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[ Abstract] Objective To study the effect of sulodexide on the repair of diabetic retinopathy and the regulation of MAPK pathway in rats. Methods Totally 72 rats were randomly divided into normal control group, diabetic retinopathy group, low, middle and high dose of sulodexide group and metformin hydrochloride group. Except normal control group, other rats were intraperitoneally injected with streptozotocin to establish the rat model of diabetic retinopathy. Rats in the low, middle and high dose sulodexide groups were given sulodexide by intragastric administration of 10 mg / kg,20 mg / kg and 40 mg / kg, respectively. Metformin hydrochloride group was given metformin hydrochloride of 200 mg / kg, once a day for 12 weeks. The levels of fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c) and serum levels of advanced glycation end products (AGEs), interleukin-6 (IL-6), IL-1β, and levels of glucose transporter 1 (GLUT-1), glucose transporter 3(GLUT-3), superoxide dismutase (SOD) and malondialdehyde (MDA) in retina were detected. The levels of p38 MAPK and phosphorylated p38 MAPK (p-p38 MAPK) in retina were detected by immunohistochemistry and Western blotting. Retinal pathological changes and ganglion cell count were examined by HE staining. Results The levels of FBG and HbA1c, serum AGEs, IL-6, IL-1 β, GLUT-1, GLUT-3, MDA and p38 MAPK mRNA, p38 MAPK, p-p38 MAPK / p38 MAPK and immunohistochemical integral optical density of retina in sulodexide group were significantly lower than those in diabetic retinopathy group (P < 0. 05), while the SOD level and ganglion cell number in retinal tissue were significantly higher than those in diabetic retinopathy group (P < 0. 05) . Conclusion Sulodexide can regulate blood glucose level and retinal glucose metabolism in diabetic retinopathy rats, and repair retinal pathological damage, and its mechanism may be related to the regulation of MAPK pathway.
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AIM:To investigate whether ceramide kinase-like protein(CERKL)alleviates oxidative stress injury of retinal pigment epithelial(RPE)cells induced by blue light via activating the silent information regulator 1(SIRT1)/E2F transcription factor 1(E2F1)axis. METHODS:Cultured human retinal pigment epithelial-19(ARPE-19)cells were irradiated with blue light to observe the morphological changes, and the expression of CERKL was detected by PCR and Western blot. ARPE-19 cells were transfected with siRNA-CERKL and pcDNA3.1-CERKL respectively. After exposure to blue light, cell viability was determined by MTT assay, apoptosis was detected by TUNEL assay, content of oxidative stress markers and the expression of SIRT1/E2F1 axis was analyzed. Then siRNA-SIRT1 was transfected into ARPE-19 cells, and the oxidative stress damage of ARPE-19 cells under blue light irradiation was detected again.RESULTS:ARPE-19 cells gradually contracted into spheres and appeared vacuoles after exposure to blue light. Blue light irradiation led to the increase of CERKL expression level(P<0.05), meanwhile, the rate of cell viability was decreased(P<0.05), the rate of the apoptosis was increased(P<0.05), contents of reactive oxygen species, malondialdehyde and 8-hydroxydeoxyguanosine were increased(P<0.05). Silence of CERKL aggravated this phenomenon, while up-regulation of CERKL could alleviate this change(P<0.05). Up-regulation of CERKL also activated the expression of SIRT1 and promoted the deacetylation of E2F1(P<0.05). Silencing SIRT1 could reverse the alleviating effect of up-regulating CERKL on oxidative stress injury of ARPE-19 cells induced by blue light(P<0.05). CONCLUSION: CERKL can reduce oxidative stress damage of ARPE-19 cells induced by blue light via activating SIRT1 expression and promoting the deacetylation of E2F1.
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Thrombospondin 4 (THBS4), a member of the THBS family, is a protein secreted by the extracellular matrix and is involved in regulating various physiological processes, such as cell proliferation, adhesion and angiogenesis. Recent studies have shown that the inflammation stimulates THBS4 production and induces the adhesion and accumulation of macrophages. Our previous study confirmed that THBS4 acts as an oncogene in hepatocellular carcinoma (HCC), the effect of THBS4 on the immune microenvironment of HCC remains unclear. This study aims to analyze the role of THBS4 in promoting the metastasis of HCC cells by inducing M2-type polarization of tumor-associated macrophages. We simulate the tumor microenvironment through HCC conditioned medium (HCM) and found that the expression of THBS4 in macrophages increased in a time-dependent manner under the action of HCM (P<0.05); THBS4 knockdown promotes the expression of M1 macrophages markers IL-1β and CD86 (P<0.01), while the expression of M2-type markers IL-10 and CD206 were decreased (P<0.01). Transwell co-culture assay was used to further detect the effect of THBS4-induced M2-type macrophages on HCC metastasis. Results from co-culture of THBS4-downregulated M2 macrophages with HepG2 cells showed that THBS4-downregulated M2-TAMs significantly inhibited the invasion and migration ability of HepG2 cells (all P < 0.01). In conclusion, the tumor microenvironment promotes the expression of THBS4 in macrophages, and THBS4 may promote the invasion and metastasis of HCC cells by inducing M2-type polarization of macrophages. This study provides some new experimental basis for exploring the establishment of THBS4-induced HCC immune microenvironment.
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OBJECTIVE@#To compare the effects of intravenous and subcutaneous injection of bortezomib on incidence and relative risk of peripheral neuropathy in patients with multiple myeloma(MM).@*METHODS@#The electronic database of PubMed, Embase, Cochrance library, CNKI and related meeting records were searched by computers. The data were derived all from a matched randomized controlled studies. The incidence, relative risk(RR) and 95% confidence interval of peripheral neuropathy caused by intravenous and subcustaneous injections were calculated by the statistical methods.@*RESULTS@#Four RCT studies were selected for meta-analysis, with a total of 911 patients (479 cases and 432 cases in the subcutaneous injection and intravenous injection groups, respectively). The incidence of peripheral neuropathy in the intravenous injection group was 41.4% (95% CI=0.137-0.692, P=0.003), and the incidence of >2 grade of peripheral neuropathy was 15.6% (95% CI=0.005-0.308, P=0.043). The corresponding incidence rates of the subcutaneous injection group were 16% (95% CI=0.021-0.299, P=0.024) and 3.4% (95% CI=-0.011-0.080, P=0.141) respectively. Compared with the intravenous injection group, the RR of peripheral neuropathy and the relative risk of peripheral neuropathy above grade 2 were 0.525, 95% CI=0.297-0.928 (P=0.027) and 0.376, 95% CI=0.196-0.722 (P=0.003) respectively.@*CONCLUSION@#Subcutaneous injection of bortezomib at therapeutic doses significantly reduces the incidence of peripheral neuropathy compared with intravenous injection.
Subject(s)
Humans , Antineoplastic Agents , Bortezomib , Incidence , Injections, Subcutaneous , Multiple Myeloma , Peripheral Nervous System DiseasesABSTRACT
OBJECTIVE@#To investigate the significance of detecting serum complement C3 and C4 in patients with multiple myeloma (MM) and to explore its correlation with myeloma bone disease (MBD).@*METHODS@#The levels of serum complement C3 and C4 in 69 MM patients and 30 healthy people were examined by scatter nephelometry. The bone density of L1-4 vertebral body, bilateral femoral neck and bilateral hip joints were measured by dual energy bone density meter (DXA).@*RESULTS@#The levels of serum complement C3 and C4 in MM patients significantly increased in comparison with that in healthy people (P＜0.01). The patients in advanced clinical stage exhibited a higher levels of C3 and C4 than those in stable stage (P＜0.01). In addition, the patients with grade C of MBD had a higher levels of serum complement C3 and C4 than those in patients with grade A and B of MBD (P＜0.01). The levels of serum complement C3 and C4 in MM patients negatively correlated with bone density in L1-4 vertebral body, bilateral femoral necks and hip joints. The correlation coefficients were r=-0.938, r=-0.659, r=-0.745, r=-0.748, r=-0.596 in complement C3 and r=-0.908, r=-0.623, r=-0.710, r=-0.714, r=-0.595 in complement C4, respectively.@*CONCLUSION@#The levels of complement C3 and C4 positively correlate with the severity of bone disease and bone density in MM patients, which suggests that complement C3 and C4 plays important roles in the development of MBD. The levels of serum C3 and C4 may be the sensitive biomarkers of MBD.
Subject(s)
Humans , Biomarkers , Complement C3 , Metabolism , Complement C4 , Metabolism , Femur Neck , Multiple MyelomaABSTRACT
Aseptic loosening is one of the most commonly seen longterm complications after joint arthroplasty. Previous stud-ies have shown that prosthetic wear is one of the major causes of chronic inflammation in tissues surrounding the prosthesis,and that macrophage is the key factor responsible for the interaction between prostheses-derived wear particles and the host. Wear particles acti-vate macrophages and secretion of inflammatory mediators stimulate osteoclastic bone resorption,resulting in reduction of bone mass a-round the prosthesis. However,the balance of bone turnover depends not only on osteoclast-mediated bone resorption but also on osteo-blast-mediated bone formation,both of which are in close cooperation. Osteoblasts are mainly derived from mesenchymal stem cells. A growing body of research shows that wear particles can significantly inhibit the differentiation of mesenchymal stem cell into osteoblasts and subsequent bone formation. However,some characteristics of mesenchymal stem cells enable them one of the main candidates for the treatment of aseptic loosening. We reviewed the current research advances on the aseptic loosening post arthroplasty using mesen-chymal stem cells as target.
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OBJECTIVE@#To investigate the role of survivin in osteosarcoma metastasis.@*METHODS@#Small interfering RNA (siRNA) was used to knockdown the expression of survivin and α5 integrin in the human osteosarcoma cell line MG63. Western blotting and immunostaining methods were used to assessed the effect of survivin knockdown on the expression of α5 integrin through flow cytometry and fluorescence microscopy detection. Meanwhile, the invasion and migration of transfected cells in Transwell and wound healing assays were probed, and the growth situation of these cells transplanted into nude mice was monitored.@*RESULTS@#Knockdown of survivin expression could inhibit the invasion and migration of osteosarcoma MG64 cells in vitro and the expression of α5 integrin on osteosarcoma MG64 cell surface, suggesting that survivin can inhibit the invasion and migration of osteosarcoma cells through downregulation of α5 integrin. Anti-α5 integrin antibody could also markedly decrease the capability of invasion and migration of osteosarcoma MG64 cells. Additionally, knockdown of survivin expression could slow the growth of osteosarcoma MG63 cells transplanted into nude mice.@*CONCLUSIONS@#Survivin-directed anti-tumor strategies might be an effective method in the treatment of osteosarcoma.
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Objective To investigate the role of survivin in osteosarcoma metastasis. Methods Small interfering RNA (siRNA) was used to knockdown the expression of survivin and α5 integrin in the human osteosarcoma cell line MG63. Western blotting and immunostaining methods were used to assessed the effect of survivin knockdown on the expression of α5 integrin through flow cytometry and fluorescence microscopy detection. Meanwhile, the invasion and migration of transfected cells in Transwell and wound healing assays were probed, and the growth situation of these cells transplanted into nude mice was monitored. Results Knockdown of survivin expression could inhibit the invasion and migration of osteosarcoma MG64 cells in vitro and the expression of α5 integrin on osteosarcoma MG64 cell surface, suggesting that survivin can inhibit the invasion and migration of osteosarcoma cells through downregulation of α5 integrin. Anti-α5 integrin antibody could also markedly decrease the capability of invasion and migration of osteosarcoma MG64 cells. Additionally, knockdown of survivin expression could slow the growth of osteosarcoma MG63 cells transplanted into nude mice. Conclusions Survivin-directed anti-tumor strategies might be an effective method in the treatment of osteosarcoma.
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<p><b>OBJECTIVE</b>To evaluate the erectile and ejaculatory function of sacral tumor patients after sacral nerve root resection and investigate the relationship of erectile and ejaculatory dysfunction (EED) with the level of sacral nerve injury.</p><p><b>METHODS</b>This retrospective study included 47 male patients aged 16 to 63 (32.6 +/- 6.8) years treated by sacral tumor resection between January 2008 and August 2013. According to the levels of the sacral nerve roots spared in surgery, the patients were divided into four groups: bilateral S1-S3 (n=16), unilateral S1-S3 (n=21), unilateral S1-S2 (n=6), and unilateral S1 (n=4). The patients were followed up for 12 to 41 (27.2 +/- 10.9) months by questionnaire investigation, clinic review, and telephone calls about their erectile and ejaculatory function at 3, 6 and 12 months after surgery and in August 2013.</p><p><b>RESULTS</b>In the bilateral S1-S3 group, the incidence rates of EED were 31.25% (5/16), 25% (4/16), and 12.5% (2/16) at 3, 6, and 12 months respectively after surgery, with recovery of erectile and ejaculatory function in August 2013. The incidence rates of EED in the unilateral S1-S3 group were 85.71% (18/21), 71.43% (15/21), 52.38% (11/21), and 42.86% (9/21) at 3, 6 and 12 months and in August 2013, respectively; those in the unilateral S1-S2 group were 100% (6/6), 83.33% (5/6), 83.33% (5/6), and 66.67% (4/6) at the four time points; and those in the unilateral S1 group were all 100% (4/4). No statistically significant differences were found in the incidence rate of EED among the patients of different ages or tumor types (P > 0.05).</p><p><b>CONCLUSION</b>The incidence of postoperative EED in male patients treated by sacral tumor resection is closely related to the mode of operation. Sparing the S3 nerve root at least unilaterally in sacral tumor resection is essential for protecting the erectile and ejaculatory function of the patient.</p>
Subject(s)
Adolescent , Adult , Female , Humans , Male , Middle Aged , Young Adult , Ejaculation , Physiology , Erectile Dysfunction , Epidemiology , Incidence , Organ Sparing Treatments , Peripheral Nervous System Neoplasms , General Surgery , Postoperative Complications , Epidemiology , Postoperative Period , Retrospective Studies , Sacrum , Spinal Nerve Roots , Wounds and Injuries , General Surgery , Surveys and QuestionnairesABSTRACT
<p><b>OBJECTIVE</b>To investigate the management experience with transnasal endoscopic technique for meningoencephalocele.</p><p><b>METHODS</b>Nine patients with endonasal encephalomeningocele were managed by transnasal endoscopic surgery, and the skull base defect was repaired by fascia.</p><p><b>RESULTS</b>Eight cases were successfully managed at the time of the first operation, and no relapse case was found during 1 to 4 years follow-up. Only one case of a two years old child relapsed with cerebrospinal fluid rhinorrhea one month after operation. During the second operation, titanium mesh uncovering was found, and replacement of titanium mesh by fascia via skull base defect was done, without relapse one and half years after the second operation. Another case of a one year old child got a fever one day after operation, but no white blood cell was found in the cerebrospinal fluid, and the temperature recovered to normal after release cerebrospinal fluid management. There were no complications of cranial infection, hemorrhage, edema and water retention in brain to be found in all cases.</p><p><b>CONCLUSIONS</b>It is not only minimally invasive, safety and efficiency of transnasal endoscopic technique for meningoencephalocele, but also had a clear operating view for better recolonization of the position of leak and the structure of operating field, therefore, transnasal endoscopic technique is the first choice for the management of endonasal encephalomeningocele. The accurate localization of leak and selection of the appropriate repairing materials are the key point for the successful operation.</p>