ABSTRACT
Long non-coding RNA (lncRNA) is a hot topic in the field of researching tumor pathogenesis, and the importance in hematologic malignancies has been gradually being elucidated. LncRNA not only regulates hematological tumorigenesis and progression through affecting various biological processes such as cell proliferation, differentiation, pluripotency and apoptosis; moreover, abnormal expression and mutation of lncRNA are closely related to drug resistance and prognosis. Thus lncRNA can be used as novel biomarker and potential therapeutic target for hematological tumors. In this review, we will focus on the latest progress of lncRNA in hematological tumors to provide new ideas for the clinical diagnosis, prognostic evaluation together with research and development of target drugs for hematologic malignancies.
Subject(s)
Humans , RNA, Long Noncoding/metabolism , Hematologic Neoplasms/genetics , Neoplasms , Carcinogenesis/pathology , Cell Transformation, Neoplastic/genetics , Gene Expression Regulation, NeoplasticABSTRACT
OBJECTIVE@#To investigate the effect and underlying mechanism of hispidulin on the proliferation and apoptosis of leukemia K562 cells.@*METHODS@#K562 cells were cultured in vitro and treated with 0, 5, 25 or 100 μmol/L hispidulin for 24 h. Cell proliferation and apoptosis were detected by CCK-8 and flow cytometry, respectively. Western blot was used to assess the expression of Bax, Bcl-2 and interleukin (IL)-37 proteins. Bone marrow mononuclear cells were extracted from 17 chronic myeloid leukemia patients and 21 healthy individuals by Ficoll-Hypaque density gradient method, and the expression of IL-37 protein was measured by Western blot. K562 cells with IL-37 overexpression or knockdown were constructed, and then treated with 0 or 100 μmol/L hispidulin for 24 h. Cell proliferation, apoptosis and protein expression of Bax and Bcl-2 were determined in the same way as above.@*RESULTS@#After K562 cells were treated with hispidulin, the cell inhibition rate, apoptosis rate, and the protein expression of Bax and IL-37 were significantly increased (P <0.05), but the cell proliferation and expression of Bcl-2 protein were decreased (P <0.05). The expression of IL-37 protein in bone marrow mononuclear cells of the leukemia patient was 0.24±0.03, which was significantly lower than 0.91±0.05 of healthy controls (P <0.05). Overexpression of IL-37 significantly promoted inhibition rate, apoptosis rate, and expression of Bax protein in K562 cells (P <0.05), but suppressed the expression of Bcl-2 protein (P <0.05). In addition, knockdown of IL-37 could reverse the effects of hispidulin on proliferation and apoptosis of K562 cells.@*CONCLUSION@#Hispidulin inhibits the proliferation and induces apoptosis of leukemia K562 cells, which may be related to the up-regulation of IL-37 protein in cells.
Subject(s)
Humans , K562 Cells , bcl-2-Associated X Protein/pharmacology , Apoptosis , Leukemia , Proto-Oncogene Proteins c-bcl-2 , Cell ProliferationABSTRACT
Although the body has a strong immune system which can resists the invasion of leukemia cells, leukemia cells disseminate systemically and form an immunosuppressive microenvironment through a variety of mechanisms, including regulation of antigen presentation, utilization of immunosuppressive enzyme AXL, immune cell inhibitory checkpoint NKG2A and immunoregulatory gene VISTA, resulting in immune escape. Therefore, most types of leukemia are inevitable for the affliction of drug resistance or relapse, and the immune efficacy is not as significant as that of other hematological tumors and the prognosis is suboptimal. This article reviews the immune heterogeneity of leukemia microenvironment from many aspects, including anti-leukemia immunity and immune escape. In addition, it also reviews the latest progress and future prospects of immune checkpoint inhibition, adoptive cell therapy and vaccine therapy in leukemia, providing a theoretical basis for the development of personalized combination therapy strategies with less toxic side effects.
Subject(s)
Humans , Immunotherapy/methods , Leukemia/therapy , Immunity , Combined Modality Therapy , Prognosis , Tumor MicroenvironmentABSTRACT
Anemoside B4 (B4), a main triterpenoid saponin from a traditional Chinese medicine plant, Pulsatilla chinensis, is a novel anti-inflammatory agent for protection from acute lung injury. We investigated the pulmonary availability and anti-inflammatory efficacy of B4 after intratracheal and intravenous dosing with a view to evaluating the suitability of inhalation delivery. All animal studies were performed under the guidelines approved by the Animal Care and Use Committee of Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences (Approval No: SLXD-20181113046). In vitro evaluation of the aerodynamic characteristics and droplet size distribution showed that the aerosols generated by a commercially available nebulizer were well deposited in the respiratory tract. Following intratracheal administration, B4 underwent pulmonary absorption into the bloodstream, rendering an absolute bioavailability of 103%. Compared to intravenous delivery, intratracheal administration dramatically increased the drug availability in lung tissue of rats by more than 1 000-fold, leading to improved and prolonged concentrations of B4 in lung tissue up to 48 h. In addition, the intratracheal administration of B4 resulted in dose-dependent and prolonged anti-inflammatory efficacy in a lipopolysaccharide (LPS)-induced lung injury model in mice. The present results demonstrate that inhalation delivery of B4 is a promising approach to treat pulmonary inflammation with once-daily dosing.
ABSTRACT
Pyrrolizidine alkaloids(PAs) are a group of naturally occurring alkaloids with a pyrrolizidine skeleton which can be found in about 3% of the world's flowering plants. It is notorious that PAs are cause the hepatoxic and genotoxic-carcinogenic effects by taking PA-containing herbs, food and dietary supplements. In order to control the poisoning caused by PAs, European Medicines Agency has set a limit of intake of PAs from herbal medicinal products at 0.007 μg of 1,2-unsaturated PAs/kg body weight. Nonetheless, a systematic overview of the amount of PAs in the herb has not been provided. Therefore, this paper is to systematically review the current status of PAs content analysis of herbal medicines and foods reported in the literature, and to provide theoretical and experimental support for the safety risk assessment and control of PAs in Chinese herbal medicines.
Subject(s)
Food , Herbal Medicine , Phytotherapy , Plants, Medicinal , Pyrrolizidine Alkaloids/toxicityABSTRACT
Early nutritional status, lifestyle and life experiences are critical to the health and development of one’s whole life. Previous studies on the effect of earthquake, flood, ice storm and hurricane, famine on population health were reviewed and sorted out from a perspective of life cycle. It turned out that catastrophic events exposure during the fetus period could have some adverse effects on the growth and development of fetuses, newborns and children, and also on mental health during the life cycle from newborns to adults. Based on the research results at home and abroad, future research on the long-term impacts of early-life adverse events on mental health could be further explored from such aspects as expanding research objects, improving research methods, and extending research content.
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Objective To evaluate the instant effects and five-year clinical outcomes of coronary artery disease patients complicated with diabetes mellitus after StentBoost-optimized percutaneous coronary intervention (PCI). Methods From March 2009 to July 2010, 184 patients undergoing PCI at our hospital were found stent underexpansion or malapposition by StentBoost after stents implantation and were divided into the diabetic (=73, 39.67%) and the non-diabetic group (=111, 60.33%). All patients received StentBoost-guided post-dilatation after stent implantation. The instant procedural results were measured and clinical outcome after five-year follow-up was analyzed in each group. Between-group comparisons were performed using Chi-square test or Student's test. Multivariate logistic regression analysis was carried out to reveal the independent predictors for long-term clinical outcomes of StentBoost-optimized PCI . Results After StentBoost-guided post-dilatation, the minimum diameter (MinLD), maximum diameter (MaxLD) and average diameter in both groups increased significantly than before (<0.001), the (MaxLD-MinLD)/MaxLD ratio and the in-stent residual stenosis decreased accordingly (<0.001). The five-year follow-up showed similar mortality rate (4.92% . 2.86%, =0.67) and major adverse cardiac event rate (11.48% . 11.43%, = 1.0) between the diabetic and the non-diabetic group, whereas the recurrence of angina pectoris was higher in the diabetic group compared to the non-diabetic group (47.54% . 29.52%; =0.02). A multivariate logistic regression analysis revealed that age and left ventricular ejection fraction rather than diabetes mellitus were independent predictors for long-term clinical outcomes. Conclusions StentBoost could effectively improve instant PCI results; the long-term clinical outcomes of StentBoost-optimized PCI were similar between diabetic and non-diabetic patients. Age and left ventricular ejection fraction were the independent predictors for long-term clinical outcomes.
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Objectives: To analyze the relationship between lung ultrasound B line and NT-proBNP, E/e' in order to explore the accuracy of B lines for diagnosing pulmonary edema in patients with acute heart failure (AHF). Methods: A total of 124 AHF patients admitted in out hospital from 2016-02 to 2017-02 were enrolled. According to the number of B line, patients were divided into 3 groups: Mild pulmonary edema group, patients with B line<15, Moderate pulmonary edema group, 15≤B line<30 and Severe pulmonary edema group, B line≥30. Basic clinical condition and echocardiography parameters were compared among 3 groups; relationships between B line and NT-proBNP, E/e', EF, pulmonary artery pressure were analyzed respectively; the sensitivity and specificity for B-line diagnosing NT-proBNP≥5000 pg/ml and E/e'≥14 were evaluated by ROC curve analysis. Results: Compared with Mild and Moderate pulmonary edema groups, Severe pulmonary edema group had the severer NYHA grade, more wet rale, higher NT-proBNP level and more chest X-ray of pulmonary congestion, P<0.05. Compared with Mild pulmonary edema group, Moderate and Severe pulmonary edema groups had decreased LVEF, P<0.05; Severe pulmonary edema group showed increased diastolic function such as elevated E/A, pulmonary artery pressure and E/e',P<0.05.B line was positively related to NT-proBNP,E/e'and pulmonary artery pressure,negatively related to EF.B line had the best correlation to NT-proBNP (r=0.803, P<0.001), the next was E/e'(r=0.794, P<0.001) and the worst was pulmonary artery pressure (r=0.330, P<0.001). The cutoff values of B line for diagnosing NT-proBNP≥5000pg/ml and E/e'≥14 were both 30, the AUC of ROC=0.823 and 0.768 respectively. Conclusions: Lung ultrasound B line had good correlation to NT-proBNP and E/e', which could accurately assess the pulmonary edema in AHF patients.
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Objective: To compare the clinical features between very late stent thrombosis (VLST) and very late in-stent restenosis, to discuss the potential risk factors for VLST occurrence. Methods: Our research included in 2 groups: VLST group, 21 ACS patients with coronary angiography (CAG) confirmed VLST admitted in our hospital and Control group, 38 ACS patients with CAG confirmed very late in-stent restenosis at same period of time. Basic clinical data, laboratory tests and relevant examinations were compared between 2 groups; potential risk factors for VLST occurrence were studied by Logistic regression analysis. Results: ① There were 8 (38.1%) patients discontinued anti-platelet therapy in a month by themselves in VLST group and 5 (13.2%) in Control group, P=0.03. ② 13 (61.9%) patients presented as ST-segment elevation myocardial infarction (STEMI) in VLST group, while all (100%) patients presented as Non-ST-segment elevation ACS (NST-ACS) in Control group, P<0.001. ③ The age, gender, previous histories of hypertension, diabetes, MI, smoking and interventional therapy were similar between 2 groups, P>0.05. ④ Compared with Control group, VLST group had decreased LVEF, P=0.001, increased peak values of TnI and NT-pro BNP, elevated WBC and hs-CRP, all P<0.001. ⑤ The index of echocardiography, blood lipid profiles, glucose and creatinine were similar between 2 groups, P>0.05. ⑥ Logistic regression analysis showed that discontinued anti-platelet therapy, elevated NT-pro BNP and hs-CRP were the independent risk factors for VLST occurrence, P<0.05. Conclusion: VLST may have life-threatening clinical features, insisted anti-platelet therapy and improved cardiac function could reduce VLST occurrence.
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RNA interference (RNAi) is a newly developed technology. It is the different levels of gene silencing induced by specific degradation of targeted genes in vivo, and both exogenous and endogenous double-stranded RNAs could induce the specific degradation. RNAi has been applied in tumor therapy, viral infection, hepatitis B and many other diseases. siRNA is the effector molecule which induces the RNAi in vivo. But naked siRNA is easily degradated by RNases in vivo, and the half-life is short. Meanwhile, the transfection efficiency of the naked siRNA is comparatively low. So the naked siRNA needs the help of vectors to penetrate the cell membrane and take action. Viral vectors have the potential immunogenicity and mutagenicity in gene therapy. Therefore, non-viral vectors are drawing more and more attention. The latest development of the non-viral vectors is summarized in this review.
Subject(s)
Animals , Humans , Cell-Penetrating Peptides , Chemistry , Chitosan , Chemistry , Drug Carriers , Chemistry , Genetic Vectors , Half-Life , Imines , Chemistry , Liposomes , Chemistry , Neoplasms , Therapeutics , Polyethylenes , Chemistry , RNA Interference , RNA, Small Interfering , Genetics , Therapeutic Uses , TransfectionABSTRACT
<p><b>BACKGROUND</b>StentBoost (SB) is a novel angiographic technique which can enhance stent visualization and improve detection of inadequate stent expansion. Studies of SB that compare it with intravascular ultrasound (IVUS), which is the current gold standard for detection of stent underexpansion, remain inadequate. This study aimed to test the correlation of IVUS and SB, and to evaluate the effect of SB guiding the stent postdilatation.</p><p><b>METHODS</b>From March 2009 to June 2010, 52 patients were analyzed using quantitative coronary angiography (QCA), IVUS, and SB. They included 37 patients (54 stents) with postdilatation and 15 patients (21 stents) without postdilatation. Correlations of stent diameter between the three modalities were determined.</p><p><b>RESULTS</b>The minimum diameter, maximum diameter and average diameter of postdilatation obtained by QCA, IVUS, SB were significantly larger than that of poststenting, and the ratio (maximum stent diameter (MaxLD)-minimum stent diameter (MinLD))/MaxLD of postdilatation was smaller. Correlations of MinLD were the highest between IVUS and SB (r = 0.979, P < 0.0001) when compared with QCA and SB (r = 0.973, P < 0.0001), and QCA and IVUS (r = 0.964, P < 0.0001).</p><p><b>CONCLUSIONS</b>SB has superior correlations for stent expansion measured by IVUS when compared with QCA. In addition, there is an important advantage for SB in guiding the stent postdilatation.</p>
Subject(s)
Aged , Female , Humans , Male , Middle Aged , Coronary Angiography , Methods , Coronary Disease , Therapeutics , Stents , Ultrasonography, Interventional , MethodsABSTRACT
<p><b>OBJECTIVE</b>The effects of various postconditioning algorithm on reperfusion injury and the role of mitochondrion pathway were investigated in a rat model of reperfusion/injury.</p><p><b>METHODS</b>Rats were divided into 5 groups: sham, reperfusion/injury (R/I group), reverse algorithm of postconditioning (R-Post, 30/10-25/15-15/25-10/30 s of reperfusion/re-occlusion), standard algorithm of postconditioning (S-Post, 4 cycles of 20/20 s of reperfusion/re-occlusion), and gradual algorithm of postconditioning (G-Post, 10/30-15/25-25/15-30/10 s of reperfusion/re-occlusion).</p><p><b>RESULTS</b>The levels of Bax, Cytochrome-c, Caspase-9, serum marker of myocardium and apoptosis index were significantly lower while the level of Bcl-2 was significantly higher in the three postconditioning groups than those in R/I group (all P < 0.05). The levels of Bax (0.35 +/- 0.10 vs. 0.50 +/- 0.02, P < 0.05), Cytochrome-c (0.66 +/- 0.16 vs. 1.68 +/- 0.22, P < 0.05), Caspase-9 (0.61 +/- 0.17 vs. 1.66 +/- 0.55, P < 0.05), serum marker of myocardium [CK: (251.00 +/- 45.16) U/L vs. (388.56 +/- 75.01) U/L, P < 0.05; CK-MB: (146.00 +/- 60.12) U/L vs. (291.16 +/- 52.41) U/L, P < 0.05] and apoptosis index [(4.32 +/- 1.16)% vs. (8.58 +/- 1.12)% , P < 0.05] were all significantly lower while Bcl-2 level (2.00 +/- 0.34 vs. 1.40 +/- 0.18, P < 0.05) was significantly higher in G-Post group than those in S-Post group. Moreover, above mentioned cardiac protective effects were significantly stronger in the G-Post group compared to R-Post group (all P < 0.05).</p><p><b>CONCLUSION</b>In conclusion, gradual algorithm of postconditioning could attenuate reperfusion injury more significantly than standard algorithm, and mitochondrion pathway plays an important role in this cardioprotective process.</p>
Subject(s)
Animals , Rats , Algorithms , Caspase 9 , Metabolism , Cytochromes c , Metabolism , Ischemic Postconditioning , Mitochondria , Metabolism , Myocardial Reperfusion Injury , Metabolism , Proto-Oncogene Proteins c-bcl-2 , Metabolism , Rats, Sprague-Dawley , bcl-2-Associated X Protein , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To test whether postconditioning could inhibit the expression of phospho-JNK (P-JNK) mitogen activated protein kinase (MAPK) and study its relation to apoptosis of cardiocyte.</p><p><b>METHODS</b>Sixty rats were randomly divided into six groups: sham, reperfusion injury (R/I), postconditioning (Post), SP600125 (I_JNK), anisomycin and postconditioning (Ani+Post) and anisomycin (Ani) groups. After acute myocardial infarction was induced in rats, placebo solution (DMSO), SP600125 (6 mg/kg) or anisomycin (2 mg/kg) was injected through jugular vein 5 min before reperfusion; 6 h later 3 rats of each group were executed and the hearts were separated to measure the signaling molecules (phospho-JNK, TNF alpha, Caspase-8, Bcl-2/Bax, cytochrome-c). Twenty-two hours later hemodynamic data were measured in the left rats, and then blood samples were taken to determine serum markers of cardiac damage, and hearts were separated to measure the infarction area and cardiocyte apoptosis.</p><p><b>RESULT</b>Postconditioning improved +/-DP/DTmax of left ventricle, limited infarct area, relieved apoptosis and necrosis of cardiocytes, and inhibited the expression of P-JNK (1.12 +/-0.21 Compared with 1.90 +/-0.32, P<0.05). At the same time the levels of TNFalpha Caspase-8, Bax and Cyt-c were lower in Post group than those in R/I group, but Bcl-2 expression levels were higher. I_JNK group presented the similar protection effect of postconditioning [TUNEL index: (6.23 +/-2.43)% Compared with (18.22 +/-5.10)%, P<0.05; Infarct area: (23.44 +/-6.34)% Compared with (42.31 +/-8.21)%, P<0.05]. On the other hand, Ani+Post group partially lost cardioprotection effect [TUNEL index: (14.12 +/-2.00)% Compared with (18.22 +/-5.10)%,P>0.05; Infarct area: (35.27 +/-5.28)% Compared with (42.31+/-8.21)%,P>0.05], because of the activation of JNK MAPK.</p><p><b>CONCLUSION</b>Postconditioning can inhibit phosphorylation of JNK MAPK, which attenuates cardiocyte apoptosis by both extrinsic and mitochondria pathway.</p>