Expression of peptidylarginine deiminase 4 and protein tyrosine phosphatase nonreceptor type 22 in the synovium of collagen-induced arthritis rats / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To study the expression level of peptidylarginine deiminase 4 (PADI4) and protein tyrosine phosphatase nonreceptor type 22 (PTPN22) in the synovium of rat model of collagen-induced arthritis, and to explore their possible therapeutic role in rheumatoid arthritis.</p><p><b>METHODS</b>Thirty-two female Wistar rats weighing 100±20 g were randomly assigned into 3-week collagen-induced arthritis (CIA) model group (n=8), 4-week CIA model group (n=8), 6-week CIA model group (n=8), and the control group (n=8). The body weight changes of each group were recorded. The expression levels of PADI4 and PTPN22 were detected and compared by the methods of immunohistochemical staining and Western blot.</p><p><b>RESULTS</b>Arthritis of rat began to form 14 days after sensitization and the joint swelling reached peak at 28 days. The weights of the rats slowly grew both in CIA model groups and the control group. Immunohistochemical staining results showed that the positive expression of PADI4 and PTPN22 was mainly located in cartilage peripheral mononuclear cells, the cytoplasm of infiltrated cells, and bone marrow cavity. There were significant differences in the optical density of PADI4 and PTPN22 among CIA model groups and the control group (PADI4, 0.2898±0.012, 0.2982±0.022, 0.2974±0.031, 0.2530±0.013 in 3-week CIA model, 4-week CIA model, 6-week CIA model and control groups; PTPN22, 0.2723±0.004, 0.2781±0.010, 0.2767±0.008, 0.2422±0.019; all P <0.05). The expression bands of PADI4 were observed in Western blot 3 weeks after initial immunization, the thickest in the 4th week, and decreased in the 6th week. The expression bands of PTPN2 were observed at all the time points, with no obvious time-dependent trend.</p><p><b>CONCLUSIONS</b>PADI4 and PTPN22 are obviously correlated with CIA in rat model. PADI4 is expressed at early stage of the disease, while the expression of PTPN22 sustains throughout the course.</p>

La ketamina mejora la supervivencia en lesión por quemadura severa en ratas, a través de la expresión de la proteina de choque 70 / Ketamine improves survival in severe burn injury in rats via the expression of heat shock protein 70

Se ha demostrado que la ketamina, una anestésico general, produce una respuesta de choque térmico (HSR) en algunos animales experimentales. Examinamos si la ketamina mejora la supervivencia en lesión por quemadura severa en ratas, a través de la expresión de la proteína de choque 70. Un total de 124 ratas Wistar machos se dividieron aleatoriamente en 3 grupos: un grupo de control (grupo C, n = 20), un grupo quemado (grupo B, n = 52) y un grupo quemado + ketamina (grupo K, n = 52). Las ratas de los grupos B y K presentaban quemaduras de espesor completo en el 30% del total de su superficie corporal. Las ratas del grupo K se trataron con ketamina (40mg/kg, i.m.) a los 15min después de la lesión y las del grupo B se inyectaron con igual volumen de solución salina. Luego de practicar la eutanasia a las ratas, se examinó la expresión de HSP70 en muestras del miocardio y del cerebro con análisis Western blot. En las ratas que no se sacrificaron se evaluó el estado de supervivencia. Luego de 10 días, la tasa de supervivencia en las ratas del grupo K era superior a las del grupo B (70% versus 30%). Los análisis Western blot mostraron que la expresión de proteína HSP70 en el miocardio en respuesta a la administración de ketamina es más fuerte que en respuesta a la administración de solución salina a las 3 h (158% versus 65%) y a las 6h (165% versus 68%). En comparación con el grupo B, la ketamina aumentó marcadamente el nivel de expresión de la proteína HSP70 en tejido cerebral a las 3h y a las 6 h (79% versus 51% a las 3 h; 123% versus 98% a las 6 h). Concluimos que el tratamiento con ketamina mejora la supervivencia en lesión por quemadura severa, mediante la expresión de la proteína de choque 70 en los tejidos del miocardio y del cerebro.

Ketamine, a general anesthetic, has been shown to elicit the heat-shock response (HSR) in some of the animal models. We examined whether ketamine improves survival in severe burn injury in rats via the expression of heat shock protein 70. 124 male Wistar rats were randomly divided into three groups: a control group (group C, n = 20), burned group (group B, n = 52), and burned + ketamine group (group K, n = 52). The rats in groups B and K had full-thickness burns of 30% of their total body surface. The rats in group K were treated with ketamine (40 mg/kg, i.m.) 15 min after injury, and those in group B were injected with saline at the same volume. After the rats were euthanized, HSP70 expression in myocardium and brain samples was examined by Western blot analysis. Survival status was evaluated for the rats not euthanized. After 10 days, survival rate of rats in group K was higher than that of group B (70% versus 30%). Western blot analyses revealed that HSP70 protein expression in myocardium in response to ketamine administration is stronger than that in response to saline administration at 3 h (158% versus 65%) and 6 h (165% versus 68%). Compared with that in group B, ketamine strongly increased HSP70 protein expression level in cerebral tissue at 3 h and 6 h (79% versus 51%, at 3 h; 123% versus 98%, at 6 h). We concluded that ketamine therapy improves survival in severe burn injury via the expression of heat shock protein 70 in myocardial and cerebral tissues.

Increased interleukin-23 is associated with increased disease activity in patients with rheumatoid arthritis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Interleukin-23 (IL-23) is a pro-inflammatory cytokine that is thought to be central to the development of autoimmune diseases. This study was conducted to determine whether or not the serum concentration of IL-23 is elevated in patients with rheumatoid arthritis (RA), and to determine the relationship between the IL-23 level and disease activity in RA patients.</p><p><b>METHODS</b>Serum samples were obtained from 59 patients with RA and 30 healthy controls. The clinical parameters of disease activity were determined, including the 28-joint disease activity score (DAS28), C-reactive protein (CRP), rheumatoid factor (RF) levels, and the degree of bony erosions based on X-rays. The levels of IL-23 and IL-17 were determined by enzyme-linked immunosorbent assay (ELISA). The correlations between the serum levels of IL-23 and disease activity parameters of patients with RA were determined.</p><p><b>RESULTS</b>The serum IL-23 level was significantly elevated in patients with RA compared to healthy controls. The serum IL-23 levels in the RA patients correlated with IL-17 and CRP levels, and the DAS28. The levels of IL-23 based on X-ray classification phase I, II, III, and IV were gradually elevated in RA patients.</p><p><b>CONCLUSIONS</b>The levels of serum IL-23 in RA patients were higher than in healthy controls. Thus, elevated serum IL-23 levels may be useful markers to detect active RA. In addition, IL-23 is involved in disease progression and bony erosions in patients with RA.</p>

cAMP response-element binding protein participates in the phosphorylated extracellular signal-regulate kinase mediated neuropathic pain / 生理学报

It has been reported that extracellular signal-regulate kinase (ERK) is involved in the modulation of nociceptive information and central sensitization produced by intense noxious stimuli and/or peripheral tissue inflammation. Few studies have explored the relationship between ERK and cAMP response-element binding protein (CREB) in neuropathic pain after nerve injury, such as chronic constriction injury (CCI) of the sciatic nerve. In the present study, CCI model was employed to investigate the activation of ERK on the expression of phosphorylated CREB (pCREB) in chronic neuropathic pain. Lumbar intrathecal catheters were chronically implanted in male Sprague-Dawley rats. The left sciatic nerve was loosely ligated proximal to the sciatica's trifurcation at around 1.0- mm intervals with 4-0 silk suture. Mitogen-activated protein kinase kinase (MEK) inhibitor U0126 and phosphorothioate-modified antisense oligonucleotides (ODN) were intrathecally administered one day before and three consecutive days after CCI. Thermal and mechanical nociceptive thresholds were assessed with the paw withdrawal lantency (PWL) to radiant heat and von Frey filaments respectively. The expression of pCREB and Fos were assessed by both Western blot and immunohistochemical analysis. The results showed that intrathecal injection of U0126 or ERK antisense ODN attenuated significantly CCI-induced mechanical and thermal hyperalgesia. Correlating with behavior results, the injection also markedly suppressed the increase of CCI-induced pCREB and c-Fos expression. The results obtained suggest that CREB participates in the pERK-mediated neuropathic pain.

Activation of the spinal extracellular signal-regulated kinase is involved in morphine dependence and naloxone-precipitated withdrawal response / 生理学报

Extracellular signal-regulated kinase (ERK), a mitogen-activated protein kinase (MAPK), transduces a broad range of extracellular stimuli into diverse intracellular responses. It has been reported that ERK is involved in the modulation of nociceptive information and central sensitization produced by intense noxious stimuli or peripheral tissue inflammation. Our previous studies showed that the spinal neurons sensitization was involved in morphine withdrawal response. This study was to investigate the role of the spinal ERK in morphine dependence and naloxone-precipitated withdrawal response. To set up morphine-dependent model, rats were subcutaneously injected with morphine (twice a day, for 5 d). The dose of morphine was 10 mg/kg on the first day and was increased by 10 mg/kg each day. On day 6, 4 h after the injection of morphine (50 mg/kg), morphine withdrawal syndrome was precipitated by an injection of naloxone (4 mg/kg, i.p.). Using anti-phospho-ERK (pERK) antibody, the time course of pERK expression was detected by Western blot. U0126, a mitogen-activated protein kinase kinase (MEK) inhibitor, or phosphorothioate-modified antisense oligonucleotides (ODN) was intrathecally injected 30 min or 36, 24 and 12 h before naloxone-precipitated withdrawal. The scores of morphine withdrawal symptom and morphine withdrawal-induced allodynia were observed. One hour after naloxone-precipitated withdrawal, pERK expression in the spinal dorsal horn was assessed by immunohistochemical analysis and Western blot was used to detect the expression of cytosolic and nuclear fraction of pERK in the rat spinal cord. The results showed that the expression of cytosolic and nuclear fraction of pERK, not non-phospho-ERK, in the spinal cord was gradually increased following the injection of morphine. When morphine withdrawal was precipitated with naloxone, the expression of the spinal pERK further increased. Intrathecal administration of U0126 or antisense ODN against ERK decreased the scores of morphine withdrawal, attenuated morphine withdrawal-induced allodynia and also inhibited the increase of pERK expression in the spinal cord of morphine withdrawal rats. These results suggest that activation of the spinal ERK is involved in morphine-dependent and naloxone-precipitated withdrawal response.