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Angiopoietin-like protein 8(ANGPTL8)secreted by liver and adipose tissue,is a glycoprotein exerting paramount effects on facilitation of vascular remodeling and regulation of inflammatory response;ANGPTL8 is in-volved in the initiation and progression of cardiovascular diseases including coronary artery disease,hypertension,aortic aneurysm and pathological cardiac hypertrophy,and holds promise for being a new target for the prevention and treatment of cardiovascular diseases.
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Selenium (Se) is an essential trace element for organisms. Se deficiency will cause diseases such as Keshan disease and Kashin-Beck in human being, and huge loss to animal husbandry. Currently available Se supplements have such problems as low Se content, poor bioavailability, and poor safety. Chlorella pyrenoidosa can produce bioavailable and safe organic Se under suitable conditions, which is thus a promising Se supplement. Therefore, in this study, we tried to improve the Se tolerance and accumulation of C. pyrenoidosa by directional adaptation. To be specific, we gradually increased the concentration of Na2SeO3 in medium to domesticate C. pyrenoidosa and optimized the adapting time and concentration gradient of Na2SeO3 during the adaptation. The results showed that the adapted C. pyrenoidosa was more tolerant to Se and had stronger Se enrichment ability. In 5 L fermenter, the adapted strains could tolerate 40 mg/L Na2SeO3 and the synthesis rate of organic Se was 175.6% higher. Then, Se addition method in the 5 L fermenter was optimized. The result demonstrated that addition of Na2SeO3 at 40 mg/L during heterotrophic culture achieved the final dry weight of C. pyrenoidosa cells at 106.4 g/L, content of organic Se at 1 227 mg/kg, and synthesis rate of organic Se at 1.36 mg/(L·h). Compared with the reported highest cell density of 75 g/L and the highest organic Se content of 560 mg/kg, the corresponding figures in this study were 41.9% and 119.1% higher, respectively. In conclusion, directional adaptation can remarkably improve the Se tolerance and enrichment of C. pyrenoidosa.
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Animals , Humans , Selenium/pharmacology , Chlorella , Heterotrophic ProcessesABSTRACT
Objective To investigate the efficacy and safety of domestic bortezomibˉbased chemotherapy for patients with multiple myeloma (MM). Methods The clinical data of 60 MM patients treated with domestic bortezomibˉbased chemotherapy regimen (the observation group) in the First Affiliated Hospital of Zhengzhou University from April 2018 to October 2018 were retrospectively analyzed, which were compared with 112 MM patients treated with original treatment regimen (the control group) at the same hospital from November 2010 to November 2014. According to the disease stage, the patients were divided into newly diagnosed MM (NDMM) group and relapsed refractory MM (RRMM) group, and efficacy and adverse reactions of domestic bortezomib were evaluated. Results The total response rate (ORR) of the observation group was 71.7% (43/60), severe complete response (sCR) + complete response (CR) rate was 16.7% (10/60), very good partial response (VGPR) rate was 18.3% (11/60), and partial response (PR) rate was 36.7% (22/60). The ORR of NDMM group (45 cases) and RRMM group (15 cases) was 82.2% (37/45) and 40.0% (6/15), respectively, and the difference was statistically significant (χ2= 9.877, P < 0.05). There was no significant difference between ISS stage Ⅰ+Ⅱ and stage Ⅲ [ORR: 75.7% (28/37) vs. 65.2% (15/23), respectively; χ2=0.764, P >0.05]. ORR and CR rates in the NDMM group and RRMM group of the observation group and the control group were not statistically different (all P>0.05). In the treatment of bortezomibˉbased chemotherapy, the common adverse reaction was peripheral neuropathy, mostly belonging to grade 1-2. Other side effects included hematocytopenia, gastrointestinal events and herpes zoster, which could be alleviated or restored to normality after supportive treatments. One patient died of pulmonary infection, respiratory failure and septic shock during the intermittent period of chemotherapy. Conclusion ORR of domestic bortezomibˉbased chemotherapy in treatment of the patients with MM is high, and the incidence of adverse reactions shows no significant increase compared with original drugs.
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To explore the efficacy and influencing factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with myeloid leukemia and granulocytic sarcoma (GS).Clinical outcome including hematopoietic reconstitution,transplant-related complications,survival and relapse were collected and retrospectively analyzed in 9 patients with myeloid leukemia and GS after allo-HSCT.Hematopoiesis reconstitution was achieved in all the 9 recipients.Four cases developed acute graft-versus-host disease (GVHD),and 1 with chronic GVHD.The median follow-up time after transplantation was 10(4-81) months.Only 2 cases survived,the other 7 died of relapse.The median time of relapse after transplantation was 5(3-19) months.Allo-HSCT is relatively effective treatment for patients with myeloid leukemia and GS.Relapse after transplantation remains the major factor of mortality.
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Objective To summarize the clinical characteristics,diagnosis,treatment and prognosis of EBV related post-transplantation lymphoproliferative diseases (PTLD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods The clinical data of 262 cases of allo-HSCT were retrospectively,and EBV-associated PTLD occurred in 9 cases after transplantation with a incidence of 3.44% (9/262).Of the 9 patients,6 were males and 3 were females,with a median age of 19 years;the primary disease was severe aplastic anemia (SAA) in 6 cases,acute myeloid leukemia in 2 cases and chronic myeloid leukemia in 1 case Results The occurring median time of EBV associated PTLDs was 58 d (44-271 d).The clinical manifestations of most PTLD recipients were recurrent fever with no reaction to any antibiotics,antiadoncus and lymphadenectasis.Of the 9 recipients,6 cases obtained pathological diagnosis,and 3 cases clinical diagnosis.Superficial lymph node and central nervous system (CNS) involved in 8 and 4 recipients,respectively;lung and bone involvement occurred in 2 recipients and 1 case,respectively.The median number of peripheral blood EBV DNA in 9 recipients was 7.21 × 104 copies/ml (6.37 × 103-4.56 × 105 copies/ml) at the time of onset.EBV DNA in peripheral blood was positive in only one ease of 4 CNS recipients.Among 9 recipients after therapy,4 cases were cured and 4 cases were partially effective,and 1 recipient was ineffective After follow-up for 28 months (2-48 months),6 cases died,and 3 survived.Conclusion Incidence of EBV related PTLD in SAA patients undergoing allo-HSCT is relatively higher than leukemia recipients.Reduction or withdrawal of immunosuppressant,Rituximab and low dose of DLI is effective treatment.
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BACKGROUND:Whether there are breast cancer stem cel microspheres in the breast cancer tissues and whether these microspheres have an impact on isolation and culture of breast cancer stem cel s after different cycles of neoadjuvant chemotherapy are stil unclear. OBJECTIVE:To explore the proliferation and differentiation of breast cancer stem cel s in breast cancer tissues after different cycles of neoadjuvant chemotherapy. METHODS:Breast cancer stem cel microspheres were isolated from the breast cancer tissues after different cycles of neoadjuvant chemotherapy to drawn a cel growth curve. Immunocytochemical method was used to detect ALDH1 expression. RESULTS AND CONCLUSION:Microspheres could be obtained from the specimens of neoadjuvant chemotherapy for two, three and four cycles rather than one cycle. At 3 days prior to culture, there was no difference in the number of cel s isolated after two-and three-cycle neoadjuvant chemotherapy;but after 3 days, the cel s from the three-cycle neoadjuvant chemotherapy proliferated faster than those from the two-cycle neoadjuvant chemotherapy;after 6 days, the cel growth curve of two-cycle neoadjuvant chemotherapy was in the plateau stage, and the proliferation of cel s from the three-cycle neoadjuvant chemotherapy showed a rapid increase trend. The positive expression of ALDH1 in the microspheres from the three-cycle neoadjuvant chemotherapy was higher than that from the two-cycle neoadjuvant chemotherapy. These findings indicate that breast cancer stem cel s from the specimens of two-and three-cycle neoadjuvant chemotherapy both have proliferation and differentiation potentials, and the specimens of three-cycle neoadjuvant chemotherapy or above are preferred.
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Background and purpose:Thalidomide can enhance the radiation sensitivity on tumor effectively, but the mechanism of radiosensitization is still unclear. The present study aimed to investigate whether thalidomide could enhance the radiation sensitivity on colon cancer transplanted tumor of mouse, and to investigate the underlying mechanism. Methods: We established the model of colon26 colonic carcinoma, and the mice were divided into 4 groups:Control group, the thalidomide group, the radiotherapy group and thalidomide+radiotherapy group. From the day of treatment, tumors were measured every other day. Then, the xenograft tumor growth curve was depicted. Tumor volumes were measured in different treatment groups, then, the inhibitory rates of tumor growth were calcutated. Using immunohistochemical method in to detect the expression of microvessel density (MVD) in tumor tissue. Results:The mean tumor volumes at day 22 were (4.97±1.20)cm3 (control group), (2.90±0.92)cm3 (T group), (2.66±0.88)cm3 (R group), and (1.89±0.76)cm3 (T+R group). The tumor inhibition rate in the combination group (61.9%) was signiifcantly higher than the other groups (41.7%, 46.5%, P<0.05). The radiotherapy sensitization enhancement ratio of the combined treatment group was 2.27 times than in the radiotherapy group. Thalidomide combined with radiation therapy can significantly inhibit microvessel density of tumor:The decreasing MVD of T+R group, T group and R group were respectively 46.8%, 40.7%and 37.7%, and there was statistical significance between T+R group and T group (P<0.05 ), so as between T+R group and R group. It could be found more necrotic cells in tumor of group, and there was statistical signiifcance between T+R group and control group (P<0.05). Conclusion:Thalidomide can enhance the radiosensitivity mice of colonic carcinoma, and its mechanism may be related to the inhibition of tumor angiogenesis related.
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Background and purpose: As one of the important epigenetic phenomena, DNA methylation plays an important regulatory function for the expression of genes. Study shows that abnormal changes of DNA methy-lation patterns of normal tumor cell genome leads to dysfunction of cancer related gene, and this may be associated with tumor occurrence and development. The study investigated the promoter methylation and expression of caveolin-1 (CAV-1) gene in esophageal squamous cell carcinoma (ESCC), and to elucidate its role in ESCC. Methods:We used MSP approach, RT-PCR, and immunohistochemistry method respectively to examine the methylation status of the 5’CpG island of CAV-1 gene and its expression at mRNA and protein levels in tumors and corresponding normal tissues. Results: CAV-1 mRNA expression in tumor tissues (0.86±0.56) was signiifcantly higher than that in corresponding normal tissues (0.40±0.36, P0.05). The promoter methylation frequency of CAV-1 in tumor specimens was 2.0%(1/51), and the methylation phenomenon has not been found in corresponding normal tissues. The promoter methylation fre-quency of CAV-1 in tumor specimens showed no signiifcant difference compared with the corresponding normal tissues (P>0.05). Conclusion:The mRNA and protein expression of CAV-1 in tumor specimens was signiifcantly higher than that in corresponding normal tissues. Aberrant high expression of CAV-1 has played a certain role in promoting tumori-genesis and lymph node metastasis. The expression both in ESCC and corresponding normal tissues has no correlation with the promoter methylation status.
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Objective To prepare transferring and R8 co-modified liposome (TF/R8-LP)for forhepatoma targeting.Methods The co-modified liposome were prepared by film-ultrasonic method.The appearance,particle size,Zeta potential were evaluated.The cellular uptake by HepG2 cell in vitro was used to evaluate the targeting efficiency and in vivo imaging were used to evaluate the targeting efficiency. Results The particle diameter of the co-modified liposome was(108.5 ±12.6)nm and the Zeta potential was(24.15 ±4.78)mV.The liposome kept stable in 50% FBS at 24 h.The result demonstrated that the co-modified liposome uptaken by HepG2 were 2.4,2.6 times higher than that of R8-LP and TF-LP,respectively(P<0.05).The evaluation of tumor spheroid penetration and in vivo imaging results showed the co-modified liposome had the strongest fluorescence intensity. Conclusion The co-modified liposome might serve as a promising hepatoma delivery system of antitumor drugs.
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Objective To analyse the etiology,clinical characteristics and risk factors of central nervous system (CNS) complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods The clinical features of CNS complications in patients who underwent allo-HSCT were observed,and analysis its causes and risk factors.Results 8 cases of CNS complications occured in 69 patients within 6 months after allo-HSCT and the incidence was 11.6 %,the occurrence rate of CNS complications was 21.4 % (6/28) in HLA mismatched group,higher than HLA matehed group [49 % (2/41)] (P < 0.05).Analogously,the incidence was 44.4 % (4/60) in patients with graft-versus-host disease (GVIID) (>grade 2),which was significantly higher than patients with 2 or below grade 2 GVHD [6.7 % (4/9)] (P < 0.01).But there was no significant difference in the incidence of CNS complications between ≤14 years old and >14 years old,with or without ATG,different stages of diseases,whether pretreatment with maryland respectively (P >0.05),either.Epilepsy and intracranial infection were the most common CNS complications in allo-HSCT,followed by intracranial hemorrhage.Conclusion HLA mismatched and above grade 2 GVHD are the risk factors of CNS complications in allo-HSCT.Epilepsy,intracranial infection and bleeding are common CNS complications in allo-HSCT.
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Objective To investigate the characteristics of co-infection in initial treatment acute leukemia induction chemotherapy.Methods The clinical features of 179 untreated acute leukemia patients with nosocomial infection were analyzed after combined chemotherapy.Results In the 179 patients,151cases achieved complete remission,the complete remission rate was 84.4 %,82 cases suffered from nosocomial infections,the incidence of infection was 45.8 %.The sites of infection were oral,anal,lung,as well as primary foci was not clear bacteremia.In 428 specimens,the isolated bacterial colony counted a total of 66,the number of fungal colonies was 9,the bacterial colony was G-bacteria-based.G-bacteria had different degrees of resistance to many antibiotics.Extended-spectrum β-lactamases strains had not been detected in these specimens.Conclusion Acute leukemia patients is easy to co-infection after chemotherapy.Control and prevention of nosocomial infections should run throughout the entire treatment process,application of laminar flow bed helps reduce the newly diagnosed acute leukemia patients with nosocomial infection incidence.
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Objective To explore the role and their relationship of Ki-67, VEGF and p27 expressed in adult patients with acute leukemia. Methods The expression of Ki-67, VEGF and p27 in bone marrow mononuclear cells (BMMNC) were analyzed by immunocytochemical staining, and their correlations of Ki-67, VEGF and p27 were statistically analyzed. Results The expression of Ki-67(42.48±25.78)% or VEGF (44.89±24.01)% on BMMNC from acute leukemia cells was significantly higher than that in the control (11.40±9.94)% or (16.90±12.54)% (P<0.01). But the expression of p27 (23.65±13.30)% was significantly lower than that in the control (50.23±22.68)% (P<0.01). The expressions of Ki-67 were positively correlated with and VEGF in patients with acute leukemia were positively correlated(r=-0.666, P<0.01), and the expressions of Ki-67 and p27 were negatively correlated with p27 in patients with acute leukemia (r=-0.316, P<0.05).Conclusion The evaluation of expression of Ki-67, VEGF and p27 on acute leukemic cells provides new insights to the pathogenesis is helpful in mechanism and is helpful in the diagnosis of acute leukemia.