Exploration of the mechanism of reinfusion of fresh autologous blood in type 2 diabetes mice to induce macrophage polarization and inhibit erythrocyte damage.

AIMS/INTRODUCTION: Type 2 diabetes triggers an inflammatory response that can damage red blood cells. M2 macrophages have inhibitory effects on inflammation, and play an important role in tissue damage repair and fibrosis. Autologous blood transfusion has the potential to inhibit red blood cell damage by mediating macrophage polarization. MATERIALS AND METHODS: Swiss mice were used to establish a suitable type 2 diabetes model, and autologous blood transfusion was carried out. The mice were killed, the blood of the mice was collected and CD14+ monocytes were sorted. The expression levels of phenotypic molecules CD16, CD32 and CD206 in CD14+ monocytes were analyzed by flow cytometry. The proportion of M1 and M2 macrophages were analyzed by flow cytometry. The Q value, P50 , 2,3-diphosphoglycerate and Na+ -K+ -ATPase of red blood cells were detected. The red blood cell osmotic fragility test analyzed the red blood cell osmotic fragility. Western blot analysis was used to analyze the expression changes of erythrocyte surface membrane proteins or transporters erythrocyte membrane protein band 4.1, sphingosine-1-phosphate, glycolipid transfer protein and signal peptide peptidase-like 2A. RESULTS: Autologous blood transfusion induced a significant increase in the number of macrophages. The state and capacity of blood cells improved with autologous blood transfusion. Reinfusion of fresh autologous blood in type 2 diabetes mice made erythrocytes shrink. The expression of erythrocyte-related proteins proved that the erythrocyte injury in the reinfusion of fresh autologous blood + type 2 diabetes group was significantly reduced. CONCLUSION: The reinfusion of fresh autologous blood into the body of patients with type 2 diabetes can induce macrophage polarization to M2, thereby inhibiting red blood cell damage.

Characteristics and Burdens of Disease in Patients from Beijing with Generalized Pustular Psoriasis and Palmoplantar Pustulosis: Multicenter Retrospective Cohort Study Using a Regional Database.

BACKGROUND AND OBJECTIVE: Pustular psoriasis is a chronic and recurrent autoimmune disease, although little is known about the disease burden of pustular psoriasis in China. We analyzed the characteristics and disease burdens of patients from Beijing who had generalized pustular psoriasis (GPP) or palmoplantar pustulosis (PPP). METHODS: This multicenter retrospective cohort study used a regional electronic health database that covered 30 public hospitals in Beijing. From June 2016 to June 2021, all patients with a diagnosis of GPP, PPP, or psoriasis vulgaris (PV) were identified by International Statistical Classification of Diseases and Related Health Problems, 10th Revision codes. The GPP and PPP cohorts were separately matched with patients with PV in a 3:1 ratio for comparisons. Demographic data, clinical characteristics, healthcare resource utilization, and costs were collected. Descriptive and comparative analyses were used to compare the cohorts. RESULTS: There were 744 patients with GPP (46.8% men; age 42.14 ± 21.47 years) and 4808 patients with PPP (35.5% men; age 51.65 ± 16.12 years); 14.5% of patients with GPP had concomitant PV and 7.5% of patients with PPP had concomitant PV. Relative to matched patients with PV, patients with GPP had a higher prevalence of erythrodermic psoriasis (5.9% vs 0.4%, p < 0.0001), psoriatic arthritis (3.1% vs 1.5%, p = 0.007), and organ failure (1.1% vs 0.2%, p = 0.002). Relative to matched patients with PV, patients with PPP had a higher prevalence of cerebrovascular disease (4.7% vs 1.2%, p < 0.0001), thyroid dysfunction (3.9% vs 3.3%, p = 0.035), and type 2 diabetes mellitus (6.8% vs 5.9%, p = 0.030). More patients with GPP than patients with PV received systemic non-biological agents (27.9% vs 3.3%, p < 0.0001) and biologic agents (4.8% vs 2.0%, p = 0.010). More patients with PPP than patients with PV received topical agents (50.9% vs 34.7%, p < 0.0001) and systemic non-biological agents (17.8% vs 2.7%, p < 0.0001). More patients with GPP than patients with PV required inpatient hospitalization (22.0% vs 7.8%, p < 0.0001). Hospitalization stay was longer in patients with GPP than patients with PV (11.72 ± 0.45 vs 10.38 ± 0.45 days, p = 0.022). More patients with PPP than patients with PV had emergency visits (16.3% vs 12.8%, p < 0.0001). The GPP and PPP cohorts and their matched PV cohorts had no significant differences in costs. However, patients with PPP had lower outpatient costs than patients with PV (368.20 ± 8.19 vs 445.38 ± 5.90 Chinese Yuan per patient per month, p < 0.0001). CONCLUSIONS: Patients from Beijing with GPP and PPP had higher disease burdens than matched PV cohorts, including the prevalence of comorbidities, healthcare resource utilization, and medication burden. However, the economic burden of pustular psoriasis was similar to that of PV. Practical and specific therapies are needed to reduce the burdens of pustular psoriasis.

An update on therapeutic options for palmoplantar pustulosis: a narrative review and expert recommendations.

INTRODUCTION: Palmoplantar pustulosis (PPP) is a chronic inflammatory skin disease belonging to the localized form of pustular psoriasis. It is characterized by sterile pustule formation in palms and soles and a recurrent disease course. Although we have many treatments for PPP, there is no authoritative guidance. AREAS COVERED: A thorough search of PubMed was conducted to identify studies in PPP from 1973 onwards, with additional references to specific articles. Any treatment methods were outcomes of interest, including topical treatment, systemic treatment, biologics, other targeted treatments, phototherapy, and tonsillectomy. EXPERT OPINION: Topical corticosteroids are suggested as first-line therapy. Oral acitretin has become the most applied systemic retinoid recommended in PPP without joint involvement. For patients with arthritis, immunosuppressants like cyclosporin A and methotrexate are more recommended. UVA1, NB-UVB, and 308-nm excimer laser are effective phototherapy options. The combinations of topical or systemic agents and phototherapy may enhance the efficacy, particularly in recalcitrant cases. Secukinumab, ustekinumab, and apremilast are the most investigated targeted therapies. However, heterogeneous reported outcomes in clinical trials provided low-to-moderate quality evidence of their efficacy. Future studies are required to address these evidence gaps. We suggest managing PPP based on the acute phase, maintenance phase, and comorbidities.

Localized molecular chaperone synthesis maintains neuronal dendrite proteostasis.

Proteostasis is maintained through regulated protein synthesis and degradation and chaperone-assisted protein folding. However, this is challenging in neuronal projections because of their polarized morphology and constant synaptic proteome remodeling. Using high-resolution fluorescence microscopy, we discovered that neurons localize a subset of chaperone mRNAs to their dendrites and use microtubule-based transport to increase this asymmetric localization following proteotoxic stress. The most abundant dendritic chaperone mRNA encodes a constitutive heat shock protein 70 family member (HSPA8). Proteotoxic stress also enhanced HSPA8 mRNA translation efficiency in dendrites. Stress-mediated HSPA8 mRNA localization to the dendrites was impaired by depleting fused in sarcoma-an amyotrophic lateral sclerosis-related protein-in cultured mouse motor neurons and expressing a pathogenic variant of heterogenous nuclear ribonucleoprotein A2/B1 in neurons derived from human induced pluripotent stem cells. These results reveal a crucial and unexpected neuronal stress response in which RNA-binding proteins increase the dendritic localization of HSPA8 mRNA to maintain proteostasis and prevent neurodegeneration.

The Effect of Pre-operative Autologous Blood Donation on Bone Marrow Hematopoietic Functions in Rabbits after Hepatectomy.

BACKGROUND: Pre-operative autologous blood donation (PABD) is one of the most widely distributed autologous blood donation means, which has positive effects on erythropoiesis. However, whether PABD can stimulate the bone marrow hematopoiesis after hepatectomy has not been reported. METHODS: Totally 80 New Zealand rabbits were randomly divided into 4 groups that included control group, surgery group, hemodilutional autotransfusion (HA) group and PABD group. Automatic reticulocyte examination was performed to detect the content of reticulocyte and immature reticulocyte fractions (IRF). Flow cytometric analysis was employed to monitor the level of CD34+ cells and the cell cycle status. Southern blotting was conducted to determine the telomere length of CD34+ cells. RESULTS: The content of high fluorescence reticulocytes (HFR) and IRF was decreased at 6 h and 24 h after autotransfusion. However, the level of CD34+ cells was upregulated after PABD. Cell cycle status analysis revealed that the majority of the CD34+ cells in HA and PABD group were maintained in G0/G1 phase. The telomere length in HA and PABD group was shortened than that of the control group and surgery group. CONCLUSION: PABD could promote the bone marrow hematopoietic functions in rabbits after hepatectomy via stimulating proliferation of CD34+ cells and shortening the telomere length of CD34+ cells, but the content of HFR was not increased immediately because of the stuck of CD34+ cells in the G0/G1 phase.

Mobile Phone Addiction and Academic Procrastination Negatively Impact Academic Achievement Among Chinese Medical Students.

The problem of mobile phone addiction and academic procrastination among medical students has been widely acknowledged. This study aimed to explore the influence of demographic factors on mobile phone addiction, academic procrastination, and academic achievement among medical students. Further, it investigated the association between mobile phone addiction, academic procrastination, and academic achievement. This cross-sectional study was conducted between May and June 2019. A total of 3 511 medical students participated in an online questionnaire survey (effective response rate = 81.7%). Demographic factors, the Scale of Academic Achievement, the short scale of the Mobile Phone Problem Use (MPPUS-10), and the Academic Procrastination Scale-Short (APS-S) were used. Hierarchical multiple regression analysis revealed that the average scores for academic procrastination, mobile phone addiction, and academic achievement were 2.66 ± 0.91, 5.13 ± 1.53, and 4.51 ± 0.71, respectively. Moreover, there were significant differences in gender, grade, leadership experience, and family monthly income across mobile phone addiction, academic procrastination, and academic achievement. Mobile phone addiction was negatively associated with learning dedication, learning performance, and relationship facilitation. Academic procrastination was negatively associated with learning dedication, learning performance, relationship facilitation, and objective achievement. Mobile phone addiction and academic procrastination was revealed as prevalent among Chinese medical students, and negatively influences their academic achievement. It is critical to establish a more efficient learning environment for Chinese medical students to minimize the negative impact of mobile phone addiction and academic procrastination.

The effect of erythrocyte transfusion on macrophage pyroptosis and inflammation in a sepsis model.

BACKGROUND: Sepsis is one of most common causes of death in the intensive care unit (ICU) due to infection and inflammation. The Duffy antigen receptor for chemokines (DARC) regulates pro-inflammatory cytokines, thus playing an important role in inflammation. OBJECTIVES: This study aimed to elucidate the correlation among erythrocyte transfusion, macrophage pyroptosis and inflammation in the progression of sepsis. MATERIAL AND METHODS: Alanine aminotransferase (ALT/GPT) activity was measured with the ALT/GPT activity measurement kit (Jiancheng Bio, Nanjing, China) according to the kit manual. The ET-1 concentration was measured with enzyme-linked immunosorbent assay (ELISA) using the endothelin-1 (ET-1) measurement kit (Jiancheng Bio) according to the kit manual. Apoptosis was evaluated using flow cytometry-based Annexin V staining assay. The cells were collected using centrifugation and resuspended in binding buffer. Ultrastructural analysis of pyroptotic body, the levels of interleukin (IL)-1ß, IL-18, IL-33, MIP-2, CXCL8, reactive oxygen species (ROS), and LTB4 were measured with ELISA. RESULTS: Our results showed that septic rats had impaired hepatic function and ET-1 levels. Erythrocyte transfusion upregulated DARC expression in the sepsis model. Erythrocyte transfusion also affected pyroptosis in macrophages, reduced the production of inflammatory cytokines, such as IL-1ß, IL-18 and IL-33, and alleviated cytotoxicity in the sepsis model. CONCLUSIONS: Erythrocyte transfusion may function as a therapeutic tool against sepsis by regulating pyroptosis, inflammation and cytotoxicity.

Exploration on the effect of predeposit autotransfusion on bone marrow hematopoiesis after femoral shaft fracture.

OBJECTIVE: By observing the changes in the number and activity of CD34+ cells in bone marrow after predeposit autotransfusion (PAT) to patients with femoral shaft fracture (FSF), to evaluate the effects of PAT on hematopoietic function and hematopoietic stem cells in bone marrow. METHODS: Selected FSF patients were randomly divided into 2 groups: the control group (patients did not receive blood transfusion after surgery) and PAT group (patients received PAT after surgery). The content of RBC and Plt in blood samples were counted by blood routine. The cell cycle and proportion of CD34+ myelinated cells in blood samples was analyzed by flow cytometry. The telomere DNA length of hematopoietic stem cells (HSCs) in the control groups and PAT group at postoperation 24 was analyzed by southern blot. RESULTS: The content of RBC and Plt in postoperation 6h and 24h in the control group was evidently higher compared to that in PAT group, while Hb content in control group was significantly lower compared to that in PAT group. The proportion of CD34+ myelinated cells in post-transfusion 6h and postoperation 24h in PAT group was evidently higher compared to that in the control group. In PAT group, S phase at postoperation 24h was significantly larger compared to that at post-transfusion 6h. The telomere DNA length of HSCs in PAT group was longer than that in the control group. CONCLUSION: PAT can increase the number of HSC, while does not cause the abnormal aging of HSCs. PAT is suitable for postoperative blood transfusion of patients with FSF.

Influence of different erythrocyte storage times on the macrophage response in haemorrhagic shock mice.

OBJECTIVE: To investigate the characteristics of the macrophage response to transfusion of erythrocytes kept at different storage times in the mouse model of haemorrhagic shock. METHODS: Erythrocytes were isolated from mice and stored for 7, 21 or 35 days and samples injected intravenously into haemorrhagic shock mice. Changes in macrophages, inflammatory cytokines and T cell differentiation were assessed using flow cytometry or enzyme-linked immunosorbent assay (ELISA). In a second experiment, haemorrhagic shock mice were injected with 21D-erythrocytes and the expression of nuclear factor erythroid 2 p45-related factor 2 (Nrf2), arginine -1 (Arg-1) and inducible nitrous oxide (iNOS) determined. RESULTS: The proportion of M1-polarized macrophages was greatest in the 21D group while M2 macrophages tended to increase with the erythrocyte storage time. Levels of inflammatory cytokines and T helper 1 (Th1) cells increased in proportion to erythrocytes storage time. Most regulatory T cells (Treg) were found at 21D. Arg-1 expression was significantly increased in a group that received an heme oxygenase 1 (HO-1) agonist and significantly decreased in a group that received an HO-1 inhibitor but there were no differences in the expression of iNOS or Nrf2. CONCLUSION: 21D storage time may be an important time point for erythrocyte storage and immunity response and Arg-1 may have a role in the macrophage response to erythrocyte infusion.

Correction to: Arsenic concentration, speciation, and risk assessment in sediments of the Xijiang River basin, China.

In the original paper, there was an error in the communication unit 1. The communication unit was "Liaoning Engineering Research Center for Treatment and Recycling of Industrially Discharged Heavy Metals, Shenyang University of Chemical Technology, Shenyang 110142, People's Republic of China".

Arsenic concentration, speciation, and risk assessment in sediments of the Xijiang River basin, China.

In order to acquire the spatial distribution, speciation, and risk assessment of arsenic (As), 18 sediment samples were collected in the middle and upper reaches (Nanpan River, Beipan River, Hongshui River, Diaojiang River, and Duliu River) of the Xijiang River basin, China. The chemical fractions of As in the collected sediments were mainly dominated by the residual fraction and the Fe (Mn, Al) oxide/oxyhydroxides fractions. The correlation analysis results showed that the chemical fraction of As in sediments had close correlations with Mn, good correlations with Fe and organic matter (OM), while weak correlations with Al and carbonate. In addition, it also showed that Diaojiang River basin was found to have an extremely high As pollution status and suffered from high ecological risk. Duliu River and Nanpan River had moderately polluted levels of As and showed a low ecological risk. The other sample sites of Xijiang River basin were uncontaminated of As. The assessment results from this study indicated that the different types of species present based on the chemical fractionation of As from the Xijiang River basin showed different risks. Graphical abstract.

A Gyroidal MOF with Unprecedented Interpenetrating utc-c Network Exhibiting Exceptional Thermal Stability and Ultrahigh CO2 Affinity.

A zeolite-like gyroidal MOF (denoted as SCNU-1) constructed with Cu ions and 4-(1H-imidazo[4,5-f][1,10]phenanthrolin-2-yl)phenol has a featured interpenetrating uninodal utc-c network which is for the first time found in the real structure. Moreover, SCNU-1 exhibits high thermal (>773 K), solvent, and acid/base stabilities; the largest CO2 affinity, 90 kJ/mol, among the MOFs functionalized with an aromatic hydroxyl group; and excellent CO2/N2 selectivity.

Scutellarein suppresses Aß-induced memory impairment via inhibition of the NF-κB pathway in vivo and in vitro.

The flavonoid compound scutellarin (Scu) is a traditional Chinese medicine used to treat a variety of diseases; however, the use of scutellarein (Scue), the hydrolysate of Scu, and its mechanisms of action in Alzheimer's disease (AD) have not been fully elucidated. In the present study, the effects of Scue on amyloid ß (Aß)-induced AD-like pathology were investigated. An in vitro model of inflammation and an aged rat model were used to confirm the effects of Scue. In vitro MTT assays and flow cytometry were used to assess the effects of Scue on cell viability and apoptosis, respectively. A Morris water maze was used to evaluate spatial learning and memory, and the levels of Aß deposition, superoxide dismutase, malondialdehyde, apoptosis, neuro-inflammatory factors and nuclear factor-κB (NF-κB) activation in hippocampal tissues in vivo were measured to determine the effect of Scue in AD. Scue may be protective, as it decreased the apoptosis of hippocampal cells in vitro, inhibited Aß-induced cognitive impairment, suppressed hippocampal neuro-inflammation and suppressed activation of NF-κB in vivo. Therefore, Scue may be a useful agent for the treatment of Aß-associated pathology in the central nervous system through inhibition of the protein kinase B/NF-κB signaling pathway and thus, future studies are required to investigate the efficacy of Scue in patients with AD.

A membranous structure separating the adenohypophysis and neurohypophysis: an anatomical study and its clinical application for craniopharyngioma.

OBJECT This study aimed to identify the membranous septation between the adeno- and neurohypophysis. The clinical impact of this septation in the surgical removal of infradiaphragmatic craniopharyngioma (Id-CP) is also clarified. METHODS The sellar regions from 8 fetal and 6 adult cadavers were dissected. After staining first with H & E and then with picro-Sirius red, the membranous structures were observed and measured under normal light and polarization microscopy. The pre- and postsurgical images and intraoperative procedures in 28 cases of childhood Id-CP were reviewed and analyzed. RESULTS There is a significant membranous septation (termed the adenoneurohypophysis septation [ANHS]) lying behind the intermediate lobe to separate the adeno- and neurohypophysis. The average thicknesses are 21.9 ± 16.9 µm and 79.1 ± 43.2 µm in fetal and adult heads, respectively. The median segment of the septation is significantly thicker than the upper and lower segments. The ANHS extends from the suprasellar pars tuberalis to the sellar floor, where it is fused with the pituitary capsule. During Id-CP surgery performed via a transcranial approach, the ANHS can be identified to reserve the neurohypophysis. Moreover, by understanding the anatomy of this membrane, the pituitary stalk was preserved in 3 patients (10.7%). CONCLUSIONS There is a significant membrane separating the anterior and posterior lobes of the pituitary gland, which lies behind the intermediate lobe. Understanding the anatomy of this septation is important for identifying and preserving the neurohypophysis and pituitary stalk during Id-CP surgery.

Effect of high-pressure homogenization preparation on mean globule size and large-diameter tail of oil-in-water injectable emulsions.

The effect of different high pressure homogenization energy input parameters on mean diameter droplet size (MDS) and droplets with > 5 µm of lipid injectable emulsions were evaluated. All emulsions were prepared at different water bath temperatures or at different rotation speeds and rotor-stator system times, and using different homogenization pressures and numbers of high-pressure system recirculations. The MDS and polydispersity index (PI) value of the emulsions were determined using the dynamic light scattering (DLS) method, and large-diameter tail assessments were performed using the light-obscuration/single particle optical sensing (LO/SPOS) method. Using 1000 bar homogenization pressure and seven recirculations, the energy input parameters related to the rotor-stator system will not have an effect on the final particle size results. When rotor-stator system energy input parameters are fixed, homogenization pressure and recirculation will affect mean particle size and large diameter droplet. Particle size will decrease with increasing homogenization pressure from 400 bar to 1300 bar when homogenization recirculation is fixed; when the homogenization pressure is fixed at 1000 bar, the particle size of both MDS and percent of fat droplets exceeding 5 µm (PFAT5) will decrease with increasing homogenization recirculations, MDS dropped to 173 nm after five cycles and maintained this level, volume-weighted PFAT5 will drop to 0.038% after three cycles, so the "plateau" of MDS will come up later than that of PFAT5, and the optimal particle size is produced when both of them remained at plateau. Excess homogenization recirculation such as nine times under the 1000 bar may lead to PFAT5 increase to 0.060% rather than a decrease; therefore, the high-pressure homogenization procedure is the key factor affecting the particle size distribution of emulsions. Varying storage conditions (4-25°C) also influenced particle size, especially the PFAT5.

Emerging role of mast cells and macrophages in cardiovascular and metabolic diseases.

Mast cells are essential in allergic immune responses. Recent discoveries have revealed their direct participation in cardiovascular diseases and metabolic disorders. Although more sophisticated mechanisms are still unknown, data from animal studies suggest that mast cells act similarly to macrophages and other inflammatory cells and contribute to human diseases through cell-cell interactions and the release of proinflammatory cytokines, chemokines, and proteases to induce inflammatory cell recruitment, cell apoptosis, angiogenesis, and matrix protein remodeling. Reduced cardiovascular complications and improved metabolic symptoms in animals receiving over-the-counter antiallergy medications that stabilize mast cells open another era of mast cell biology and bring new hope to human patients suffering from these conditions.

Separation and purification of Escherichia coli-expressed human thymosin-α1 using affinity chromatography and high-performance liquid chromatography.

In this study, a human thymosin-α1 (hTα1) fusion protein was overexpressed in Escherichia coli (E. coli). The hexahistidine-tagged hTα1 fusion protein was obtained in soluble form in cells of the engineered E. coli strain BL21 (DE3)/pET-28a-hTα1 that had been induced with isopropyl -D-1-thiogalactopyranoside (IPTG). The recombinant protein accounted for approximately 50-60% of the total protein. We then developed and validated a separation method for hTα1 from E. coli cells based on thermal denaturation, nickel-resin affinity chromatography and high-performance liquid chromatography. The purification method showed good reproducibility and was easy to operate. Purified recombinant hTα1 of high homogeneity was characterized and found to be of high purity (over 99%), as determined by high-voltage electrophoresis and high-performance liquid chromatography analysis. Isoelectric focusing analysis indicated a pI of approximately 4.0, and full wavelength screening showed an optimal absorbance wavelength at around 214nm.

Bioactivity, pharmacokinetics, and immunogenicity assays in preclinical and clinical trials for recombinant human endostatin.

AIM: To determine the in vitro and in vivo bioactivity of recombinant human endostatin (rhEndostatin) and to analyze its pharmacokinetics and immunogenicity in rhesus monkeys and patients. METHODS: The physical chemical characteristics of rhEndostatin were detected according to Pharmacopoeia of the People's Republic of China (2005 edition, part III). Its in vitro and in vivo bioactivities were assayed via proliferation-inhibition on human umbilical vein endothelial cells and their inhibitory effect on tumor-bearing mice models. Serum concentrations of rhEndostatin in monkeys and patients were determined by an enzyme immunoassay method. RESULTS: The corresponding specific in vitro activities of rhEndostatin obtained from the cell counting method, 3-(4,5-dimethylthiazol-2- yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and lactate dehydrogenase assay, respectively, were 6.4 x 10(7), 6.7 x 10(7), and 3.8 x 10(8) U/mg, and the in vivo antitumoral potency was 4.04 x 10(7) U/mg. In rhesus monkeys, there were no gender differences in all pharmacokinetic parameters. Serum anti-rhEndostatin immunoglobulin (Ig)G antibodies were generated quickly after intravenous (iv) administration and decreased rapidly when therapy was stopped. In phase I clinical trials, linearity in the pharmacokinetics of rhEndostatin was indicated by dose-proportionate increases in the area under the curve and the maximum serum concentration. Serum rhEndostatin reached a steady-state level after 7 d of successive administration with the average concentration at a steady state of 272.44+/-91.98 ng/mL. Neither IgG nor IgM antibodies against rhEndostatin were observed in patients. CONCLUSION: RhEndostatin exhibited a definite proliferation- inhibition effect on HUVEC, and significant antitumoral activity in mice. The immunoreactivity of rhesus monkeys to rhEndostatin is common, and rhEndostatin showed no immunogenicity in patients in this trial. The results provide a basis for further clinical trials.

A quantitative method for measuring the antitumor potency of recombinant human endostatin in vivo.

Recombinant human endostatin (rhEndostatin) has been shown to inhibit tumor growth, but the variable antitumor activity of different rhEndostatin preparations has necessitated the development of an accurate, reproducible in vivo bioassay for evaluating the rhEndostatin activity. To assess the in vivo antitumor efficacy of rhEndostatin, H22 tumor-bearing mice received three doses of rhEndostatin and the potency of rhEndostatin preparations in inhibiting tumor growth was determined by ED(50)-potency assay and validated by dose-response parallel-line assay. There was a consistent and highly reproducible linear regression relationship between rhEndostatin dosage and tumor growth inhibition rate. The ED(50) values were determined from dose-response regression lines for seven rhEndostatin preparations with high reproducibility. On the basis of the current study, the potency of rhEndostatin preparations was assigned a value of 6.09 x 10(5) U/ampoule and a 95% confidence limit of 5.96 x 10(5)-6.22 x 10(5). We consider that this procedure can be served as a potential candidate pharmacopoeial method for potency measurement of different rhEndostatin preparations.