inglês | MEDLINE | ID: mdl-35178106

RESUMO

BACKGROUND: The occurrence and development of hepatocellular carcinoma (HCC) are closely related to immune function, as is the capacity of hepatoma cells to escape. Immunosurveillance is a key mechanism. Catgut implantation at acupoint (CIAA) is a promising acupuncture improvement method that can regulate immunity and has been widely used in the clinical treatment of a variety of diseases. The aim of this study is to observe the therapeutic effect of CIAA on HCC and to investigate the potential mechanism of immune escape. MATERIALS AND METHODS: A total of 40 mice were randomly divided into three groups: the HCC model group (n = 15), the CIAA treatment group (n = 15), and the control group (n = 10). HCC was chemically induced in 30 mice by the combination of DEN, carbon tetrachloride, and ethanol for 150 days. Among them, 15 were selected for CIAA treatment to ascertain the therapeutic effect. The mRNA expression levels of AFP, IL-10, PD-1, and CTLA-4 in three groups were examined by using RT-PCR. AFP and AKT expressions were measured by using western blotting. PD1, CTLA-4, IL-10, CD4+, and CD8+ protein expression levels were evaluated by using IHC. The mortality rate, body weight, and psychological conditions of three groups were also compared. RESULTS: The mRNA and protein expression levels of AFP, PD-1, CTLA-4, and IL-10 were significantly downregulated in the CIAA-treated mice in comparison with HCC mice. IHC assay shows that CD4+ and CD8+ expression levels were notably upregulated after CIAA treatment. Western blotting assay shows that AKT pathway was deactivated in CIAA-treated mice. CIAA notably reduced the mortality rate and inhibited weight loss caused by HCC and improved the overall psychological condition of the mice. CONCLUSIONS: Taken together, our data corroborate the effective potency of CIAA in the treatment of HCC by and inhibiting immune escape and deactivating the AKT pathway.

2.
J Huazhong Univ Sci Technolog Med Sci ; 36(2): 237-242, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27072969

RESUMO

The aim of this study is to evaluate the efficacy of total saponins of Dioscorea (TSD), an extract of the Chinese herbal Bi Xie, on hyperuricemia and to elucidate the underlying mechanisms. The rat hyperuricemia model was established by administration of adenine. Thirty-two rats were randomly allocated into 4 groups: model group, low/high-dose TSD-treated groups, and allopurinol-treated group. Meanwhile, 8 rats were used as normal controls. Serum uric acid (UA), blood urea nitrogen (BUN), serum creatinine (Scr), and organic anion transporting polypeptide 1A1 (OATP1A1) levels were measured. Comparison between the model group and treatment (allopurinol and TSD) groups showed the serum UA levels were significantly decreased in treatment groups. TSD had similar effects to allopurinol. It was found that the OATP1A1 protein expression levels in treatment groups were higher than in model group and normal controls. And different from the allopurinol-treated groups, TSD-treated group had elevated OATP1A1 expression levels in the stomach, liver, small intestine and large intestine tissues. It was suggested that TSD may facilitate the excretion of UA and lower UA levels by up-regulating OATP1A1 expression.


Assuntos
Dioscorea/química , Medicamentos de Ervas Chinesas/farmacologia , Hiperuricemia/tratamento farmacológico , Transportadores de Ânions Orgânicos Sódio-Independentes/metabolismo , Saponinas/farmacologia , Ácido Úrico/sangue , Animais , Creatinina/sangue , Medicamentos de Ervas Chinesas/uso terapêutico , Mucosa Gástrica/metabolismo , Mucosa Intestinal/metabolismo , Intestinos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Transportadores de Ânions Orgânicos Sódio-Independentes/genética , Ratos , Ratos Sprague-Dawley , Saponinas/uso terapêutico , Estômago/efeitos dos fármacos , Regulação para Cima
3.
PLoS One ; 10(5): e0127685, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26010770

RESUMO

Brachial plexus root avulsion (BPRA) leads to dramatic motoneuron death and glial reactions in the corresponding spinal segments at the late stage of injury. To protect spinal motoneurons, assessment of the affected spinal segments should be done at an earlier stage of the injury. In this study, we employed 18F-FDG small-animal PET/CT to assess the severity of BPRA-induced cervical spinal cord injuries. Adult Sprague-Dawley rats were randomly treated and divided into three groups: Av+NS (brachial plexus root avulsion (Av) treated with normal saline), Av+GM1 (treated with monosialoganglioside), and control. At time points of 3 day (d), 1 week (w), 2 w, 4 w and 8 w post-injury, 18F-FDG micro-PET/CT scans and neuropathology assessments of the injured spinal roots, as well as the spinal cord, were performed. The outcomes of the different treatments were compared. The results showed that BPRA induced local bleeding and typical Wallerian degeneration of the avulsed roots accompanied by 18F-FDG accumulations at the ipsilateral cervical intervertebral foramen. BPRA-induced astrocyte reactions and overexpression of neuronal nitric oxide synthase in the motoneurons correlated with higher 18F-FDG uptake in the ipsilateral cervical spinal cord during the first 2 w post-injury. The GM1 treatment reduced BPRA-induced astrocyte reactions and inhibited the de novo nNOS expressions in spinal motoneurons. The GM1 treatment also protected spinal motoneurons from avulsion within the first 4 w post-injury. The data from this study suggest that 18F-FDG PET/CT could be used to assess the severity of BPRA-induced primary and secondary injuries in the spinal cord. Furthermore, GM1 is an effective drug for reducing primary and secondary spinal cord injuries following BPRA.


Assuntos
Traumatismos do Nervo Acessório , Gangliosídeo G(M1)/farmacologia , Glucose-6-Fosfato/análogos & derivados , Tomografia por Emissão de Pósitrons , Traumatismos da Medula Espinal , Medula Espinal/diagnóstico por imagem , Microtomografia por Raio-X , Traumatismos do Nervo Acessório/diagnóstico por imagem , Traumatismos do Nervo Acessório/tratamento farmacológico , Animais , Plexo Braquial/diagnóstico por imagem , Glucose-6-Fosfato/farmacologia , Masculino , Neurônios Motores/diagnóstico por imagem , Ratos , Ratos Sprague-Dawley , Traumatismos da Medula Espinal/diagnóstico por imagem , Traumatismos da Medula Espinal/tratamento farmacológico , Fatores de Tempo
4.
BMC Neurosci ; 15: 92, 2014 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-25055855

RESUMO

BACKGROUND: Spinal root avulsion induces multiple pathophysiological events consisting of altered levels of specific genes and proteins related to inflammation, apoptosis, and oxidative stress, which collectively result in the death of the affected motoneurons. Recent studies have demonstrated that the gene changes involved in spinal cord injury can be regulated by microRNAs, which are a class of short non-coding RNA molecules that repress target mRNAs post-transcriptionally. With consideration for the time course of the avulsion-induced gene expression patterns within dying motoneurons, we employed microarray analysis to determine whether and how microRNAs are involved in the changes of gene expression induced by pathophysiological events in spinal cord motoneurons. RESULTS: The expression of a total of 3,361 miRNAs in the spinal cord of adult rats was identified. Unilateral root-avulsion resulted in significant alterations in miRNA expression. In the ipsilateral half compared to the contralateral half of the spinal cord, on the 3rd day after the injury, 55 miRNAs were upregulated, and 24 were downregulated, and on the 14th day after the injury, 36 miRNAs were upregulated, and 23 were downregulated. The upregulation of miR-146b-5p and miR-31a-3p and the downregulation of miR-324-3p and miR-484 were observed. Eleven of the miRNAs, including miR-21-5p, demonstrated a sustained increase; however, only miR-466c-3p presented a sustained decrease 3 and 14 days after the injury. More interestingly, 4 of the miRNAs, including miR-18a, were upregulated on the 3rd day but were downregulated on the 14th day after injury.Some of these miRNAs target inflammatory-response genes in the early stage of injury, and others target neurotransmitter transport genes in the intermediate stages of injury. The altered miRNA expression pattern suggests that the MAPK and calcium signaling pathways are consistently involved in the injury response. CONCLUSIONS: This analysis may facilitate the understanding of the time-specific altered expression of a large set of microRNAs in the spinal cord after brachial root avulsion.


Assuntos
Neuropatias do Plexo Braquial/fisiopatologia , MicroRNAs/metabolismo , Neurônios Motores/fisiologia , Degeneração Neural/fisiopatologia , Radiculopatia/fisiopatologia , Medula Espinal/fisiopatologia , Animais , Neuropatias do Plexo Braquial/patologia , Vértebras Cervicais , Progressão da Doença , Lateralidade Funcional , Expressão Gênica , Masculino , Análise em Microsséries , Neurônios Motores/patologia , Degeneração Neural/patologia , Radiculopatia/patologia , Ratos Sprague-Dawley , Medula Espinal/patologia , Vértebras Torácicas , Fatores de Tempo
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