[Nutrient uptake strategy selection by first-order roots of Juglans mandshurica under shading and phosphorus limitation]. / 遮阴和磷限制下胡桃楸1çº§æ ¹å »åˆ†å¸æ”¶ç­–ç•¥é€‰æ‹©.

We investigated root growth of 1-year-old Juglans mandshurica seedlings under different light environments and varying doses of phosphorus fertilizer, to understand the relationship between root resource acquisition strategies and the variations of light and phosphorus availability. There were four shading intensities (full light, 65% full light, 35% full light, and 20% full light) along with three doses of phosphate fertilizer (0 (CK), 200% soil background available phosphorus, and 500% soil background available phosphorus). We measured in root morphology characteristics, architectural characteristics, and mycorrhizal colonization rates of first-order roots. The results showed that average diameter, average root length, and mycorrhizal colonization rates of first-order roots gradually decreased, and the specific root length, specific surface area, branching ratio and branching intensity showed a trend of first increasing and then decreasing with the increases of shading degree. As the phosphorus content decreased, the first-order root diameter gradually became thinner, and the mycorrhizal infection rate gradually increased. Root morphology and architecture of J. mandshurica would undergo adaptive changes under shade, adapting to the shading environment by expanding specific root length, specific surface area, branching ratio and branching intensity. Under phosphorus limitation, root system of J. mandshurica would increase phosphorus absorption through symbiosis with mycorrhizal fungi. When J. mandshurica was artificially regenerate in forest land with a light transmittance of 35%, root morphology and architecture would adapt to the shading environment. The symbiosis between J. mandshurica and mycorrhizal fungi would be enhanced under phosphorus limitation, which could improve phosphorus absorption of roots.

Early detection of circulating tumor DNA and successful treatment with osimertinib in thr790met-positive leptomeningeal metastatic lung cancer: A case report.

BACKGROUND: Patients diagnosed with non-small-cell lung cancer with activated epidermal growth factor receptor mutations are more likely to develop leptomeningeal (LM) metastasis than other types of lung cancers and have a poor prognosis. Early diagnosis and effective treatment of leptomeningeal carcinoma can improve the prognosis. CASE SUMMARY: A 55-year-old female with a progressive headache and vomiting for one month was admitted to Peking University First Hospital. She was diagnosed with lung adenocarcinoma with osseous metastasis 10 months prior to admittance. epidermal growth factor receptor (EGFR) mutation was detected by genomic examination, so she was first treated with gefitinib for 10 months before acquiring resistance. Cell-free cerebrospinal fluid (CSF) circulating tumor DNA detection by next-generation sequencing was conducted and indicated the EGFR-Thr790Met mutation, while biopsy and cytology from the patient's CSF and the first enhanced cranial magnetic resonance imaging (MRI) showed no positive findings. A month later, the enhanced MRI showed linear leptomeningeal enhancement, and the cytology and biochemical examination in CSF remained negative. Therefore, osimertinib (80 mg/d) was initiated as a second-line treatment, resulting in a good response within a month. CONCLUSION: This report suggests clinical benefit of osimertinib in LM patients with positive detection of the EGFR-Thr790Met mutation in CSF and proposes that the positive findings of CSF circulating tumor DNA as a liquid biopsy technology based on the detection of cancer-associated gene mutations may appear earlier than the imaging and CSF findings and may thus be helpful for therapy. Moreover, the routine screening of chest CT with the novel coronavirus may provide unexpected benefits.

A uracil auxotroph Toxoplasma gondii exerting immunomodulation to inhibit breast cancer growth and metastasis.

BACKGROUND: Breast cancer is the most common cause of cancer-related death among women, and prognosis is especially poor for patients with triple-negative breast cancer (TNBC); therefore, there is an urgent need for new effective therapies. Recent studies have demonstrated that the uracil auxotroph Toxoplasma gondii vaccine displays anti-tumor effects. Here, we examined the immunotherapy effects of an attenuated uracil auxotroph strain of T. gondii against 4T1 murine breast cancer. METHODS: We constructed a uracil auxotroph T. gondii RH strain via orotidine 5'-monophosphate decarboxylase gene deletion (RH-Δompdc) with CRISPR/Cas9 technology. The strain's virulence in the T. gondii-infected mice was determined in vitro and in vivo by parasite replication assay, plaque assay, parasite burden detection in mice peritoneal fluids and survival analysis. The immunomodulation ability of the strain was evaluated by cytokine detection. Its anti-tumor effect was evaluated after its in situ inoculation into 4T1 tumors in a mouse model; the tumor volume was measured, and the 4T1 lung metastasis was detected by hematoxylin and eosin and Ki67 antibody staining, and the cytokine levels were measured by an enzyme-linked immunosorbent assay. RESULTS: The RH-Δompdc strain proliferated normally when supplemented with uracil, but it was unable to propagate without the addition of uracil and in vivo, which suggested that it was avirulent to the hosts. This mutant showed vaccine characteristics that could induce intense immune responses both in vitro and in vivo by significantly boosting the expression of inflammatory cytokines. Inoculation of RH-Δompdc in situ into the 4T1 tumor inhibited tumor growth, reduced lung metastasis, promoted the survival of the tumor-bearing mice and increased the secretion of Th1 cytokines, including interleukin-12 (IL-12) and interferon-γ (INF-δ), in both the serum and tumor microenvironment (TME). CONCLUSION: Inoculation of the uracil auxotroph RH-Δompdc directly into the 4T1 tumor stimulated anti-infection and anti-tumor immunity in mice, and resulted in inhibition of tumor growth and metastasis, promotion of the survival of the tumor-bearing mice and increased secretion of IL-12 and IFN-γ in both the serum and TME. Our findings suggest that the immunomodulation caused by RH-Δompdc could be a potential anti-tumor strategy.

Comparison of vaginal progesterone gel combined with oral dydrogesterone versus intramuscular progesterone for luteal support in hormone replacement therapy-frozen embryo transfer cycle.

BACKGROUND: It remains under subject of debate regarding the optimal route of luteal support for hormone replacement therapy- frozen embryo transfer (HRT-FET) cycles. We compared efficacy of vaginal progesterone gel combined with oral dydrogesterone and intramuscular progesterone for HRT-FET lutein support. METHODS: This is a retrospective observational study. After matching for propensity score of getting vaginal + oral treatment, a total of 208 FET cycles in the vaginal progesterone combined with oral dydrogesterone and 624 cycles in the intramuscular progesterone group were enrolled. Pregnancy outcomes and neonatal outcomes including chemical pregnancy rate, clinical pregnancy rate, implantation rate, spontaneous abortion rate, live birth rate, gestational weeks, pre-term delivery, birth weight, and congenital anomalies rate were compared. RESULTS: No significant differences were observed in patient characteristics such as age, duration of infertility, type of infertility, or hormone level after matching. Chemical pregnancy rate (68.3 % versus 70.5 %), clinical pregnancy rate (64.9 % versus 64.4 %), implantation rate (52.3 % versus 50.2 %), spontaneous abortion rate (21.5 % versus 18.4 %), and live birth rate (49.0 % versus 51.3 %) were similar in both group without statistically significant difference. No significant differences in neonatal outcomes were observed between the two groups. CONCLUSION: We observed similar pregnancy outcomes in both vaginal progesterone gel combined with oral dydrogesterone and intramuscular progesterone protocol. Vaginal progesterone gel combined with oral dydrogesterone can be substituted for intramuscular progesterone given that vaginal plus oral use has good safety and is more convenient and may be associated with less side effect caused by intramuscular injection.

Molecular characteristics of Brucella melitensis isolates from humans in Qinghai Province, China.

BACKGROUND: The prevalence of human brucellosis in Qinghai Province of China has been increasing rapidly, with confirmed cases distributed across 31 counties. However, the epidemiology of brucellosis transmission has not been fully elucidated. To characterize the infecting strains isolated from humans, multiple-locus variable-number tandem repeats analysis (MLVA) and whole-genome single-nucleotide polymorphism (SNP)-based approaches were employed. METHODS: Strains were isolated from two males blood cultures that were confirmed Brucella melitensis positive following biotyping and MLVA. Genomic DNA was extracted from these two strains, and whole-genome sequencing was performed. Next, SNP-based phylogenetic analysis was performed to compare the two strains to 94 B. melitensis strains (complete genome and draft genome) retrieved from online databases. RESULTS: The two Brucella isolates were identified as B. melitensis biovar 3 (QH2019001 and QH2019005) following conventional biotyping and were found to have differences in their variable number tandem repeats (VNTRs) using MLVA-16. Phylogenetic examination assigned the 96 strains to five genotype groups, with QH2019001 and QH2019005 assigned to the same group, but different subgroups. Moreover, the QH2019005 strain was assigned to a new subgenotype, IIj, within genotype II. These findings were then combined to determine the geographic origin of the two Brucella strains. CONCLUSIONS: Utilizing a whole-genome SNP-based approach enabled differences between the two B. melitensis strains to be more clearly resolved, and facilitated the elucidation of their different evolutionary histories. This approach also revealed that QH2019005 is a member of a new subgenotype (IIj) with an ancient origin in the eastern Mediterranean Sea.

[Association of fatty acid composition in human milk with breast milk jaundice in neonates].

OBJECTIVE: To study the association of fatty acid composition in human milk with breast milk jaundice (BMJ) in neonates. METHODS: A total of 30 full-term neonates who were admitted to the neonatal intensive care unit from October 2016 to October 2017 and were diagnosed with late-onset BMJ were enrolled as the BMJ group. Thirty healthy neonates without jaundice or pathological jaundice who were admitted to the confinement center during the same period of time were enrolled as the control group. Related clinical data were collected, including sex, mode of birth, feeding pattern, gestational age, birth weight, gravida, parity, and peak level of total serum bilirubin. Breast milk was collected from the mothers, and the MIRIS human milk analyzer was used to measure macronutrients (fat, protein, and carbohydrate) and calorie. Gas chromatography was used to analyze the content of different fatty acids in breast milk. RESULTS: The control group had higher levels of macronutrients in human milk than the BMJ group, with significant differences in fat, dry matter, and calorie (P < 0.05). In addition, 25 fatty acids were detected in breast milk, including 9 saturated fatty acids, 6 monounsaturated fatty acids, and 10 polyunsaturated fatty acids. The comparison of the percentage composition of different fatty acids showed that compared with the control group, the BMJ group had significantly lower percentage compositions of C15:0, C16:0, C17:0, C18:0, C20:0, C18:1n9t, C20:1n9, C18:3n6, C22:2, and C22:6n3 (DHA) and higher percentage compositions of C10:0, C12:0, C14:0 in breast milk (P < 0.05). CONCLUSIONS: Some macronutrients and fatty acid composition in human milk may be associated with the pathogenesis of BMJ in neonates.

[Root architecture and fine root characteristics of Juglans mandshurica saplings in different habitats in the secondary forest on the west slope of Zhangguangcailing, China]. / å¼ å¹¿æ‰å²­è¥¿å¡æ¬¡ç”Ÿæž—ä¸åŒç”Ÿå¢ƒèƒ¡æ¡ƒæ¥¸å¹¼æ ‘æ ¹ç³»æž„åž‹åŠç»†æ ¹ç‰¹å¾.

The whole root excavation method was used to examine root configuration of Juglans mandshurica, with the age of 5-6 years in three habitats (forest edge, gap, and canopy) in a secondary forest on the western part of Zhangguangcailing Mountains. Root structure and fine root function were measured. The root topological index, average joint length, cross-sectional area ratio before and after root branching were calculated and fine root chemical compositions were analyzed. Roots of J. mandshurica at forest edge tended to be dichotomous branch (Topological index:TI=0.68), that under the canopy were herringbone-like branch (TI=0.79), and the gap was between the two (TI=0.72). The average connection length of roots among the three habitats was not significant. The cross-sectional area ratio of roots before and after root branching in three habitats was 1.06, 1.04 and 1.07, respectively, which was not affected by root diameter, in accordance with the Leonardo da Vinci rule. For the same order fine root in different habitats, its length and specific surface area gradually increased from the edge of the forest to the canopy. The N content decreased first and then increased, while the C content and C/N increased first and then decreased. From the forest edge to the gap and to the under canopy, roots tended to move from the dichotomous branch to the herringbone-like branch by reducing the overlap between the secondary branches and roots, increasing specific root length, specific surface area and changing the contents of C and N to cope with environmental change and improve nutrient absorption efficiency.

The early diagnostic value of serum neopterin and cartilage oligomeric matrix protein for osteoarticular changes among brucellosis patients at an early period.

BACKGROUND: Brucellosis is an important public health problem in China. Brucellosis can cause many osteoarticular changes, especially chronic brucellosis. Brucellosis presents various diagnostic difficulties because it mimics many other diseases. Because of the poor sensitivity and ability of X-ray image, it is necessary to find a good method of early diagnosis for osteoarticular changes among brucellosis patients at an early period. The aim of this study was to find early changes biomarkers for osteoarticular changes among brucellosis patients at an early period and provide a better understanding of the osteoarticular changes in this disease at an early stage. METHODS: Sixty-one cases of brucellosis patients at an early period (within 6 months) and 67 cases of volunteers were selected and divided into brucellosis vs. control groups. Serum samples were detected with serological tests for brucellosis, including rose bengal plate test (RBPT), agglutination test (SAT), and IgG and IgM with ELISA. Meanwhile, cartilage oligomeric matrix protein (COMP) and neopterin (NPT) levels in all samples were measured simultaneously with ELISA. The data were analyzed using SPSS 17.0 software. RESULTS: Together with the clinical examination, epidemiological investigation, and serological tests of RBPT, SAT, and IgG and IgM with ELISA, the patients from brucellosis group all were diagnosed as brucellosis cases at an early period, while the results of RBPT, SAT, and IgG and IgM with ELISA from the healthy control group were negative. Comparing with the healthy control, the medians of serum NPT and COMP in the patients group were 9.26 ng/l, 1.70 ng, respectively, which were higher than that of the healthy control group with significant differences (Z = 5.512, 3.614, all p = 0.000). CONCLUSION: The serum NPT and COMP levels of brucellosis patients at an early period were increased. The serum NPT and COMP levels might be the indicator biomarker for osteoarticular changes of human brucellosis at an early stage.

Genetic polymorphisms identify in species/biovars of Brucella isolated in China between 1953 and 2013 by MLST.

BACKGROUND: Brucellosis incidence in China is divided into three stages: high incidence (1950s-1960s), decline (1970s-1980s), and re-emergence (1990s-2010s). At the re-emergence stage, Brucellosis incidence grew exponentially and spread to all 32 provinces. We describe the magnitude and the etiological distribution changes in mainland China by genotyping data and emphasize its recent reemergence. We also provide the genetic diversity and molecular epidemiological characteristics of Brucella. RESULTS: From a total of 206 Brucella isolates, 19 MLST genotypes (STs) were identified and 13 new STs(ST71-83)were found. MLST grouped the population into three clusters. B. melitensis, B. abortus and B. suis were grouped into cluster 1, 2 and 3 respectively. The predominant genotype in the first cluster by MLST, remained unchanged during the three stages. However, the proportion of genotypes in the three stages had changed. More isolates were clustered in ST8 at the re-emergence stage. STs71-74, which were not found in the two former stages, appeared at the re-emergence stage. CONCLUSIONS: The changing molecular epidemiology of brucellosis improve our understanding of apparent geographic expansion from the historically affected north of China to southern provinces in recent reemergence.

Multi-locus variable-number tandem repeat analysis of Chinese Brucella strains isolated from 1953 to 2013.

BACKGROUND: Brucellosis was a common human and livestock disease caused by Brucella strains, the category B priority pathogens by the US Center for Disease Control (CDC). Identified as a priority disease in human and livestock populations, the increasing incidence in recent years in China needs urgent control measures for this disease but the molecular background important for monitoring the epidemiology of Brucella strains at the national level is still lacking. METHODS: A total of 600 Brucella isolates collected during 60 years (from 1953 to 2013) in China were genotyped by multiple locus variable-number tandem repeat analysis (MLVA) and the variation degree of MLVA11 loci was calculated by the Hunter Gaston Diversity Index (HGDI) values. The charts and map were processed by Excel 2013, and cluster analysis and epidemiological distribution was performed using BioNumerics (version 5.1). RESULTS: The 600 representative Brucella isolates fell into 104 genotypes with 58 singleton genotypes by the MLVA11 assay, including B. melitensis biovars 2 and 3 (five main genotypes), B. abortus biovars 1 and 3 (two main genotypes), B. suis biovars 1 and 3 (three main genotypes), and B. canis (two main genotypes) respectively. While most B. suis biovar 1 and biovar 3 were respectively found in northern provinces and southern provinces, B. melitensis and B. abortus strains were dominant in China. Canine Brucellosis was only found in animals without any human cases reported. Eight Brucellosis epidemic peaks emerged during the 60 years between 1953 and 2013: 1955 - 1959, 1962 - 1969, 1971 - 1975, 1977 - 1983, 1985 - 1989, 1992 - 1997, 2000 - 2008 and 2010 - 2013 in China. CONCLUSIONS: Brucellosis has its unique molecular epidemiological patterns with specific spatial and temporal distribution according to MLVA. TRIAL REGISTRATION: IDOP-D-16-00101.

MLVA and MLST typing of Brucella from Qinghai, China.

BACKGROUND: The Qinghai-Tibet Plateau (QTP) of China is an extensive pastoral and semi-pastoral area, and because of poverty and bad hygiene conditions, Brucella is highly prevalent in this region. In order to adequately prevent this disease in the QTP region it is important to determine the identity of Brucella species that caused the infection. METHODS: A total of 65 Brucella isolates were obtained from human, livestock and wild animals in Qinghai, a Chinese province in east of the QTP. Two molecular typing methods, MLVA (multi-locus variable-number tandem-repeat analysis) and MLST (multi locus sequence typing) were used to identify the species and genotypes of these isolates. FINDINGS: Both MLVA and MLST typing methods classified the 65 isolates into three species, B. melitensis, B. abortus and B. suis, which included 60, 4 and 1 isolates respectively. The MLVA method uniquely detected 34 (Bm01 ~ Bm34), 3 (Ba01 ~ Ba03), and 1 (Bs01) MLVA-16 genotypes for B. melitensis, B. abortus and B. suis, respectively. However, none of these genotypes exactly matched any of the genotypes in the Brucella2012 MLVA database. The MLST method identified five known ST types: ST7 and ST8 (B. melitensis), ST2 and ST5 (B. abortus), and ST14 (B. suis). We also detected a strain with a mutant type (3-2-3-2-?-5-3-8-2) of ST8 (3-2-3-2-1-5-3-8-2). Extensive genotype-sharing events could be observed among isolates from different host species. CONCLUSIONS: There were at least three Brucella (B. melitensis, B. abortus and B. suis) species in Qinghai, of which B. melitensis was the predominant species in the area examined. The Brucella population in Qinghai was very different from other regions of the world, possibly owing to the unique geographical characteristics such as extremely high altitude in QTP. There were extensive genotype-sharing events between isolates obtained from humans and other animals. Yaks, sheep and blue sheep were important zoonotic reservoirs of brucellosis causing species found in humans.

A Primary Investigation on Serum CTX-II Changes in Patients Infected with Brucellosis in Qinghai Plateau, China.

Brucellosis is one of the most widespread zoonotic diseases, with the most frequent complication being osteoarticular changes. The aim of this study was to assess the changes of C-terminal telopeptide of type II collagen (CTX-II) in patients infected with brucellosis. A total of 84 brucellosis patients and 43 volunteers were selected and divided into brucellosis vs. control groups. Serum samples were subjected to serological tests for brucellosis, and CTX-II levels in all samples were measured simultaneously with ELISA. The results showed that serum CTX-II levels in human brucellosis were higher than those of healthy controls, without a statistically significant difference, but serum CTX-II levels in male patients were significantly higher than those of female patients (P<0.05). This finding could indicate the biological changes in the cartilage and bone in human brucellosis.

Analogy to a Chinese knot in an ion-pair copper(II)-neodymium(III) complex based on a hexadentate Schiff base condensation product of 5-bromosalicylaldehyde and glycylglycine.

Self-assembly of CuCl2, NdCl3, 5-bromosalicylaldehyde and glycylglycine yields the ion-pair copper(II)-neodymium(III) complex, poly[[decaaquabis[µ3-2-({2-[(5-bromo-2-oxidobenzylidene)amino]acetyl}azanidyl)acetato]bis[µ2-2-({2-[(5-bromo-2-oxidobenzylidene)amino]acetyl}azanidyl)acetato]tetracopper(II)dineodymium(III)] bis{[2-({2-[(5-bromo-2-oxidobenzylidene)amino]acetyl}azanidyl)acetato]cuprate(II)} tetradecahydrate], {[Cu4Nd2(C11H8BrN2O4)4(H2O)10][Cu(C11H8BrN2O4)]2·14H2O}n. The anion is planar and mononuclear, showing an approximately square-planar coordination of the metal atom, while the cation is a hexanuclear centrosymmetric transition metal-lanthanide (Cu-Nd) heterometallic complex, with the independent copper cations in square-planar and square-pyramidal coordinations. The asymmetric unit comprises one half of this cation, one anion and seven solvent water molecules. The positions of the six metal centres in the cation reproduce a Chinese knot arrangement. The dipeptidic Schiff base releases three H atoms and can act as a tetradentate, a pentadentate or a hexadentate ligand. Longer interactions between the pentadentate ligands and the Jahn-Teller Cu(II) cation link the hexanuclear aggregates into cationic chains in the [010] direction in which 14- and 22-membered subloops occur. Extensive hydrogen bonding in three dimensions involves both the coordinated and the solvent water molecules.

Association between inflammatory mediators and angiographic morphologic features indicating thrombus formation in patients with acute myocardial infarction.

BACKGROUND: Inflammatory mechanisms had played an important role in the occurrence and prognosis of acute myocardial infarction, inflammatory mediators was associated with adverse outcomes of acute myocardial infarction. This study tested the hypothesis that in the acute phase of myocardial infarction with ST-segment elevation, neutrophil count and high-sensitivity C-reactive protein are predictive of angiographic morphologic features that indicate thrombus formation in the infarct-related artery. METHODS: This retrospective study included 182 consecutive patients with acute myocardial infarction and ST-segment elevation. Patients were assigned to a thrombus-formation group (n = 77) and a non-thrombus-formation group (n = 106). All patients had a Killip's classification

Heme oxygenase-1 attenuates ovalbumin-induced airway inflammation by up-regulation of foxp3 T-regulatory cells, interleukin-10, and membrane-bound transforming growth factor- 1.

Cumulative evidence suggests the up-regulation of interleukin (IL)-10 and T-regulatory (Treg) cells is implicated in anti-inflammatory effect of heme oxygenase-1 (HO-1). Thus, we postulated that induction of HO-1 could augment IL-10 and transforming growth factor (TGF)-beta production and foxp3+CD4+CD25+ Treg cell function, thereby leading to attenuation of airway inflammation. In this study, CD4+CD25+ Treg cells isolated from mouse spleen were either transfected with a HO-1 expression vector (pcDNA3HO-1) or treated with a HO-1 inducer (hemin). Up-regulation of HO-1 enhanced foxp3 expression and IL-10 secretion in the Treg cells in vitro. Next, BALB/c, C57/B6.129, and IL-10-deficient B6.129P2-Il10tm1Cgn/J mice were challenged by ovalbumin to induce airway inflammation. Consistent with in vitro findings, hemin treatment resulted in induction of HO-1 and foxp3 and production of IL-10 and membrane-bound TGF-beta1 in vivo. This was further correlated with decrease of ovalbumin-specific immunoglobulin E level and eosinophil infiltration in bronchial alveolar lavage fluid from the asthmatic mice. Furthermore, hemin significantly enhanced the biological activity of CD4+CD25+ Treg cells. This protective effect was specifically blocked by Sn-protoporphyrin, a HO-1 enzymatic inhibitor. Finally, hemin failed to up-regulate the function of CD4+CD25+ Treg cells from IL-10-deficient mice. Our study indicates that HO-1 exerts its protective effect on asthma through a mechanism mediated by foxp3+CD4+CD25+ Treg cells, IL-10, and membrane-bound TGF-beta1.

Reduction of bilirubin by targeting human heme oxygenase-1 through siRNA.

Neonatal hyperbilirubinemia is a common clinical condition caused mainly by the increased production and decreased excretion of bilirubin. Current treatment is aimed at reducing the serum levels of bilirubin. Heme oxygenase-1 (HO-1) is a rate-limiting enzyme that generates bilirubin. In this study we intended to suppress HO-1 using the RNA interference technique. Small interfering RNA (siRNA)-A, -B, and -C were designed based on human HO-1 (hHO-1) mRNA sequences. siRNA was transfected into a human hepatic cell line (HL-7702). hHO-1 transcription and protein levels were then determined. In addition, the inhibitory effect of siRNA on hHO-1 was assessed in cells treated with hemin or transfected with an hHO-1 plasmid. siRNA-C showed the most potent suppressive effect on hHO-1. This inhibition is dose and time dependent. Compared with control, both hemin and hHO-1 plasmids up-regulated hHO-1 expression in HL-7702 cells. However, the up-regulation was significantly attenuated by siRNA-C. Furthermore, the decrease in hHO-1 activity was coincident with the suppression of its transcription. Finally, siRNA-C was shown to reduce hHO-1 enzymatic activity and bilirubin levels. Thus, this study provides a novel therapeutic rationale by blocking bilirubin formation via siRNA for preventing and treating neonatal hyperbilirubinemia and bilirubin encephalopathy at an early clinical stage.

Heme oxygenase-1-mediated CD4+CD25high regulatory T cells suppress allergic airway inflammation.

Heme oxygenase-1 (HO-1) has anti-inflammatory effects in asthma. CD4+CD25(high) regulatory T cells (Treg) are a potent immunoregulator that suppresses the immune response. We studied the effects of HO-1-mediated CD4+CD25(high) Treg on suppression of allergic airway inflammation by comparing mice treated with hemin, OVA, Sn-protoporphyrin (SnPP), and hemin plus SnPP. Airway responsiveness, airway eosinophil infiltration, the level of OVA-specific IgE, and the numbers of cells in general and eosinophils in particular in bronchial alveolar lavage fluid were lower in the hemin group than in the OVA, SnPP, and hemin plus SnPP groups. The expressions of HO-1 mRNA and protein in the lung were increased by repeated administrations of hemin and SnPP. However, the activity of HO-1 was highest in hemin mice. The percentage and suppressive function of CD4+CD25(high) Treg and the expression of Foxp3 mRNA were obviously enhanced after treatment with hemin. This increase was diminished by the administration of SnPP. The concentration of serum IL-10 was higher in the hemin group than in the other groups, whereas the level of serum TGF-beta did not significantly differ across groups. Furthermore, the ratio of IFN-gamma/IL-4 mRNA in the lung was higher in hemin-treated mice than in OVA and SnPP mice. The suppressive capacity of CD4+CD25(high) Treg was not enhanced in the IL-10-deficient mice treated with hemin. In conclusion, our experiments in the animal model demonstrated that HO-1 has anti-inflammatory effects, probably via enhancement of the secretion of IL-10 and promotion of the percentage of CD4+CD25(high) Treg.

Radioimmunotherapy of human colon cancer xenografts by using 131I labeled-CAb1 F(ab')2.

PURPOSE: Therapeutic efficacy, suitable dose, and administration times of 131I-CAb1 F(ab')2, a new monoclonal antibody therapeutics specifically directed against a cell surface-associated glycoprotein of colon cancer, were investigated in this article. METHODS AND MATERIALS: In human colon cancer xenografts, 131I-CAb1 F(ab')2 at the dose of 125 muCi, 375 muCi, and 1125 muCi were administrated intraperitoneally on Days 6 and 18 after implantation of HR8348 cells with CAb1 high reactivity. Survival time and tumor growth inhibition rate were used to evaluate the efficacy and safety of 131I-CAb1 F(ab')2 in treatment of colon cancer xenografts. RESULTS: Treatment of 125, 375, and 1125 muCi 131I-CAb1 F(ab')2 did not significantly decrease the mean survival time of nude mice when compared with nontreated groups (p = 0.276, 0.865, 0.582, respectively). Moreover, the mean survival times of nude mice receiving 375 muCi and 1125 muCi 131I-CAb1 F(ab')2 were significantly longer than that of 5-FU-treated groups (p = 0.018 and 0.042). Tumor growth inhibition rates of the first therapy were 35.67% and 41.37%, with corresponding 131I-labeled antibody dosage of 375 muCi and 1125 muCi. After single attack dosage, second reinforcement therapy may rise efficacy significantly. Tumor growth inhibition rates of 125 muCi, 375 muCi, and 1125 muCi 131I-labeled antibody on Day 20 posttherapy were 42.65%, 56.56%, and 84.41%, respectively. Histopathology examination revealed that tissue necrosis of various degrees was found in 131I-CAb1 F(ab')2-treated groups. CONCLUSION: 131I-CAb1 F(ab')2 is safe and effective for colon cancer. It may be a novel and potentially adjuvant therapeutics for colon cancer.