Inhibitory Effect of Cinobufotalin on Macrophage Inflammatory Factor Storm and Its Mechanism / 中国实验血液学杂志

OBJECTIVE@#To investigate the inflammatory effects of Cinobufotalin on monocytes in resting state and macrophages in activated state and its molecular mechanism.@*METHODS@#THP-1 cells were stimulated with Phorbol 12-myristate 13-acetate to induce differentiation into macrophages. Lipopolysaccharides was added to activate macrophages in order to establish macrophage activation model. Cinobufotalin was added to the inflammatory cell model for 24 h as a treatment. CCK-8 was used to detect cell proliferation, Annexin V /PI double staining flow cytometry was used to detect cell apoptosis, flow cytometry was used to detect macrophage activation, and cytometric bead array was used to detect cytokines. Transcriptome sequencing was used to explore the gene expression profile regulated by Cinobufotalin. Changes in the significantly regulated molecules were verified by real-time quantitative polymerase chain reaction and Western blot.@*RESULTS@#1∶25 concentration of Cinobufotalin significantly inhibited the proliferation of resting monocytes(P<0.01), and induced apoptosis(P<0.01), especially the activated macrophages(P<0.001, P<0.001). Cinobufotalin significantly inhibited the activation of macrophages, and significantly down-regulated the inflammatory cytokines(IL-6, TNF-α, IL-1β, IL-8) released by activated macrophages(P＜0.001). Its mechanism was achieved by inhibiting TLR4/MYD88/P-IκBa signaling pathway.@*CONCLUSION@#Cinobufotalin can inhibit the inflammatory factors produced by the over-activation of macrophages through TLR4/MYD88/P-IκBa pathway, which is expected to be applied to the treatment and research of diseases related to the over-release of inflammatory factors.

Clinical Use of Acid Suppressants and Risk of Dementia in the Elderly: A Pharmaco-Epidemiological Cohort Study.

BACKGROUND: Results of studies regarding the potential link between acid suppressant use and dementia risk are inconsistent. This study aimed to evaluate the association of cumulative exposure to histamine 2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) with dementia risk in an Asian older cohort aged ≥65 years. METHODS: Patients initiating H2RA (the H2RA user cohort, n = 21,449) or PPI (the PPI user cohort, n = 6584) and those without prescription for H2RA (the H2RA non-user cohort, n = 21,449) or PPI (the PPI non-user cohort, n = 6584) between 1 January 2000 and 31 December 2005 without a prior history of dementia were identified from Taiwan's National Health Insurance Research Database (NHIRD). The outcome of interest was all-cause dementia. Patients' exposure to H2RAs or PPIs was followed-up from dates of initial prescription to the earliest outcome of incident dementia, death, or the end of 2013. Potential associations between acid suppressant use and dementia risk were analyzed using time-dependent Cox regression estimated hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: After mutual adjustment for H2RA and PPI use and other potential confounders, patients with H2RA use had significantly higher risk of developing dementia as compared to those not treated with H2RAs (adjusted HR, 1.84; 95% CI, 1.49-2.20). Likewise, PPI users had significantly elevated risk of dementia compared to PPI non-users (adjusted HR, 1.42; 95% CI, 1.07-1.84). CONCLUSIONS: Our results indicate that exposures to H2RAs and PPIs are associated with increased dementia risk.

Advances in research on infection of Myeloid-derived suppressor cells / 医学研究生学报

Myeloid-derived suppressor cells (MDSCs) are newly discovered cells derived from bone marrow that suppress immunity, playing an immunosuppressive role in tumors, infections, and autoimmune diseases. It has been confirmed in disease model studies that their immunosuppressive effect is mainly achieved by suppressing the function of T cells. At present, the treatment of infectious diseases is still a major obstacle, especially in the treatment of chronic infectious diseases. Studies have found that MDSCs have increased aggregation in infectious diseases. As MDSCs are gaining more attention in infectious diseases, their potential therapeutic effects may be further explored. This article mainly reviews the immunosuppressive mechanisms of MDSCs in infections such as bacteria, viruses, parasites and fungi and their relationship with the diseases.

Time-specific blockade of PDGFR with Imatinib (Glivec®) causes cataract and disruption of lens fiber cells in neonatal mice.

This study aimed at investigating the response of lens epithelial cells in postnatal mice to Imatinib (Glivec®, a potent inhibitor of platelet-derived growth factor receptor (PDGFR)) treatment. Mouse eyes were sampled 10 days after administration of Imatinib (0.5 mg·g(-1)·day(-1)) for 3 days, at either 7, 14, or 21 days postpartum. Structural changes of lens were revealed by routine H.E. staining. Levels of proliferation and apoptosis were revealed by BrdU incorporation and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, respectively, and immunofluorescent staining with anti-PDGFRα antibody was carried out on the sections of eyeball. PDGFRα and p-PDGFRαprotein levels were evaluated by Western blot. Our results indicated that administration of Imatinib led to blockade of PDGFR signaling. Formation of cataracts was found only in those mice where treatment started from 7 days postpartum (P7), but was not observed in those samples from P14 nor P21. Fiber cells were disorganized in cataract lens core as observed histologically, and migration of epithelial cells was also inhibited. No apoptosis was detected with the TUNEL method. Our results indicated blockade of PDGFR at the neonatal stage (P7) would lead to cataracts and lens fiber cells disorganization, suggesting that PDGFR signaling plays a time-specific and crucial role in the postnatal development of lens in the mouse, and also may provide a new approach to produce a congenital cataract animal model.

Osteoclast-like giant cell carcinoma of the urinary bladder.

Extraskeletal osteoclast-like giant cell (OGC) tumors are uncommon and have mainly been found in the breast and pancreas. OGC neoplasms of the urinary tract are extremely rare, and their histogenesis and biologic behavior remain controversial. Gross hematuria is the most common presenting symptom, as in transitional cell carcinoma. The prognosis is poor in patients with extraskeletal OGC tumors. Here, we present the case of a 62-year-old man who received transurethral bladder tumor resection due to painless gross hematuria. Pathology showed OGC carcinoma. Abdominal computed tomography showed tumor invasion over the right lateral wall of the bladder and distal third of the ureter. The patient received radical cystectomy and partial distal ureterectomy with transureteroureterostomy. No local tumor recurrence or distant metastasis was found at the 5-month follow-up.

Successful rescue of an early interstitial pregnancy after failed systemic methotrexate treatment: a case report.

BACKGROUND: Interstitial (cornual) pregnancy is a rare and life-threatening disease. Although systemic treatment with methotrexate (MTX) in an unruptured interstitial pregnancy has been used to preserve the entirety of the uterus, surgery is often used as a rescue method in failed cases. Use of an ultrasound-guided local injection can be a good alternative to surgery. CASE: A 30-year-old woman, gravida 1, para 0, with an interstitial pregnancy at 10 weeks of gestation, was successfully treated with an ultrasound-guided 100-mg MTX injection after a failed response to 3-dose intramuscular 100-mg MTX treatment (300 mg in total). Regular menstruation occurred 1 month after the local MTX injection. The serum beta-human chorionic gonadotropin level was undetectable 49 days later, and the residual mass had disappeared 6 months later, CONCLUSION: Local injection of MTX may be a good means of managing an unruptured interstitial pregnancy to preserve the entirety of the uterus after failed systemic MTX treatment. Use of a local MTX injection may be a better choice than that of systemic MTX treatment.

Acardiac syndrome coexisting with complex skeletal dysplasia in the co-twin: 3D sonographic findings.

We present a case of twin reversed arterial perfusion syndrome complicated by an acardius acephalus fetus and complex skeletal dysplasia in the co-twin, including a reduction of the right arm and absence of the right scapula and 4 ribs, as evaluated with three-dimensional sonography and MRI.

Influence of lead acetate on soil microbial biomass and community structure in two different soils with the growth of Chinese cabbage (Brassica chinensis).

A greenhouse pot experiment was conducted to evaluate the impact of different concentrations of lead acetate on soil microbial biomass and community structure during growth of Chinese cabbage (Brassica chinensis) in two different soils. The field soils were used for a small pot, short-term 60-day growth chamber study. The soils were amended with different Pb concentrations, ranging from 0 to 900mgkg(-1) soil. The experimental design was a 2 soilx2 vegetation/non-vegetationx6 treatments (Pb)x3 replicate factorial experiment. At 60 days the study was terminated and soils were analyzed for microbial parameters, namely, microbial biomass, basal respiration and PLFAs. The results indicated that the application of Pb at lower concentrations (100 and 300mgkg(-1)) as lead acetate resulted in a slight increase in soil microbial biomass, whereas Pb concentrations >500mgkg(-1) caused an immediate gradual significant decline in biomass. However, the degree of impact on soil microbial biomass and basal respiration by Pb was related to management (plant vegetation) or the contents of clay and organic matter in soils. The profiles of 21 phospholipid fatty acids (PLFAs) were used to assess whether observed changes in functional microbial parameters were accompanied by changes in the composition of the microbial communities after Pb application at 0, 300 and 900mg Pbkg(-1) soil. The results of principal component analyses (PCA) indicated that there were significant increases in fungi biomarkers of 18:3omega6c, 18:1omega9c and a decrease in cy17:0, which is an indicator of gram-negative bacteria for the high levels of Pb treatments In a word, soil microbial biomass and community structure, therefore, may be sensitive indicators reflecting environmental stress in soil-Pb-plant system. However, further studies will be needed to better understand how these changes in microbial community structure might actually impact soil microbial community function.

Single-dose sertaconazole vaginal tablet treatment of vulvovaginal candidiasis.

BACKGROUND: Vulvovaginal candidiasis (WC) is a bothersome disease in women. Poor compliance with the continuous use of antifungal vaginal drugs often results in treatment failure. The aim of the present study was to evaluate the efficacy, acceptability, and safety of single-dose sertaconazole vaginal tablet (500 mg) treatment compared with conventional 3-dose econazole vaginal tablet (150 mg) treatment for VVC. METHODS: In this open, randomized, and comparative study, 40 symptomatic patients with VVC confirmed by the smear method were enrolled. Patients in group A were treated with single-dose sertaconazole vaginal tablet and those in group B were treated continuously with econazole vaginal tablet for 3 days. RESULTS: The characteristics of the patients in both groups were comparable and without statistical difference. Group A showed a significantly better clearance rate for candidiasis than group B (100% vs. 72.2% on day 7, p = 0.013; 100% vs. 77.8% on day 14, p = 0.030), based on smear method results. Group A showed a more rapid response for symptom relief than group B on day 7, but there was no difference in overall symptom relief between group A and group B on day 14. CONCLUSION: Single-dose sertaconazole proved to be a more convenient and symptom-relieving treatment for VVC. The advantages of such management are worthy of further study in women with relapse VVC.

Effects of lead contamination on soil microbial activity and rice physiological indices in soil-Pb-rice (Oryza sativa L.) system.

The effect of lead (Pb) treatment on the soil microbial activities (soil microbial biomass and soil basal respiration) and rice physiological indices were studied by greenhouse pot experiment. Pb was applied as lead acetate at six different levels in two different paddy soils, namely 0 (control), 100, 300, 500, 700, 900 mg kg-1 soil. The results showed that the application of Pb at lower level (<300 mg kg-1) as lead acetate resulted in a slight increase in soil microbial activities compared with the control, and had an inhibitory influence at high concentration (>500 mg Pb kg-1 soil), which might be the critical concentration of Pb causing a significant decline in the soil microbial activities. However, the degree of influence on soil microbial activities by Pb was related to the clay and organic matter contents of the soils. On the other hand, when the level of Pb treatments increased to 500 mg kg-1, there was ecological risk for both soil microbial activities and plants. The results also revealed that there was a consistent trend that the chlorophyll contents increased initially, and then decreased gradually with increase in Pb concentration. Pb was effective in inducing proline accumulation and its toxicity causes oxidative stress in rice plants. In a word, soil microbial activities and rice physiological indices, therefore, may be sensitive indicators reflecting environmental stress in soil-Pb-rice system.

Effect of heavy metals on soil microbial activity and diversity in a reclaimed mining wasteland of red soil area.

The microbial biomass, basal respiration and substrate utilization pattern in copper mining wasteland of red soil area, southern China, were investigated. The results indicated that soil microflora were obviously different compared with that of the non-mine soil. Microbial biomass and basal respiration were negatively affected by the elevated heavy metal levels. Two important microbial ecophysiological parameters, namely, the ratio of microbial biomass C(Cmic)/organic C(Corg) and metabolic quotient(qCO2) were closely correlated to heavy metal stress. There was a significant decrease in the Cmic/Corg ratio and an increase in the metabolic quotient with increasing metal concentration. Multivariate analysis of Biolog data for sole carbon source utilization pattern demonstrated that heavy metal pollution had a significant impact on microbial community structure and functional diversity. All the results showed that soil microbiological parameters had great potential to become the early sensitive, effective and liable indicators of the stresses or perturbations in soils of mining ecosystems.

Effect of combined pollution by heavy metals on soil enzymatic activities in areas polluted by tailings from Pb-Zn-Ag mine.

Some enzymatic activities were determined in the areas polluted by tailings from Tiantai Pb-Zn-Ag Mine in Zhejiang Province of China. The results indicated the soil enzymatic activities decreased significantly with increase of concentrations of heavy metals or the distance away from mining tailing center, especially dehydrogenase and urease activities. Multivariate regression analysis between heavy metal contents and soil enzymatic activities indicated that single dehydrogenase activity was very significantly correlated to combined effect of soil heavy metals in mine area. Moreover, single urease, protease and acid phosphatase activities were significantly related to the combined effect of heavy metals. The results suggest it is feasible to use soil enzymatic activities to indicate the pollution situation by combined heavy metals in the soil of mine area.

Nuchal translucence incorporated into a one-stage multifactorial screening model for Down syndrome prediction at second-trimester pregnancy.

The aim of this study was to achieve one-stage screening for trisomy 21 using a combination of nuchal translucency (NuT) measurement and maternal serum alpha-fetoprotein (AFP) and free beta-human chorionic gonadotrophin (hCG) biochemistry levels in the second trimester among a high-risk study population. From January 1998 to June 2001, 45 cases of trisomy 21 were prenatally found and confirmed in the hospital-based cytogenetic diagnosis laboratory. A total of 867 normal singleton pregnancies were enrolled as controls from the antenatal care clinics in the hospital. All study and control subjects between 13 weeks and 18 weeks of gestation with a mean age of 15.2 +/- 1.3 weeks underwent one-stage nuchal translucence measurements and maternal serum biochemical screening for Down syndrome. The final logistic model contained beta-hCG (multiples of the gestational median or MoM), maternal age (matA), nuchal translucence (NuT MoM) and AFP (MoM) as covariates. Also, the estimated coefficients of the regression were highly significant. This model provided the estimated probability of Down syndrome as follows: Pr (Down syndrome) = exp (Z)/ [1 + exp (Z)], where Z = -11.18 + 0.64 x (beta-hCG MoM) + 0.25 x matA + 1.32 x NuT MoM -2.23 x AFP MoM. The logistic regression with estimated coefficients was installed in a Palm digital assistant (PDA) equipped with Excel (Microsoft). The risk probability of Down syndrome could be readily calculated after inputting data for all four predictor variables.

Prenatal diagnosis of mosaic tetrasomy 10p associated with megacisterna magna, echogenic focus of left ventricle, umbilical cord cysts and distal arthrogryposis.

We present the first report of mosaic isochromosome 10p associated with multiple congenital anomalies including megacisterna magna, echogenic focus of the left ventricle, umbilical cord cysts, and distal arthrogryposis. The most obvious anomalies found on prenatal ultrasound were enlarged cisterna magna and lower limb flexion contractures which resembled clubfeet. Analyses of GTG-banded chromosomes of 42 cells harvested from 32 independent tissue culture colonies were examined. Thirty-five cells from 27 colonies had 46 chromosomes and appeared to be 46,XX, female karyotype. Seven cells from independent colonies had 47 chromosomes with abnormal karyotypes. The extra chromosome material was identified as isochromosome 10p without involvement of the heterochromatic region of the long arm [47,XX,+ i(10p)]. Mosaic tetrasomy 10p was confirmed using fluorescent in situ hybridization (FISH) of a 10p-specific probe to metaphase chromosomes of this patient.

Successful conservative treatment for advanced interstitial pregnancy. A case report.

BACKGROUND: Interstitial pregnancy is a relatively rare and life-threatening disease, occurring in 2-4% of all extrauterine pregnancies, and the maternal mortality rate is 2-2.5%. Laparoscopic surgery and, less commonly, methotrexate are the treatments of choice for interstitial pregnancy. However, there is another treatment, ultrasound-guided direct injection of etoposide, the effect and safety of which are unclear. CASE REPORT: In a 32-year-old woman with interstitial pregnancy at 12 weeks of gestation, ultrasound-guided direct injection of etoposide (100 mg) was used successfully after intravenous high-dose methotrexate, 300 mg (200 mg/m2), therapy failed to produce a response. The patient's posttherapeutic course was smooth. Twelve months after treatment, she conceived and later delivered a healthy infant vaginally without adverse events. CONCLUSION: Ultrasound-guided direct injection of etoposide offers another choice for treating advanced interstitial pregnancy, but further study is needed to define its efficacy and safety.