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To explore the action mechanism of berberine in improving adipocytic insulin resistance(IR) by mediating brain and muscle arnt-like 1(BMAL1): circadian locomotor output cycles kaput(CLOCK) complex and regulating glucose and lipid metabolism. After the IR-3T3-L1 adipocyte model was established by dexamethasone induction for 96 h, 0.5, 1, 5, 10, and 20 µmol·L~(-1) berberine was administered for 24 h. The glucose oxidase method and cell counting kit-8(CCK-8) were used to detect extracellular glucose content and cell viability, respectively. The triglyceride(TG) and glycerol contents were detected by enzyme colorimetry. Oil red O staining was used to detect lipid droplets, and fluorescence staining was used to detect Ca~(2+), mitochondrial structure, and reactive oxygen species(ROS). Adiponectin(ADPN), BMAL1, CLOCK, hormone-sensitive triglyceride lipase(HSL), carbohydrate-response element-binding protein(ChREBP), sterol regulatory element-binding protein 1C(SREBP-1C), peroxisome proliferator-activated receptor γ coactivator 1α(PGC1α), carnitine palmitoyl transferase 1α(CPT1α), and peroxisome proliferator-activated receptor α(PPARα) were detected by Western blot(WB). Moreover, the nuclear localization of BMAL1 was detected by immunofluorescence. In addition, 20 µmol·L~(-1) CLK8 inhibitor was added to detect glucose consumption and BMAL1/ChREBP/PPARα protein. The results showed that berberine increased glucose consumption in IR-3T3-L1 adipocytes without affecting cell viability and reduced TG content. In addition, 5 µmol·L~(-1) berberine increased glycerol content and reduced lipid droplet accumulation due to enhanced lipolysis, while 10 µmol·L~(-1) berberine did not affect glycerol content, and fewer lipid droplets were observed due to enhanced lipolysis and glycerol utilization. Berberine improved mitochondrial function by reducing intracellular Ca~(2+) and ROS in IR-3T3-L1 adipocytes and upregulated PGC1α to improve the mitochondrial structure. The results also showed that berberine elevated ADPN to increase the insulin sensitivity of IR-3T3-L1 adipocytes, upregulated peripheral rhythm-related proteins BMAL1 and CLOCK, and strengthened the nuclear localization of BMAL1. In addition, berberine increased key lipolysis protein and lipid oxidation rate-limiting enzyme CPT1α and downregulated the key protein of TG synthesis, SREBP-1C. Moreover, ChREBP and PPARα in IR-3T3-L1 adipocytes were upregula-ted. All the above results suggested that berberine may transform glucose into lipids to enhance the hypoglycemic effect. By considering that CLK8 specifically inhibited the CLOCK acylation to modify BMAL1 and form complex, the results showed that the addition of CLK8 to the berberine group reduced glucose consumption, which suggested that berberine upregulated the formation of BMAL1:CLOCK complex to improve glucose metabolism. The addition of CLK8 to the berberine group upregulated BMAL1 but downregulated ChREBP and PPARα, which suggested that berberine mediated BMAL1:CLOCK complex for the regulation of glucose and lipid metabo-lism to improve adipocytic IR.
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Células 3T3-L1 , Factores de Transcripción ARNTL , Adipocitos , Berberina , Proteínas CLOCK , Glucosa , Resistencia a la Insulina , Metabolismo de los Lípidos , Animales , Ratones , Metabolismo de los Lípidos/efectos de los fármacos , Factores de Transcripción ARNTL/genética , Factores de Transcripción ARNTL/metabolismo , Berberina/farmacología , Adipocitos/metabolismo , Adipocitos/efectos de los fármacos , Adipocitos/citología , Glucosa/metabolismo , Proteínas CLOCK/genética , Proteínas CLOCK/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Triglicéridos/metabolismoRESUMEN
BACKGROUND: Hyperuricemia can lead to synovial hyperplasia in the wrist. In severe cases, it can lead to the deposition of gouty stone in the carpal tunnel, resulting in increased pressure in the carpal tunnel and compression of the median nerve to cause carpal tunnel syndrome (CTS), which is called gouty carpal tunnel syndrome (GCTS). As for the surgical treatment of gouty carpal tunnel syndrome, scholars have different opinions on whether it is necessary to remove the superficial flexor tendon. The purpose of this study was to compare the clinical efficacy of trimming and resection of the diseased superficial flexor tendon in the treatment of gouty carpal tunnel syndrome. METHODS: Clinical data were collected from May 2016 to July 2021 from 10 patients (13 affected wrists) diagnosed with gouty carpal tunnel syndrome and classified into two groups according to the surgical modality: the diseased portion of the gout-eroded superficial finger tendon was trimmed in 9 wrists, and the diseased superficial finger flexor tendon was excised in 4 wrists. Values related to flexion and extension functions, 2-PD, DASH, BCTQ, VAS and recurrence in the affected fingers were compared between the two groups as well as before and after surgery in each group. RESULTS: All affected limbs used were cleared of gouty stones, finger numbness improved, no skin necrosis occurred, and all incisions healed at stage I. At follow-up (13.58 ± 5.53 months), there was no significant difference between groups in flexion and extension function, 2-PD, DASH, BCTQ, and VAS with respect to the affected fingers, and patients in both groups improved significantly before and after surgery. Treatment of only one wrist involved trimming to remove lesion-affected portions of tendon, which reappeared 1 year after surgery, and there was one case of poor recovery from greater piriformis muscle atrophy in both procedures. CONCLUSION: Regarding surgical treatment of patients with gouty carpal tunnel syndrome in which the gouty stone has invaded the superficial flexor tendons of the fingers, the diseased superficial flexor tendons can be selectively excised, and the postoperative mobility of the affected fingers may not be impaired.
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Síndrome del Túnel Carpiano , Gota , Humanos , Dedos , Muñeca , Gota/complicaciones , Gota/cirugía , Tendones/cirugía , Tendones/fisiologíaRESUMEN
This study investigated the mechanism of Gegen Qinlian Decoction(GQD) in improving glucose metabolism in vitro and in vivo by alleviating endoplasmic reticulum stress(ERS). Molecular docking was used to predict the binding affinity between the main effective plasma components of GQD and ERS-related targets. Liver tissue samples were obtained from normal rats, high-fat-induced diabetic rats, rats treated with metformin, and rats treated with GQD. RNA and protein were extracted. qPCR was used to measure the mRNA expression of ERS marker glucose-regulated protein 78(GRP78), and unfolded protein response(UPR) genes inositol requiring enzyme 1(Ire1), activating transcription factor 6(Atf6), Atf4, C/EBP-homologous protein(Chop), and caspase-12. Western blot was used to detect the protein expression of GRP78, IRE1, protein kinase R-like ER kinase(PERK), ATF6, X-box binding protein 1(XBP1), ATF4, CHOP, caspase-12, caspase-9, and caspase-3. The calcium ion content in liver tissues was determined by the colorimetric assay. The ERS-HepG2 cell model was established in vitro by inducing with tunicamycin for 6 hours, and 2.5%, 5%, and 10% GQD-containing serum were administered for 9 hours. The glucose oxidase method was used to measure extracellular glucose levels, flow cytometry to detect cell apoptosis, glycogen staining to measure cellular glycogen content, and immunofluorescence to detect the expression of GRP78. The intracellular calcium ion content was measured by the colorimetric assay. Whereas Western blot was used to detect GRP78 and ERS-induced IRE1, PERK, ATF6, and eukaryotic translation initiation factor 2α(eIF2α) phosphorylation. Additionally, the phosphorylation levels of insulin receptor substrate 1(IRS1), phosphatidylinositol 3-kinase regulatory subunit p85(PI3Kp85), and protein kinase B(Akt), which were involved in the insulin signaling pathway, were also measured. In addition, the phosphorylation levels of c-Jun N-terminal kinases(JNKs), which were involved in both the ERS and insulin signaling pathways, were measured by Western blot. Molecular docking results showed that GRP78, IRE1, PERK, ATF4, and various compounds such as baicalein, berberine, daidzein, jateorhizine, liquiritin, palmatine, puerarin and wogonoside had strong binding affinities, indicating that GQD might interfere with ERS-induced UPR. In vivo results showed that GQD down-regulated the mRNA transcription of Ire1, Atf6, Atf4, Grp78, caspase-12, and Chop in diabetic rats, and down-regulated GRP78, IRE1, PERK, as well as ERS-induced apoptotic factors ATF4 and CHOP, caspase-12, caspase-9, and caspase-3, while up-regulating XBP1 to enhance adaptive UPR. In addition, GQD increased the calcium ion content in liver tissues, which facilitated correct protein folding. In vitro results showed that GQD increased glucose consumption in ERS-induced HepG2 cells without significantly affecting cell viability, increased liver glycogen synthesis, down-regulated ATF6 and p-eIF2α(Ser51), and down-regulated IRE1, PERK, and GRP78, as well as p-IRS1(Ser312) and p-JNKs(Thr183/Tyr185), while up-regulating p-PI3Kp85(Tyr607) and p-Akt(Ser473). These findings suggested that GQD alleviates excessive ERS in the liver, reduces insulin resistance, and improves hepatic glucose metabolism in vivo and in vitro.
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Diabetes Mellitus Experimental , Proteínas Proto-Oncogénicas c-akt , Ratas , Animales , Chaperón BiP del Retículo Endoplásmico , Caspasa 3 , Caspasa 9 , Caspasa 12 , Calcio/farmacología , Simulación del Acoplamiento Molecular , Estrés del Retículo Endoplásmico , Proteínas Serina-Treonina Quinasas/genética , Hígado , Apoptosis , Insulina , Glucosa , Glucógeno/farmacología , ARN MensajeroRESUMEN
BACKGROUND: Laparoscopic adrenalectomy for pheochromocytoma is associated with high risk of intraoperative hemodynamic instability. Our study aimed to identify predictive factors for hemodynamic instability during laparoscopic resection of pheochromocytoma. METHODS: Between January 2011 and December 2021, 136 patients underwent unilateral laparoscopic adrenalectomy for pheochromocytoma. The patients were divided into 2 groups depending on the presence or absence of hemodynamic instability during surgery. Intraoperative hemodynamic parameters were compared between the 2 groups. Patient demographic characteristics and preoperative evaluations were assessed for their prognostic relevance with respect to intraoperative hemodynamic instability via both univariate analysis and multivariate logistic regression analysis. RESULTS: There was greater blood pressure fluctuations and higher maximum blood pressure and heart rate in the hemodynamic instability group. More patients need intraoperative administration of vasoactive drugs in the hemodynamic instability group. In the univariate analysis, presence of coronary artery disease, tumour size, and previous hypertension history were significantly associated with intraoperative hemodynamic instability. The multivariate logistic regression analysis showed that tumour size and previous hypertension history were independent risk factors for intraoperative hemodynamic instability. CONCLUSION: Tumour size and previous hypertension history were associated with hemodynamic instability during laparoscopic resection of pheochromocytoma.
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Neoplasias de las Glándulas Suprarrenales , Hipertensión , Laparoscopía , Feocromocitoma , Neoplasias de las Glándulas Suprarrenales/cirugía , Adrenalectomía/efectos adversos , Adrenalectomía/métodos , Hemodinámica , Humanos , Hipertensión/etiología , Laparoscopía/efectos adversos , Laparoscopía/métodos , Feocromocitoma/complicaciones , Feocromocitoma/cirugía , Estudios Retrospectivos , Factores de RiesgoRESUMEN
T-helper (Th) 22 cells serve an essential role in different types of tumors and autoimmune diseases. No research has been conducted to study the role of Th22 cells in the pathogenesis of renal cell carcinoma (RCC). We aimed to evaluate the prognostic value of circulating Th22, Th17, and Th1 cells in RCC patients. Thirty-two newly diagnosed RCC patients and thirty healthy controls were enlisted in the research. Their peripheral blood was collected, and the frequencies of circulating Th22, Th17, and Th1 cells were detected by flow cytometry. Plasma IL-22 concentrations were examined by an enzyme-linked immunosorbent assay (ELISA). Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to identify the mRNA expression levels of aromatic hydrocarbon receptor (AHR) and RAR-associated orphan receptor C (RORC) in peripheral blood mononuclear cells (PBMC). Compared with the healthy control group, the frequency of circulating Th22 and Th17 cells and concentrations of plasma IL-22 were significantly increased in RCC patients. However, there was no significant difference in the frequency of Th1 cells. A positive correlation between Th22 cells and plasma IL-22 levels was found in RCC patients. Also, there was a significant positive correlation between Th22 and Th17 cells in RCC patients. An up-regulated expression of AHR and RORC transcription factors were also observed in RCC patients. As tumor stage and grade progressed, the frequencies of Th22 and Th17 cells and the level of plasma IL-22 significantly increased. Meanwhile, there was a positive correlation between Th22 and Th17 cells and RCC tumor stage or grade. Furthermore, patients with high Th22 or Th17 cells frequency displayed a decreased trend in survival rate. Our research indicated that the increased circulating Th22 and Th17 cells and plasma IL-22 may be involved in the pathogenesis of RCC and may be involved in the occurrence and development of tumors. Th22 cells, plasma IL-22, and Th17 cells may be promising new clinical biomarkers and may be used as cellular targets for RCC therapeutic intervention.
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Carcinoma de Células Renales/diagnóstico , Interleucinas/metabolismo , Neoplasias Renales/diagnóstico , Subgrupos de Linfocitos T/inmunología , Células Th17/inmunología , Adulto , Carcinoma de Células Renales/sangre , Carcinoma de Células Renales/inmunología , Carcinoma de Células Renales/cirugía , Estudios de Casos y Controles , Progresión de la Enfermedad , Femenino , Voluntarios Sanos , Humanos , Interleucinas/sangre , Neoplasias Renales/sangre , Neoplasias Renales/inmunología , Neoplasias Renales/cirugía , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Nefrectomía , Periodo Preoperatorio , Subgrupos de Linfocitos T/metabolismo , Células TH1/inmunología , Células TH1/metabolismo , Adulto Joven , Interleucina-22RESUMEN
INTRODUCTION: Myocardial bridging (MB) is a common and usually benign inborn coronary abnormality that may lead to anginal symptoms, acute coronary syndrome, arrhythmias, and rarely sudden cardiac death. MB are most commonly localized in the middle segment of the left anterior descending coronary artery (LAD). The treatment of LAD-MB is still challenging. Our objective was to assess the short- and long-term results of surgical procedures in patients with LAD-MB who had chest pain refractory to medical therapy. METHODS: Between March 2005 and January 2020, 26 patients (19 males and 7 females; mean 55.8 ± 12.4 years) with MB underwent surgery. All MB was located in the mid-segment of the LAD with a mean length of 4.2 ± 1.7 cm. Coronary angiography before surgery demonstrated LAD-MB with systolic compression more than or equal to 70% in all patients. RESULTS: Twenty-five patients underwent myotomy and one patient underwent coronary artery bypass grafting (CABG). All patients survived and recovered uneventfully. Neither hospital or late death nor major complications occurred. Follow-up time was 3-173 months (mean 55.7 months). Follow-up of coronary angiography or computed tomography scan performed in 16 patients demonstrated restoration of coronary blood flow and myocardial perfusion without significant residual compression of the artery. All patients were symptom-free and are currently in NYHA Class I. CONCLUSION: The symptomatic LAD-MB patients who are refractory to medication should actively undergo the surgical intervention such as myotomy and CABG to eliminate the clinical symptoms and achieve satisfactory results by follow-up findings. Myotomy is a preferred procedure because of its safety and satisfactory results.
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Puente Miocárdico , Dolor en el Pecho , Angiografía Coronaria , Puente de Arteria Coronaria , Femenino , Humanos , Masculino , Puente Miocárdico/cirugía , Resultado del TratamientoRESUMEN
BACKGROUND: There is a lack of data regarding the appropriateness of transperitoneal and retroperitoneal approaches for homolateral laparoscopic adrenalectomy. The aim of this study is to compare lateral transperitoneal and retroperitoneal approach for left-sided and right-sided laparoscopic adrenalectomy respectively. METHODS: Between January 2014 and December 2019, 242 patients underwent left-sided and 252 patients underwent right-sided laparoscopic adrenalectomy. For left side, transperitoneal approach was used in 132 (103 with tumors < 5 cm and 29 with tumors ≥ 5 cm) and retroperitoneal approach in 110 (102 with tumors < 5 cm and 8 with tumors ≥ 5 cm). For right side, transperitoneal approach was used in 139 (121 with tumors < 5 cm and 18 with tumors ≥ 5 cm) and retroperitoneal approach in 113 (102 with tumors < 5 cm and 11 with tumors ≥ 5 cm). Patient characteristics and perioperative outcomes were recorded. For each side, both approaches were compared for tumors < 5 cm and ≥ 5 cm respectively. RESULTS: For left-sided tumors < 5 cm, transperitoneal approach demonstrated shorter operative time, less blood loss and longer time to oral intake. For left-sided tumors ≥ 5 cm, the peri-operative data of both approaches was comparable. For right-sided tumors < 5 cm, transperitoneal approach demonstrated shorter operative time and less blood loss. For right-sided tumors ≥ 5 cm, the peri-operative data was comparable. CONCLUSIONS: Lateral transperitoneal and retroperitoneal approach are both effective for laparoscopic adrenalectomy. Lateral transperitoneal approach is faster with less blood loss for tumors < 5 cm.
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Adrenalectomía , Laparoscopía , HumanosRESUMEN
Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney tumor. Previous studies have shown that the interaction between tumor cells and microenvironment has an important impact on prognosis. Immune and stromal cells are two vital components of the tumor microenvironment. Our study aimed to better understand and explore the genes involved in immune/stromal cells on prognosis. We used the Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data algorithm to calculate immune/stromal scores. According to the scores, we divided ccRCC patients from The Cancer Genome Atlas database into low and high groups and identified the genes which were differentially expressed and significantly associated with prognosis. The result of functional enrichment analysis and protein-protein interaction networks indicated that these genes mainly were involved in extracellular matrix and regulation of cellular activities. Then another independent cohort from the International Cancer Genome Consortium database was used to validate these genes. Finally, we acquired a list of microenvironment-related genes that can predict prognosis for ccRCC patients.
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Adenocarcinoma de Células Claras/diagnóstico , Adenocarcinoma de Células Claras/genética , Carcinoma de Células Renales/diagnóstico , Carcinoma de Células Renales/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Renales/diagnóstico , Neoplasias Renales/genética , Algoritmos , Biomarcadores de Tumor/genética , Femenino , Perfilación de la Expresión Génica , Humanos , Sistema Inmunológico , Estimación de Kaplan-Meier , Masculino , Pronóstico , Mapeo de Interacción de Proteínas , Mapas de Interacción de Proteínas/genética , Resultado del Tratamiento , Microambiente TumoralRESUMEN
BACKGROUND: We aimed to identify which part of the patients with metastatic renal cell carcinoma (mRCC) is not suitable for cytoreductive nephrectomy (CN). METHODS: The data of mRCC patients was acquired from the Surveillance, Epidemiology, and End Results (SEER) database. Multivariate cox regression analysis and nomogram were performed for selecting factors independently associated with survival. Propensity score matching (PSM) was applied to reduce potential bias when comparing survival of mRCC patients treated by CN or non-surgery (NS). The survival analysis of subgroups was estimated by the Kaplan-Meier method and compared by log-rank testing. The summary of subgroup analysis was showed by forest plots. RESULTS: The records of 21,411 patients with mRCC were obtained from the SEER database. After screening, a total of 6532 patients were included for further analysis, of which 6043 underwent CN and 489 underwent NS. Age, T stage, N stage and tumor size were involved in subgroup analysis by PSM according to the result of multivariate cox regression analysis and clinical experience. Survival benefit was not found in T4 stage patients. Further analysis showed that T4&N1 and T4&age ≥ 76 yr subgroups could not obtain survival benefit from CN. CONCLUSION: CN should not be performed in T4 stage mRCC patients who were in status of N1 stage or older than 76 years, because surgery cannot take significant survival benefit for them.
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Carcinoma de Células Renales/cirugía , Procedimientos Quirúrgicos de Citorreducción/métodos , Neoplasias Renales/cirugía , Nefrectomía/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Renales/patología , Niño , Bases de Datos Factuales , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias , Nomogramas , Supervivencia sin Progresión , Puntaje de Propensión , Estudios Retrospectivos , Adulto JovenRESUMEN
We report the first simultaneous, common-volume lidar observations of thermosphere-ionosphere Fe (TIFe) and Na (TINa) layers in Antarctica. We also report the observational discovery of nearly one-to-one correspondence between TIFe and aurora activity, enhanced ionization layers, and converging electric fields. Distinctive TIFe layers have a peak density of ~384 cm-3 and the TIFe mixing ratio peaks around 123 km, ~5 times the mesospheric layer maximum. All evidence shows that Fe+ ion-neutralization is the major formation mechanism of TIFe layers. The TINa mixing ratio often exhibits a broad peak at TIFe altitudes, providing evidence for in situ production via Na+ neutralization. However, the tenuous TINa layers persist long beyond TIFe disappearance and reveal gravity wave perturbations, suggesting a dynamic background of neutral Na, but not Fe, above 110 km. The striking differences between distinct TIFe and diffuse TINa suggest differential transport between Fe and Na, possibly due to mass separation.
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BACKGROUND This population study aimed to identify suitable candidates for cytoreductive nephrectomy in patients with metastatic sarcomatoid renal cell carcinoma (RCC) from the US Surveillance, Epidemiology, and End Results (SEER) database. MATERIAL AND METHODS Demographic and clinical data from 1,229 patients with metastatic sarcomatoid RCC were retrieved from the SEER database. Patients were divided into the cytoreductive nephrectomy group (n=937) and the no surgery group (n=292). Multivariate Cox regression analysis identified factors associated with overall survival (OS) and propensity score matching identified factors that significantly impacted the OS. Survival of propensity score-matched subgroups of patients with metastatic sarcomatoid RCC treated by cytoreductive nephrectomy or no surgery was determined by the Kaplan-Meier method and compared by the log-rank test. RESULTS Of the 1,229 patients with metastatic sarcomatoid RCC retrieved from the SEER database, age, tumor size, T stage, and N stage were independent risk factors for patient survival. There were no significant differences in age, N stage, and tumor size between the cytoreductive nephrectomy-treated and non-surgically treated T stage cases following propensity score matching. OS benefits were found in cases with stage T1 (12 months increase), T2 (7.5 months increase), T3a (2 months increase), and T4 (3 months increase), but not in the T3b or T3c subgroups treated by cytoreductive nephrectomy, compared with patients with no surgical treatment. CONCLUSIONS Data from the SEER database showed that cytoreductive nephrectomy improved OS in patients with T1 and T2 metastatic sarcomatoid RCC with a significant long-term survival benefit of >6 months.
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Carcinoma de Células Renales/cirugía , Procedimientos Quirúrgicos de Citorreducción/métodos , Anciano , Carcinoma de Células Renales/metabolismo , Carcinoma de Células Renales/patología , Bases de Datos Factuales , Femenino , Genética de Población , Humanos , Estimación de Kaplan-Meier , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Nefrectomía/métodos , Puntaje de Propensión , Factores de Riesgo , Programa de VERFRESUMEN
Paired basic amino acid-cleaving enzyme 4 (PACE4), a proprotein convertase, is involved in the activation of aggrecanases (ADAMTS-4 and ADAMTS-5) in osteoarthritic and cytokine-stimulated cartilage. Activated aggrecanases cause aggrecan degradation and thus, contribute to osteoarthritis (OA). In this study, we investigated the association between PACE4 gene polymorphisms and OA risk. One single-nucleotide polymorphism (rs4965833) in the PACE4 gene was genotyped in 432 OA patients and 523 healthy controls using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Quantitative reverse transcription PCR (qRT-PCR) was used to determine the relative expression of PACE4 in blood samples from 90 OA patients (30 for each genotype). The relative expression level of PACE4 mRNA was higher in the GG genotype as compared to the AA/AG group. Moreover, the PACE4 rs4965833 polymorphism was associated with increased risk of OA, especially among individuals aged ≥55 years and with a body mass index ≥25. There was no significant association between the PACE4 rs4965833 polymorphism and clinical parameters of OA patients, such as erythrocyte sedimentation rate, C-reactive protein, Visual Analog Scale for pain and Lequesne's index. In conclusion, the rs4965833 polymorphism in the 3'-UTR of PACE4 is associated with OA susceptibility.
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BACKGROUND Worldwide, the increasing use of antibiotics has resulted in antimicrobial resistance, leading to studies to find alternative antimicrobial treatments. Tea polyphenols have antibacterial properties. Bacteriocins produced by probiotic lactobacilli can inhibit Gram-positive bacteria. This study used a rabbit model of infection, following femoral fracture with internal fixation, to evaluate the efficacy of the combined use of tea polyphenols and Lactobacillus plantarum ST8SH bacteriocin. MATERIAL AND METHODS Twenty-four New Zealand White rabbits underwent femoral fracture, internal fixation, and insertion of a mini-titanium implant, and were inoculated intravenously with suspensions of Staphylococcal bacteria. Four treatment groups included group A, injected with tea polyphenols and bacteriocins (N=6); group B, injected with cefradine and bacteriocins (N=6); group C, injected with tea polyphenols and cefradine (N=6); and group D (controls), injected with saline (N=6). Blood samples were collected at 1, 6, 12, 24, and 48 hours after the injection of bacteriocins. Biofilms that formed on the mini-titanium implant were studied by fluorescence microscopy. Serum levels of level of interleukin (IL)-8, IL-6, and tumor necrosis factor-α (TNF-α) were measured using an enzyme-linked immunosorbent assay (ELISA). RESULTS The combination of tea polyphenols and bacteriocins (group A) had a significant inhibitory effect on Staphylococcus aureus (P<0.05) and significant differences in serum levels of IL-8, TNF-α, and IL-6 levels in serum (P<0.05) when compared with groups, B, C, and D. CONCLUSIONS In a rabbit model of femoral fracture with internal fixation, the combined use of tea polyphenols and Lactobacillus plantarum ST8SH bacteriocin effectively controlled Staphylococcus aureus infection.
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Bacteriocinas/farmacología , Infecciones/terapia , Polifenoles/farmacología , Animales , Antibacterianos/farmacología , Biopelículas/efectos de los fármacos , Citocinas/análisis , Citocinas/sangre , Modelos Animales de Enfermedad , Fracturas del Fémur/terapia , Fijación Interna de Fracturas/métodos , Interleucina-8 , Lactobacillus plantarum/metabolismo , Conejos , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/patogenicidad , Té , Factor de Necrosis Tumoral alfaRESUMEN
Bladder cancer is currently considered the most common malignancy of the urinary tract. Thulium laser en bloc resection of bladder tumor (TmLRBT) and plasmakinetic transurethral resection of bladder tumor (PK-TURBT) are two alternative common procedures used in our department to manage patients with primary non-muscle invasive bladder cancer (NMIBC) over the past decade. In this work, the safety and efficacy of TmLRBT were retrospectively compared to those of PK-TURBT in patients with primary NMIBC. From January 2013 to December 2015, 256 patients diagnosed with primary NMIBC were selected for this retrospective study. A total of 136 consecutive patients diagnosed with primary NMIBC were enrolled in the TmLRBT group. A similar historical cohort of 120 consecutive patients who underwent PK-TURBT was used to compare the two procedures. Clinical data, including age, gender, tumor characteristics, operation duration, hospitalization, irrigation, catheterization, and intraoperative and postoperative complications, were recorded. There were no significant differences in age, gender, mean tumor size, mean tumor number, tumor location, or risk between the TmLRBT and PK-TURBT groups. The TmLRBT group was associated with a significantly shorter operation duration (25.96 ± 21.19 min vs 37.18 ± 25.77 min, P = 0.018) and a shorter hospitalization time (3.11 ± 1.05 days vs 5.24 ± 2.06 days, P = 0.036). The postoperative irrigation time (6.33 ± 4.05 h vs 14.76 ± 6.28 h, P = 0.027) and catheterization time (2.03 ± 1.61 days vs 4.27 ± 1.17 days, P = 0.035) in the TmLRBT group were lower than those in the PK-TURBT group. No significant differences in fever and rebleeding were found in the TmLRBT and PK-TURBT groups. There were no significant differences in the overall, low-risk, intermediate-risk, and high-risk recurrence-free rates between the two groups (P = 0.43, P = 0.68, P = 0.71, and P = 0.24, respectively). The proportion of bladder detrusor muscle (BDM) identified in pathologic specimens of the TmLRBT group was higher than that in the PK-TURBT group (P = 0.006). TmLRBT may reduce operation duration time, hospitalization time, postoperative irrigation time, and catheterization time. TmLRBT is considered safer and more effective in treating primary NMIBC. Recurrence-free rates did not differ between groups.
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Músculos/patología , Tulio/uso terapéutico , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/cirugía , Anciano , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Recurrencia Local de Neoplasia/patología , Estudios Retrospectivos , Factores de TiempoRESUMEN
Recently, ZnO nanowire field effect transistors (FETs) have received renewed interest due to their extraordinary low dimensionality and high sensitivity to external chemical environments and illumination conditions. These prominent properties have promising potential in nanoscale chemical and photo-sensors. In this article, we have fabricated ZnO nanowire FETs and have found hysteresis behavior in their transfer characteristics. The mechanism and dynamics of the hysteresis phenomena have been investigated in detail by varying the sweeping rate and range of the gate bias with and without light irradiation. Significantly, light irradiation is of great importance on charge trapping by regulating adsorption and desorption of oxygen at the interface of ZnO/SiO2. Carriers excited by light irradiation can dramatically promote trapping/detrapping processes. With the assistance of light illumination, we have demonstrated a photon-assisted nonvolatile memory which employs the ZnO nanowire FET. The device exhibits reliable programming/erasing operations and a large on/off ratio. The proposed proto-type memory has thus provided a possible novel path for creating a memory functionality to other low-dimensional material systems.
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PURPOSE: As a novel hepatokine, fetuin B involves in various functions of energy metabolism. Recent advance reveals a complex interaction between bone and liver via the secretion of hepatokines. The association between serum fetuin B and osteoporosis was evaluated in a 4-year hospital-based prospective study of 1,370 Chinese postmenopausal women. METHODS: Bone mineral densities (BMDs) were obtained on femoral neck and lumbar spines by dual energy X-ray absorptiometry. Serum fetuin B level was tested by enzyme-linked immunosorbent assay. RESULTS: Of the 1,370 participants in the baseline study (2012), 650 subjects were included in the 4-year follow-up study (2016). Serum fetuin B level presented higher in subjects with osteoporosis (106.7 ± 17.6 µg/ml) than it in controls (86.3 ± 17.5 µg/ml) (P < 0.001). Meanwhile, fetuin B positively correlated with triglycerides (r = 0.227, P = 0.001), femoral BMD (r = -0.426, P < 0.001) and lumbar BMD (r = -0.332, P < 0.001). At the 4-year follow-up, 116 subjects had developed osteoporosis. Serum fetuin B concentration was significantly higher in subjects who developed (P < 0.001). The osteoporosis incidence increased from Q1 9.9%, Q2 14.7%, and Q3 17.8% to Q4 30.2% (P for trend < 0.001), among the quartiles of baseline fetuin B. A higher fetuin B baseline level was linked to the incidence of osteoporosis (adjusted OR = 1.179, 95% CI [1.119 - 1.243], P = 0.009). CONCLUSION: Serum fetuin B levels increased with the development of osteoporosis.
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Fetuína-B/metabolismo , Osteoporosis/sangre , Anciano , Anciano de 80 o más Años , Densidad Ósea , Femenino , Cuello Femoral/metabolismo , Cuello Femoral/patología , Estudios de Seguimiento , Humanos , Incidencia , Vértebras Lumbares/metabolismo , Vértebras Lumbares/patología , Masculino , Persona de Mediana Edad , Osteoporosis/epidemiología , Osteoporosis/patología , Estudios Prospectivos , Triglicéridos/sangreRESUMEN
BACKGROUND Bladder cancer (BC) is the most common urological malignant tumor. In BC, aberrant DNA methylation is believed to be associated with carcinogenesis. Therefore, the identification of key genes and pathways could help determine the potential molecular mechanisms of BC development. MATERIAL AND METHODS Microarray data on gene expression and gene methylation were downloaded from the Gene Expression Omnibus (GEO) database. Abnormal methylated/expressed genes were analyzed by GEO2R and statistical software R. Gene Ontology term enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed using the DAVID database and KOBAS 3.0. STRING and Cytoscape software were used to construct protein-protein interaction (PPI) networks and analyze modules of the PPI network. RESULTS A total of 71 hypomethylated/upregulated genes were significantly enriched in cell-cell adhesion and blood vessel development. KEGG pathway analysis highlighted p53 signaling and metabolic pathways. Five core genes in the PPI network were determined: CDH1, DDOST, CASP8, DHX15, and PTPRF. Additionally, 89 hypermethylated/downregulated genes were found. These genes were enriched mostly in cell adhesion and signal transduction. KEGG pathway analysis revealed enrichment in focal adhesion. The top 5 core genes in the PPI network were GNG4, ADCY9, NPY, ADRA2B, and PENK. We found most of the core genes were also significantly altered in the Cancer Genome Atlas database. CONCLUSIONS Abnormal methylated/expressed genes and key signaling pathways involved in BC were identified through integrated bioinformatics analysis. In the future, these genes may serve as biomarkers for diagnosis and therapeutic targets in BC.
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Metilación de ADN/genética , Regulación Neoplásica de la Expresión Génica , Redes Reguladoras de Genes , Neoplasias de la Vejiga Urinaria/genética , Bases de Datos Genéticas , Perfilación de la Expresión Génica , Ontología de Genes , Humanos , Mapas de Interacción de Proteínas/genética , Reproducibilidad de los ResultadosRESUMEN
OBJECTIVE: The purpose of this study was to investigate the effect of simvastatin on periprosthetic bone mineral density (BMD) in hypercholesterolaemic patients after total hip arthroplasty. METHODS: From January 2012 to December 2015, a total of 42 consecutive hypercholesterolaemic patients with total hip arthroplasty were recruited for this study. The simvastatin group was 21 patients (15 males, 6 females) with average age of 69.4 ± 6.6 years treated with simvastatin for one year post-operatively, and the control group was the other 21 patients (12 males, 9 females) who did not take simvastatin. These parameters of the periprosthetic bone mineral density after total hip arthroplasty were collected by dual energy X-ray absorptiometry(DEXA) one week and three, six, 12 months post-operatively. RESULTS: In the control group patients showed significant loss of periprosthetic BMD in ROIs 1, 2, 6, and 7 throughout the study period. The loss of BMD in ROIs 3 and 5 was only significantly observed at three months follow-up and recovered thereafter. There were no significant detected changes of BMD in ROI 4. In the Simvastatin group, the percentage of BMD loss was significantly less (P < 0.05) in ROI 1, 2, 6 and 7 throughout the study period than the control group. The percentage of BMD loss were significant observed in ROI 3 and 5 at three months follow-up, which were also significantly less (P < 0.05) than in the control group. A slight gain of BMD was measured in ROI 4 at 12 months follow-up (1.419%, P < 0.05). CONCLUSION: Simvastatin administered for one year post-operatively can effectively prevent periprosthetic bone loss after total hip arthroplasty.
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Anticolesterolemiantes/uso terapéutico , Artroplastia de Reemplazo de Cadera/efectos adversos , Densidad Ósea/efectos de los fármacos , Hipercolesterolemia/tratamiento farmacológico , Simvastatina/uso terapéutico , Absorciometría de Fotón , Adulto , Anciano , Femenino , Fracturas del Cuello Femoral/cirugía , Estudios de Seguimiento , Humanos , Hipercolesterolemia/complicaciones , Hipercolesterolemia/cirugía , Masculino , Persona de Mediana Edad , Osteoporosis/etiología , Osteoporosis/prevención & control , Periodo Posoperatorio , Estudios ProspectivosRESUMEN
In this study, we evaluated the prognostic potential and functional regulation of human nature antisense, brain-derived neurotrophic factor antisense, in non-small cell lung cancer. Non-small cell lung cancer carcinoma and adjacent non-carcinoma lung tissues were extracted from 151 patients. Their endogenous brain-derived neurotrophic factor antisense expression levels were compared by quantitative reverse transcription polymerase chain reaction. Clinical relevance between endogenous brain-derived neurotrophic factor antisense expression level and patients' clinicopathological variances or overall survival was analyzed. The potential of brain-derived neurotrophic factor antisense being an independent prognostic factor in non-small cell lung cancer was also evaluated. In in vitro non-small cell lung cancer cell lines, brain-derived neurotrophic factor antisense was upregulated through forced overexpression. The effects of brain-derived neurotrophic factor antisense upregulation on non-small cell lung cancer in vitro survival, proliferation, and migration were evaluated by viability, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, and transwell assays. Brain-derived neurotrophic factor antisense is lowly expressed in non-small cell lung cancer carcinoma tissues and further downregulated in late-stage carcinomas. Brain-derived neurotrophic factor antisense downregulation was closely associated with non-small cell lung cancer patients' advanced tumor, lymph node, metastasis stage, and positive status of lymph node metastasis, and confirmed to be an independent prognostic factor for patients' poor overall survival. In non-small cell lung cancer A549 and H226 cell lines, forced overexpression of brain-derived neurotrophic factor antisense did not alter cancer cell viability but had significantly tumor suppressive effect in inhibiting in vitro non-small cell lung cancer proliferation and migration. Endogenous brain-derived neurotrophic factor antisense in non-small cell lung cancer carcinoma could be a potential biomarker for predicting patients' prognosis. Overexpressing brain-derived neurotrophic factor antisense may also have a therapeutic potential in inhibiting non-small cell lung cancer tumor growth.
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Biomarcadores de Tumor/genética , Factor Neurotrófico Derivado del Encéfalo/biosíntesis , Carcinoma de Pulmón de Células no Pequeñas/genética , Pronóstico , ARN Largo no Codificante/genética , Células A549 , Anciano , Biomarcadores de Tumor/biosíntesis , Factor Neurotrófico Derivado del Encéfalo/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Supervivencia Celular/genética , Supervivencia sin Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , ARN sin Sentido/biosíntesis , ARN sin Sentido/genética , ARN Largo no Codificante/biosíntesisRESUMEN
Primary cardiac tumors in infancy and childhood are rare and usually benign. We report two children with giant left ventricular fibromas and discuss their surgical management.