Exosome miRNA-203 promotes M1 macrophage polarization and inhibits prostate cancer tumor progression.

Prostate cancer (PCa) is a prevalent malignant neoplasm affecting the male reproductive system globally. However, the diagnostic and therapeutic approaches fall short of meeting the demands posed by PCa. Poor expression of miRNA-203 (miR-203) within PCa tissues and cells implies its potential utility as a diagnostic indicator for PCa. Exosomes (Exo), membranous vesicles released by various cells, are rich reservoirs of miRNAs. However, the presence of miR-203 presents within Exo derived from PCa cells remains unclarified. In this study, Exo was isolated from urine specimens collected from clinical PCa patients and LNCaP cells to detect miR-203 expression. Meanwhile, the impact of overexpressed miR-203 on M0 macrophages (mø) was analyzed. Subsequently, alterations in the proliferative, migratory, and invasive capacities of LNCaP cells were examined within a co-culture system featuring elevated miR-203 levels in both macrophages and LNCaP cells. Furthermore, the repercussions of miR-203 upregulation or inhibition were explored in a murine PCa tumor model. The results revealed that Exo manifested a circular or elliptical morphology, encapsulating a phospholipid bilayer approximately 100 nm in diameter. Notably, Exo readily infiltrated, with both Exo and miR-203-overexpressing Exo prompting macrophage polarization toward the M1 subtype. In the co-culture system, miR-203 exhibited pronounced suppression of LNCaP cell proliferation, migration, and invasion, while concurrently fostering apoptosis as compared with the LNCaP group (Control). In vivo experiments further disclosed that miR-203 greatly inhibited the growth of PCa tumors in nude mice. Markedly heightened expression of M1 macrophage markers such as IL-1ß, IL-6, IL-12, CXCL9, and CXCL10 was observed within the tumor microenvironment following miR-203 intervention, as opposed to the model group. However, the introduction of miR-203 antagomir led to a reversal in tumor growth trends. This investigation indicates the presence of miR-203 within the urine of PCa patients and Exo originating from cells, and that miR-203 exerted antitumor effect by facilitating M1 macrophage polarization. Our study furnishes valuable insights into the potential applicability of miR-203 as a diagnostic biomarker and therapeutic target for PCa.

Risk stratification and outcomes of intracranial hemorrhage in patients with immune thrombocytopenia under 60 years of age.

Intracranial hemorrhage (ICH) is a devastating complication of immune thrombocytopenia (ITP). However, information on ICH in ITP patients under the age of 60 years is limited, and no predictive tools are available in clinical practice. A total of 93 adult patients with ITP who developed ICH before 60 years of age were retrospectively identified from 2005 to 2019 by 27 centers in China. For each case, 2 controls matched by the time of ITP diagnosis and the duration of ITP were provided by the same center. Multivariate analysis identified head trauma (OR = 3.216, 95%CI 1.296-7.979, P =.012), a platelet count ≤ 15,000/µL at the time of ITP diagnosis (OR = 1.679, 95%CI 1.044-2.698, P =.032) and severe/life-threatening bleeding (severe bleeding vs. mild bleeding, OR = 1.910, 95%CI 1.088-3.353, P =.024; life-threatening bleeding vs. mild bleeding, OR = 2.620, 95%CI 1.360-5.051, P =.004) as independent risk factors for ICH. Intraparenchymal hemorrhage (OR = 5.191, 95%CI 1.717-15.692, P =.004) and a history of severe bleeding (OR = 4.322, 95%CI 1.532-12.198, P =.006) were associated with the 30-day outcome of ICH. These findings may facilitate ICH risk stratification and outcome prediction in patients with ITP.

Development of a High-Sensitivity Optical Accelerometer for Low-Frequency Vibration Measurement.

Low-frequency vibration is a harmful factor that affects the accuracy of micro/nano-measuring machines. Low-frequency vibration cannot be completely eliminated by passive control methods, such as the use of air-floating platforms. Therefore, low-frequency vibrations must be measured before being actively suppressed. In this study, the design of a low-cost high-sensitivity optical accelerometer is proposed. This optical accelerometer mainly comprises three components: a seismic mass, a leaf spring, and a sensing component based on a four-quadrant photodetector (QPD). When a vibration is detected, the seismic mass moves up and down due to the effect of inertia, and the leaf spring exhibits a corresponding elastic deformation, which is amplified by using an optical lever and measured by the QPD. Then, the acceleration can be calculated. The resonant frequencies and elastic coefficients of various seismic structures are simulated to attain the optimal detection of low-frequency, low-amplitude vibration. The accelerometer is calibrated using a homemade vibration calibration system, and the calibration experimental results demonstrate that the sensitivity of the optical accelerometer is 1.74 V (m·s-2)-1, the measurement range of the accelerometer is 0.003⁻7.29 m·s-2, and the operating frequencies range of 0.4⁻12 Hz. The standard deviation from ten measurements is under 7.9 × 10-4 m·s-2. The efficacy of the optical accelerometer in measuring low-frequency, low-amplitude dynamic responses is verified.

[Procalcitonin impact analysis, respiratory function and blood gas analysis on Xiaoqinglong decoction combined with non-invasive ventilation in treatment of AECOPD patients].

To observe the effect of Xiaoqinglong decoction combined with noninvasive ventilation on procalcitonin (PCT), blood gas analysis and respiratory functions in acute exacerbation of chronic obstructive pulmonary disease in the elderly (AECOPD), and investigate its correlation and clinical significance. Eighty-four elderly AECOPD patients with respiratory failure in our hospital from January 2015 to October 2017, were randomly divided into control group and observation group, 42 cases in each group. The control group received western medicine combined with noninvasive ventilator therapy, and the patients in observation group additionally received Xiaoqinglong decoction on the basis of the treatment in control group. Both groups were treated for 2 weeks. The clinical effects of two groups were observed and their PCT, blood gas analysis outcomes [arterial oxygen partial pressure (PaO2), arterial partial pressure of carbon dioxide (PaCO2), respiratory function, forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), FEV1/FVC], TCM syndrome score and other indexes and adverse reactions were compared before and after treatment. The total efficiency was 95.24% (40/42) in observation group, higher than 76.19% (32/42) in control group, with statistically significant difference (P<0.05). There were no statistically significant differences in PCT, PaO2, PaCO2, FVC, FEV1/FVC, FEV1, and TCM syndrome scores between two groups before treatment. But after treatment, PCT and PaCO2 levels in the observation group were lower and PaO2, FVC, FEV1/FVC, FEV1 levels was higher than those in the control group (P<0.05); TCM syndrome scores were lower than those in the control group (P<0.05); both groups had no obvious adverse reactions. The results showed that Xiaoqinglong decoction combined with noninvasive ventilator could significantly reduce the procalcitonin level, effectively improve the respiratory function and blood gas analysis indexes, and significantly reduce the clinical symptoms in AECOPD patients, so it is worthy of promotion.

Optical trapping of microparticles with two tilted-focused laser beams.

We present an optical method for the manipulation of microparticles using two tilted-focused beams. First, the action on the microparticles is studied with a single tilted-focused beam. The beam is used to drive the directional motion of a dielectric particle. When the optical scattering force is larger than the optical gradient force, the particle is pushed to the tilted side of the optical axis by the optical force. Second, two tilted-focused beams with the same power and complementary tilt angles are used to assemble an optical trap. The trap can be used to realize the optical trapping of the dielectric particles and opto-thermal trapping of the light absorbing particles. The trapping mechanism is the balance of the forces exerted on the particles, including the optical scattering force, optical gradient force, gravity, and thermal gradient force. The trap center is away from the focal spots, which effectively prevents the laser beam from being focused on the trapped object.

BET in hematologic tumors: Immunity, pathogenesis, clinical trials and drug combinations.

The bromodomain and extra-terminal (BET) proteins act as "readers" for lysine acetylation and facilitate the recruitment of transcriptional elongation complexes. BET protein is associated with transcriptional elongation of genes such as c-MYC and BCL-2, and is involved in the regulation of cell cycle and apoptosis. Meanwhile, BET inhibitors (BETi) have regulatory effects on immune checkpoints, immune cells, and cytokine expression. The role of BET proteins and BETi in a variety of tumors has been studied. This paper reviews the recent research progress of BET and BETi in hematologic tumors (mainly leukemia, lymphoma and multiple myeloma) from cellular level studies, animal studies, clinical trials, drug combination, etc. BETi has a promising future in hematologic tumors, and future research directions may focus on the combination with other drugs to improve the efficacy.

Gut microbiota deficiency ameliorates multiple myeloma and myeloma-related bone disease by Th17 cells in mice models.

Purpose: Multiple myeloma, the second most common hematological tumor, is currently incurable. Multiple myeloma-related bone disease is a characteristic clinical symptom that seriously affects the survival and prognosis of patients. In recent years, gut microbiota has been shown to play an important role in the occurrence and development of multiple myeloma. However, whether and how it affects the development of myelomatous bone disease is unclear. Methods: To investigate the mechanism and influence of the microbiota on multiple myeloma and myeloma bone disease, a myeloma-gut microbiota deletion mice model was established. 16S rRNA sequencing was used to analysis of bacterial flora changes. Histochemical staining and bone micro-CT were used to assess the severity of bone disease. Bone marrow tumor load and spleen Th17 cells were detected by flow cytometry. Results: Histochemical staining revealed a reduced tumor burden after eliminating gut microbial communities in mice by administering a mixture of antibiotics. According to the 16S rRNA sequencing of intestinal contents, antibiotic treatment resulted in a significant change in the microbiota of the mice. Bone micro-CT demonstrated that antibiotic treatment could reduce bone lesions caused by myeloma while increasing mineral density, bone volume fraction, trabecular bone thickness, and trabecular number. Meanwhile, histochemical staining of the bone found that the enhanced bone resorption was weakened by the change of flora. These results were consistent with the concentration of IL17 in serum and the frequency of Th17 cells in spleen. Conclusions: Herein, the effects of the gut microbiome on myeloma bone disease are investigated for the first time, providing new insight into its pathogenesis and suggesting that gut microbiota may serve as a therapeutic target in multiple myeloma-associated bone diseases.

NORAD promotes multiple myeloma cell progression via BMP6/P-ERK1/2 axis.

Multiple myeloma (MM) is one of the most common tumors of the hematological system and remains incurable. Recent studies have shown that long noncoding RNA NORAD is a potential oncogene in a variety of tumors. However, the general biological role and clinical value of NORAD in MM remains unknown. In this study, we measured NORAD expression in bone marrow of 60 newly diagnosed MM, 30 post treatment MM and 17 healthy donors by real-time quantitative polymerase chain reaction (qPCR). The NORAD gene was knockdown by lentiviral transfection in MM cell lines, and the effects of NORAD on apoptosis, cell cycle and cell proliferation in MM cells were examined by flow cytometry, CCK8 assay, EDU assay and Western blot, and the differential genes after knockdown of NORAD were screened by mRNA sequencing, followed by in vivo experiments and immunohistochemical assays. We found that knockdown of NORAD promoted MM cell apoptosis, induced cell cycle G1 phase arrest, and inhibited MM cell apoptosis in in vivo and in vitro experiments. Mechanistically, NORAD plays these roles through the BMP6/P-ERK1/2 axis. We discuss a novel mechanism by which NORAD acts pro-tumorigenically in MM via the BMP6/P-ERK1/2 axis.

Developing and validating a mortality prediction model for ICH in ITP: a nationwide representative multicenter study.

Intracranial hemorrhage (ICH) is a rare and life-threatening hemorrhagic event in patients with immune thrombocytopenia (ITP). However, its mortality and related risk factors remain unclear. Herein, we conducted a nationwide multicenter real-world study of ICH in adult ITP patients. According to data from 27 centers in China from 2005 to 2020, the mortality rate from ICH was 33.80% (48/142) in ITP adults. We identified risk factors by logistic univariate and multivariate logistic regression for 30-day mortality in a training cohort of 107 patients as follows: intraparenchymal hemorrhage (IPH), platelet count ≤10 × 109/L at ICH, a combination of serious infections, grade of preceding bleeding events, and Glasgow coma scale (GCS) level on admission. Accordingly, a prognostic model of 30-day mortality was developed based on the regression equation. Then, we evaluated the performance of the prognostic model through a bootstrap procedure for internal validation. Furthermore, an external validation with data from a test cohort with 35 patients from 11 other centers was conducted. The areas under the receiver operating characteristic (ROC) curves for the internal and external validation were 0.954 (95% confidence interval [CI], 0.910-0.998) and 0.942 (95% CI, 0.871-1.014), respectively. Both calibration plots illustrated a high degree of consistency in the estimated and observed risk. In addition, the decision curve analysis showed a considerable net benefit for patients. Thus, an application (47.94.162.105:8080/ich/) was established for users to predict 30-day mortality when ICH occurred in adult patients with ITP.

Opportunities and Challenges for Gut Microbiota in Acute Leukemia.

Acute leukemia (AL) is a highly heterogeneous hematologic malignancy, and although great progress has been made in the treatment of AL with allogeneic hematopoietic stem cell transplantation (Allo-HSCT) and new targeted drugs, problems such as infection and GVHD in AL treatment are still serious. How to reduce the incidence of AL, improve its prognosis and reduce the side effects of treatment is a crucial issue. The gut microbiota plays an important role in regulating disease progression, pathogen colonization, and immune responses. This article reviews recent advances in the gut microbiota and AL pathogenesis, infection, treatment and its role in allo-HSCT.

Aggressive natural killer cell leukemia with skin manifestation associated with hemophagocytic lymphohistiocytosis: A case report.

BACKGROUND: Aggressive natural killer cell leukemia (ANKL) is a rare natural killer cell neoplasm characterized by systemic infiltration of Epstein-Barr virus and rapidly progressive clinical course. ANKL can be accompanied with hemophagocytic lymphohistiocytosis (HLH). Here, we report a case of ANKL with rare skin lesions as an earlier manifestation, accompanied with HLH, and review the literature in terms of etiology, clinical manifestation, diagnosis and treatment. CASE SUMMARY: A 30-year-old woman from Northwest China presented with the clinical characteristics of jaundice, fever, erythema, splenomegaly, progressive hemocytopenia, liver failure, quantities of abnormal cells in bone marrow, and associated HLH. The immunophenotypes of abnormal cells were positive for CD2, cCD3, CD7, CD56, CD38 and negative for sCD3, CD8 and CD117. The diagnosis of ANKL complicated with HLH was confirmed. Following the initial diagnosis and supplementary treatment, the patient received chemotherapy with VDLP regimen (vincristine, daunorubicin, L-asparaginase and prednisone). However, the patient had severe adverse reactions and complication such as severe hematochezia, neutropenia, and multiple organ dysfunction syndrome, and died a few days later. CONCLUSION: This is the first reported case of ANKL with rare skin lesions as an earlier manifestation and associated with HLH.

Bendamustine treatment of Chinese patients with relapsed indolent non-Hodgkin lymphoma: a multicenter, open-label, single-arm, phase 3 study.

BACKGROUND: Bendamustine was approved in China on May 26th, 2019 by the National Medical Product Administration for the treatment of indolent B-cell non-Hodgkin lymphoma (NHL). The current study was the registration trial and the first reported evaluation of the efficacy, safety, and pharmacokinetics of bendamustine in Chinese adult patients with indolent B-cell NHL following relapse after chemotherapy and rituximab treatment. METHODS: This was a prospective, multicenter, open-label, single-arm, phase 3 study (NCT01596621; C18083/3076) with a 2-year follow-up period. Eligible patients received bendamustine hydrochloride 120 mg/m2 infused intravenously on days 1 and 2 of each 21-day treatment cycle for at least six planned cycles (and up to eight cycles). The primary endpoint was the overall response rate (ORR); and secondary endpoints were duration of response (DoR), progression-free survival (PFS), safety, and pharmacokinetics. Patients were classified according to their best overall response after initiation of therapy. Proportions of patients in each response category (complete response [CR], partial response [PR], stable disease, or progressive disease) were summarized along with a two-sided binomial exact 95% confidence intervals (CIs) for the ORR. RESULTS: A total of 102 patients were enrolled from 20 centers between August 6th, 2012, and June 18th, 2015. At the time of the primary analysis, the ORR was 73% (95% CI: 63%-81%) per Independent Review Committee (IRC) including 19% CR and 54% PR. With the follow-up period, the median DoR was 16.2 months by IRC and 13.4 months by investigator assessment; the median PFS was 18.6 months and 15.3 months, respectively. The most common non-hematologic adverse events (AEs) were gastrointestinal toxicity, pyrexia, and rash. Grade 3/4 neutropenia was reported in 76% of patients. Serious AEs were reported in 29 patients and five patients died during the study. Pharmacokinetic analysis indicated that the characteristics of bendamustine and its metabolites M3 and M4 were generally consistent with those reported for other ethnicities. CONCLUSION: Bendamustine is an active and effective therapy in Chinese patients with relapsed, indolent B-cell NHL, with a comparable risk/benefit relationship to that reported in North American patients. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, No. NCT01596621; https://clinicaltrials.gov/ct2/show/NCT01596621.

Effects of Celastrol on growth inhibition of U937 leukemia cells through the regulation of the Notch1/NF-kappaB signaling pathway in vitro.

BACKGROUND AND OBJECTIVE: Leukemia is a malignant tumor highly dependent on nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB), which is relevant for the occurrence, metastasis, proliferation, apoptosis, and drug resistance of tumor cells. Research has confirmed that the NF-kappaB family is one of the target genes in the Notch signaling pathway. This study investigated the effects of Celastrol on the apoptosis of U937 cells and the expression levels of Notch1 and NF-kappaB in these cells. METHODS: U937 cells were treated with various concentrations Celastrol (0.5-16.0) micromol/L for 12-60 h. MTT assay was performed to examine the effect of Celastrol on growth inhibition of U937 cells. Cell apoptosis was detected through both Annexin-V FITC/PI double-labeled cytometry and transmission electron microscopy (TEM). Cell cycle regulation was studied by propidium iodide. Western blot analysis and reverse transcription-polymerase chain reaction (RT-PCR) technologies were applied to assess the expression level of Notch1 in U937 cells. Subcellular distributions of NF-kappaB/p65 were detected through confocal microscopy. RESULTS: Celastrol presented striking growth inhibition and apoptosis induction potency on U937 cells in vitro in a time- and dose-dependent manner. The IC50 value of Celastrol for 24 h was (6.21 +/- 0.242) micromol/L. Moreover, Celastrol induced apoptosis in U937 cells in a cell-cycle dependent manner, which means that Celastrol could arrest U937 cells in the G0/G1 phase. Through TEM, apoptotic bodies containing nuclear fragments were found in Celastrol-treated U937 cells. Overexpression of Notch1 was found in U937 cells, while Celastrol could downregulate it at both the protein and mRNA level in a dose-dependent manner, and expression of NF-kappaB decreased in nuclei and increased in the cytoplasm (P < 0.05). CONCLUSIONS: Celastrol inhibited cell proliferation and induced apoptosis in U937 cells in a concentration-dependent manner. The possible mechanism might be involved in the regulation of a survival signaling pathway, such as Notch or NF-kappaB.

Effects of endoplasmic reticulum stress on autophagy and apoptosis of human leukemia cells via inhibition of the PI3K/AKT/mTOR signaling pathway.

The present study aimed to explore the regulatory effects of endoplasmic reticulum stress (ERS) on the phosphoinositide 3­kinase (PI3K)/AKT serine/threonine kinase 1 (AKT)/mammalian target of rapamycin (mTOR) signaling pathway, and its subsequent effects on autophagy and apoptosis of human leukemia cells. Human leukemia cells were cultured and treated with various concentrations of tunicamycin for 0, 24, 48, 72 and 90 h. Subsequently, human leukemia cells were assigned into the ER activation group, which was treated with 100 ng/ml tunicamycin, the ER activation + TO901317 (PI3K inhibitor) group, and the control group. An MTT assay was conducted to detect cell proliferation. In addition, a monodansylcadaverine (MDC) assay was used to detect the formation of autophagosomes and Annexin V­fluorescein isothiocyanate/propidium iodide double staining was used to examine cell apoptosis. Western blotting was performed to detect the expression levels of 78­kDa glucose­regulated protein (GRP78), phosphorylated (p)­protein kinase R­like endoplasmic reticulum kinase (PERK), p­α subunit of eukaryotic initiation factor 2 (eIF2α), microtubule­associated protein 1A/1B­light chain 3 (LC3), caspase­3, CCAAT­enhancer­binding protein homologous protein (CHOP), PI3K, AKT and mTOR. Treatment with 100 ng/ml tunicamycin for 72 h was considered the optimal condition for further experiments. Compared with in cells prior to treatment, human leukemia cells treated with tunicamycin exhibited increased expression of p­PERK, p­eIF2α and GRP78 after 72 h (P<0.05). In addition, the expression levels of mTOR, AKT and PI3K were decreased in the ER activation group compared with in the control and ER activation + TO901317 groups (P<0.05). Compared with in the control group, cell proliferation was inhibited and MDC fluorescence intensity was increased in the ER activation group (P<0.05). Furthermore, compared with in the control and ER activation + TO901317 groups, western blotting indicated that the expression levels of LC3­II were increased in the ER activation group (P<0.05). The apoptotic rate was also higher in the ER activation group compared with in the control group (P<0.05), and caspase­3 and CHOP expression was elevated in the ER activation group (P<0.05). These findings indicated that ERS may induce autophagy and apoptosis of human leukemia cells via inhibiting the PI3K/AKT/mTOR signaling pathway.

[Killing activity of co-cultured cytokine-induced killer cells and dendritic cells against multi-drug resistant tumor cell lines].

OBJECTIVE: A lot of studies have suggested that a certain amount of T cells may be involved among cytokine-induced killer (CIK) cells. The aim of the present study was to prove whether an antigen-specific killing effect on tumor cells is involved during the CIKs-induced killing process. METHODS: Bone marrow mononuclear cells (BMMNCs) derived from healthy subjects were separately cultured to generate dendritic cells (DC) and CIKs. A human mammary cancer cell line MCF-7/ADR, expressing P-gp antigen, was frozen-thawed and the lysate including P-gp antigen was obtained. The DC pulsed with or without tumor antigen lysate was co-cultured with CIK (pulsed-DC + CIK and DC + CIK), and CIK cultured alone was used as control. The cell phenotype of DC and CIK was analyzed by flow cytometry. The secretion of IL-12 and IFN-gamma was assayed by ELSA. The antitumor effect of the three CIK groups targeted at MCF-7/ADR cells expressing P-gp antigen and MCF-7 cells was detected by MTT. RESULTS: Pulsed-DC + CIK group and DC + CIK group showed a higher expression level of DC mature phenotypes than those before co-culture with CIK, with a significant difference (P = 0.003, P = 0.001, respectively). The phenotypes (CD3, CD8, CD56) of CIK in pulsed-DC + CIK group and DC + CIK group was higher than those in CIK group (P = 0.003, P = 0.011, respectively). Among the three CIK groups, pulsed-DC + CIK group had the highest phenotypes on CD3+ CD56 (pulsed-DC + CIK vs. DC + CIK, P = 0.001; pulsed-DC + CIK vs. CIK, P < 0.001) and CD3 CD8 (P = 0.002, P = 0.002, respectively). Among the three groups, the pulsed-DC + CIK group showed the lowest CD45RA phenotype (pulsed-DC + CIK vs. DC + CIK, P < 0.001; pulsed-DC + CIK vs. CIK, P = 0.004). Among the three groups the secretion of IL-12 and IFN-gamma had the highest level in pulsed-DC + CIK group, with a value of 254 +/- 14.5 pg/ml and 3100 +/- 286 pg/ml, respectively. The antitumor killing effect on MCF-7/ADR cells had a significant difference between any two groups (pulsed-DC + CIK VS. DC + CIK, P = 0.039; pulsed-DC + CIK VS. CIK, P = 0.002; DC + CIK vs. CIK, P = 0.049). The highest was in pulsed-DC + CIK group and the lowest was in CIK group. The CIK group showed a significantly lower antitumor effect on MCF-7 cells than the other two groups (pulsed-DC + CIK vs. CIK, P = 0.007; DC + CIK vs. CIK, P = 0.048), but no significant difference between the pulsed-DC + CIK and DC + CIK groups. CONCLUSION: In the present study, DC and CIK cells have been successfully obtained and cultured from bone marrow mononuclear cells. After their co-culture, not only both their specific phenotypes were increased, but also the associated cytokines were secreted. An improved antitumor killing effect and some possible specific immunocytotoxicity were observed. Our findings provided a basis for experimental and clinical research on bio-immunotherapy targeted at multi-drug resistant tumor cells.

Chaperonin containing TCP-1 subunit 3 is critical for gastric cancer growth.

BACKGROUND: Members of eukaryotic chaperonin family are essential for cell survival. Dysregulation of Chaperonin containing TCP-1 subunit 3 (CCT3) has been implicated in the development of several types of cancers. However, the role of CCT3 in the development of gastric cancer has yet to be determined. METHODS: The expression patterns of CCT3 in the surgical specimens from 26 gastric cancer patients were evaluated using immunohistochemistry methods. To study the possible roles of CCT3 in the growth and survival of gastric cancer cells, RNA interference was used to knockdown CCT3 expression in gastric cancer cell lines BGC-823 and MGC-803. The effects of CCT3 knockdown on cancer cell proliferation, apoptosis and in vivo growth were examined. Finally, gene expression changes related to CCT3 knockdown were studied using gene array analysis and western blotting. RESULTS: Higher level of CCT3 expression was detected in the gastric cancer tissue compared to adjacent non-cancerous epithelium. Knockdown of CCT3 inhibited proliferation and colony formation while promoted apoptosis of gastric cancer cells in vitro. Gastric cancer cells exhibited lower growth potential in nude mice when CCT3 expression was suppressed. Gene expression analysis showed that CCT3 knockdown was associated with down-regulation of mitogen-activated protein kinase kinase kinase 7, cell division cycle 42, cyclin D3 and up-regulation of cyclin-dependent kinase 2 and 6. CONCLUSION: Our results suggested that CCT3 played a critical role in gastric cancer growth and survival. Further studies on the mechanisms of CCT3 function is mandated to develop novel cancer treatment targeting CCT3.

Neuroprotective effects of curdione against focal cerebral ischemia reperfusion injury in rats.

BACKGROUND: Curdione is one of the most highly concentrated component of the active constituents in E-zhu, which has been reported to possess a variety of activities. However, the pharmacologic neuroprotective activity of curdione has not been evaluated. The present study aimed to investigate the protective effect of curdione on focal cerebral ischemia reperfusion-induced injury in rats and further exploring the underlying mechanisms. MATERIALS AND METHODS: Adult male Sprague Dawley rats were subjected to middle cerebral artery occlusion (MCAO) surgery for 2 h, followed by reperfusion stage. All animals received treatment once a day for 7 days before surgery and 14 days from 4 h after the reperfusion started. The neurological deficit test and Morris water maze test were performed at 1, 4, 7 and 14 days after MCAO. The infarct size of animals was determined by the 2,3,5-triphenyltetrazolium chloride staining, and pathological brain damage was estimated by hematoxylin-eosin staining. The malonaldehyde (MDA) levels and the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-PX) were detected by enzyme-linked immunosorbent assay. Expression of apoptotic proteins was measured by Western blot. RESULTS: Our results showed that curdione could significantly reduce the infarct size and neurological deficits, promote cognitive function recovery and recover neuronal morphologic damages in MCAO rats. It also blocked the increase of MDA content and elevated the activities of SOD, CAT and GSH-PX. Moreover, curdione attenuated the expression of Cyt-C, c-caspase-3 and c-caspase-9 increased the Bcl-2/Bax ratio and hence decreased the cellular apoptosis. CONCLUSION: Curdione possessed potential neuroprotective effect on rats in the MCAO model. The anti-oxidative and anti-apoptotic properties may be involved in the underlying mechanisms.

The effects of the long non-coding RNA MALAT-1 regulated autophagy-related signaling pathway on chemotherapy resistance in diffuse large B-cell lymphoma.

OBJECTIVE: Our study aimed to investigate the effects of the long non-coding RNA MALAT-1 (lncRNA MALAT-1) regulated autophagy-related signaling pathway on chemotherapy resistance in diffuse large B-cell lymphoma (DLBCL). METHODS: Human normal B lymphocytes (IM-9I) and DLBCL cell lines (Farage, Pfeiffer, Raji, Daud, Ly1, Ly3, Ly8 and Ly10) were chosen for our experiment. qRT-PCR was applied to detect the expression of lncRNA MALAT-1 in each DLBCL cell line. Farage and Daud cells were induced to be drug-resistant using 0.05µg/ml Adriamycin. LncRNA MALAT-1 interfering stable transfected cell lines were constructed and cells were transfected with lentivirus. The cells were divided into the blank, siNC, and siRNA-MALAT-1 groups. CCK-8 assay, flow cytometry, and Transwell assay were performed to detect cell survival rate, cycle, apoptosis, and invasion, respectively. The autophagosome formation in each group was observed under a transmission electron microscope. Western blotting was used to detect the expressions of the autophagy-related proteins and genes. The in vivo drug sensitivity of the tumor was observed using a subcutaneous tumor xenograft model in nude mice. RESULTS: The expression of lncRNA MALAT-1 in each DLBCL cell line was higher than in the IM-9 cells, with the Farage cells ranking highest (all P<0.05). When compared with the blank and the siNC groups, the siRNA-MALAT-1 group showed a decreased cell survival rate, an increased percentage of cells in G0/G1 phase, a decreased proportion of cells in S and G2/M phases, and a reduced number of migratory cell at each time point (all P<0.05). When compared with the blank and the siNC groups, the formation of autophagosomes, increased LC3-II/LC3-I expression, decreased p62 expression, and increased expression of the autophagy gene ATG5 were observed in the siRNA-MALAT-1 group at each time point (all P<0.05). Also, the siRNA-MALAT-1 group had a decreased tumor volume and weight in the subcutaneous tumor xenograft model in nude mice, and increased LC3-II/LC3-I expression but decreased p62 expression in tumor tissues when compared with the blank group and the siNC group (all P<0.05). CONCLUSION: Our study provides evidence that inhibiting lncRNA MALAT-1 can improve the chemotherapy sensitivity of DLBCL by enhancing autophagy-related proteins.

Hematology oncology practice in the Asia-Pacific APHCON survey results from the 6th international hematologic malignancies conference: bridging the gap 2015, Beijing, China.

This report serves as a snapshot of the state-of-knowledge in the Asia Pacific (APAC) Hematology Oncology community, and establishes a baseline for longitudinal investigations to follow changes in best practices over time. The objective of this study was to understand the approach to hematologic diseases, common standards of care and best practices, issues that remain controversial or debated, and educational or resource gaps that warrant attention. We used mobile application to disseminate and distribute questionnaires to delegates during the 6th international hematologic malignancies conference hosted by the APAC Hematology Consortium at Beijing, China. User responses were collected in an anonymous fashion. We report survey results in two ways: the overall responses, and responses as stratified between Chinese physicians and "Other" represented nationalities. Overall geographical concordance in survey responses was positive and strong. Perhaps more interesting than instances of absolute agreement, these data provide a unique opportunity to identify topics in which physician knowledge or opinions diverge. We assigned questions from all modules to broad categories of: patient information; diagnosis; treatment preference; transplantation; and general knowledge/opinion. On average, we observed a geographic difference of 15% for any particular answer choice, and this was fairly constant across survey modules. These results reveal utility and need for widespread and ongoing initiatives to assess knowledge and provide evidence-based education in real time. The data will be made more valuable by longitudinal participation, such that we can monitor changes in the state of the art over time.