Genetically engineered pre-microRNA-34a prodrug suppresses orthotopic osteosarcoma xenograft tumor growth via the induction of apoptosis and cell cycle arrest.

Osteosarcoma (OS) is the most common primary malignant bone tumor in children, and microRNA-34a (miR-34a) replacement therapy represents a new treatment strategy. This study was to define the effectiveness and safety profiles of a novel bioengineered miR-34a prodrug in orthotopic OS xenograft tumor mouse model. Highly purified pre-miR-34a prodrug significantly inhibited the proliferation of human 143B and MG-63 cells in a dose dependent manner and to much greater degrees than controls, which was attributed to induction of apoptosis and G2 cell cycle arrest. Inhibition of OS cell growth and invasion were associated with release of high levels of mature miR-34a from pre-miR-34a prodrug and consequently reduction of protein levels of many miR-34a target genes including SIRT1, BCL2, c-MET, and CDK6. Furthermore, intravenous administration of in vivo-jetPEI formulated miR-34a prodrug significantly reduced OS tumor growth in orthotopic xenograft mouse models. In addition, mouse blood chemistry profiles indicated that therapeutic doses of bioengineered miR-34a prodrug were well tolerated in these animals. The results demonstrated that bioengineered miR-34a prodrug was effective to control OS tumor growth which involved the induction of apoptosis and cell cycle arrest, supporting the development of bioengineered RNAs as a novel class of large molecule therapeutic agents

Poly[[di-μ3-nicotinato-μ3-oxalato-samarium(III)silver(I)] dihydrate]

In the title three-dimensional heterometallic complex, {[AgSm(C6H4NO2)2(C2O4)]·2H2O}n, the SmIII ion is eight-coordinated by four O atoms from four different nicotinate ligands and four O atoms from two different oxalate ligands. The three-coordinate AgI ion is bonded to two N atoms from two different nicotinate anions and one O atom from an oxalate anion. These metal coordination units are connected by bridging nicotinate and oxalate ligands, generating a three-dimensional network. The uncoordinated water mol­ecules link the carboxyl­ate groups via O—H⋯O hydrogen bonding. The crystal structure is further stabilized by hydrogen bonds between the water mol­ecules

Poly[[di-μ3-nicotinato-μ3-oxalato-samarium(III)silver(I)] dihydrate]. Corrigendum

Corrigendum to Acta Cryst. (2009), E65, m1105

AZI23'UTR Is a New SLC6A3 Downregulator Associated with an Epistatic Protection Against Substance Use Disorders

Regulated activity of SLC6A3, which encodes the human dopamine transporter (DAT), contributes to diseases such as substance abuse disorders (SUDs); however, the exact transcription mechanism remains poorly understood. Here, we used a common genetic variant of the gene, intron 1 DNP1B sequence, as bait to screen and clone a new transcriptional activity, AZI23'UTR, for SLC6A3. AZI23'UTR is a 3' untranslated region (3'UTR) of the human 5-Azacytidine Induced 2 gene (AZI2) but appeared to be transcribed independently of AZI2. Found to be present in both human cell nuclei and dopamine neurons, this RNA was shown to downregulate promoter activity through a variant-dependent mechanism in vitro. Both reduced RNA density ratio of AZI23'UTR/AZI2 and increased DAT mRNA levels were found in ethanol-naive alcohol-preferring rats. Secondary analysis of dbGaP GWAS datasets (Genome-Wide Association Studies based on the database of Genotypes and Phenotypes) revealed significant interactions between regions upstream of AZI23'UTR and SLC6A3 in SUDs. Jointly, our data suggest that AZI23'UTR confers variant-dependent transcriptional regulation of SLC6A3, a potential risk factor for SUDs

Herbal Foot Bath improving Quality of Life for cancer patient

目的  评价“活血通络方”中药泡洗对周围神经损伤的改善疗效以及在改善晚期肿瘤患者生存质量的干预效果。方法  选取2014年1—9月在中国中医科学院西苑医院肿瘤科的晚期肿瘤住院患者40 例，按照患者入组先后顺序随机分成试验组（活血通络方中药泡洗，14例)，阳性药组（黄芪桂枝五物汤方中药泡洗，14例）和安慰剂组（安慰剂中药泡洗，12例）。分别对三组患者进行连续14天的干预。采用CIPN20症状自评量表、EORTC生命质量测定量表QLQ-C30、Karnofsky 体能状况评分进行测量，分别在干预前（第0天）和第7天和14天干预后进行资料收集。结果  干预后第7天和第14天与干预前的情绪状态、失眠得分在三组间差异有统计学意义（P<0.05），试验组好于阳性药组，安慰剂组好于阳性药组，试验组与安慰剂组之间差异无显著性；同时缓解恶心与呕吐，气促得分在三组间差异有统计学意义（P<0.05），试验组好于安慰剂组，试验组与阳性药组之间差异无显著性。结论  无论采用中药还是单独温水泡洗，都能改善肿瘤患者生活质量，尤其在缓解情绪功能，失眠方面的改善作用突显,，虽然在缓解化疗引起的神经毒反应的治疗中，短期内中药泡洗没有显示出疗效。Objective: To evaluate the effects of herbal foot bath for chemotherapy-induced peripheral neuropathy (CIPN), to improve quality of life for cancer patients. Methods: With a randomized controlled trial, 48 advanced cancer patients were randomly assigned to three groups: the experimental group (using promoting blood circulation herbal for 18 patients), the control group 1 (using Astragaloside herbal for 18 cases), and the control group 2 (using placebo herbal for 12 patients). Patients in the experimental group accepted the promoting blood circulation herbal. Patients in the control group 1 accepted the astragaloside herbal, and the patients in the control group 2 accepted the placebo herbal respectively. A course of treatment was 14 days, with 20 min each day, 14 consecutive days for one cycle.The Chemotherapy-induced peripheral neuropathy 20(CIPN20)、European Organization for Research and Treatment of Cancer-quality of life-C30(EORTC-QLQ-C30)、and Karnofsky performance score (KPS) were measured in the three groups for every 7 days, 2 times in total. Results: There was a significant difference for emotional state and insomnia in the  experimental group when comparing with the other two groups in 7and 14 days respectively （P<0.05）, the curative effect in the experiment group was better than one in the positive group, the effect in the placebo group was better than one in the positive group, no difference in the experiment group and the placebo group. Similarly, there was a significant difference for nausea and vomiting, shortness of breath when comparing with the other two groups in 7 and 14 days respectively（P<0.05），the curative effect in the experiment group was better than one in the placebo group, the same result in the positive group was better than one in the placebo group, no difference in the experiment group and the placebo group. Conclusion: No matter what using Traditional Chinese medicine (TCM) or warm water foot bath alone, can improve the quality of life in patients with cancer, especially in easing emotional function, improving insomnia, however, TCM foot bath didn’t highlight the curative effect of relieving chemotherapy-induced peripheral neuropathy for cancer in a short time

BCL9 enhances the development of cervical carcinoma by deactivating CPEB3/EGFR axis

Purpose: To investigate the differential expression of BCL9 in cervical carcinoma samples, analyze its biological functions in regulating malignant phenotypes of cervical carcinoma cells, and to explore its potential molecular mechanism.Methods: Expression levels of BCL9 in 58 pairs of cervical carcinoma tissues and paracancerous tissues were determined using quantitative real time-polymerase chain reaction (qRT-PCR). Kaplan- Meier curves were used to analyze the prognostic potential of BCL9 in cervical carcinoma. After knockdown using BCL9 by lentivirus transfection, proliferative and migratory changes in Siha and HeLa cells were determined by CCK-8, colony formation and Transwell assays. Cytoplasmic polyadenylation element binding protein 3 (CPEB3), the potential downstream target of BCL9, was confirmed via dualluciferase reporter assay. Western blot analyses were conducted to determine the protein levels of CPEB3, EGFR, AKT and p21 in Siha and HeLa cells with BCL9 knockdown. The co-regulation of BCL9 and CPEB3 on phenotypes of cervical carcinoma cell was investigated.Results: BCL9 was upregulated in cervical carcinoma tissues. The high level of BCL9 was predicted by the tumor size, advanced stage and poor prognosis. The knockdown of BCL9 significantly weakened proliferative and migratory abilities of Siha and HeLa cells (p < 0.05). CPEB3 was the downstream target of BCL9, and was lowly expressed in cervical carcinoma tissues. The knockdown of BCL9 upregulated CPEB3, and downregulated EGFR, AKT and p21 (p < 0.05). The knockdown of CPEB3 also reversed the influence of silenced BCL9 in regulating its proliferative and migratory abilities in cervical carcinoma cells (p < 0.05).Conclusion: BCL9 drives the deterioration of cervical carcinoma by inhibiting the CPEB3/EGFR axis.Thus, BCL9 may be a novel molecular target for cervical carcinoma treatment

Integrating machine learning algorithms to systematically assess reactive oxygen species levels to aid prognosis and novel treatments for triple -negative breast cancer patients

IntroductionBreast cancer has become one of the top health concerns for women, and triple-negative breast cancer (TNBC) leads to treatment resistance and poor prognosis due to its high degree of heterogeneity and malignancy. Reactive oxygen species (ROS) have been found to play a dual role in tumors, and modulating ROS levels may provide new insights into prognosis and tumor treatment.MethodsThis study attempted to establish a robust and valid ROS signature (ROSig) to aid in assessing ROS levels. The driver ROS prognostic indicators were searched based on univariate Cox regression. A well-established pipeline integrating 9 machine learning algorithms was used to generate the ROSig. Subsequently, the heterogeneity of different ROSig levels was resolved in terms of cellular communication crosstalk, biological pathways, immune microenvironment, genomic variation, and response to chemotherapy and immunotherapy. In addition, the effect of the core ROS regulator HSF1 on TNBC cell proliferation was detected by cell counting kit-8 and transwell assays.ResultsA total of 24 prognostic ROS indicators were detected. A combination of the Coxboost+ Survival Support Vector Machine (survival-SVM) algorithm was chosen to generate ROSig. ROSig proved to be the superior risk predictor for TNBC. Cellular assays show that knockdown of HSF1 can reduce the proliferation and invasion of TNBC cells. The individual risk stratification based on ROSig showed good predictive accuracy. High ROSig was identified to be associated with higher cell replication activity, stronger tumor heterogeneity, and an immunosuppressive microenvironment. In contrast, low ROSig indicated a more abundant cellular matrix and more active immune signaling. Low ROSig has a higher tumor mutation load and copy number load. Finally, we found that low ROSig patients were more sensitive to doxorubicin and immunotherapy.ConclusionIn this study, we developed a robust and effective ROSig model that can be used as a reliable indicator for prognosis and treatment decisions in TNBC patients. This ROSig also allows a simple assessment of TNBC heterogeneity in terms of biological function, immune microenvironment, and genomic variation

Clinical and Renal Biopsy Findings Predicting Outcome in Renal Thrombotic Microangiopathy: A Large Cohort Study from a Single Institute in China

Objective. The current study aimed to investigate the spectrum of etiologies and associated disorders of renal biopsy-proven thrombotic microangiopathy (TMA) patients. Methods. The clinical, laboratory, and renal histopathological data of patients with renal TMA from 2000 to 2012 in our institute were collected and reviewed. Results. One hundred and nine TMA patients were enrolled in this study. The mean age was 34.0 ± 11.1 years. Seventy patients (64.2%) were male and thirty-nine patients (35.8%) were female. There were eight patients (7.3%) with hemolytic uremic syndrome (HUS). Sixty-one patients (56.0%) were secondary to malignant hypertension. Fourteen patients (12.8%) were pregnancy-associated TMA. Other associated disorders included 17 patients with connective tissue disorders, 2 patients with hematopoietic stem cell transplantation, 4 patients with Castleman’s disease, 1 patient with cryoglobulinemia, and 2 patients with glomerulopathy. During followup, 8 patients died due to severe infection, 17 patients had doubling of serum creatinine, and 44 had end-stage renal disease. In multivariate analysis, male, elevated serum creatinine, and decreased hemoglobin were independently associated with poor renal outcomes. Conclusions. Renal TMA changes consisted of different disorders with various etiologies. aHUS, pregnancy-associated TMA, and malignant hypertension accounted for the majority of patients in our cohort