Dorsal root ganglion-derived exosomes deteriorate neuropathic pain by activating microglia via the microRNA-16-5p/HECTD1/HSP90 axis.

BACKGROUND: The activated microglia have been reported as pillar factors in neuropathic pain (NP) pathology, but the molecules driving pain-inducible microglial activation require further exploration. In this study, we investigated the effect of dorsal root ganglion (DRG)-derived exosomes (Exo) on microglial activation and the related mechanism. METHODS: A mouse model of NP was generated by spinal nerve ligation (SNL), and DRG-derived Exo were extracted. The effects of DRG-Exo on NP and microglial activation in SNL mice were evaluated using behavioral tests, HE staining, immunofluorescence, and western blot. Next, the differentially enriched microRNAs (miRNAs) in DRG-Exo-treated microglia were analyzed using microarrays. RT-qPCR, RNA pull-down, dual-luciferase reporter assay, and immunofluorescence were conducted to verify the binding relation between miR-16-5p and HECTD1. Finally, the effects of ubiquitination modification of HSP90 by HECTD1 on NP progression and microglial activation were investigated by Co-IP, western blot, immunofluorescence assays, and rescue experiments. RESULTS: DRG-Exo aggravated NP resulting from SNL in mice, promoted the activation of microglia in DRG, and increased neuroinflammation. miR-16-5p knockdown in DRG-Exo alleviated the stimulating effects of DRG-Exo on NP and microglial activation. DRG-Exo regulated the ubiquitination of HSP90 through the interaction between miR-16-5p and HECTD1. Ubiquitination alteration of HSP90 was involved in microglial activation during NP. CONCLUSIONS: miR-16-5p shuttled by DRG-Exo regulated the ubiquitination of HSP90 by interacting with HECTD1, thereby contributing to the microglial activation in NP.

Dorsal root ganglion-derived exosomes deteriorate neuropathic pain by activating microglia via the microRNA-16-5p/HECTD1/ HSP90 axis

Background The activated microglia have been reported as pillar factors in neuropathic pain (NP) pathology, but the molecules driving pain-inducible microglial activation require further exploration. In this study, we investigated the effect of dorsal root ganglion (DRG)-derived exosomes (Exo) on microglial activation and the related mechanism. Methods A mouse model of NP was generated by spinal nerve ligation (SNL), and DRG-derived Exo were extracted. The effects of DRG-Exo on NP and microglial activation in SNL mice were evaluated using behavioral tests, HE staining, immunofluorescence, and western blot. Next, the differentially enriched microRNAs (miRNAs) in DRG-Exo-treated microglia were analyzed using microarrays. RT-qPCR, RNA pull-down, dual-luciferase reporter assay, and immunofluorescence were conducted to verify the binding relation between miR-16-5p and HECTD1. Finally, the effects of ubiquitination modification of HSP90 by HECTD1 on NP progression and microglial activation were investigated by Co-IP, western blot, immunofluorescence assays, and rescue experiments. Results DRG-Exo aggravated NP resulting from SNL in mice, promoted the activation of microglia in DRG, and increased neuroinflammation. miR-16-5p knockdown in DRG-Exo alleviated the stimulating effects of DRG-Exo on NP and microglial activation. DRG-Exo regulated the ubiquitination of HSP90 through the interaction between miR-16-5p and HECTD1. Ubiquitination alteration of HSP90 was involved in microglial activation during NP. Conclusions miR-16-5p shuttled by DRG-Exo regulated the ubiquitination of HSP90 by interacting with HECTD1, thereby contributing to the microglial activation in NP.

Research on the improved image tracking algorithm of athletes' cervical health / Pesquisa sobre o algoritmo de rastreamento de imagem aprimorado da saúde do colo do útero de atletas / Investigación sobre el algoritmo de seguimiento de imágenes mejorado de la salud cervical de los atletas

ABSTRACT Objective: With the increasing number and youth of patients with cervical spondylosis, people pay more and more attention to the cervical spine. Early diagnosis, intervention and treatment play an important role in the recovery of cervical spondylosis. With the continuous development of computer technology, the improvement of various modeling theories, and the application of image processing methods in orthopedics, new ideas are opened to observe cervical vertebra motion health. Methods: In this paper, the measurement of cervical motion is achieved by machine vision. A method of parameter measurement based on the constraint relationship of lower cervical motion is proposed. Based on image preprocessing, the left edge of the cervical vertebra was extracted and analyzed. Results: With the horizontal coordinate of registration point as the reference line, the changing trend of the angle between the left edge curve and the reference line of C4 and C5 vertebrae in the process of spontaneous flexion and extension of the cervical vertebrae was observed, and the movement rate of the cervical vertebrae was analyzed. Conclusions: It was found that the speed of the cervical vertebrae in the process of movement of the patients with cervical spondylosis showed jumping changes. Level of evidence II; Therapeutic studies - investigation of treatment results.

RESUMO Objetivo: Com o aumento do número e da juventude dos pacientes com espondilose cervical, as pessoas prestam cada vez mais atenção à coluna cervical. O diagnóstico, intervenção e tratamento precoces desempenham um papel importante na recuperação da espondilose cervical. Com o desenvolvimento contínuo da tecnologia computacional, o aprimoramento de várias teorias de modelagem e a aplicação de métodos de processamento de imagens na ortopedia, novas ideias se abrem para observar a saúde do movimento das vértebras cervicais. Métodos: Neste trabalho, a mensuração do movimento cervical é realizada por meio de visão artificial. É proposto um método de medição de parâmetro baseado na taxa de restrição de movimento cervical inferior. Com base no pré-processamento da imagem, a borda esquerda da vértebra cervical foi extraída e analisada. Resultados: Com a coordenada horizontal do ponto de registro como linha de referência, a tendência de mudança do ângulo entre a curva da borda esquerda e a linha de referência das vértebras C4 e C5 foi observada no processo de flexão espontânea e extensão do vértebras, vértebras cervicais e a taxa de movimento das vértebras cervicais. Conclusões: Verificou-se que a velocidade das vértebras cervicais no processo de movimentação de pacientes com espondilose cervical apresentou alterações de salto. Nível de evidência II; Estudos terapêuticos- investigação dos resultados do tratamento.

RESUMEN Objetivo: Con el número creciente y la juventud de pacientes con espondilosis cervical, las personas prestan cada vez más atención a la columna cervical. El diagnóstico, la intervención y el tratamiento tempranos juegan un papel importante en la recuperación de la espondilosis cervical. Con el desarrollo continuo de la tecnología informática, la mejora de varias teorías de modelado y la aplicación de métodos de procesamiento de imágenes en ortopedia, se abren nuevas ideas para observar la salud del movimiento de las vértebras cervicales. Métodos: En este trabajo, la medición del movimiento cervical se logra mediante visión artificial. Se propone un método de medición de parámetros basado en la relación de restricción del movimiento cervical inferior. Sobre la base del preprocesamiento de imágenes, se extrajo y analizó el borde izquierdo de la vértebra cervical. Resultados: Con la coordenada horizontal del punto de registro como línea de referencia, se observó la tendencia cambiante del ángulo entre la curva del borde izquierdo y la línea de referencia de las vértebras C4 y C5 en el proceso de flexión y extensión espontánea de las vértebras cervicales, y Se analizó la tasa de movimiento de las vértebras cervicales. Conclusiones: Se encontró que la velocidad de las vértebras cervicales en el proceso de movimiento de los pacientes con espondilosis cervical mostró cambios de salto. Nivel de evidencia II; Estudios terapéuticos- investigación de los resultados del tratamiento.

Therapeutic effects of dimethyldiguanide combined with clomifene citrate in the treatment of polycystic ovary syndrome.

OBJECTIVE: In view of the high incidence of polycystic ovary syndrome (PCOS) and the unsatisfactory therapeutic effects of dimethyldiguanide or clomifene citrate alone, our study aimed to investigate the therapeutic effects of dimethyldiguanide combined with clomifene citrate in the treatment of PCOS. METHODS: A total of 79 patients with POCS and 35 healthy females were included, and endometrial biopsies were obtained. The sterol regulatory element-binding protein-1 (SREBP1) expression in endometrial tissues was detected by qRT-PCR. POC patients were randomly divided into group A (n=40) and group B (n=39). Patients in group A were treated with dimethyldiguanide combined with clomifene citrate, while patients in group B were treated with clomifene citrate alone. The number of mature follicles and cervical mucus score, follicular development rate and single follicle ovulation rate, cycle pregnancy rate, early miscarriage rate, ovulation rate, endometrial thickness, positive rate of three lines sign, follicle stimulating hormone level and luteinizing hormone level were compared between the two groups. RESULTS: The expression level of SREBP1 was higher in PCOS patients than that in the healthy control. SREBP1 expression was inhibited after treatment, while the inhibitory effects of combined treatment were stronger than those of clomifene citrate alone. Compared with clomifene citrate alone, the combined treatment improved cervical mucus score, follicle development rate, single follicle ovulation rate, endometrial thickness, positive rate of three lines sign, and follicle-stimulating hormone level. CONCLUSION: The therapeutic effect of combined treatment is better than clomifene citrate alone in the treatment of PCOS.

Therapeutic effects of dimethyldiguanide combined with clomifene citrate in the treatment of polycystic ovary syndrome

SUMMARY OBJECTIVE In view of the high incidence of polycystic ovary syndrome (PCOS) and the unsatisfactory therapeutic effects of dimethyldiguanide or clomifene citrate alone, our study aimed to investigate the therapeutic effects of dimethyldiguanide combined with clomifene citrate in the treatment of PCOS. METHODS A total of 79 patients with POCS and 35 healthy females were included, and endometrial biopsies were obtained. The sterol regulatory element-binding protein-1 (SREBP1) expression in endometrial tissues was detected by qRT-PCR. POC patients were randomly divided into group A (n=40) and group B (n=39). Patients in group A were treated with dimethyldiguanide combined with clomifene citrate, while patients in group B were treated with clomifene citrate alone. The number of mature follicles and cervical mucus score, follicular development rate and single follicle ovulation rate, cycle pregnancy rate, early miscarriage rate, ovulation rate, endometrial thickness, positive rate of three lines sign, follicle stimulating hormone level and luteinizing hormone level were compared between the two groups. RESULTS The expression level of SREBP1 was higher in PCOS patients than that in the healthy control. SREBP1 expression was inhibited after treatment, while the inhibitory effects of combined treatment were stronger than those of clomifene citrate alone. Compared with clomifene citrate alone, the combined treatment improved cervical mucus score, follicle development rate, single follicle ovulation rate, endometrial thickness, positive rate of three lines sign, and follicle-stimulating hormone level. CONCLUSION The therapeutic effect of combined treatment is better than clomifene citrate alone in the treatment of PCOS.

RESUMO OBJETIVO Tendo em vista a alta incidência de síndrome dos ovários policísticos (SOP) e os efeitos terapêuticos insatisfatórios da dimetildiguanida ou do citrato de clomifeno isoladamente, nosso estudo teve como objetivo investigar os efeitos terapêuticos da dimetildiguanida associada ao citrato de clomifeno no tratamento da SOP. MÉTODOS Um total de 79 pacientes com POCS e 35 mulheres saudáveis foram incluídos, e biópsias endometriais foram obtidas. A expressão da proteína de ligação do elemento regulador de esterol-1 (SREBP1) nos tecidos endometriais foi detectada por qRT-PCR. Pacientes POC foram divididos aleatoriamente em grupo A (n=40) e grupo B (n=39). Os pacientes do grupo A foram tratados com dimetildiguanida combinada com citrato de clomifeno, enquanto os pacientes do grupo B foram tratados apenas com citrato de clomifeno. O número de folículos maduros e muco cervical, taxa de desenvolvimento folicular e taxa de ovulação, taxa de gravidez, abortamento precoce, taxa de ovulação, espessura endometrial, taxa positiva de três linhas, nível de hormônio folículo estimulante e nível de hormônio luteinizante foram comparados entre os dois grupos. RESULTADOS O nível de expressão do SREBP1 foi maior nos pacientes com SOP do que no controle normal. A expressão de SREBP1 foi inibida após o tratamento, enquanto os efeitos inibidores do tratamento combinado foram mais fortes do que os do citrato de clomifeno isoladamente. Comparado com o citrato de clomifeno sozinho, o tratamento combinado melhorou significativamente a pontuação do muco cervical, a taxa de desenvolvimento folicular, a taxa de ovulação do folículo único, a espessura endometrial, a taxa positiva de três linhas de sinal e o nível de hormônio folículo estimulante. CONCLUSÃO O efeito terapêutico do tratamento combinado é melhor do que o citrato de clomifeno isolado no tratamento da SOP.