Efficacy of Qingfei oral liquid for idiopathic pulmonary fibrosis in rats and related network pharmacology study / 浙江大学学报·医学版

To investigate the therapeutic effect and mechanism of Qingfei oral liquid in idiopathic pulmonary fibrosis. Seventy-two male SD rats were divided into control group, model group, pirofenidone group and Qingfei group with 18 animals in each group. The idiopathic pulmonary fibrosis was induced in last three groups by intratracheal injection of bleomycin; pirofenidone group was given oral administration of pirofenidone b.i.d for 21 d, and Qingfei group was given Qingfei oral liquid 3.6 mL/kg q.d for Lung tissues were obtained for HE staining, Masson staining and transforming growth factor (TGF)-β immunohistochemical staining. Superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione (GSH) were detected in tissue homogenates. The BATMAN-TCM database was used to retrieve the chemical components and their corresponding targets of Qingfei oral solution by network pharmacology method, and then the component-target-disease network diagram was constructed. Finally, the pathway enrichment analysis was carried out to explore the molecular mechanism of Qingfei oral liquid against idiopathic fibrosis. Histopathology results showed that Qingfei oral liquid had a similar relieving effect on pulmonary fibrosis as the positive drug pirfenidone; TGF-β secretion had a significant reduction in lung tissues of Qingfei group; and Qingfei oral liquid had better regulatory effect on SOD, MDA and GSH than pirfenidone. The results of component-target-disease network and pathway enrichment analysis showed that the related molecular pathways were concentrated in inflammation, extracellular matrix and cytokines. Qingfei oral liquid has a good therapeutic effect on idiopathic pulmonary fibrosis in rats via regulation of inflammation, extracellular matrix and cytokines.

Vascular sclerosing effects of bleomycin on cutaneous veins: a pharmacopathologic study on experimental animals

Abstract: Background: Varicose veins and the complications of venous disease are common disorders in humans. Objective: To study the effects of bleomycin as a potential new sclerosing agent and its adverse events in treating varicose veins. Methods: Bleomycin-loaded liposomes 0.1ml was injected in the dorsal ear veins of white New Zealand rabbits. Sodium tetradecyl sulfate was used as a positive control. Normal saline was used as negative control. The blood vessels of the treated ears were photographed before and at one hour and two, eight and 45 days after treatment. Biopsies from the treated areas were obtained for histological examination. Blood samples were collected to determine any possible toxicity. Results: Bleomycin by itself was ineffective; therefore, liposomes were used as a vector to deliver bleomycin to the vein lumen. Subsequently, bleomycin started showing its sclerosing effects. Toxicity monitoring showed no apparent hematologic, pulmonary, hepatic or renal toxicities. This study revealed that bleomycin induced vasculitis, which led to vascular occlusion, which was observed on day 1 and day 8. No bleomycin-related injury was noted by histopathological examination of lung sections. The calculation of the lung/body weight coefficient indicated that edema was present in the experimental groups compared with the negative and positive controls. Study limitations: Relatively small number of experimental animals used. Conclusions: This study showed that bleomycin-loaded liposomes were able to induce vasculitis and vascular occlusion without any toxicity or complications. It might be useful, hence, to treat patients suffering from Varicose veins and other ectatic vascular diseases with this agent.

microRNA-142-3p inhibits apoptosis and inflammation induced by bleomycin through down-regulation of Cox-2 in MLE-12 cells

microRNA (miR)-142-3p is implicated in malignancy and has been identified as a biomarker for aggressive and recurrent lung adenocarcinomas. This study aimed to evaluate the inhibitory effect of miR-142-3p on apoptosis and inflammation induced by bleomycin in MLE-12 cells. MLE-12 cells were first transfected either with miR-142-3p mimic or miR-142-3p inhibitor and then the cells were exposed to 50 μg/mL of bleomycin. Thereafter, cell viability, apoptosis and the expression of pro-inflammatory cytokines were assessed using CCK-8, flow cytometry, RT-PCR and western blot analyses. Cox-2, PI3K, AKT and mTOR expressions were detected by western blotting after bleomycin was administered together with NS-398 (an inhibitor of Cox-2). As a result, cell viability was significantly decreased, as well as apoptosis and the expression of IL-1 and TNF-α were remarkably increased after 50 and 100 μg/mL of bleomycin administration. miR-142-3p overexpression alleviated bleomycin-induced apoptosis and overproduction of these two pro-inflammatory cytokines, while miR-142-3p suppression exhibited completely opposite results. Up-regulation of Cox-2 and inactivation of PI3K/AKT/mTOR were found in bleomycin-pretreated cells, while these abnormal regulations were partially abolished by miR-142-3p overexpression and NS-398. In conclusion, this study demonstrated that miR-142-3p overexpression protected bleomycin-induced injury in lung epithelial MLE-12 cells, possibly via regulating Cox-2 expression and PI3K/AKT/mTOR signaling pathway. These findings provide evidence that miR-142-3p may be a therapeutic strategy for idiopathic pulmonary fibrosis (IPF) treatment.

Quimioterapia neoadyuvante en cáncer de cuello uterino localmente avanzado / Neoadjuvant chemotherapy in advanced cervical cancer

Se presentan los resultados de una serie clínica de 15 pacientes portadoras de cáncer escamoso de cuello uterino localmente avanzado, estadios clínico I B2-II B, a quienes se les administró una quimioterapia neoadyuvante con cisplatino, vincristina y bleomicina durante 3 ciclos y luego fueron evaluadas para cirugía radical. Se logró una respuesta parcial o completa que permitió realizar la cirugía en 14 de las 15 pacientes tratadas. Cuando los márgenes o los ganglios estuvieron positivos para tumor se agregó raditerapia pelviana

Bleomycin sensitivity in patients with familial and sporadic polyposis: a pilot study

Human peripheral blood lymphocytes from 10 patients with familial adenomatous polyposis (FAP) showed a significantly higher incidence of chromatid breaks when compared to cells from 10 normal individuals, after exposure to bleomycin (BLM) during the G2 phase. However, no significant increase in bleomycin sensitivity was observed in lymphocytes from 10 patients with sporadic adenomatous polyps (AP) vs. 10 normal individuals (P = 0.67). Individuals that exhibited an average number of chromatid breaks per cell higher than 0.80 were considered sensitive to the drug. No control showed susceptibility to BLM, as compared to 3 out of 20 patients.

Sensibilidade aos efeitos genotóxicos da bleomicina: colite ulcerativa versus câncer colorretal / Sensibility genotoxic effects of bleomycin: ulcerative colitis versus colorectal cancer

Neste estudo foram selecionados 35 pacientes, sendo 13 sadios (grupo I); 10 pacientes com colite ulcerativa (grupo II); e 12 pacientes com câncer colorretal (grupo III). Para determinar a resposta aos efeitos mutagênicos da bleomicina em cultura de linfócitos de sangue periférico, foram realizados dois tipos de cultura para cada paciente: a primeira, sem tratamento com bleomicina (cultura espontânea) e, a segunda, tratada com bleomicina (cultura induzida). Na avaliaçäo microscópica dos linfócitos em metástase, foram determinados o índice mitótico e as alteraçöes cromossômicas estruturais. Os três grupos de pacientes diferiram entre si quanto às determinaçöes do índice mitótico nas culturas espontâneas (p < 0,01) e significativamente maiores que os dos grupos I e III. Quanto à freqüência de quebras cromatídicas espontâneas por célula, näo houve diferença significativa entre os três grupos de pacientes (p = 0,39). Quanto à freqüência de quebras cromatídicas induzidas por célula, observou-se que havia diferença significativa entre os três grupos de pacientes (p < 0,001). O grupo III apresentou valores significativamente superiores aos verificados no grupo II, e este significativamente maiores que os do grupo I. Com base nos resultados, observou-se que a bleomicina induziu ao aumento significativo de aberraçöes cromossômicas nos linfócitos dos grupos de pacientes com colite ulcerativa e com câncer colorretal. A sensibilidade aos efeitos genotóxicos da bleomicina em pacientes com colite ulcerativa pode expressar maior predisposiçäo ao câncer colorretal

Chromosome sensitivity to bleomycin in G2 lymphocytes from Down syndrome patients

Inúmeros trabalhos têm demonstrado que linfócitos de pacientes com síndrome de Down apresentam uma maior freqüência de aberraçöes cromossômicas quando expostos a radiaçäo ionizante ou agentes químicos nas fases G0 ou G1 do ciclo celular, mas näo em G2, quando comparados com controles normais. Para determinar a sensibilidade de linfócitos de pacientes com síndrome de Down, na fase G2, usou-se o radiomimético bleomicina em culturas de linfócitos de 24 pacientes. Todos os pacientes mostraram trissomia livre do cromossomo 21 (47,XX + 21 ou 47, XY + 21). Indivíduos que apresentaram freqüência média de quebras cromatídicas por célula superior a 0,8 foram considerados sensíveis a droga. Nenhum controle apresentou suscetibilidade a bleomicina e entre os 24 pacientes com síndrome de Down somente um foi sensível à droga. Näo se observou qualquer diferença significativa entre os dois grupos em relaçäo as freqüências de quebras cromatídicas em linfócitos em G2, o que está de acordo com outros trabalhos. A distribuiçäo das quebras induzidas pela bleomicina, em cada grupo cromossômico, foi igual para pacientes e controles. Nenhuma diferença significativa foi observada na resposta a bleomicina entre homens e mulheres, nos dois grupos. Provavelmente, o principal fator envolvido na sensibilidade cromossômica de linfócitos de pacientes com síndrome de Down seja a fase do ciclo celular na qual a célula é tratada.

Effect of bleomycin and methotrexate on healing of bone and soft tissues in oral surgery

Twenty-four guinea pigs were divided into three major groups: Group I was the control group, in group II animals were given bleomycin [1.42 mg/kg, i.m.] and in group III animals were given methotrexate [4.725 mg/kg, i.m.]. The animals were sacrificed at 1, 2, 4 and 6 weeks postoperatively. The left lower incisor was extracted under ether anesthesia, one day after injection of the cytotoxic agent or saline. H and E-stained sections were examined. Histologically, bleomycin reduced collagen formation, which is reflected in reduced wound breaking strength in the first phase of healing, retarded wound healing in the second phase of healing, but had little or no effect in the third phase of healing. Methotrexate did not affect collagen formation in the first and second phases, but caused the abnormal proliferation and aggregation of bone cells in the 3rd phase of healing

A case of bleomycin-induced scleroderma

The association of exposure to bleomycin with the development of scleroderma-like cutaneous abnormalities has been reported. We experienced a case of scleroderma involving the hands, feet, and forearms after bleomycin chemotherapy. The present report supports the possible causal relation of bleomycin with scleroderma. Regarding the widespread use of bleomycin, this complication is thought to be under appreciated.

Quimioterapia basada en cisplatino más vincristina, bleomicina y etoposide en ciclos semanales para neoplasias de células germinales / Chemotherapy based on cisplatin plus, bleomycin and ethoposide in weekly cycles for germ-cell malignancies

La finalidad de esta investigación prospectiva fue evaluar la eficacia de los fármacos quimioterapéuticos para las neoplasias de células germinales. El protocolo consistió en cisplatino, bleomicina, vincristina y etoposide en dosis semanales (6 ciclos), que se administraron a siete varones con etapas B (5) y C (2) identificadas según historia clínica, exploración física, exámenes de laboratorio y de imágenes y marcadores tumorales. Se estableció una eficacia posquimioterapéutica de 71 por ciento, con 86 por ciento de reacciones completas, 14 por ciento de reacciones parciales y promedio de recaídas de 28 por ciento, con resultados similares a los de otros estudios. Se observó tolerancia adecuada con toxicidad mínima, sólo estadísticamente significativa para leucocitos y eritrocitos, pues esta protocolo resultó menos tóxico y más seguro que otros esquemas con una estancia hospitalaria menor (promedio 2 días por ciclo), lo que además redujo costos. El periodo de seguimiento fue de 13.2 ñ 6.5 meses

Genetic susceptibility to bleomycin: a twin study

Foram analisadas as freqüencias de quebras cromatídicas em metáfases obtidas a partir da cultura de linfócitos, em 16 pares de gêmeos monozigóticos (MZ) e 16 pares de gêmeos dizigóticos (DZ) normais. Foram ainda analisadas as freqüências de quebras cromatídicas induzidas pela bleomicina (BLM), na concentraçäo final de 0,03 unidade/ml de cultura. Observou-se uma diferença intrapar, altamente significante, na freqüência de quebras entre gêmeos dizigóticos e monozigóticos, antes e depois do tratamento com BLM. O coeficiente de herdabilidade foi de 85,5 por cento, e concluiu-se que fatores genéticos contribuem significativamente para a variaçäo individual que foi observada na freqüência de quebras induzidas pela bleomicina.

Importancia del pH del derrame pleural maligno en la efectividad de la pleurodesis química con Bleomycina

Con el objeto de averiguar si el pH del Líquido Pleural del paciente con Derrame Pleural Maligno (DPM) altera la eficiencia de la Preurodesis Química con Bleomycyna, se realizó este procedimiento con dosis de 1mg/k, a 33 pacientes del Hospital Santa Clara de Bogotá entre los meses de febrero de 1991 y enero de 1993. Para ingresar al estudio los pacientes debían cumplir los siguientes requisitos: 1) No haber recibido tratamiento previo para su enfermedad neoplásica (radio, quimioterapia, drenajes previos, etc.). 2) Reexpansión completa del pulmón y drenaje total del derrame pleural Post-toracostomía cerrada. 3. Puntaje de Karnofsky mayor de 60. 4) Medición del pH del líquido pleural. 5) Comprobación por biopsia pleural de compromiso metastásico de la pleura. Se realizó control clínico y radiológico de los pacientes a los 30 días de realizada la Pleurodesis Química. 3 pacientes no ingresaron a este análisis: Uno por fallecer antes del plazo descrito y dos por haber presentado Empiema como complicación. Se comparó la efectividad de la Pleurodesis con Bleomycina en los pacientes que tenían pH del líquido pleural menor a 7.3 con el grupo de pacientes que tenían cifras mayores e iguales a esa cifra: se encontró que la efectividad del procedimiento era del 30 por ciento en el primer grupo y del 85 por ciento en el segundo. (p = 0.01). La "respuesta parcial" se consideró como efectividad en ambos grupos. Así se sugiere, por primera vez en la literatura disponible, que la efectividad de la pleurodesis con Bleomycina, del mismo modo que ocurre con la Tetraciclina, varía de acuerdo al pH previo del líquido pleural.

effects of bleomycin sulphate [blenoxane] on the thymus and peyer's patches of albino rat

Our present study investigated the effect of bleomycin sulphate as an antineoplaslitc drug on thymus and Peyer's patches of adult male albino rats. Bleomycin was injected intraperitoneally in a single dose of 3 mg/kg body weight. The specimens were taken three days, one week, two weeks and three weeks after drug administration. The lymphocytes showed varied sensitivity to the action of bleomycin. In the first week after drug injection, the majority of lymphocytes showed the classic manifestations of degenerated cells, namely, pyknosis, karyorrhexis and karyolysis. Moreover, extensive karyolysis, lymphocytic depletion and loss of the normal lymphatic architecture of both regions were observed in the second and third weeks of experiment. However, normal lymphocytes were detected side by side with the degenerated cells. Throughout the experiment, increasing numbers of mast cells were noticed only in the thymus. Loss of the reticular pattern was marked in both regions particularly in the second and third weeks. In the third week, an increase in the number of PAS positive cells was recorded in Peyer's patches. No collagen deposition was observed in the sections examined

Correlation of fragile sites and bleomycin induced chromosome break points.

Bleomycin (Blm) induced break points in human chromosome preparations were compared with the known fragile sites. A total of 136 breaks were observed from 100 well spread G-banded plates (1.3 bps/cell). These correspond to a total of 57 break prone sites. Of these 57 sites, 24 correspond to the known fragile sites, 5 to sites of protooncogenes and neoplasia, 26 sites correspond to more than one known site of fragility, protooncogene, neoplasia or reciprocal translocation sites, and 2 unknown sites. The findings suggest that fragile sites, either commonly expressed or induced, might be a predisposing factor for chromosome aberrations in human. The expression of fragile sites induced by Blm and their correlation with the known cancer chromosome break points, oncogenes and reciprocal translocation, suggest that the fragile sites are prone to mutagenic action.