Alantolactone attenuates high-fat diet-induced inflammation and oxidative stress in non-alcoholic fatty liver disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a chronic disease with an increasing incidence, which can further develop into liver fibrosis and hepatocellular carcinoma at the end stage. Alantolactone (Ala), a sesquiterpene lactone isolated from Asteraceae, has shown anti-inflammatory effects in different models. However, the therapeutic effect of Ala on NAFLD is not clear. METHODS: C57BL/6 mice were fed a high-fat diet (HFD) to induce NAFLD. After 16 weeks, Ala was administered by gavage to observe its effect on NAFLD. RNA sequencing of liver tissues was performed to investigate the mechanism. In vitro, mouse cell line AML-12 was pretreated with Ala to resist palmitic acid (PA)-induced inflammation, oxidative stress and fibrosis. RESULTS: Ala significantly inhibited inflammation, fibrosis and oxidative stress in HFD-induced mice, as well as PA-induced AML-12 cells. Mechanistic studies showed that the effect of Ala was related to the induction of Nrf2 and the inhibition of NF-κB. Taken together, these findings suggested that Ala exerted a liver protective effect on NAFLD by blocking inflammation and oxidative stress. CONCLUSIONS: The study found that Ala exerted a liver protective effect on NAFLD by blocking inflammation and oxidative stress, suggesting that Ala is an effective therapy for NAFLD.

Hepatitis B virus X protein promotes tumor glycolysis by downregulating lncRNA OIP5-AS1/HKDC1 in HCC.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide, with Hepatitis B virus (HBV) infection being the leading cause. This study aims to investigate the role of HBV in HCC pathogenesis involving glucose metabolism. Long non-coding RNA (lncRNA) OIP5-AS1 was significantly downregulated in HBV-positive HCC patients, and its low expression indicated a poor prognosis. This lncRNA was primarily localized in the cytoplasm, acting as a tumor suppressor. HBV protein X (HBx) repressed OIP5-AS1 expression by inhibiting a ligand-activated transcriptional factor peroxisome proliferator-activated receptor α (PPARα). Furthermore, mechanistic studies revealed that OIP5-AS1 inhibited tumor growth by suppressing Hexokinase domain component 1 (HKDC1)-mediated glycolysis. The expression of HKDC1 could be enhanced by transcriptional factor sterol regulatory element-binding protein 1 (SREBP1). OIP5-AS1 facilitated the ubiquitination and degradation of SREBP1 to suppress HKDC1 transcription, which inhibited glycolysis. The results suggest that lncRNA OIP5-AS1 plays an anti-oncogenic role in HBV-positive HCC via the HBx/OIP5-AS1/HKDC1 axis, providing a promising diagnostic marker and therapeutic target for HBV-positive HCC patients.

A Comparative Study of Two Radiomics-Based Blood Flow Modes with Thyroid Imaging Reporting and Data System in Predicting Malignancy of Thyroid Nodules and Reducing Unnecessary Fine-Needle Aspiration Rate.

RATIONALE AND OBJECTIVES: We aimed to compare superb microvascular imaging (SMI)-based radiomics methods, and contrast-enhanced ultrasound (CEUS)-based radiomics methods to the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) for classifying thyroid nodules (TNs) and reducing unnecessary fine-needle aspiration biopsy (FNAB) rate. MATERIALS AND METHODS: This retrospective study enrolled a dataset of 472 pathologically confirmed TNs. Radiomics characteristics were extracted from B-mode ultrasound (BMUS), SMI, and CEUS images, respectively. After eliminating redundant features, four radiomics scores (Rad-scores) were constructed. Using multivariable logistic regression analysis, four radiomics prediction models incorporating Rad-score and corresponding US features were constructed and validated in terms of discrimination, calibration, decision curve analysis, and unnecessary FNAB rate. RESULTS: The diagnostic performance of the BMUS + SMI radiomics method was better than ACR TI-RADS (area under the curve [AUC]: 0.875 vs. 0.689 for the training cohort, 0.879 vs. 0.728 for the validation cohort) (P < 0.05), and comparable with BMUS + CEUS radiomics method (AUC: 0.875 vs. 0.878 for the training cohort, 0.879 vs. 0.865 for the validation cohort) (P > 0.05). Decision curve analysis showed that the BMUS+SMI radiomics method could achieve higher net benefits than the BMUS radiomics method and ACR TI-RADS when the threshold probability was between 0.13 and 0.88 in the entire cohort. When applying the BMUS+SMI radiomics method, the unnecessary FNAB rate reduced from 43.4% to 13.9% in the training cohort and from 45.6% to 18.0% in the validation cohorts in comparison to ACR TI-RADS. CONCLUSION: The dual-modal SMI-based radiomics method is convenient and economical and can be an alternative to the dual-modal CEUS-based radiomics method in helping radiologists select the optimal clinical strategy for TN management.

Costunolide attenuates high-fat diet-induced inflammation and oxidative stress in non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is a progressive disease that can further evolve towards liver fibrosis and hepatocellular carcinoma in the end stage. Costunolide (Cos) is a natural sesquiterpene lactone that exhibits both anti-inflammatory and antioxidant properties. However, the therapeutic effect of Cos on NAFLD is not clear. In this study, we explored the potential protective effect and mechanism of Cos on NAFLD. C57BL/6 mice were fed with high-fat diet (HFD) to induce NAFLD. Cos was administered by gavage to observe the effect of Cos on NAFLD. We demonstrated that oral administration of Cos reduced HFD-induced hepatic fibrosis and the release of inflammatory cytokines, limiting the generation of reactive oxygen species. In vitro experiments revealed that pretreatment with Cos significantly decreased PA-induced production of inflammatory cytokines and fibrosis in AML-12 cells. Mechanism study showed that the effect of Cos was correlated to the induction of Nrf-2 and inhibition of NF-κB pathways. Collectively, these findings indicated that Cos exerts hepatoprotective effect against NAFLD through blocking inflammation and oxidative stress. Our study suggested that Cos might be an effective pharmacotherapy for the treatment of NAFLD.

Malignant cell receptor-ligand subtypes guide the prediction of prognosis and personalized immunotherapy of liver cancer.

OBJECTIVE: Liver cancer is a prevalent disease with a dismal prognosis. The aim of the research is to identify subgroups based on malignant cell receptor ligand gene from single-cell RNA, which might lead to customized immunotherapy for patients with liver cancer. METHODS: Based on scRNA-seq data, we identified the receptor-ligand genes associated with prognosis and classify patients into molecular subtypes by univariate Cox regression and consensus clustering. LASSO regression was performed to construct a prognostic model, which was validated in TCGA and ICGC datasets. Immune infiltration and prediction of immunotherapy response were analyzed using ssGSEA, ESTIMATE, TIDE, and TRS score calculation. Finally, qPCR and Western blot validation of key genes and protein levels in cell lines. RESULTS: A risk model using 16-gene expression levels predicted liver cancer patients' prognosis. The RiskScore associated significantly with tumor clinical characteristics and immunity, integrated with clinicopathological features for survival prediction. Differential expression of SRXN1 was verified in hepatocellular carcinoma and normal liver cells. CONCLUSION: Our study utilizes single-cell analysis to investigate the communication between malignant cells and other cell types, identifying molecular subtypes based on malignant cell receptor ligand genes, offering new insights for the development of personalized immunotherapy and prognostic prediction models.

Dual-modal radiomics nomogram based on contrast-enhanced ultrasound to improve differential diagnostic accuracy and reduce unnecessary biopsy rate in ACR TI-RADS 4-5 thyroid nodules.

BACKGROUND: American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS, TR) 4 and 5 thyroid nodules (TNs) demonstrate much more complicated and overlapping risk characteristics than TR1-3 and have a rather wide range of malignancy possibilities (> 5%), which may cause overdiagnosis or misdiagnosis. This study was designed to establish and validate a dual-modal ultrasound (US) radiomics nomogram integrating B-mode ultrasound (BMUS) and contrast-enhanced ultrasound (CEUS) imaging to improve differential diagnostic accuracy and reduce unnecessary fine needle aspiration biopsy (FNAB) rates in TR 4-5 TNs. METHODS: A retrospective dataset of 312 pathologically confirmed TR4-5 TNs from 269 patients was collected for our study. Data were randomly divided into a training dataset of 219 TNs and a validation dataset of 93 TNs. Radiomics characteristics were derived from the BMUS and CEUS images. After feature reduction, the BMUS and CEUS radiomics scores (Rad-score) were built. A multivariate logistic regression analysis was conducted incorporating both Rad-scores and clinical/US data, and a radiomics nomogram was subsequently developed. The performance of the radiomics nomogram was evaluated using calibration, discrimination, and clinical usefulness, and the unnecessary FNAB rate was also calculated. RESULTS: BMUS Rad-score, CEUS Rad-score, age, shape, margin, and enhancement direction were significant independent predictors associated with malignant TR4-5 TNs. The radiomics nomogram involving the six variables exhibited excellent calibration and discrimination in the training and validation cohorts, with an AUC of 0.873 (95% CI, 0.821-0.925) and 0.851 (95% CI, 0.764-0.938), respectively. The marked improvements in the net reclassification index and integrated discriminatory improvement suggested that the BMUS and CEUS Rad-scores could be valuable indicators for distinguishing benign from malignant TR4-5 TNs. Decision curve analysis demonstrated that our developed radiomics nomogram was an instrumental tool for clinical decision-making. Using the radiomics nomogram, the unnecessary FNAB rate decreased from 35.3 to 14.5% in the training cohort and from 41.5 to 17.7% in the validation cohorts compared with ACR TI-RADS. CONCLUSION: The dual-modal US radiomics nomogram revealed superior discrimination accuracy and considerably decreased unnecessary FNAB rates in benign and malignant TR4-5 TNs. It could guide further examination or treatment options.

Bronchiole adenoma/pulmonary ciliated mucinous nodular papillary tumor: Case series and literature review.

OBJECTIVE: To analyze the clinical-pathological characteristics of 3 cases of bronchiolar adenoma/pulmonary ciliary mucinous nodular papillary tumors, and to improve the understanding of bronchiolar adenoma (BA)/ciliated muconodular papillary tumors (CMPT) (bronchiolar adenoma/ciliated muconodular papillary tumor). METHODS: Retrospective analysis was done on the clinical information, diagnosis, and treatment of 3 instances of BA/CMPT at the Second People's Hospital of Weifang City. By scanning the CNKI, Wanfang, VIP database, and Pubmed database using the English key words "bronchiolar adenoma, ciliated muconodular papillary tumor," respectively patients with comprehensive clinical data were gathered, and studies from January 2002 to August 2021 that were relevant to the patients were examined. RESULTS: A total of 35 articles and 71 instances were found, including 3 cases in our hospital, for a total of 74 cases. There were 31 males and 43 females among them, ranging in age from 18 to 84 years (average 63 years), and 15 cases had a smoking history. The majority of them were discovered by physical examination and had no clinical symptoms. The majority of the imaging revealed solid nodules with variable forms, with some ground-glass nodules displaying vacuole and bronchial inflation signs. BA/CMPT are generally gray-white, gray-brown solid nodules with obvious boundaries but no envelope with a maximum dimension of 4 to 45 mm (average 10.6 mm) on gross examination. Acinar, papillary, and lepidic formations can be seen under the microscope at high magnification; the majority of these structures are made up of tripartite epithelial components, including basal cells, mucous cells, ciliated columnar cells, and alveolar epithelial cells, demonstrating a variety of combinations. An important basis for diagnosis in immunohistochemistry is the continuous positive basal cell layer that is shown by p63, p40, and CK5/6. BRAF and epidermal growth factor receptor are the genes that are most frequently mutated. All of the patients showed no signs of metastasis or recurrence during follow-up period. CONCLUSION: BA/CMPT is a rare benign tumor of lung epithelium. Because imaging and intraoperative cryosection diagnosis are easy to be misdiagnosed as malignant, it is necessary to further improve understanding and improve immunohistochemistry and genetic examination.

A Numerical Study of ITZ Percolation in Polyphase Concrete Systems Considering the Synergetic Effect of Aggregate Shape- and Size-Diversities.

The percolation of the interfacial transition zone (ITZ) is generally regarded as an important factor that may accelerate the penetration of aggressive agents in concrete materials, and its threshold is largely determined by the features of aggregates. In most numerical studies about ITZ percolation, both fine aggregates and coarse aggregates are assumed to be the particles of uniform shape, and their size distributions are generally strung together by a single function, which is quite different from reality. To quantify the ITZ percolation associated with the polydispersity of aggregate shapes and size gradations in a more realistic way, the two-dimensional (2D) meso-scale model of concrete is generated by simplifying coarse aggregates and fine aggregates as polygons and ovals, respectively. Moreover, the size gradations of them are also represented by two separate expressions. By combining these models with percolation theory, the percolation of ITZ in the 2D case is explicitly simulated, and the influence of aggregate shape- and size-diversities on the critical threshold ϕagg,c is studied in detail. Based on the simulated results of ϕagg,c, an empirically analytical expression is further proposed to fast predict the ITZ percolation, and its reliability is verified. The results show that the ITZ thickness, average aggregate fineness, coarse aggregate shape, and fine aggregate shapes are the four main contributing factors to the ITZ percolation. Compared with the existing literature, the proposed model here has a broader range of applications (e.g., mortar, concrete, and other granular systems) in the 2D case and can provide the larger predicted results, which may be closer to reality.

miR-135a inhibits the proliferation of HBV-infected hepatocellular carcinoma cells by targeting HOXA10.

Background: The incidence of hepatocellular carcinoma (HCC) in patients with hepatitis B virus (HBV) is extremely high. MicroRNAs (miRNAs) are a type of endogenous non-coding small RNA with novel molecular therapeutic mechanisms that plays an important role in the occurrence and development of cancers. This study aimed to explore the regulation mechanism of miR-135a and HOXA10 in the proliferation, invasion, and apoptosis of HCC cells. Methods: Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis was used to detect the expression level of miR-135a. Overexpression of miR-135a was used to measure the roles of miR-135a in the proliferation, invasion, and apoptosis of HCC cells. A dual luciferase experiment was performed to assess the relationship between HOXA10 and miR-135a. Western blot was applied to observe the protein levels of p-p38, p-ERK, and p-JNK. Results: The expression levels of miR-135a were significantly decreased in HCC tissues and cells. Overexpression of miR-135a inhibited the proliferation and invasion but promoted the apoptosis of HCC cells. Importantly, our results confirmed that HOXA10 was a direct target of miR-135a. Under HBV infection, silencing of HOXA10 significantly blocked the proliferation and invasion and promoted the apoptosis of HCC cells. In addition, miR-135a/HOXA10 regulated the expressions of p-p38, p-ERK, and p-JNK through the miR-135a/HOXA10 axis, thereby inhibiting the activation of the MAPK pathway. Conclusions: HBV promoted the proliferation and invasion, and inhibited the apoptosis of HCC cells by regulating the miR-135a/HOXA10 pathway. These findings provide a theoretical basis for improving the treatment of HBV-infected HCC patients.

Temperature- and pH-responsive injectable chitosan hydrogels loaded with doxorubicin and curcumin as long-lasting release platforms for the treatment of solid tumors.

The efficacy of treating solid tumors with chemotherapy is primarily hindered by dose-limiting toxicity due to off-target effects and the heterogeneous drug distribution caused by the dense extracellular matrix. The enhanced permeability and retention (EPR) effect within tumors restricts the circulation and diffusion of drugs. To overcome these obstacles, hydrogels formed in situ at the tumor site have been proposed to promote drug accumulation, retention, and long-lasting release. We developed a thiolated chitosan (CSSH) hydrogel with a gelation point of 37°C. Due to the pH-sensitive characteristics of disulfides, the prepared hydrogel facilitated drug release in the acidic tumor environment. A drug release system composed of hydrophilic doxorubicin (Dox) and hydrophobic liposome-encapsulated curcumin (Cur-Lip) was designed to enhance the long-lasting therapeutic impacts and reduce adverse side effects. These composite gels possess a suitable gelation time of approximately 8-12 min under physiological conditions. The cumulative release ratio was higher at pH = 5.5 than at pH = 7.4 over the first 24 h, during which approximately 10% of the Dox was released, and Cur was released slowly over the following 24-120 h. Cell assays indicated that the Cur-Lip/Dox/CSSH gels effectively inhibited the growth of cancer cells. These in situ-formed Cur-Lip/Dox gels with long-term drug release capabilities have potential applications for tumor suppression and tissue regeneration after surgical tumor resection.

HBV Promotes the Proliferation of Liver Cancer Cells through the hsa_circ_0000847/miR-135a Pathway.

Hepatocellular carcinoma (HCC) is currently one of the most common tumors, with a high morbidity and mortality rate. HCC induced by persistent hepatitis B virus (HBV) infection is the most common liver cancer subtype at present, and HBV-related HCC is highly malignant and its development mechanism still needs to be explored in depth. This study aimed to explore the molecular mechanism of hsa_circ_0000847 targeting miR-135a-5p (miR-135a) to regulate the proliferation, invasion, and apoptosis of liver cancer cells. The study found that the expression level of hsa_circ_0000847 in liver cancer tissues and cells was significantly increased, while the expression level of miR-135a was significantly decreased. Hsa_circ_0000847 promoted the proliferation of liver cancer cells and elevated the expression of the proliferation-related protein. In addition, hsa_circ_0000847 could promote the invasion of HBV-infected liver cancer cells and inhibit the cell apoptosis of liver cancer cells. At the same time, it significantly promoted the expression of antiapoptotic proteins and inhibited the expression of proapoptotic protein. Interestingly, the dual luciferase experiment proved that hsa_circ_0000847 directly targeted miR-135a. On the other hand, the combined effect of hsa_circ_0000847 and miR-135a further illustrated the effect of hsa_circ_0000847 on the proliferation, invasion, and apoptosis of liver cancer cells. In addition, further experiments have also found that HBV could promote the expression of p-p38, p-ERK, and p-JNK through the hsa_circ_0000847/miR-135a axis, thereby further activating the MAPK pathway. In short, HBV promotes the proliferation and invasion of liver cancer cells and inhibits apoptosis by regulating the hsa_circ_0000847/miR-135a pathway, which provided a theoretical basis for effective treatment of HBV-infected liver cancers.

The clinical profiles and outcomes of HIV-negative cryptococcal meningitis patients in type II diabetes mellitus.

BACKGROUND: The clinical profiles and outcomes of cryptococcal meningitis have been shown to vary depending on the underlying condition. The aim of this study was to investigate clinical characteristics and outcomes in patients with and without type II diabetes mellitus. METHODS: A retrospective study was performed. Clinical data of HIV-negative cryptococcal meningitis patients with type II diabetes mellitus (n = 26) and without type II diabetes mellitus (n = 52) referring to the Jiangxi Chest Hospital between January 2012 to December 2018 were analyzed. The data were analyzed using chi square, none-parametric tests, and logistic regression. P-values < 0.05 were considered significant. RESULTS: In this study, cryptococcal meningitis patients suffering from type II diabetes mellitus had a higher mortality (23.08% vs. 7.69%; P = 0.055), and required longer hospitalization (59.58 vs. 42.88 days; P = 0.132). Moreover, cerebrospinal fluid examinations revealed that cryptococcal meningitis patients with type II diabetes mellitus had higher opening pressure (271.54 vs. 234.23 mmH2O; P = 0.125).The results of multivariate regression analysis revealed that cryptococcal meningitis patients with type II diabetes were more often presented with visual disorders (28.54% vs. 11.54%; [95% CI 0.056-0.705]; p = 0.012), and had higher cerebrospinal fluid protein levels (1027.62 ± 594.16 vs. 705.72 ± 373.88 mg/l; [95% CI 1.000-1.002]; p = 0.016). Among patients with type II diabetes mellitus, nausea and vomiting was more frequent at the initial visit in those died (100% vs. 50%; p = 0.027), and 66% of died type II diabetes mellitus patients were poorly controlled blood glucose level, compared with 30% in survival type II diabetes mellitus patients. CONCLUSION: This study suggests that cryptococcal meningitis patients with type II diabetes mellitus differ significantly from cryptococcal meningitis patients without type II diabetes mellitus with respect to clinical symptoms such as visual disorders and cerebrospinal fluid examination. The presence of nausea and vomiting among type II diabetes mellitus patients could have implication in mortality.

EFFECT OF PKP ON SERUM SOST IN PATIENTS WITH VERTEaBRAL COMPRESSION FRACTURES.

OBJECTIVE: This study sought to determine serum sclerostin (SOST) expression in patients with osteoporotic thoracolumbar vertebral compression fractures before and after percutaneous kyphoplasty (PKP). METHODS: Serum SOST levels were quantified with a sandwich enzyme-linked immunosorbent assay (ELISA) preoperatively and six months postoperatively. Anterior vertebral height, kyphotic angles, and Visual Analogue Scale (VAS) scores were also recorded. RESULTS: Serum SOST was highly expressed in patients and remained negatively correlated with bone mineral density (BMD). Vertebral heights, local kyphotic angles, and VAS scores were all significantly improved after PKP. However, serum SOST was positively correlated with BMD six months after surgery. CONCLUSION: PKP was an effective treatment strategy for osteoporotic thoracolumbar vertebral compression fractures, improving BMD and decreasing serum SOST levels. Level of Evidence II, Prospective comparative study.

OBJETIVO: Este estudo teve por objetivo determinar a expressão de esclerostina (SOST) em pacientes com fraturas vertebrais osteoporóticas por compressão na coluna toracolombar antes e depois da Cifoplastia Percutânea (PKP). MÉTODOS: Os níveis de SOST no soro foram quantificados por meio de um Ensaio de Imunoadsorção Ligado à Enzima (ELISA) sanduíche, realizado no pré-operatório e aos seis meses pós-operatório. Foram também registrados a altura do corpo vertebral anterior, os ângulos cifóticos, e os valores obtidos na escala analógica visual (VAS). RESULTADOS: O nível de SOST no soro foi altamente expresso nos pacientes, e permaneceu correlacionado negativamente com a densidade mineral óssea (DMO). As alturas vertebrais, os ângulos cifóticos locais, e as pontuações obtidas na escala VAS foram significativamente melhores após o PKP. No entanto, o SOST foi correlacionado positivamente com a DMO aos seis meses pós-operatório. CONCLUSÃO: O PKP foi uma estratégia eficaz para o tratamento de fraturas vertebrais osteoporóticas por compressão na coluna toracolombar, melhorando os níveis de DMO e diminuindo os níveis de SOST no soro. Nível de Evidência II, Estudo prospectivo comparativo.

Effect of pkp on serum sost in patients with vertebral compression fractures / Efeito de pkp em sost soro em pacientes com fraturas de compressão vertebral

ABSTRACT Objective: This study sought to determine serum sclerostin (SOST) expression in patients with osteoporotic thoracolumbar vertebral compression fractures before and after percutaneous kyphoplasty (PKP). Methods: Serum SOST levels were quantified with a sandwich enzyme-linked immunosorbent assay (ELISA) preoperatively and six months postoperatively. Anterior vertebral height, kyphotic angles, and Visual Analogue Scale (VAS) scores were also recorded. Results: Serum SOST was highly expressed in patients and remained negatively correlated with bone mineral density (BMD). Vertebral heights, local kyphotic angles, and VAS scores were all significantly improved after PKP. However, serum SOST was positively correlated with BMD six months after surgery. Conclusion: PKP was an effective treatment strategy for osteoporotic thoracolumbar vertebral compression fractures, improving BMD and decreasing serum SOST levels. Level of Evidence II, Prospective comparative study.

RESUMO Objetivo: Este estudo teve por objetivo determinar a expressão de esclerostina (SOST) em pacientes com fraturas vertebrais osteoporóticas por compressão na coluna toracolombar antes e depois da Cifoplastia Percutânea (PKP). Métodos: Os níveis de SOST no soro foram quantificados por meio de um Ensaio de Imunoadsorção Ligado à Enzima (ELISA) sanduíche, realizado no pré-operatório e aos seis meses pós-operatório. Foram também registrados a altura do corpo vertebral anterior, os ângulos cifóticos, e os valores obtidos na escala analógica visual (VAS). Resultados: O nível de SOST no soro foi altamente expresso nos pacientes, e permaneceu correlacionado negativamente com a densidade mineral óssea (DMO). As alturas vertebrais, os ângulos cifóticos locais, e as pontuações obtidas na escala VAS foram significativamente melhores após o PKP. No entanto, o SOST foi correlacionado positivamente com a DMO aos seis meses pós-operatório. Conclusão: O PKP foi uma estratégia eficaz para o tratamento de fraturas vertebrais osteoporóticas por compressão na coluna toracolombar, melhorando os níveis de DMO e diminuindo os níveis de SOST no soro. Nível de Evidência II, Estudo prospectivo comparativo.

Cerebrospinal fluid microscopy as an index for predicting the prognosis of cryptococcal meningitis patients with and without HIV.

Aim: To evaluate the clinical data and quantitative cerebrospinal fluid for associations with the outcome of cryptococcal meningitis (CM) patients in the hospital. Patients & methods: We retrospectively analyzed a total of 139 CM patients comprising 108 without HIV and 31 with HIV admitted in a Jiang Xi hospital. Resµlts: We found that CM patients with the high fungal burden (≥10 yeasts/µl) (26.3%) had a worse prognosis than those with the low fungal burden (<10 yeasts/µl). (4.9%) (p = 0.0007 <0.05). Conclusion: In CM patients, a fungal burden of 10 yeasts/µl in the first cerebrospinal fluid test may be used as an indicator of patient prognosis, and we can personalize patients' treatment based on the fungal burden to improve prognosis.

Expression and clinical significance of latent-transforming growth factor beta-binding protein 2 in primary hepatocellular carcinoma.

The present study aimed to explore the expression of latent transforming growth factor ß binding protein 2 (LTBP2) in patients with hepatocellular carcinoma (HCC) and their correlation to clinicopathologial features.Serum levels of LTBP2 in 60 patients with HCC, 35 patients with hepatocellular benign tumors, 60 patients with precancerous lesions of HCC, and 60 healthy volunteers were determined by enzyme-linked immunosorbent assay. The expression levels of LTBP2 at messenger RNA (mRNA) and protein levels in 60 cases of HCC and adjacent tissues were detected by quantitative real-time polymerase chain reaction and immunohisochemistry. Statistical analysis was used to analyze the relationship between LTBP2 and clinical characteristics of patients with HCC.The mRNA and protein levels of LTBP2 were significantly upregulated in HCC tissues compared to adjacent tissues. Additionally, higher serum LTBP2 level was also observed in HCC patients relative to normal controls. Further investigation demonstrated that LTBP2 expression was associated with malignant degree of tumor, tumor progression, tumor differentiation, tumor size, tumor stage and hepatitis virus infection, and has prognostic implications in HCC patients.LTBP2 might be served as a potential biomarker in diagnosis and treatment of HCC.

Catalase ameliorates diabetes-induced cardiac injury through reduced p65/RelA- mediated transcription of BECN1.

Catalase is an antioxidative enzyme that converts hydrogen peroxide (H2 O2 ) produced by superoxide dismutase from highly reactive superoxide (O2- ) to water and oxygen molecules. Although recent findings demonstrate that catalase, autophagy and the nuclear factor κB (NF-κB) signalling pathway are centrally involved in diabetic cardiomyopathy (DCM), the interplay between the three has not been fully characterized. Thus, the mechanism responsible for catalase-mediated protection against heart injury in diabetic mice was investigated in this study, as well as the role of NF-κB-p65 in the regulation of autophagic flux was investigated in this study. Western blot analysis revealed that catalase inhibited NF-κB activity and decreased LC3-II (microtubule-associated protein 1 light chain 3) and beclin-1 (Atg6) expression. Furthermore, up-regulation of autophagy was detrimental for cardiac function in diabetic mice. Catalase overexpression reduced the level of NF-κB subunit in the nucleus, where it initiates autophagy through activation of the key autophagy gene BECN1. To evaluate the role of the NF-κB pathway in diabetes-induced autophagy, Bay11-7082, an NF-κB inhibitor, was injected into diabetic mice, which suppressed NF-κB and attenuated diabetes-induced autophagy and myocardial apoptosis. In agreement with the in vivo results, Bay11-7082 also inhibited high-glucose-induced activation of NF-κB and the up-regulation of LC3-II and beclin-1 expression in H9c2 cells. In addition, high-glucose-induced activation of autophagic flux and apoptosis were largely attenuated by p65 siRNA, suggesting that catalase ameliorates diabetes-induced autophagy, at least in part by increasing the activity of the NF-κB pathway and p65-mediated transcription of BECN1.

Long noncoding RNA ZEB1-AS1 acts as an oncogene in osteosarcoma by epigenetically activating ZEB1.

Long noncoding RNAs (lncRNAs) have been demonstrated to be dysregulated in many disease states and have pivotal roles in various pathophysiological processes. However, the expression, roles and potential mechanism of lncRNA ZEB1-AS1 in osteosarcoma are still unknown. In this study, we measured ZEB1-AS1 expression and the results showed that ZEB1-AS1 was upregulated in osteosarcoma tissues and cells. Increased expression of ZEB1-AS1 is correlated with larger tumor size, progressed Enneking stage, tumor metastasis, worse recurrence-free and overall survival of osteosarcoma patients. Functional experiments showed that enhanced expression of ZEB1-AS1 promotes osteosarcoma cells proliferation and migration. By contrast, ZEB1-AS1 knockdown inhibits osteosarcoma cells proliferation and migration. Mechanistically, ZEB1-AS1 directly binds and recruits p300 to the ZEB1 promoter region, induces an open chromatin structure, and activates ZEB1 transcription. There is a significant correlation between the expression of ZEB1-AS1 and ZEB1 in osteosarcoma tissues. ZEB1 depletion abrogates the roles of ZEB1-AS1 on the proliferation and migration of osteosarcoma cells. Collectively, these findings demonstrated that ZEB1-AS1 functions as an oncogene in osteosarcoma via epigenetically activating ZEB1 and could be a potential target for osteosarcoma treatment.

AGT M235T variant is not associated with risk of cancer.

OBJECTIVE: The angiotensinogen (AGT) gene has been considered to be implicated in the development of cancer. However, the results have been inconsistent. In this study, we performed a meta-analysis to clarify the association of AGT M235T variant with cancer risk. METHODS: Published literature from PubMed and Embase were retrieved. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using a fixed- or random-effects model. RESULTS: A total of seven articles including eight studies (3639 cancer cases and 6684 controls) for AGT M235T variant were included. The present meta-analysis showed that AGT M235T variant was marginally associated with cancer risk under dominant model (OR=1.12, 95% CI=1.02-1.24). However, the positive association was not stable after sensitivity analysis. Further subgroup analysis by cancer type did not suggest any association of AGT M235T variant with various cancers (all p>0.05). CONCLUSION: The present meta-analysis demonstrated that AGT M235T variant was not associated with risk of all cancer or various cancers. Further well-designed studies with large sample size should be conducted to confirm or refute the non-significant association.

Sulforaphane induces Nrf2 and protects against CYP2E1-dependent binge alcohol-induced liver steatosis.

BACKGROUND: The mechanism(s) by which alcohol causes cell injury are still not clear but a major mechanism appears to be the role of lipid peroxidation and oxidative stress in alcohol toxicity. CYP2E1-generated ROS contributes to the ethanol-induced oxidant stress and inhibition of CYP2E1 activity decreases ethanol-induced fatty liver. The transcription factor Nrf2 regulates the expression of many cytoprotective enzymes which results in cellular protection against a variety of toxins. METHOD: The current study was designed to evaluate the ability of sulforaphane, an activator of Nrf2, to blunt CYP2E1-dependent, ethanol-induced steatosis in vivo and in vitro. RESULTS: The sulforaphane treatment activated Nrf2, increased levels of the Nrf2 target heme oxygenase-1 and subsequently lowered oxidant stress as shown by the decline in lipid peroxidation and 3-nitrotyrosine protein adducts and an increase in GSH levels after the acute ethanol treatment. It decreased ethanol-elevated liver levels of triglycerides and cholesterol and Oil Red O staining. Similar results were found in vitro as addition of sulforaphane to HepG2 E47 cells, which express CYP2E1, elevated Nrf2 levels and decreased the accumulation of lipid in cells cultured with ethanol. Sulforaphane treatment had no effect on levels of or activity of CYP2E1. CONCLUSIONS: Sulforaphane proved to be an effective in vivo inhibitor of acute ethanol-induced fatty liver in mice. GENERAL SIGNIFICANCE: The possible amelioration of liver injury which occurs under these conditions by chemical activators of Nrf2 is of clinical relevance and worthy of further study.