RBC Transfusion Strategy in Oncological Patients with Chronic RBC Transfusion Therapy.

BACKGROUND: Red blood cell (RBC) transfusion therapy has greatly reduced mortality and morbidity in multiply transfused patients with oncological malignancies. The aim of this study was to underline the necessity of introducing a policy for extended RBC phenotyping of these patients and for the issuing of antigen-matched blood (at least for E antigen). METHODS: Multivariate logistic regression analysis was used to evaluate the associations of age, gender, transfusion history, and various malignancies with the development of red cell alloimmunization. RESULTS: Given the results of antibody identification, we finally obtained 732 cases to be analyzed, designating them as the p group. The respiratory system (231/732; 31.6%), digestive system (273/732; 37.3%), and female reproductive system (127/732; 17.3%) had the three highest alloimmunization rates in the p group. We screened 81 cases from the p group for which antibody screening in our laboratory had historically yielded negative results. Among the 81 cases with antibody seroconversion, anti-E was the most frequently observed antibody (37%). CONCLUSIONS: The results related to multivariate logistic regression analysis of the Rh group indicate that, in contrast to the other variates, transfusion confers a strongly increased risk of Rh blood system-related red cell alloimmunization. To reduce alloimmunization in tumor patients, it will be essential to introduce a policy for extended RBC phenotyping of high-risk patients and for the issuing of antigen-matched blood (at least for E antigen).

Comparison of demineralized bone matrix with different cycling crushing times in posterolateral fusion model of athymic rats.

Decalcified bone matrix (DBM) is a widely used alternative material for bone transplantation. In the DBM production process, an effective particle size and the highest utilization rate of raw materials can be achieved only through multiple high-speed circulating comminution. The rat posterolateral lumbar fusion model (PLF) is the most mature small animal model for the initial evaluation of the efficacy of graft materials for bone regeneration and spinal fusion. To evaluate the differences in the in vivo osteogenic effects of DBM pulverization through 1, 5, 9, and 14 high-speed cycles, sixty athymic rats were divided into six groups: single cycling crushing (CC1), 5 cycles of crushing (CC5), 9 cycles of crushing (CC9), 13 cycles of crushing (CC13), autogenous bone graft (ABG) and negative control (NC). Posterolateral lumbar fusion was performed. Six weeks after surgery, the bilateral lumbar fusion of athymic rats was evaluated through manual palpation, X-ray, micro-CT and histological sections. Rank data were tested by the rank-sum test, and nonparametric data were tested by the Kruskal‒Wallis H test. The manual palpation and X-ray results showed that the fusion rate did not significantly differ between the CC1, CC5, CC9, CC13 and ABG groups. However, cavities appeared in CC9 and CC13 on the micro-CT image. The bone mass (BV/TV) of CC1, CC5, CC9 and CC13 was better than that of the ABG group, while almost no osteogenesis was observed in the NC group. Histologically, there was no obvious difference between the four groups except that the CC9 group and CC13 group had more fibrous tissues in the new bone. In conclusion, DMB with different cycling crushing times has no obvious difference in fusion rate of PLF, but it is slightly better than the ABG group.

Anti-Inflammatory Ergosteroid Derivatives from the Coral-Associated Fungi Penicillium oxalicum HL-44.

To obtain the optimal fermentation condition for more abundant secondary metabolites, Potato Dextrose Agar (PDA) medium was chosen for the scale-up fermentation of the fungus Penicillium oxalicum HL-44 associated with the soft coral Sinularia gaweli. The EtOAc extract of the fungi HL-44 was subjected to repeated column chromatography (CC) on silica gel and Sephadex LH-20 and semipreparative RP-HPLC to afford a new ergostane-type sterol ester (1) together with fifteen derivatives (2-16). Their structures were determined with spectroscopic analyses and comparisons with reported data. The anti-inflammatory activity of the tested isolates was assessed by evaluating the expression of pro-inflammatory factors Tnfα and Ifnb1 in Raw264.7 cells stimulated with LPS or DMXAA. Compounds 2, 9, and 14 exhibited significant inhibition of Ifnb1 expression, while compounds 2, 4, and 5 showed strong inhibition of Tnfα expression in LPS-stimulated cells. In DMXAA-stimulated cells, compounds 1, 5, and 7 effectively suppressed Ifnb1 expression, whereas compounds 7, 8, and 11 demonstrated the most potent inhibition of Tnfα expression. These findings suggest that the tested compounds may exert their anti-inflammatory effects by modulating the cGAS-STING pathway. This study provides valuable insight into the chemical diversity of ergosteroid derivatives and their potential as anti-inflammatory agents.

Discovery, synthesis, and optimization of teixobactin, a novel antibiotic without detectable bacterial resistance.

Discovering new antibiotics with novel chemical scaffolds and antibacterial mechanisms presents a challenge for medicinal scientists worldwide as the ever-increasing bacterial resistance poses a serious threat to human health. A new cyclic peptide-based antibiotic termed teixobactin was discovered from a screen of uncultured soil bacteria through iChip technology in 2015. Teixobactin exhibits excellent antibacterial activity against all the tested gram-positive pathogens and Mycobacterium tuberculosis, including drug-resistant strains. Given that teixobactin targets the highly conserved lipid II and lipid III, which induces the simultaneous inhibition of both peptidoglycan and teichoic acid synthesis, the emergence of resistance is considered to be rather difficult. The novel structure, potent antibacterial activity, and highly conservative targets make teixobactin a promising lead compound for further antibiotic development. This review provides a comprehensive treatise on the advances of teixobactin in the areas of discovery processes, antibacterial activity, mechanisms of action, chemical synthesis, and structural optimizations. The synthetic methods for the key building block l-allo-End, natural teixobactin, representative teixobactin analogs, as well as the structure-activity relationship studies will be highlighted and discussed in details. Finally, some insights into new trends for the generation of novel teixobactin analogs and tips for future work and directions will be commented.

Identification of a prognostic signature based on immune-related genes in bladder cancer.

Bladder cancer (BLCA) has a high incidence and recurrence rate, and the effect of immunotherapy varies from person to person. Immune-related genes (IRGs) have been shown to be associated with immunotherapy and prognosis in many other cancers, but their role in immunogenic BLCA is less well defined. In this study, we constructed an eight-IRG risk model, which demonstrated strong prognostic and immunotherapeutic predictive power. The signature was significantly related to tumor clinicopathological characteristics, tumor class, immune cell infiltration and mutation status. Additionally, a nomogram containing the risk score and other potential risk factors could effectively predict the long-term overall survival probability of BLCA patients. The enriched mechanisms identified by gene set enrichment analysis suggested that the reason why this signature can accurately distinguish high- and low-risk populations may be closely related to the different degrees of innate immune response and T cell activation in different patients.

A novel tool for predicting the survival of endoprosthesis used for reconstruction of the knee following tumor resection: a retrospective cohort study.

BACKGROUND: Prosthesis-related complications, after knee reconstruction with endoprosthesis during operation for tumors around the knee, remain an unresolved problem which necessitate a revision or even an amputational surgery. The purpose of the current study was to identify significant risk factors associated with implant failure, and establish a novel model to predict survival of the prosthesis in patients operated with endoprostheses for tumor around knee. METHODS: We retrospectively reviewed the clinical database of our institution for patients who underwent knee reconstruction due to tumors. A total of 203 patients were included, including 123 males (60.6%) and 80 (39.4%) females, ranging in age from 14 to 77 years (mean: 34.3 ± 17.3 years). The cohort was randomly divided into training (n = 156) and validation (n = 47) samples. Univariable COX analysis was used for initially identifying potential independent predictors of prosthesis survival with the training group (p < 0.150). Multivariate COX proportional hazard model was selected to identify final significant prognostic factors. Using these significant predictors, a graphic nomogram, and an online dynamic nomogram were generated for predicting the prosthetic survival. C-index and calibration curve were used for evaluate the discrimination ability and accuracy of the novel model, both in the training and validation groups. RESULTS: The 1-, 5-, and 10-year prosthetic survival rates were 94.0, 90.8, and 83.0% in training sample, and 96.7, 85.8, and 76.9% in validation sample, respectively. Anatomic sites, length of resection and length of prosthetic stem were independently associated with the prosthetic failure according to multivariate COX regression model (p<0.05). Using these three significant predictors, a graphical nomogram and an online dynamic nomogram model were generated. The C-indexes in training and validation groups were 0.717 and 0.726 respectively, demonstrating favourable discrimination ability of the novel model. And the calibration curve at each time point showed favorable consistency between the predicted and actual survival rates in training and validation samples. CONCLUSIONS: The length of resection, anatomical location of tumor, and length of prosthetic stem were significantly associated with prosthetic survival in patients operated for tumor around knee. A user-friendly novel online model model, with favorable discrimination ability and accuracy, was generated to help surgeons predict the survival of the prosthesis.

Catalytic pyrolysis of linear low-density polyethylene using recycled coal ash: Kinetic study and environmental evaluation.

Catalytic pyrolysis offers a sustainable route to convert plastic wastes into fuel. We investigated the catalytic performance of coal ash (fly and bottom ash) at blending ratio of 5 wt%, and 15 wt% during pyrolysis of linear low-density polyethylene (LLDPE). The influence on activation energy and oil was characterized via thermogravimetric analyzer (TGA) and gas chromatography-mass spectrometry (GC-MS). Results have shown that 15 wt% bottom ash exhibited higher catalytic activity. The activation energy estimated by Coats-Redfern method decreased from 458.7 kJ·mol-1 to 437.8 kJ·mol-1, while the alicyclic hydrocarbon yield increased from 5.97% to 32.09%. This implies that CaO, which is abundant in bottom ash, could promote the conversion of LLDPE. Furthermore, a cradle-to-factory gate life cycle assessment was performed to investigate three scenarios (non-catalytic pyrolysis, 15 wt% fly ash, and 15 wt% bottom ash) of LLDPE conversion strategies via a normalization and weighting approach. It was found that LLDPE pyrolysis with 15 wt% bottom ash also showed the lowest normalized score of 2.83, implying the lowest environmental impact. This work has demonstrated that the recycling of coal ash, particularly bottom ash, as catalysts for LLDPE pyrolysis is effective.

Anti-inflammatory effects of powdered product of Bu Yang Huan Wu decoction: Possible role in protecting against Transient Focal Cerebral Ischemia.

Bu Yang Huan Wu decoction (BYHW) is a traditional Chinese medicine (TCM) that consists of several herbs and has been used in patients with ischemic stroke for centuries. Although powdered formula of BYHW has widely been prescribed in clinic nowadays, evidence-based effectiveness and mechanism of action of BYHW powdered product in stroke remain to be characterized. Adult male Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 90 min followed by reperfusion for 24 h (ischemia/reperfusion; I/R) or sham surgery. After I/R, the rats were then given low dose (0.5 g/kg) and high dose (2.5 g/kg) of BYHW or vehicle by oral gavage twice a day for seven consecutive days. The results showed that I/R induced obvious cerebral infarction and neurobehavioral defects, in parallel with histological aberrations and extensive signaling of proinflammatory cytokines, including tumor necrosis factor (TNF-α) and interleukin-6 (IL-6), in the stroke model. Post-I/R treatment with BYHW powdered product significantly reduced the infarct area and ameliorated neurofunctional defects in a dose-dependent manner. The dose dependence was associated with TNF-α downregulation and interleukin-10 (IL-10) induction. In summary, the present findings demonstrated that BYHW powdered product exhibited therapeutic efficacy for experimental stroke and a higher dose treatment may strengthen the effectiveness via inflammatory modulation.

Diagnostic Value of Peripheral Blood miR-374b-5p in Patients with Prostate Cancer.

BACKGROUND: Increased evidence suggested the important role of microRNAs (miRNAs) in the tumorigenesis of prostate cancer (PCa). The aberrant expression of miRNA (miR)-374b-5p has been observed in various types of cancers. The purpose of the current study was to evaluate the relationship between miR-374b-5p expression levels and PCa and to assess the feasibility of using peripheral blood miR-374b-5p as a potential non-invasive biomarker for PCa. METHODS: Total RNA was isolated from the whole-blood samples of 42 PCa patients whole-blood samples, 42 benign prostatic hyperplasia (BPH) patients, and 42 healthy controls (HC). The expression of miR-374b-5p was assessed by reverse transcription quantitative polymerase chain reaction. Normalized data were subjected to the receiver operating characteristic (ROC) and Kaplan-Meier analysis. RESULTS: The expression of peripheral blood miR-374b-5p was significantly higher in PCa patients than in HC individuals and patients with BPH (p < 0.001). Upregulation of miR-374b-5p was observed to be related to certain parameters, including Gleason score > 7 (p < 0.001), and PSA > 20 ng/mL (p < 0.01). To further evaluate the role of miR-374b-5p in patients with PCa, ROC analysis was carried out. Our data showed that peripheral blood miR-374b-5p could screen PCa patients from HC individuals (area under the curve (AUC), 0.851; 95% CI, 0.766 - 0.936; p < 0.001) and patients with BPH (AUC, 0.831; 95% CI, 0.742 - 0.920; p < 0.001). CONCLUSIONS: Increased miR-374b-5p expression in peripheral blood may serve as a potential biomarker to distinguish PCa patients from healthy controls and BPH patients.

Prognostic factors for overall survival in patients with spinal metastasis secondary to prostate cancer: a systematic review and meta-analysis.

BACKGROUND: To guide the selection of treatments for spinal metastases, the expected survival time is one of the most important determinants. Few scoring systems are fully applicable for spinal metastasis secondary to prostate cancer (PCa). This study aimed to identify the independent factors to predict the overall survival (OS) of patients with spinal metastases from PCa. METHODS: The PubMed, Embase and CENTRAL were retrieved by two reviewers independently, to identify studies analyzed the prognostic effect of different factors in spinal metastasis from PCa. A systematic review and quantitative meta-analysis was conducted with hazard ratio (HR) and 95% confidence interval (95%CI) as the effect size. RESULTS: A total of 12 retrospective cohort studies (1566 patients) were eligible for qualitative synthesis and 10 for quantitative meta-analyses. The OS was significantly influenced by performance status, visceral metastasis, ambulatory status and time from PCa diagnosis in more than half of the available studies. The meta-analyses demonstrated that OS was significantly influenced by visceral metastasis (HR = 2.24, 95%CI:1.53-3.27, p < 0.001), pre-treatment ambulatory status (HR = 2.64, 95%CI:1.82-3.83, p < 0.001), KPS (HR = 4.45, 95%CI:2.01-9.85, p < 0.001), ECOG (HR = 2.96, 95%CI:2.02-4.35, p < 0.001), extraspinal bone metastasis (HR = 2.04, 95%CI:1.13-3.68, p = 0.018), time developing motor deficit (HR = 1.57, 95%CI:1.30-1.88, p < 0.001) and time from PCa diagnosis (HR = 1.37, 95%CI:1.17-1.59, p < 0.001). CONCLUSIONS: Visceral metastasis, ambulatory status, extraspinal bone metastasis, performance status, time developing motor deficit and time interval from primary tumor diagnosis were significantly associated with the OS for spinal metastasis from PCa. When selecting the treatment modality, clinicians should fully consider the patients' systematic status based on all potential prognostic factors. LEVEL OF EVIDENCE: I Meta-analysis.

Impact of prostate cancer radiotherapy on the biological behavior and specific mortality of subsequent bladder cancer.

BACKGROUND: The impact of different radiotherapy modalities on the development and characteristics of second primary bladder cancers (BCa) and BCa-specific mortality (BCa-SM) remains unclear. Thus, we evaluated the incidence and biological behavior of subsequent BCa and related survival in patients who underwent radiation therapy for prostate cancer (PCa). METHODS: A total of 530,581 patients in the surveillance, epidemiology, and end results database with localized PCa between 1988 and 2013 were identified. PCa treatments included radical prostatectomy (RP), external beam radiotherapy (EBRT), radioactive implants (RI), and combined EBRT and RI (EBRI). A multivariable competing risk analysis based on a proportional sub distribution hazards model was used to determine the impact of different radiotherapy modalities on BCa incidence and specific mortality. RESULTS: Incidence of BCa was significantly high in patients treated with EBRT, RI, and EBRI vs. RP [sub distribution hazard ratio (SHR) 1.41, P < 0.001; SHR 1.58, P < 0.001; SHR 1.56, P < 0.001, respectively]. BCa following EBRT, RI, and EBRI were more commonly non-urothelial (3.3%, 2.9%, 3.3%, respectively, versus 1.2%) and T4 (3.5%, 6.1%, 5.0%, respectively, versus 1.6%) compared with RP. RI associated with a higher rate of BCa metastasis than RP (2.6% vs. 1.1%). Prior EBRT, RI, and EBRI increased BCa-SM (SHR 1.44, P = 0.001; SHR 1.21, P = 0.047; and SHR 1.42, P = 0.032, respectively). CONCLUSIONS: Patients receiving radiotherapy for PCa have a higher risk of BCa. BCa after EBRT, RI, and EBRI is more likely to be non-urothelial, stage T4, and with increased BCa-SM. Prior RI associated with a higher rate of BCa metastasis.

Anti-Cancer Effects of Radix Angelica Sinensis (Danggui) and N-Butylidenephthalide on Gastric Cancer: Implications for REDD1 Activation and mTOR Inhibition.

BACKGROUND/AIMS: Radix Angelica Sinensis (danggui in Chinese) is widely used in traditional chinese medicine (TCM). N-butylidenephthalide (BP), a bioactive compound in danggui, is a potential antitumor agent for various cancer types. However, its clinical effect and mechanism in the treatment of gastric cancer remain undetermined. METHODS: The in vivo protective effect of danggui in patients with gastric cancer were validated using data from Taiwan's National Health Insurance Research Database (NHIRD). The genes induced by BP-treatment were analyzed by whole transcriptome RNA sequencing (RNA-seq) and validated by real-time PCR, western blot and siRNA transfection. The effect of BP on AGS cell migration and invasion was evaluated in transwell assays. The antitumor effects of BP were evaluated in vivo in an AGS xenograft animal model. RESULTS: Danggui users were found to have an increased survival rate when compared with danggui nonusers (log-rank test p = 0.002) . The use of danggui highly associated with decreased mortality (the adjusted hazard ratio (HR) of danggui user was 0.72 [95 % CI, 0.57-0.92] (p = 0.009). The in vitro results showed that BP inhibited gastric cancer cell proliferation, and triggered cellular apoptosis depending on the activation of mitochondrial apoptotic pathway. Using RNA-seq analysis we found that REDD1 was the highest transcript induced by BP in gastric cancer cells. BP induce an increase of REDD1 expression that inhibits mTOR signaling, thus inhibiting gastric cancer growth. We used RNA interference to demonstrate that the knock-down of REDD1 attenuated the BP-induced mTORC1 activation and growth inhibition. BP suppressed the growth of AGS xenografts tumor in vivo. CONCLUSION: Danggui can prolong the survival rate of gastric cancer patients in Taiwan. BP caused gastric cancer cell death through the activation of mitochondria-intrinsic pathway and induced the REDD1 expression leading to mTOR signal pathway inhibition in gastric cancer cells. BP inhibited the in vivo growth of AGS xenograft tumors. These results may provide the basis for a new therapeutic approach toward the treatment of gastric cancer progression.

Brain Magnetic Resonance Imaging of Intracerebral Hemorrhagic Rats after Alcohol Consumption.

BACKGROUND: Alcoholism is one of the risk factors for cerebrovascular diseases. Our previous study demonstrated that acute alcohol intoxication enhances brain injury and neurological impairment in rats suffering from intracerebral hemorrhage (ICH). We plan to investigate the effect of chronic alcohol consumption (CAC) in rats with ICH by magnetic resonance imaging (MRI). METHODS: Sixteen Sprague-Dawley male rats were divided into 2 groups: CAC group (fed with 10% alcohol drinking water for 4 weeks, n = 8), and Control group (plain drinking water, n = 8). ICH was induced by collagenase infusion into the right striata of all rats. Coronal T1-weighted imaging, T2-weighted imaging, T2*-weighted imaging, and diffusion-weighted imaging were generated with a 3.0T MRI scanner to investigate the changes of hemorrhagic volume and edema throughout the injury and recovery stages of ICH in rats. RESULTS: T2-weighted imaging is ideal for monitoring hematoma volume in rats. The hematoma volume was larger in the CAC group than in the control group (P < .001), however, did not correlate to post-ICH progressive edema formation (P > .7), and neurological impairment (P > .28) between the 2 groups, respectively. DISCUSSION: Although our findings indicate that CAC induces larger hematoma in rats with ICH, the underlying mechanism should be studied in the future.

The prevalence and mortality of hyponatremia is seriously underestimated in Chinese general medical patients: an observational retrospective study.

BACKGROUND: Hyponatremia (serum sodium concentration < 135 mmol/L) is the most common electrolyte abnormality and is a predictor of the mortality of hospitalized patients in Western countries. However, hyponatremia data are lacking in Asian countries. Here we evaluate the epidemiology and mortality of hyponatremia in general medical hospitalized patients in China. METHODS: This is a cohort study of 154,378 adults who were hospitalized between 2008 and 2012 at a teaching hospital in Beijing. We identified hospital patients with hyponatremia and calculated the prevalence and in-hospital mortality of hyponatremia. We also conducted a comprehensive retrospective review of the medical records of patients who had severe hyponatremia (serum sodium <120 mmol/L) during hospitalization in 2012. RESULTS: The overall prevalence of hyponatremia at some point during hospitalization was 17.5% (26,990 patients), but only 0.26% (394 patients) of cases were identified with the diagnostic code of hyponatremia. Hyponatremia was more common in patients with infectious disease, cancer, or cardiovascular disease as the primary reason for hospitalization based on discharge diagnosis, with prevalences of 33.0, 25.9 and 24.9%, respectively. The in-hospital mortality was 0.48% amongst patients without hyponatremia compared to 3.57 and 20.23% in patients with serum sodium levels of 130-134 and <120 mmol/L, resulting in multivariable adjusted odds ratios (ORs) of 4.8 (95% CI 4.3-5.4) and 32.9 (95% CI 25.2-42.3), respectively. The mortality risk increased with increasing severity of hyponatremia in all diagnostic groups. After the multivariate adjustment, only the Charlson Comorbidity Index and age were independently associated with death risk (OR 1.36, 95% CI 1.14-1.64 and OR 1.04, 95% CI 1.00-1.09, respectively) in the patients with severe hyponatremia. CONCLUSIONS: Hyponatremia is highly prevalent among Chinese hospitalized patients and is associated with increased in-hospital mortality risk. Physicians should raise awareness to improve the prognosis of hyponatremia.

Potential therapeutic effects of N-butylidenephthalide from Radix Angelica Sinensis (Danggui) in human bladder cancer cells.

BACKGROUND: N-butylidenephthalide (BP) isolated from Radix Angelica Sinensis (Danggui) exhibits anti-tumorigenic effect in various cancer cells both in vivo and in vitro. The effect of BP in bladder cancer treatment is still unclear and worth for further investigate. METHODS: Changes of patients with bladder cancer after Angelica Sinensis exposure were evaluated by analysis of Taiwan's National Health Insurance Research Database (NHIRD) database. The anti-proliferative effect of BP on human bladder cancer cells was investigated and their cell cycle profiles after BP treatment were determined by flow cytometry. BP-induced apoptosis was demonstrated by Annexin V-FITC staining and TUNEL assay, while the expressions of apoptosis-related proteins were determined by western blot. The migration inhibitory effect of BP on human bladder cancer cells were shown by trans-well and wound healing assays. Tumor model in NOD-SCID mice were induced by injection of BFTC human bladder cancer cells. RESULTS: The correlation of taking Angelica sinensis and the incidence of bladder cancer in NHIRD imply that this herbal product is worth for further investigation. BP caused bladder cancer cell death in a time- and dose- dependent manner and induced apoptosis via the activation of caspase-9 and caspase-3. BP also suppressed the migration of bladder cancer cells as revealed by the trans-well and wound healing assays. Up-regulation of E-cadherin and down-regulation of N-cadherin were evidenced by real-time RT-PCR analysis after BP treatment in vitro. Besides, in combination with BP, the sensitivity of these bladder cancer cells to cisplatin increased significantly. BP also suppressed BFTC xenograft tumor growth, and caused 44.2% reduction of tumor volume after treatment for 26 days. CONCLUSIONS: BP caused bladder cancer cell death through activation of mitochondria-intrinsic pathway. BP also suppressed the migration and invasion of these cells, probably by modulating EMT-related genes. Furthermore, combination therapy of BP with a lower dose of cisplatin significantly inhibited the growth of these bladder cancer cell lines. The incidence of bladder cancer decreased in patients who were exposed to Angelica sinensis, suggesting that BP could serve as a potential adjuvant in bladder cancer therapy regimen.

Collagenase-Induced Rat Intra-Striatal Hemorrhage Mimicking Severe Human Intra-Striatal Hemorrhage.

Basal ganglia hemorrhage accounts for approximately 50% of all hemorrhagic strokes. A good rat model that produces severe intrastriatal hemorrhage (ISH) mimicking human severe ISH is lacking. The present study compared the intra-striatal injection of 0.2 U with that of 0.6 U of collagenase in inducing severe ISH in rats. Three-Tesla (3T) magnetic resonance imaging (MRI) was used to evaluate brain injuries in terms of hematoma size (volume), midline shift (MLS), and brain edema. This evaluation was further substantiated by determination of behavior and neurologic functions and mortality over 56 h. The 0.2 U collagenase caused hematoma volume increases for 10.3 to 30.1 mm³, while the 0.6 U caused 36.4 to 114.8 mm³, at post-ISH 1 h to 56 h. The 0.6 U collagenase significantly increased MLS to 1.5-3.0 times greater than the 0.2 U did at all post-intracerebral hemorrhage (ICH) time points. The MLS increased dependently with hematoma expansion with high correlation coefficients, yet no mortality occurred. These two dosages, nevertheless, caused the same pattern and severity in relative apparent diffusion coefficient (rADC) changes for three regions of interest (ROIs). Both ISH models induced consistent behavior deficits. The larger dosage produced severe brain injuries as well as neurological deficits, more closely mimicking severe human ISH. Hematoma volume and MLS can be the most useful parameters for evaluating the ISH severity in the present experimental model. The larger dosage, therefore, would be useful for investigating the pathophysiology of the severer ISH in the striatum. This may be applied for evaluating potential therapeutic strategies and outcomes in the future.

MicroRNA-20a-5p contributes to hepatic glycogen synthesis through targeting p63 to regulate p53 and PTEN expression.

Recently, it is implicated that aberrant expression of microRNAs (miRs) is associated with insulin resistance. However, the role of miR-17 family in hepatic insulin resistance and its underlying mechanisms remain unknown. In this study, we provided mechanistic insight into the effects of miR-20a-5p, a member of miR-17 family, on the regulation of AKT/GSK pathway and glycogenesis in hepatocytes. MiR-20a-5p was down-regulated in the liver of db/db mice, and NCTC1469 cells and Hep1-6 cells treated with high glucose, accompanied by reduced glycogen content and impaired insulin signalling. Notably, inhibition of miR-20a-5p significantly reduced glycogen synthesis and AKT/GSK activation, whereas overexpression of miR-20a-5p led to elevated glycogenesis and activated AKT/GSK signalling pathway. In addition, miR-20a-5p mimic could reverse high glucose-induced impaired glycogenesis and AKT/GSK activation in NCTC1469 and Hep1-6 cells. P63 was identified as a target of miR-20a-5p by bioinformatics analysis and luciferase reporter assay. Knockdown of p63 in the NCTC1469 cells and the Hep1-6 cells by transfecting with siRNA targeting p63 could increase glycogen content and reverse miR-20a-5p inhibition-induced reduced glycogenesis and activation of AKT and GSK, suggesting that p63 participated in miR-20a-5p-mediated glycogenesis in hepatocytes. Moreover, our results indicate that p63 might directly bind to p53, thereby regulating PTEN expression and in turn participating in glycogenesis. In conclusion, we found novel evidence suggesting that as a member of miR-17 family, miR-20a-5p contributes to hepatic glycogen synthesis through targeting p63 to regulate p53 and PTEN expression.

MiR-139-5p is Increased in the Peripheral Blood of Patients with Prostate Cancer.

BACKGROUND: Emerging evidence suggested that microRNAs (miRNAs) play a causal role in cancer tumorigenesis. Aberrant expression of miRNA (miR)-139-5p has been observed in various types of cancers. The present study evaluated the relationship between miR-139-5p expression levels and prostate cancer (PCa), to assess the feasibility of using peripheral blood miR-139-5p as a potential non-invasive biomarker for PCa. METHODS: Total RNA was extracted from peripheral whole blood samples from 45 PCa patients, 45 benign prostatic hyperplasia (BPH) patients and 50 healthy controls (HC). The expression of miR-139-5p was assessed by reverse transcription quantitative polymerase chain reaction. RESULTS: MiR-139-5p in peripheral blood was significantly higher in PCa patients than in patients with BPH and HC individuals (P<0.001). Higher miR-139-5p expression was observed to be associated with certain clinicopathological parameters, including PSA>20ng/ml (P<0.05), pathological tumor stage 3/4 (P<0.05) and Gleason score >7 (P<0.01). A receiver operating characteristic (ROC) curve analysis revealed that miR-139-5p distinguished PCa patients from BPH patients [area under the curve (AUC), 0.936; 95% CI, 0.878-0.993; P<0.001]. CONCLUSIONS: Peripheral blood miR-139-5p may be utilized as a potential novel non-invasive biomarker for PCa screening.

Epigenetic regulation contributes to urocortin-enhanced midbrain dopaminergic neuron differentiation.

The production of midbrain dopaminergic (mDA) neurons requires precise extrinsic inductive signals and intrinsic transcriptional cascade at a specific time point in development. Urocortin (UCN) is a peptide of the corticotropin-releasing hormone family that mediates various responses to stress. UCN was first cloned from adult rat midbrain. However, the contribution of UCN to the development of mDA neurons is poorly understood. Here, we show that UCN is endogenously expressed in the developing ventral midbrain (VM) and its receptors are exhibited in Nurr1(+) postmitotic mDA precursors and TH(+) neurons, suggesting possible roles in regulating their terminal differentiation. UCN treatment increased DA cell numbers in rat VM precursor cultures by promoting the conversion of Nurr1(+) precursors into DA neurons. Furthermore, neutralization of secreted UCN with anti-UCN antibody resulted in a reduction in the number of DA neurons. UCN induced an abundance of acetylated histone H3 and enhanced late DA regulator Nurr1, Foxa2, and Pitx3 expressions. Using pharmacological and RNA interference approaches, we further demonstrated that histone deacetylase (HDAC) inhibition and late transcriptional factors upregulation contribute to UCN-mediated DA neuron differentiation. Chromatin immunoprecipitation analyses revealed that UCN promoted histone acetylation of chromatin surrounding the TH promoter by directly inhibiting HDAC and releasing of methyl CpG binding protein 2-CoREST-HDAC1 repressor complex from the promoter, ultimately leading to an increase in Nurr1/coactivators-mediated transcription of TH gene. Moreover, UCN treatment in vivo also resulted in increased DA neuron differentiation. These findings suggest that UCN might contribute to regulate late mDA neuron differentiation during VM development.

Hg(0) Capture over CoMoS/γ-Al2O3 with MoS2 Nanosheets at Low Temperatures.

CoMoS/γ-Al2O3 sorbent was prepared via incipient wetness impregnation (IWI) and sulfur-chemical vapor reaction (S-CVR) methods and tested in terms of its potential for Hg(0) capture. It was observed that the CoMoO/γ-Al2O3 showed a Hg(0) capture efficiency around 75% at a temperature between 175 and 325 °C while CoMoS/γ-Al2O3 achieved almost 100% Hg(0) removal efficiency at 50 °C. The high removal efficiency for CoMoS/γ-Al2O3 remained unchanged for 2000 min in the test. Its theoretical capacity for Hg(0) capture was found to be 18.95 mg/g based on the Elovich model. The ability of this material for Hg(0) capture is atributed to the MoS2 nanosheets coated on surface of the maro- and meso-pores of γ-Al2O3. These MoS2 are two-dimensional transition-metal dichalcogenide (2D TMDC) assembled with unsulfided cobalt atoms at the edges. It is believed that these MoS2 nanosheets provided dense active sites for Hg(0) capture. The removal of Hg(0) at low temperatures was achieved via the combination of Hg(0) with the chalcogen (S) atoms on the entire basal plane of the MoS2 nanosheets with coordinative unsaturated sites (CUS) to form a stable compound, HgS.