RESUMO
Three days after being stung by wasps in a rural area, a 60-year-old man was admitted to the emergency department with headaches. The physical examination showed that the patient was conscious, had moderate pain, had four head and back stings with local edema and erythema around the wounds, and had a stiff neck. Brain computed tomography upon admission revealed no abnormalities. Following lumbar puncture, the patient was diagnosed with subarachnoid hemorrhage (SAH) induced by wasp stings. No obvious aneurysms were found by either computed tomography angiography or three-dimensional rotational angiography. He received symptomatic treatment including antiallergy medication (chlorpheniramine and intravenous hydrocortisone), nimodipine for possible vasospasm, fluid infusion, and mannitol for intracranial pressure reduction and was discharged on the 14th day. This case of wasp sting-induced SAH is being reported to improve doctors' diagnostic abilities when encountering patients with wasp stings. It is important for emergency physicians to be aware that patients stung by wasps may develop rare complications such as SAH. Hymenoptera-induced SAH is an example of such a case.
Assuntos
Mordeduras e Picadas de Insetos , Hemorragia Subaracnóidea , Vespas , Masculino , Animais , Humanos , Pessoa de Meia-Idade , Mordeduras e Picadas de Insetos/complicações , Hemorragia Subaracnóidea/etiologia , Hemorragia Subaracnóidea/complicações , Cabeça , CefaleiaRESUMO
Recently, ferroptosis as new regulatory necrosis has attracted the scientific community. However, the study focused on the effect of ferroptosis on osteocytes in steroid (glucocorticoid)-induced osteonecrosis of the femoral head (SONFH) is still scarce. In this study, we use bioinformatic analysis to screen out differentially expressed genes (DEGs) in osteoblasts that treated by dexamethasone (Dex) in GSE10311 and found these DEGs are enriched in the ferroptosis signaling pathway. The results in vitro experiments show that Dex can induce MC3T3-E1 cells ferroptosis by down-regulating SLC7A11. Specifically, Dex inhibits the expression of SLC7A11/GPX4, decreases the activity of the intracellular antioxidant system such as intracellular glutathione (GSH), while increasing Malondialdehyde (MDA), reactive oxygen species (ROS), and lipid ROS, and reduces the volume of mitochondria, the mitochondrial ridges and a series of obvious ferroptosis features. The overexpression of SLC7A11 and the use of ferroptosis inhibitor (Fer-1) can reverse the Dex-induced MC3T3 ferroptosis. Dex can induce an increase in the expression of p53 and knocking down the expression of p53 by small interfering ribonucleic acid (siRNA) can reverse the suppression of SLC7A11 and GPX4 expression in MC3T3-E1 and MOLY4 cells, thereby reducing the production of ferroptosis. Thus, this study demonstrated that Dex induces MC3T3-E1cells ferroptosis via p53/SLC7A11/GPX4 pathway. The present finding offers novel insight to understand the underlying molecular mechanisms for glucocorticoid-induced osteonecrosis. Moreover, the suppression of ferroptosis may be a novel and promising treatment option for SONFH.
Assuntos
Ferroptose , Osteonecrose , Sistema y+ de Transporte de Aminoácidos/genética , Dexametasona/efeitos adversos , Cabeça do Fêmur/metabolismo , Glucocorticoides/efeitos adversos , Glutationa/metabolismo , Humanos , Espécies Reativas de Oxigênio/metabolismo , Proteína Supressora de Tumor p53RESUMO
Osteoarthritis (OA) is an ageing-related disease characterized by articular cartilage degradation and joint inflammation. circRNA has been known to involve in the regulation of multiple inflammatory diseases including OA. However, the mechanism underlying how circRNA regulates OA remains to be elucidated. Here, we report circANKRD36 prevents OA chondrocyte apoptosis and inflammation by targeting miR-599, which specifically degrades Casz1. We performed circRNA sequencing in normal and OA tissues and found the expression of circANKRD36 is decreased in OA tissues. circANKRD36 is also reduced in IL-1ß-treated human chondrocytes. FACS analysis and Western blot showed that the knockdown of circANKRD36 promotes the apoptosis and inflammation of chondrocytes in IL-1ß stress. We then found miR-599 to be the target of circANKRD36 and correlate well with circANKRD36 both in vitro and in vivo. By database analysis and luciferase assay, Casz1 was found to be the direct target of miR-599. Casz1 helps to prevent apoptosis and inflammation of chondrocytes in response to IL-1ß. In conclusion, our results proved circANKRD36 sponge miR-599 to up-regulate the expression of Casz1 and thus prevent apoptosis and inflammation in OA.
Assuntos
Apoptose/genética , Condrócitos/patologia , Proteínas de Ligação a DNA/genética , Inflamação/genética , MicroRNAs/metabolismo , Osteoartrite/genética , RNA Circular/metabolismo , Fatores de Transcrição/genética , Idoso , Idoso de 80 Anos ou mais , Sequência de Bases , Condrócitos/metabolismo , Proteínas de Ligação a DNA/metabolismo , Humanos , Interleucina-1beta/metabolismo , MicroRNAs/genética , Pessoa de Meia-Idade , RNA Circular/genética , Fatores de Transcrição/metabolismoRESUMO
This study was designed to investigate the effects of pulsed electromagnetic fields (PEMF) on the balance of adipogenesis and osteogenesis on steroid-induced osteonecrosis of the femoral head (OFH) in rats. Forty-two rats were divided into three groups: Steroid group (S, n = 16); Steroid + PEMF group (S + P, n = 16); and Control group (C, n = 10). For groups S and S + P, all rats were first intravenously given 10 µg/kg lipopolysaccharide on day 1, and then intramuscularly injected with 20 mg/kg methylprednisolone acetate on days 2, 3, and 4, with an interval of 24 h. After 4 weeks, the S + P group was treated with PEMF (4.5-ms square pulse, repeated at 15 Hz, with a peak of 1.2 mT) for 4 h a day for the next 8 weeks. Group S was not exposed to PEMF. Group C was chosen as the control group, without steroid use and exposure to PEMF. After 8 weeks of treatment, the histological changes, and mRNA and protein expressions of PPAR-γ2 and Runx2 were measured and analyzed. Compared with the S group, lower incidence of osteonecrosis (31% vs. 69%, P < 0.05) and empty osteocyte lacuna rate (36.16 ± 15.34 vs. 59.55 ± 21.70, P < 0.01) was observed in the S + P group. Furthermore, PEMF suppressed the expressions of PPAR-γ2 and improved the expressions of Runx2 in the femoral head (P < 0.05). All data suggest that PEMF is an effective physiotherapy in the treatment of steroid-induced ONFH, and the possible underlying mechanisms include protecting the balance between adipogenesis and osteogenesis.
Assuntos
Adipogenia , Necrose da Cabeça do Fêmur/fisiopatologia , Necrose da Cabeça do Fêmur/terapia , Cabeça do Fêmur/patologia , Magnetoterapia , Osteogênese , Animais , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Campos Eletromagnéticos , Necrose da Cabeça do Fêmur/induzido quimicamente , Necrose da Cabeça do Fêmur/patologia , Rim/patologia , Lipopolissacarídeos , Fígado/patologia , Magnetoterapia/instrumentação , Magnetoterapia/métodos , Masculino , Metilprednisolona/análogos & derivados , Acetato de Metilprednisolona , Osteócitos/patologia , Osteócitos/fisiologia , PPAR gama/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos WistarRESUMO
PA28γ (also called REGγ, 11Sγ or PSME3) negatively regulates p53 activity by promoting its nuclear export and/or degradation. Here, using the RNA ligase-mediated rapid amplification of cDNA ends (RLM-RACE) method, we identified the transcription start site of the PA28γ gene. Assessment with the luciferase assay demonstrated that the sequence -193 to +16 is the basal promoter. Three p53 binding sites were found within the PA28γ promoter utilizing a bioinformatics approach and were confirmed by chromatin immunoprecipitation and biotinylated DNA affinity precipitation experiments. The p53 protein promotes PA28γ transcription, and p53-stimulated transcription of PA28γ can be inhibited by PA28γ itself. Our results suggest that PA28γ and p53 form a negative feedback loop, which maintains the balance of p53 and PA28γ in cells.
Assuntos
Autoantígenos/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Autoantígenos/genética , Células HEK293 , Humanos , Regiões Promotoras Genéticas , Complexo de Endopeptidases do Proteassoma/genética , Ligação Proteica , Interferência de RNA , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/metabolismo , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/genética , Proteínas Recombinantes/farmacologia , Elementos de Resposta/genética , Transcrição Gênica , Proteína Supressora de Tumor p53/antagonistas & inibidores , Proteína Supressora de Tumor p53/genética , Regulação para Cima/efeitos dos fármacosRESUMO
Conventional compost sludge has a long fermentation period and is not nutrient rich. Potassium-rich mining waste was used as an additive for aerobic composting of activated sludge to make a new sludge product. The effects of different feeding ratios of potassium-rich mining waste and activated sludge on the physicochemical properties and thermophilic bacterial community structure during aerobic composting were investigated. The results showed that potassium-rich waste minerals contribute to the increase in mineral element contents; although the addition of potassium-rich waste minerals affected the peak temperature and duration of composting, the more sufficient oxygen content promoted the growth of thermophilic bacteria and thus shortened the overall composting period. Considering the requirements of composting temperature, it is recommended that the addition of potassium-rich waste minerals is less than or equal to 20%.
Assuntos
Compostagem , Temperatura , Potássio , Esgotos/microbiologia , Bactérias , SoloRESUMO
The expression of vascular endothelial growth factor (VEGF) directly correlates with the Mankin score and the degree of cartilage destruction. The biological activity of VEGF on articular cartilage remains unknown, so this study was performed to investigate the effect of VEGF on aggrecan and type II collagen expression in vitro. We carried out this study at the Center Laboratory of Renmin Hospital at Wuhan University. Rat articular chondrocytes were cultured in a monolayer. Then, the experiment was divided into 4 groups: group A (control group), without any disposal; group B, treated with 10 ng/ml VEGF; group C, treated with 10 ng/ml IL-1ß; and group D, treated with 10 ng/ml VEGF + 10 ng/ml IL-1ß. After 48 h, messenger RNA (mRNA) expression of aggrecan and type II collagen was evaluated by real-time polymerase chain reaction (real-Time PCR), and protein expression of aggrecan and type II collagen was detected by Western blotting. VEGF was found to significantly inhibit the expression of aggrecan and type II collagen at the gene and protein levels. These findings suggest that VEGF may result in degeneration of articular cartilage by inhibiting the synthesis and expression of aggrecan and type II collagen.
Assuntos
Agrecanas/metabolismo , Cartilagem Articular/efeitos dos fármacos , Condrócitos/efeitos dos fármacos , Colágeno Tipo II/metabolismo , Fator A de Crescimento do Endotélio Vascular/farmacologia , Agrecanas/genética , Animais , Cartilagem Articular/citologia , Cartilagem Articular/metabolismo , Células Cultivadas , Condrócitos/citologia , Condrócitos/metabolismo , Colágeno Tipo II/genética , Articulação do Joelho/citologia , Articulação do Joelho/efeitos dos fármacos , Articulação do Joelho/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND: Osteoarthritis (OA), caused by the destruction of joint cartilage, is the most prevalent form of arthritis, causing pain and stiffness in joints among millions of patients worldwide. Increasing evidence suggests that non-coding RNAs, including circular RNAs, play important roles in the pathogenesis of OA, but the precise signaling pathway is still unclear. METHODS: To study OA, we established a mouse model by the destabilized medial meniscus (DMM) surgery and used IL-1ß stimulated human cell line C28/I2 as an in vitro study. To further study the role of circSPI1_005 in regulating cell proliferation and apoptosis, EdU staining and FACS-based (fluorescence-activated cell sorting) apoptosis examination were performed after the manipulation of the expression of circSPI1_005. Also, bioinformatics predictions were conducted to analyze the downstream microRNAs of circSPI1_005 and the protein regulated by circSPI1_005. The luciferase assay and the RNA immunoprecipitation (RIP) assay were used to confirm the binding between circSPI1_005 and the predicted microRNA. To verify the role of circSPI1_005 in regulating OA in vivo, we also over-expressed circSPI1_005 by injecting AAV into previously injured knees to improve the OA symptoms. RESULTS: In this study, we found that circSPI1_005 was significantly down-regulated in IL-1ß treated chondrocyte cell lines and cartilage tissues of the OA mouse model. Overexpression of circSPI1_005 ameliorated OA by increasing proliferation and inhibiting apoptosis, and knockdown of circSPI1_005 in chondrocytes mimicked OA phenotypes. Bioinformatics study showed circSPI1_005 could sponge to miR-370-3p, and mechanistic studies confirmed the functional binding between circSPI1_005 and miR-370-3p. Furthermore, we conducted a TargetScan analysis and found that MAP3K9 (mitogen-activated protein kinase kinase kinase 9) could be the downstream protein effector. The expression level of MAP3K9 was regulated by miR-370-3p and overexpression of MAP3K9 could efficiently ameliorate OA. Also, we over-expressed circSPI1_005 in vivo and found that the cartilage surface in the OA mouse model was improved with overexpression of circSPI1_005. CONCLUSIONS: Collectively, circSPI1_005 could sponge to miR-370-3p to regulate the expression of MAP3K9, ameliorating the progression of osteoarthritis.
Assuntos
Cartilagem Articular , MAP Quinase Quinase Quinases/metabolismo , MicroRNAs/metabolismo , Osteoartrite , Animais , Apoptose , Cartilagem Articular/patologia , Condrócitos/metabolismo , Humanos , Interleucina-1beta/metabolismo , Camundongos , MicroRNAs/genética , Osteoartrite/metabolismoRESUMO
Background: Steroid-induced osteonecrosis of the femoral head (SONFH) is a disorder that causes severe disability in patients and has a high incidence worldwide. Although glucocorticoid (GC)-induced apoptosis of osteoblasts is an important cytological basis of SONFH, the detailed mechanism underlying SONFH pathogenesis remains elusive. PI3K/AKT signaling pathway was reported to involve in cell survival and apoptosis. Objective: We explored the role of PI3K/AKT/FOXO1 signaling pathway and its downstream targets during glucocorticoid -induced osteonecrosis of the femoral head. Methods: We obtained gene expression profile of osteoblasts subjected to dexamethasone (Dex) treatment from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were screened out and functional enrichment analysis were conducted by bioinformatics analysis. In vitro, we analyzed Dex-induced apoptosis in MC3T3-E1 cells and explored the role of PI3K/AKT/FOXO1 signaling pathway in this phenomenon by employing siRNA-FOXO1 and IGF-1(PI3K/AKT agonist). Finally, we verified our results in a rat model of SONFH. Results: In Dex-treated osteoblasts, DEGs were mainly enriched in the FOXO signaling pathway. Dex inhibited MC3T3-E1 cell viability in a dose-dependent effect and induced apoptosis by increasing the expression levels of FOXO1, Bax, cleaved-Caspase-3, and cleaved-Caspase-9, while reducing the expression of Bcl-2. Notably, these results were reversed by siRNA-FOXO1 treatment. Dex inhibited PI3K/AKT signaling pathway, upregulated FOXO1 expression and increased FOXO1 nuclear translocation, which were reversed by IGF-1. Compared to normal rats, the femoral head of SONFH showed increased expression of FOXO1, increased number of apoptotic cells, and empty osteocytic lacunas, as well as decreased bone tissue content and femoral head integrity. Significantly, the effects of GC-induced SONFH were alleviated following IGF-1 treatment. Conclusion: Dex induces osteoblast apoptosis via the PI3K/AKT/FOXO1 signaling pathway. Our research offers new insights into the underlying molecular mechanisms of glucocorticoid-induced osteonecrosis in SONFH and proposes FOXO1 as a therapeutic target for this disease.
Assuntos
Glucocorticoides , Osteonecrose , Animais , Ratos , Dexametasona/efeitos adversos , Cabeça do Fêmur/patologia , Proteína Forkhead Box O1/genética , Glucocorticoides/efeitos adversos , Fator de Crescimento Insulin-Like I/farmacologia , Osteonecrose/induzido quimicamente , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Interferente Pequeno/farmacologia , Transdução de SinaisRESUMO
BACKGROUND: Pulsed electromagnetic fields (PEMF) stimulation has been used successfully to treat nonunion fractures and femoral head osteonecrosis, but relatively little is known about its effects on preventing steroid-induced osteonecrosis. The purpose of the study was to investigate the effects of PEMF stimulation on the prevention of steroid-induced osteonecrosis in rats and explore the underlying mechanisms. METHODS: Seventy-two male adult Wistar rats were divided into three groups and treated as follows. (1) PEMF stimulation group (PEMF group, n = 24): intravenously injected with lipopolysaccharide (LPS, 10 µg/kg) on day 0 and intramuscularly injected with methylprednisolone acetate (MPSL, 20 mg/kg) on days 1, 2 and 3, then subjected to PEMF stimulation 4 h per day for 1 to 8 weeks. (2) Methylprednisolone-treated group (MPSL group, n = 24): injected the same dose of LPS and MPSL as the PEMF group but without exposure to PEMF. (3) Control group (PS group, n = 24): injected 0.9% saline in the same mode at the same time points. The incidence of osteonecrosis, serum lipid levels and the mRNA and protein expression of transforming growth factor ß1 (TGF-ß1) in the proximal femur were measured 1, 2, 4 and 8 weeks after the last MPSL (or saline) injection. RESULTS: The incidence of osteonecrosis in the PEMF group (29%) was significantly lower than that observed in the MPSL group (75%), while no osteonecrosis was observed in the PS group. The serum lipid levels were significantly lower in the PEMF and PS groups than in the MPSL group. Compared with the MPSL and PS groups, the mRNA expression of TGF-ß1 increased, reaching a peak 1 week after PEMF treatment, and remained high for 4 weeks, then declined at 8 weeks, whereas the protein expression of TGF-ß1 increased, reaching a peak at 2 weeks after PEMF treatment, and remained high for 8 weeks. CONCLUSIONS: PEMF stimulation can prevent steroid-induced osteonecrosis in rats, and the underlying mechanisms involve decreased serum lipid levels and increased expression of TGF-ß1.
Assuntos
Campos Eletromagnéticos , Magnetoterapia/métodos , Osteonecrose/radioterapia , Animais , Modelos Animais de Doenças , Expressão Gênica/efeitos da radiação , Glucocorticoides/farmacologia , Injeções Intravenosas , Lipídeos/sangue , Lipopolissacarídeos/farmacologia , Masculino , Metilprednisolona/análogos & derivados , Metilprednisolona/farmacologia , Acetato de Metilprednisolona , Osteonecrose/induzido quimicamente , Osteonecrose/metabolismo , Tratamento por Radiofrequência Pulsada , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismoRESUMO
OBJECTIVE: To evaluate the effect of human umbilical cord mesenchymal stem cells (hUC-MSCs) on preventing rats from glucocorticoid-induced osteonecrosis of femoral head (GCONFH) in the early stage in vivo and to investigate the possible mechanism of hUC-MSCs in regulating the balance of osteogenesis and adipogenesis. METHODS: All rats were randomly divided into 3 groups: control group (C group), model group (M group), and intervention group (I group). The model of GC-ONFH was developed by a sequential administration of lipopolysaccharide and methylprednisolone. The rats in the I group were treated with caudal vein injection of hUC-MSCs. Six weeks later, the blood samples were obtained to measure the activity of alkaline phosphatase (ALP) and the content of triglyceride (TG) in serum, and the femoral heads were harvested and observed by hematoxylin-eosin staining, Micro-CT, Western blot and real-time quantitative polymerase chain reaction. RESULTS: After intervention of hUC-MSCs, the necrosis rate of femoral head decreased from 83% (10/12) to 33% (4/12), the rate of empty bone lacuna was significantly decreased, the activity of ALP increased significantly, the content of TG decreased significantly, the bone density increased obviously, the expression of RUNX2 and Col I increased significantly and the expression of PPARγ decreased significantly. CONCLUSION: These results revealed that caudal vein injection of hUC-MSCs can effectively reduce the incidence of GC-ONFH in rats by increasing ALP activity and reducing TG content in serum, increasing bone mineral density, promoting the expression of RUNX2 and Col I, and inhibiting the expression of PPARγ.
Assuntos
Necrose da Cabeça do Fêmur/terapia , Glucocorticoides/efeitos adversos , Transplante de Células-Tronco Mesenquimais/métodos , Cordão Umbilical/citologia , Animais , Células Cultivadas , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Necrose da Cabeça do Fêmur/induzido quimicamente , Necrose da Cabeça do Fêmur/metabolismo , Necrose da Cabeça do Fêmur/patologia , Humanos , Masculino , Células-Tronco Mesenquimais/citologia , PPAR gama/genética , PPAR gama/metabolismo , Distribuição Aleatória , Ratos , Resultado do Tratamento , Triglicerídeos/sangue , Regulação para CimaRESUMO
BACKGROUND: Osteoarthritis (OA) and rheumatoid arthritis (RA) are well-known cause of joint disability. Although they have shown the analogous clinical features involving chronic synovitis that progresses to cartilage and bone destruction, the pathogenesis that initiates and perpetuates synovial lesions between RA and OA remains elusive. OBJECTIVE: This study is aimed at identifying disease-specific hub genes, exploring immune cell infiltration, and elucidating the underlying mechanisms associated with RA and OA synovial lesion. METHODS: Gene expression profiles (GSE55235, GSE55457, GSE55584, and GSE12021) were selected from Gene Expression Omnibus for analysis. Differentially expressed genes (DEGs) were identified by the "LIMMA" package in Bioconductor. The DEGs were identified by Gene Ontology (GO) and KEGG pathway analysis. A protein-protein interaction network was constructed to identify candidate hub genes by using STRING and Cytoscape. Hub genes were identified by validating from GSE12021. Furthermore, we employed the CIBERSORT website to assess immune cell infiltration between OA and RA. Finally, we explored the correlation between the levels of hub genes and relative proportion of immune cells in OA and RA. RESULTS: We identified 68 DEGs which were mainly enriched in immune response and chemokine signaling pathway. Six hub genes with a cutoff of AUC > 0.80 by ROC analysis and relative expression of P < 0.05 were identified successfully. Compared with OA, the RA synovial tissues consisted of a higher proportion of 7 immune cells, whereas 4 immune cells were found in relatively lower proportion (P < 0.05). In addition, the levels of 6 hub genes were closely associated with relative proportion of 11 immune cells in OA and RA. CONCLUSIONS: We used bioinformatics analysis to identify hub genes and explored immune cell infiltration of immune microenvironment in synovial tissues. Our results should offer insights into the underlying molecular mechanisms of synovial lesion and provide potential target for immune-based therapies of OA and RA.
Assuntos
Artrite Reumatoide/genética , Artrite Reumatoide/imunologia , Osteoartrite/genética , Osteoartrite/imunologia , Membrana Sinovial/imunologia , Transcriptoma , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/metabolismo , Biomarcadores/metabolismo , Quimiocinas/metabolismo , Biologia Computacional , Bases de Dados Genéticas , Perfilação da Expressão Gênica , Marcadores Genéticos , Humanos , Leucócitos/imunologia , Leucócitos/metabolismo , Sistema Fagocitário Mononuclear/imunologia , Sistema Fagocitário Mononuclear/metabolismo , Osteoartrite/diagnóstico , Osteoartrite/metabolismo , Mapas de Interação de Proteínas/genética , Curva ROC , Membrana Sinovial/metabolismoRESUMO
BACKGROUND: Cervical cancer remains a major public health issue for the Uyghur women and other women living mainly in rural areas of Xinjiang. This study aims to investigate the distribution of human papillomavirus (HPV) infection and cervical cancer in rural areas of Xinjiang, China. METHODS: Cervical cancer screening was performed on rural women aged 35 to 64 years from Xinjiang, China in 2017 through gynecological examination, vaginal discharge smear microscopy, cytology, and HPV testing. If necessary, colposcopy and biopsy were performed on women with suspicious or abnormal screening results. RESULTS: Of the 216,754 women screened, 15,518 received HPV testing. The HPV-positive rate was 6.75% (1047/15,518). Compared with the age 35-44 years group, the odds ratios (ORs) of HPV positivity in the age 45-54 years and 55-64 years groups were 1.18 (95% confidence interval [CI]: 1.02-1.37) and 1.84 (95% CI: 1.53-2.21), respectively. Compared with women with primary or lower education level, the ORs for HPV infection rates of women with high school and college education or above were 1.37 (95% CI: 1.09-1.72) and 1.62 (95% CI: 1.23-2.12), respectively. Uyghur women were less likely to have HPV infection than Han women, with an OR (95% CI) of 0.78 (0.61-0.99). The most prevalent HPV types among Xinjiang women were HPV 16 (24.00%), HPV 33 (12.70%), and HPV 52 (11.80%). The detection rate of cervical intraepithelial neoplasia (CIN)2+ was 0.14% and the early diagnosis rate of cervical cancer was 85.91%. The detection rates of vaginitis and cervicitis were 19.28% and 21.32%, respectively. CONCLUSIONS: The HPV infection rate in Xinjiang is low, but the detection rate of cervical cancer and precancerous lesions is higher than the national average level. Cervical cancer is a prominent public health problem in Xinjiang, especially in southern Xinjiang.
Assuntos
Alphapapillomavirus , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Adulto , China/epidemiologia , Detecção Precoce de Câncer , Feminino , Humanos , Pessoa de Meia-Idade , Papillomaviridae/genética , Infecções por Papillomavirus/epidemiologia , População Rural , Neoplasias do Colo do Útero/epidemiologiaRESUMO
OBJECTIVE: Nitric oxide is an important mediator in Osteoarthritis (OA), and causes apoptosis and dedifferentiation in articular chondrocytes. Protein kinase Calpha is involved in modulating apoptosis and dedifferentiation of articular chondrocytes induced by nitric oxide. Hyaluronic acid is widely used in the treatment of osteoarthritis and exerts significant chondroprotective effects. The exact mechanisms of its chondroprotective action are not yet fully elucidated. The present study was performed to investigate the effects and mechanisms of hyaluronic acid in NO-induced apoptosis and dedifferentiation of chondrocytes. METHODS: The ratio of apoptotic cell and cell viability was surveyed by TUNEL, MTT assay and flow cytometry. The expression of aggrecan, type II collagen, and PKCalpha were determined by real-time PCR and Western blot. The expression changes of caspase-3 and bcl-2 was detected by Western blot. The mitochondrial membrane potential (DeltaPsim) was evaluated by Rhodamine-123 fluorescence. RESULTS: HA reduces the TUNEL positive cell, nuclei fragment and the impairment of DeltaPsim. NO-induced chondrocyte dedifferentiation was blocked by HA, which restores expression of aggrecan and type II collagen of chondrocytes and cell viability. HA can block inhibition of PKC-alpha by NO. CONCLUSION: Our results show that HA blocks NO-induced apoptosis and dedifferentiation of articular chondrocytes by modulation of DeltaPsim and PKCalpha.
Assuntos
Apoptose/efeitos dos fármacos , Cartilagem Articular/citologia , Desdiferenciação Celular/efeitos dos fármacos , Condrócitos/efeitos dos fármacos , Condrócitos/fisiologia , Ácido Hialurônico/farmacologia , Óxido Nítrico/farmacologia , Agrecanas/metabolismo , Animais , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/ultraestrutura , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Condrócitos/citologia , Colágeno Tipo II/metabolismo , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Doadores de Óxido Nítrico/farmacologia , Nitroprussiato/farmacologia , Osteoartrite/imunologia , Osteoartrite/patologia , Osteoartrite/fisiopatologia , Proteína Quinase C-alfa/antagonistas & inibidores , Proteína Quinase C-alfa/metabolismo , Ratos , Ratos WistarRESUMO
BACKGROUND: Little is known about the expression of vascular endothelial growth factor (VEGF) and its receptor-2 (VEGFR-2) mRNA in the cartilage of a rabbit osteoarthritis model or the influence of intraarticular injection of hyaluronan (HA) on the expression of VEGF and VEGFR-2 in cartilage during the process of osteoarthritis (OA). The therapeutic mechanism of HA is not completely understood, and we hypothesize that the mechanism is through the effects of VEGF and VEGFR2. In this study, we determined the VEGF and VEGFR-2 mRNA expression in a rabbit OA model and assessed the therapeutic mechanism of HA against OA. METHODS: We carried out this study at the Center Laboratory of Renmin Hospital at Wuhan University and the Key Laboratory of Respiratory Disease of the Ministry of Public Health, Huazhong University of Science and Technology. Between October 2006 and April 2008 a total of 24 mature New Zealand white rabbits were divided into three groups: normal controls, a no-HA group, and an HA group. The no-HA and HA groups underwent unilateral anterior cruciate ligament transection. At 4 weeks after the operation, animals in the HA group received intraarticular injections of 1% sodium hyaluronate (HA) once a week for 5 weeks as per the clinical treatment presently utilized. The no-HA rabbits were not given HA. At death, 11 weeks following surgery, cartilage was harvested and total RNA was extracted. VEGF and VEGFR mRNAs were analyzed using the reverse transcription-polymerase chain reaction (RT-PCR) and real-time PCR for each group. RESULTS: Cartilage damage (both extent and grade) was less severe in the HA group than in the no-HA group. VEGF and VEGFR-2 mRNA expression was enhanced in the cartilage of the OA model. Intraarticular 1% sodium hyaluronate injection inhibited VEGFR-2 expression but had no effect on reducing the VEGF mRNA expression in cartilage. CONCLUSIONS: These results suggested that VEGF and VEGFR-2 may be involved in the progression of OA and in the therapeutic mechanism of HA at least partly through the influence of VEGFR-2 expression during the development of OA.
Assuntos
Cartilagem Articular/efeitos dos fármacos , Ácido Hialurônico/farmacologia , Osteoartrite/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Viscossuplementos/farmacologia , Animais , Cartilagem Articular/metabolismo , Regulação para Baixo , Osteoartrite/metabolismo , RNA Mensageiro/metabolismo , Coelhos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator A de Crescimento do Endotélio Vascular/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genéticaRESUMO
MicroRNA (miRNA) is known to be involved in regulating the proliferation, migration and apoptosis of cancer cells in osteosarcoma. In this study, We aim to explore the expression of hsa-let-7 g and its role in pathogenesis of osteosarcoma. By analyzing clinical data. We found high expression of hsa-let-7 g in patients with osteosarcoma. The patients with higher expression of hsa-let-7 g showed poorer prognosis and lower survival rate. After downregulation of hsa-let-7 g in cell model and animal model, we found that with downregulation of hsa-let-7 g, the proliferation of osteosarcoma cells was significantly reduced, the level of migration and invasion was down-regulated, the cell cycle was inhibited, and cell apoptosis was increased. Through Dual Luciferase Reporter, immunohistochemistry, western blot and other experiments, it was found that hsa-let-7 g down-regulated HOXB1 gene and activated NF-kB pathway to promote the development of osteosarcoma. In conclusion, hsa-let-7 g is highly expressed in osteosarcoma tissues, and high expression of hsa-let-7 g can promote the occurrence of osteosarcoma by down-regulating HOXB1 and activating NF-kB pathway.
Assuntos
Neoplasias Ósseas/metabolismo , Proteínas de Homeodomínio/metabolismo , MicroRNAs/biossíntese , NF-kappa B/metabolismo , Osteossarcoma/metabolismo , Adolescente , Animais , Neoplasias Ósseas/patologia , Feminino , Proteínas de Homeodomínio/antagonistas & inibidores , Humanos , Masculino , Camundongos Nus , Osteossarcoma/patologia , Células Tumorais Cultivadas , Adulto JovemRESUMO
We identified potassium channel tetramerization domain-containing 1 (KCTD1) gene in a human brain cDNA library. Here, we report that the KCTD1 gene contains seven exons, encoding 257 amino acid residues with a predicted molecular mass of 29.4 kDa. Sequence alignments showed KCTD1 protein contains an N-terminal broad-complex, tramtrack, and bric-a-brac (BTB) domain. Northern blot analysis revealed that KCTD1 is expressed in the mammary gland, kidney, brain, and ovary compared to other tissues. Further, the subcellular localization results showed that KCTD1 is localized in the nuclei of HeLa and HBL100 cells. Reporter gene assays in HEK293FT and NIH3T3 cells further indicated that KCTD1 acts as a potent transcriptional repressor and inhibits the transcriptional activity via its BTB domain, though KCTD1 transcriptional repression is unaffected by the HDAC inhibitors, trichostatin A, and sodium butyrate. Finally, we found that the BTB domain of KCTD1 mediates homomeric protein-protein interactions by co-immunoprecipitation and GST pull-down assays. These data present the first characterization of human KCTD1 and suggest that KCTD1 is a nuclear protein that functions as a transcriptional repressor and mediates protein-protein interactions through a BTB domain.
Assuntos
Proteínas Nucleares/genética , Proteínas Repressoras/genética , Transcrição Gênica , Sequência de Aminoácidos , Animais , Northern Blotting , Western Blotting , Núcleo Celular/metabolismo , Células Cultivadas , Clonagem Molecular , Proteínas Correpressoras , Éxons/genética , Imunofluorescência , Humanos , Imunoprecipitação , Masculino , Dados de Sequência Molecular , Proteínas Nucleares/imunologia , Proteínas Nucleares/metabolismo , Ligação Proteica , Estrutura Terciária de Proteína , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Coelhos , Proteínas Repressoras/imunologia , Proteínas Repressoras/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Homologia de Sequência de AminoácidosRESUMO
OBJECTIVE: To compare the clinical efficacy of percutaneous vertebroplasty (PVP) with percutaneous kyphoplasty (PKP) in the treatment of vertebral compression fracture (VCF). METHODS: Ninety-eight patients with VCF were treated by PVP (n=42) or PKP (n=56). The anterior midline and posterior heights of vertebrae body, preoperative and postoperative visual analogue scale (VAS), operation time and amount of blood loss were compared between 2 groups. RESULTS: There was statistical difference in vertebral height between two groups (P < 0.01). No significant difference was seen in VAS, operation time and blood loss between two groups (P < 0.05). CONCLUSIONS: PKP and PVP have the similar therapeutic efficacy in treatment of VCF with minimal invasion, less operation time and blood loss. However, PKP is superior in the recovery of vertebral height.
Assuntos
Fraturas por Compressão/cirurgia , Fraturas da Coluna Vertebral/cirurgia , Vertebroplastia/métodos , Adulto , Idoso , Cimentos Ósseos , Feminino , Humanos , Injeções , Masculino , Pessoa de Meia-IdadeRESUMO
Glucocorticoids intake has become the most common pathogenic factor for osteonecrosis of the femoral head (ONFH). Annually, tens of millions of patients suffer from pain related to ONFH. Researchers have proposed several underlying mechanisms of ONFH, including osteocyte apoptosis, cell differentiation disorder, and angiogenesis hindrance. Sesamin, isolated from Sesamum indicum seeds, was reported could affect osteocyte inflammation and differentiation in osteoarthritis and osteoporosis. We investigated the underlying influence of sesamin on ONFH rat model. Fifteen male Sprague-Dawley rats were randomly divided into three groups. The ONFH model group only received the methylprednisolone (MPS) and lipopolysaccharide (LPS) injection to promote the development of ONFH. The sesamin treatment group was injected with sesamin, MPS, and LPS. The control group was untreated. Rats from above groups were sacrificed 4 weeks later. The effect of sesamin on ONFH rats was validated by H&E staining. TUNEL staining showed that femoral head necrosis was attenuated by sesamin. Furthermore, the phosphorylation of Akt was increased and the downstream cellular apoptosis signal pathway was inhibited. Intracellular ROS level was decreased after sesamin treatment. In conclusion, our findings suggest that sesamin protects the femoral head from osteonecrosis by inhibiting ROS-induced osteoblast apoptosis.
RESUMO
In the pathophysiology of osteoarthritis (OA), articular cartilage degeneration exhibits a significant role. Vascular endothelial growth factor (VEGF) is considered to be an effective angiogenic factor and a crucial regulator of articular cartilage degeneration in the development of OA. Therefore, the present study aimed to investigate the underlying influences of exogenous VEGF on articular cartilage degeneration in OA model rat. A total of 24 male SpragueDawley rats were randomly allocated into 3 groups. In the normal saline (NS) and VEGF groups, animals received bilateral anterior cruciate ligament (ACL) transection to establish the OA model; at 4 weeks postsurgery, the rats received local intraarticular injections of 100 µl NS or VEGF solution, respectively, every week for 4 weeks. The Control group received neither surgery nor injections. All animals were sacrificed at 12 weeks following surgery. Prominent cartilage degeneration was observed in rats in the NS and VEGFinjected groups. The extent and the grade of cartilage damage in the VEGFinjected group were notably more severe compared with those in the NStreated group. Western blotting results demonstrated that the expression levels of aggrecan and type II collagen were significantly reduced in OA model rats that were treated with VEGF. In addition, the expression levels of matrix metalloproteinase (MMP)3, MMP9, MMP13, a disintegrin and metalloproteinase with thrombospondin motifs (a disintegrin and metalloproteinase; ADAMTS)4, 5 and 12, type III collagen and transforming growth factorß1 were significantly increased following VEGF administration. Results from the present study indicated that VEGF may exhibit a promoting role in the development of OA by destroying articular cartilage matrix.