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AIM To investigate the effects of Ophiopogonis Root Decoction on bleomycin(BLM)-induced idiopathic pulmonary fibrosis(IPF)in mice and to explore its metabolic modulation of immunity.METHODS The IPF mouse model was constructed by tracheal drip injection of BLM,and the mice were randomly divided into the control group,the model group,the pirfenidone group(0.3 g/kg)and the high,medium and low dose groups of Ophiopogonis Root Decoction(18,9,4.5 g/kg).HE and Masson staining,ELISA,flow cytometry and immunohistochemistry were used to detect the histopathological changes of the lung,the levels of Collagen I,HYP and TGF-β1,the proportion of PD-1+ CD4+T cells in plasma,and the expressions of p-STAT3,PD-1,PD-L1 and IL-17A in lung tissue,respectively.RESULTS Compared with the control group,the model group displayed significantly higher level of lung coefficients(P<0.01),more severe pulmonary inflammatory cell infiltration and collagen fiber deposition,and increased pulmonary fibrosis score(P<0.01),increased levels of Collagen I,HYP and TGF-β1(P<0.01),increased proportion of PD-1+ CD4+ T cells in plasma(P<0.01),increased pulmonary expression of p-STAT3,PD-1,PD-L1 and IL-17A(P<0.01).Compared with the model group,the Ophiopogonis Root Decoction groups shared lower levels of lung coefficients(P<0.05),less pulmonary inflammatory cell infiltration and collagen fiber deposition,decreased pulmonary fibrosis score(P<0.05),decreased levels of Collagen I,HYP and TGF-β1(P<0.05),decreased proportion of PD-1+ CD4+T cells in plasma(P<0.05),and decreased pulmonary expression of p-STAT3,PD-1,PD-L1,and IL-17A(P<0.05).CONCLUSION Ophiopogonis Root Decoction can significantly reduce extracellular matrix(ECM)deposition and curb the progression of IPF via inhibition of STAT3/PD-1/PD-L1 immunomodulatory signaling pathway.
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ObjectiveBased on spatial metabolomics technology combined with pharmacological indexes, to analyze the mechanism of Fritillariae Cirrhosae Bulbus(FCB) powder in improving bleomycin-induced pulmonary fibrosis in rats. MethodSixty SD rats were randomly divided into five groups, including the blank group, the model group, and high, medium, low dosage groups of FCB. Except for the blank group, rats in all other groups were injected with bleomycin by tracheal injection to establish a pulmonary fibrosis model. Postoperatively, the high, medium and low dosage groups of FCB were administered aqueous solutions of FCB powder at doses of 0.36, 0.18, 0.09 g·kg-1, respectively, continuously for 28 d. The blank and model groups were given an equal volume of distilled water by gavage. After the last administration, lung tissues and blood samples were collected, the pathological conditions of rat lung tissues were comprehensively evaluated by hematoxylin-eosin(HE) and Masson staining, and aerodynamic assisted desorption electrospray ionization mass spectrometry imaging(AFADESI-MSI) was used for MSI of rat lung tissues from different experimental groups. Spatial metabolomics analysis was conducted on the fibrotic areas of lung tissues in the model group and the high dosage group of FCB based on HE staining images. Differential metabolites between groups were screened by orthogonal partial least squares-discriminant analysis(OPLS-DA), with variable importance in the projection(VIP) values>1, t-test P<0.05, and fold change analysis. Metabolic pathway analysis of the identified differential metabolites was performed using Kyoto Encyclopedia of Genes and Genomes(KEGG). Protein expression levels of nuclear transcription factor-κB p65(NF-κB p65) and heme oxygenase-1(HO-1) in rat lung tissues were detected by Western blot. Biochemical assessments of superoxide dismutase(SOD), malondialdehyde(MDA) and glutathione(GSH) levels in rat lung tissues were conducted. Serum levels of interleukin(IL)-1β, IL-6, nuclear factor erythroid 2 related factor 2(Nrf2), and tumor necrosis factor-α(TNF-α) were measured by enzyme linked immunosorbent assay(ELISA), and some of the screened signaling pathways with strong correlation were verified. ResultThe results of MSI experiment showed that after 28 d of the administration of FCB powder to rats with pulmonary fibrosis, the content of L-arginine in the fibrotic regions of lung tissues was significantly different from that of rats in the model group, and the content of phosphatidylcholine was lower than that in the fibrotic region of lung tissues of rats in the model group. Western blot results confirmed that, in comparison to the model group, oral administration of FCB powder for 28 d could inhibit the elevated expression of NF-κB p65 protein in the lung tissues of rats with pulmonary fibrosis. Furthermore, high dose of FCB powder was able to significantly inhibit the expression of HO-1 after oral administration (P<0.05). The cytokine detection results indicated that the concentrations of IL-1β, IL-6 and TNF-α in the serum of rats from the high, medium, low dosage groups of FCB were reduced by comparing with the model group, and the high dose of Chuanbeimu powder administered by gavage could significantly inhibit the trend of decreased SOD, GSH, Nrf2 contents and increased MDA content induced by bleomycin. ConclusionOral administration of FCB powder has the potential to partially ameliorate bleomycin-induced pulmonary fibrosis in rats, and its mechanism may be related to the regulation of pathways associated with inflammation(NF-κB p65) and oxidative stress(Nrf2/HO-1).
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Abstract Objectives To evaluate the efficacy and tolerance after the electrochemotherapy treatment for local therapy of cutaneous and subcutaneous metastases of head-and-neck tumors and malignant melanoma refractory to standard therapies, mainly in neck metastasis of squamous cell carcinoma. And, to evaluate the relation of this response according to the skin reaction (healing with ulcer or dry crust). Methods prospective pase II, observational clinical study of 56 patients with metastases of head-and-neck squamous cell carcinoma (n = 13), papillary thyroid carcinoma (n = 4), adenoid cystic carcinoma of parotid gland (n = 1) or malignant melanoma (n = 37, 5 in head). Patients were treated by electrochemotherapy (application of electrical pulses into the tumor) after the administration of a single intravenous dose of bleomycin. Kaplan-Meier curves were performed. The statistical significance was evaluated using log-rank test; p-value of less than 0.05 was considered as significant. Results Overall clinical response was observed in 47 patients (84%). Local side effects were mild in all the patients. Ten patients (76.9%) with neck metastasis of squamous cell carcinoma had some degree of response, but only in one was complete. Patients even with only partial response had a higher overall survival than patients without response (p = 0.02). Most of the patients with squamous cell carcinoma had diminution of pain and anxiety. Response rate and overall survival was higher in MM patients (86.5%) than in squamous cell cancer patients (76.9%) (p = 0.043). The healing process (dry crust/ulcer) was not associated with the overall survival (p = 0.86). Conclusions Electrochemotherapy is associated a higher overall survival and diminution of pain and anxiety. Therefore, it is an option as palliative treatment for patients with neck metastasis of squamous cell carcinoma refractory to other therapies or even as a concomitant treatment with newer immunotherapies. The type of healing of the surgical wound could not be associated with a higher rate of response or survival. Level of evidence III.
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SUMMARY: The potential anti-inflammatory and antifibrotic activity of polyphenolic extracts of blueberry and grape was evaluated in a mouse model of lung damage induced by subcutaneous administration of bleomycin. The results of testing the polyphenolic extracts on two different systemic administration variants of bleomycin (intraperitoneal and subcutaneous) were compared. It was found that regardless of the method of bleomycin administration, indirect cross-acute and subacute damage to the pulmonary system was observed. Both patterns exhibited the same prevalence and severity. The administration of polyphenolic extracts of blueberry and grape to mice resulted in a significant decrease in theseverity of acute and subacute patterns of lung damage, suggesting their protective properties for the microcirculatory bed and a pronounced anti-inflammatory effect.
La potencial actividad antiinflamatoria y antifibrótica de los extractos polifenólicos de arándano y uva se evaluó en un modelo de daño pulmonar en ratón inducido por la administración subcutánea de bleomicina. Se compararon los resultados de las pruebas de los extractos polifenólicos en dos variantes diferentes de administración sistémica de bleomicina (intraperitoneal y subcutánea). Se encontró que, independientemente del método de administración de bleomicina, se observaba daño indirecto cruzado, agudo y subagudo al sistema pulmonar. Ambos patrones exhibieron la misma prevalencia y gravedad. La administración de extractos polifenólicos de arándano y uva a ratones dio como resultado una disminución significativa en la gravedad de los patrones agudos y subagudos de daño pulmonar, lo que sugiere sus propiedades protectoras del lecho micro- circulatorio y un efecto antiinflamatorio pronunciado.
Subject(s)
Animals , Mice , Bleomycin/toxicity , Plant Extracts/administration & dosage , Lung Injury/chemically induced , Lung Injury/drug therapy , Polyphenols/administration & dosage , Blueberry Plants/chemistry , Vitis/chemistry , Disease Models, Animal , Lung Injury/pathology , Lung/drug effects , Anti-Inflammatory Agents/administration & dosageABSTRACT
ABSTRACT Lymphatic malformation is a rare orbital tumor that used to be treated surgically, with high complication rates, or recently with intralesional bleomycin injection. We report for the first time the histopathological changes of eyelid lymphatic malformation after water-soluble intralesional bleomycin injection in a 20-year-old woman who had unsuccessful orbital surgical debulking during childhood. The changes confirmed the assumption of fibrosis induced by intralesional bleomycin injection. The minimal bleeding during surgical intervention made it much easier than the usual lymphatic malformation bloody procedure, without postoperative recurrences and with favorable aesthetic outcomes.
RESUMO A malformação linfática é um tumor orbital raro que costumava ser tratado cirurgicamente, com alta taxa de complicações. Mais recentemente, passou a ser tratado com uma injeção intralesional de bleomicina. Este é o primeiro relato sobre as alterações histopatológucas da malformação linfática palpebral após uma injeção intralesional de bleomicina hidrossolúvel em uma mulher de 20 anos de idade que sofreu uma cirurgia malsucedida de debulking orbital durante a infância, confirmando a suposição de fibrose induzida por injeções intralesionais de bleomicina. O sangramento mínimo durante a intervenção cirúrgica tornou esta muito mais fácil que o procedimento sangrento habitual, sem recidivas pós-operatórias e com desfechos estéticos favoráveis.
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SUMMARY: An experimental morphological and morphometric study of the antifibrotic function of blueberry and grape extracts was carried out on a model of lung injury in mice induced by intraperitoneal administration of bleomycin. During intraperitoneal administration of bleomycin to mice, acute and subacute damage to the pulmonary system was noted. Both patterns had the same prevalence and severity. The administration of polyphenolic extracts of blueberry and grape to mice showed a significant reduction in the severity of the acute and subacute pattern of lung injury. Blueberry and grape extracts reduce the acute phase of damage to the microvasculature, enhance phagocytic function, have an anti-inflammatory effect, reducing the degree of lymphohistiocytic infiltration and locoregional foci of residual inflammatory effects.
Se realizó un estudio experimental morfológico y morfométrico de la función antifibrótica de extractos de arándano y uva en un modelo de lesión pulmonar en ratones inducida por la administración intraperitoneal de bleomicina. Durante la administración intraperitoneal de bleomicina a ratones, se observaron daños agudos y subagudos en el sistema pulmonar. Ambos patrones tuvieron la misma prevalencia y severidad. La administración de extractos polifenólicos de arándano y uva a ratones mostró una reducción significativa en la severidad del patrón agudo y subagudo de lesión pulmonar. Los extractos de arándano y uva reducen la fase aguda del daño a la microvasculatura, mejoran la función fagocítica, tienen un efecto antiinflamatorio, reducen el grado de infiltración linfohistiocítica y los focos locorregionales de efectos inflamatorios residuales.
Subject(s)
Animals , Mice , Pulmonary Fibrosis/drug therapy , Bleomycin/toxicity , Plant Extracts/administration & dosage , Blueberry Plants/chemistry , Polyphenols/administration & dosage , Antifibrotic Agents/administration & dosage , Pulmonary Fibrosis/chemically induced , Disease Models, Animal , Antibiotics, Antineoplastic/toxicityABSTRACT
ObjectiveTo investigate the changes of differential metabolites in the serum of mice at different stages of bleomycin sulfate(BLM)-induced pulmonary fibrosis modeling and administration, and the mechanism of Wenfei Huaxian granules(WHG)against idiopathic pulmonary fibrosis. MethodMice were randomly divided into control group, control group of 14 days, model group, model group of 14 days, low-dose WHG group and high-dose WHG group. BLM(0.04 U per mouse)was injected into the trachea of mice in the model group, model group of 14 days, low-dose WHG group and high-dose WHG group, and sterile normal saline was injected into the trachea of mice in the control group and control group of 14 days. Mice of low-dose WHG group and high-dose WHG group were given different doses of WHG by gavage every day after injection of BLM, and mice of control group, control group of 14 days, model group and model group of 14 days were given sterile water by gavage every day. The peripheral blood of mice in the control group of 14 days and model group of 14 days were taken to prepare serum after injection of BLM for 14 days, and the peripheral blood and other materials of mice in the other groups were taken after continuous administration for 28 days. The bronchoalveolar lavage fluid(BALF)was collected for leucocyte differential count, the pathological examination and hydroxyproline(HYP)content determination of lung tissues of mice were performed, and the small molecule metabolites in serum samples of mice in each group were determined by ultra-high performance liquid chromatography-mass spectrometry(UHPLC-MS). Principal component analysis(PCA)and orthogonal partial least squares-discriminant analysis(OPLS-DA)were conducted to screen differential metabolites and their biological functions were analyzed. ResultCompared with the control group, a large number of continuous fibrotic foci appeared in the lung tissue of mice in the model group, the alveolitis score, fibrosis degree score and HYP content increased significantly(P<0.01), and the total number of leukocytes, macrophages and lymphocytes in BALF increased significantly(P<0.05). A total of 33 differential metabolites were screened between the control group of 14 days and model group of 14 days, mainly lipid metabolites, which were mainly involved in oxidative damage and inflammatory process. A total of 34 differential metabolites, mainly amino acid metabolites, were screened between the control group and model group, mainly involving nucleic acid damage and inflammatory process. Compared with the model group, the HYP content, fibrosis score and alveolitis score in the lung tissue of mice from high-dose WHG group decreased significantly(P<0.05, P<0.01), and the total number of lymphocytes in BALF decreased significantly(P<0.05). Compared with the model group, 27, 40 differential metabolites were identified in the serum of mice from the low-dose WHG group and high-dose WHG group separately. There were totally 9 common differential metabolites between the model group and low-dose WHG group/high-dose WHG group, which mainly involved in the metabolic pathways of inflammation related lipids metabolism, arginine and tryptophan metabolism, and the change trends in low-dose WHG group and high-dose WHG group were significantly back-regulated compared with the model group. ConclusionWHG can alleviate BLM-induced pulmonary fibrosis, collagen deposition and inflammatory reaction in mice, and its anti-fibrotic effect may be related to the adjusting of inflammatory factors, nitric oxide and oxidative stress related metabolic pathways.
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This study investigated the effect of Gualou Xiebai Decoction on rats with bleomycin-induced pulmonary fibrosis. The rats were randomly divided into a control group, a model group, a low-dose Gualou Xiebai Decoction group(2.4 g·kg~(-1)), a high-dose Gualou Xiebai Decoction group(4.8 g·kg~(-1)), and pirfenidone group(150 mg·kg~(-1)). The model of pulmonary fibrosis was established by intratracheal instillation of bleomycin in all groups, except the control group. Since the second day of modeling, the corresponding drugs were given to rats by intragastric administration, once a day for 14 d and 28 d. The hematoxylin-eosin(HE) staining was used to evaluate the degree of inflammatory injury in lung tissues. The immunofluorescence staining was used to detect the expression of CD68 and CD163 in lung tissues of rats. The levels of tumor necrosis factor-α(TNF-α) and interleukin-10(IL-10) in serum and brochoalveolar lavage fluid(BALF) were detected by enzyme-linked immunosorbent assay(ELISA). The expression of pyroptosis-related genes in lung tissues of rats was detected by qRT-PCR. The results of HE staining and immunofluorescence staining showed that the lung tissue structure was normal in the control group. In addition, there were alveolar collapse or even closure in lung tissues of rats in the model group, with obvious inflammatory cell infiltration, and the expression of CD68 and CD163 was significantly up-regulated. As compared with the model group, the lung tissue structure of rats in the Gualou Xiebai Decoction groups was significantly improved, with alleviated inflammation, and the expression of CD68 and CD163 was decreased. As compared with the control group, the level of TNF-α in serum and BALF of rats in the model group was significantly increased(P<0.01), the mRNA expression levels of alpha smooth muscle actin(α-SMA), collagen type Ⅰ alpha 1 chain(Col1a1), caspase-1, IL-1β, IL-18, gasdermin D(Gsdmd), and NOD-like receptor thermal protein domain associated protein 3(NLRP3) in lung tissues were significantly increased(P<0.05, P<0.01), and the mRNA expression level of E-cadherin was significantly decreased(P<0.01). As compared with the model group, the level of TNF-α in serum and BALF was significantly down-regulated in the high-dose Gualou Xiebai Decoction group(P<0.05, P<0.01), and that of IL-10 was up-regulated(P<0.05, P<0.01). The mRNA expression levels of α-SMA, Col1a1, caspase-1, IL-18, Gsdmd, NLRP3 and IL-1β in lung tissues were significantly decreased(P<0.05, P<0.01) in the high-dose Gualou Xiebai Decoction group, and the mRNA expression level of E-cadherin was significantly increased(P<0.05, P<0.01). In conclusion, Gualou Xiebai Decoction can down-regulate the levels of inflammatory factors and related genes and effectively mitigate pulmonary fibrosis by regulating the pyroptosis pathways.
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Objective To investigate the effect and potential mechanism of alpinetin(ALPN)on bleomycin(BLM)-induced pulmonary fibrosis in mice.Methods The mice were randomly divided into control group,model group(intratracheally instilled BLM),low-dose(L-ALPN group)and high-dose ALPN groups(H-ALPN group)(10 mg/kg or 30 mg/kg ALPN daily,respectively)with 10 in each.Lung tissues were collected,and the alveolar structure and pathological morphology were microscopied by HE and Masson staining;mRNA and protein expres-sions of collagen Ⅰ,TGF-β1,E-cadherin,α-SMA,p-PERK,PERK,CHOP and GRP78 in lung tissue were de-tected by RT-qPCR,immunohistochemistry and Western blot,respectively.Results Compared with control group,the lung of the model group showed fibrotic changes,and the expression of collagenⅠ,TGF-β1,α-SMA,p-PERK/PERK,CHOP and GRP78 in lung tissue was significantly increased(P<0.01).E-cadherin expression was significantly decreased(P<0.01).Compared with model group,pulmonary fibrosis was significantly alleviated in low and high doses ALPN groups,the expression of collagenⅠ,TGF-β1,α-SMA,p-PERK/PERK,CHOP and GRP78 in lung tissue were significantly decreased(P<0.05 or P<0.01),and the expressionof E-cadherin was sig-nificantly increased(P<0.05 or P<0.01).Conclusions ALPN may alleviate BLM-induced pulmonary fibrosis,and this effect may be attributed to the inhibition of endoplasmic reticulum stress.
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Objective:To explore the in vitro anticancer effect of bleomycin (Ble) combined with cisplatin (DDP) on human gastric cancer cells.Methods:CCK-8 experiment was conducted to detect the effect of Ble and DDP alone or in combination on the proliferation of gastric cancer cells; Flow cytometry was used to detect changes in cell apoptosis and changes in reactive oxygen species. Cell scratch test was employed to detect cell migration; Western blot experiment was conducted to detect protein expression.Results:The results of CCK-8 showed that 20 μM DDP could inhibit the proliferation of six types of gastric cancer cells by 40%, while the effect of 20 μM Ble was only about 20%. When used in combination, the inhibitory rate on six types of gastric cancer could reach over 60%, with the strongest inhibitory effect on AGS cells. When 10 μM Ble and 10 μM DDP were combined, the proportion of AGS apoptotic cells reached 75.68%, higher than that of the two drugs treated with 20%, respectively 20 μM processing effect. When 10 μM Ble and 10 μM DDP were used in combination, the number of migrating and invading cells was significantly reduced, and the inhibition rate reached 50%. Compared with single use, the difference was statistically significant ( P<0.05). Flow cytometry results showed that the combination of Ble and DDP promoted cancer cell apoptosis by up-regulating the level of reactive oxygen species in cells; Western blot results showed that the expression of p-JAK2 and p-STAT3 decreased after Ble and DDP were combined, indicating that the JAK2/STAT3 signal pathway was inhibited. Conclusions:The combination of Ble and DDP can inhibit the proliferation and migration of gastric cancer cells, promote the apoptosis of gastric cancer cells, and play a synergistic anti-cancer effect. Its mechanism may be related to the up-regulation of ROS levels in cells, thereby inhibiting the activation of the JAK2/STAT3 pathway.
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AIM:This study aims to investigate the histopathological and ultrastructural alterations in the lung tissues of rats induced by a single intratracheal administration of bleomycin,with the objective of establishing a reliable model for future applications.METHODS:Six to eight-week-old SD rats were randomly allocated into two groups:the control group and the model group(n=12).Pulmonary fibrosis was induced in the rat models by a single intratracheal in-stillation of bleomycin(3 mg/kg),while an equivalent volume of saline was administered to the control group.The rats were executed on the 42nd day.Twelve rats remained in the control group,while nine rats remained in the model group.Lung tissue imaging was conducted using CT scans.Lung function tests were performed to assess changes in forced vital capacity(FVC)and dynamic lung compliance(Cdyn).Lung stiffness was determined through Young's modulus testing using a rheometer.The pathological structure of lung tissues was examined using both HE and Masson staining methods.Additionally,transmission electron microscopy was employed to evaluate collagen deposition in lung tissues,alveolar type Ⅱ epithelial cells,macrophages,and ultrastructural changes of the respiratory membrane.RESULTS:CT scans revealed honeycomb patterns in the lungs of model rats,along with partial bronchiectasis/bronchiectasis.In comparison to the con-trol group,the model group exhibited significantly lower FVC and Cdyn values,while lung stiffness were increased.HE and Masson staining demonstrated that rats in the model group exhibited alveolar structure destruction,alveolar septum thickening,inflammatory cell infiltration,and collagen deposition in alveolar septum.Transmission electron microscopy revealed several abnormalities in the model group:increased collagen fibers in the alveolar septa,misalignment of micro-villi in alveolar type Ⅱ epithelial cells,wrinkled nuclei with increased heterochromatin,swollen cytoplasmic mitochon-dria,fractured or haphazardly structured mitochondrion cristaes,and a significant decrease in their number(P<0.05).Furthermore,lamellar bodies were vacuolated and reduced in number(P<0.05),and dilated endoplasmic reticulums with degranulation were observed.There was an increase in alveolar macrophages and interstitial macrophages(P<0.01).The respiratory membrane displayed structural disruptions and an increase in thickness(P<0.01).CONCLUSION:Bleomycin induces decreased lung compliance,alveolar epithelial injury,alveolar septum thickening,collagen deposi-tion,and an increase in interstitial macrophages,ultimately resulting in pulmonary fibrosis in rats.
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Pulmonary fibrosis(PF)is a progressive,interstitial fibrotic lung disease characterized by persistent scar formation in the lung parenchyma,and a reduced quality of life and poor prognosis for patients.The pathogenesis of PF is unknown and there is a lack of effective therapeutic agents;however,animal models are currently the main tool used to explore the pathogenesis of the disease and to find effective therapeutic agents.PF can be induced by various factors and to different degrees according to known etiologies.Among these,bleomycin-induced models are widely used because of their reproducibility and the similarity between the fibrosis pathology and clinical conditions.The main induction method include intratracheal drip,intratracheal nebulization,tail vein injection,intraperitoneal injection,and transnasal inhalation,and these can be classified into single and multiple doses,according to the frequency of induction.Based on the relevant literature,the current review summarizes the characteristics of the bleomycin-induced PF model using different induction frequencies and method,to provide a basis for the application of this model.
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@#To investigate whether rare ginsenosides could alleviate idiopathic pulmonary fibrosis (IPF), C57BL/6 mice were randomly divided into control group, bleomycin (BLM)-induced IPF group, rare ginsenoside Rk1 group, rare ginsenoside Rk3 group, rare ginsenoside Rh4 group and rare ginsenoside Rg5 group.All mice except those in the control group were given bleomycin injection.The IPF model was established by BLM for 28 days.The treatment group was given ginsenoside intragastrically at the same time.After the experiment, the lung tissues of mice were collected and the pathological changes of the mice lungs were observed.The content of hydroxyproline (HYP) in mouse lung tissue was measured.The expression of IPF-related genes in mouse lung tissues was detected.In in vitro experiments, Medical Research Council cell strain-5 (MRC-5) was used to induce IPF cell model using transforming growth factor-β1 (10 ng/mL).The effects of four saponins on the expression of IPF-related genes were analyzed by MTT assay, HYP content determination and RT-qPCR.All four rare ginsenosides could effectively alleviate the pathological process such as alveolar structure destruction caused by IPF, reduce the content of HYP, and down-regulate the expression of IPF-related genes, indicating that rare ginsenosides can effectively alleviate IPF.
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Aim To predict the potential mechanism of ophiopogonin D (OPD) against pulmonary fibrosis by network pharmacology, and further verify it by experiment in vivo. Methods This study found that ophiopogon was the most frequently used drug in the treatment of pulmonary fibrosis with deficiency of Qi and Yin through data mining. In order to explore its material basis, network pharmacology analysis was carried out. A model of pulmonary fibrosis was established by bleomycin, and different concentrations of ophiopogonin D were administered to verify the results of the pharmacological network. Results Firstly, through network pharmacology analysis, it was found that mitophagy might be the potential target for ophiopogon to exert anti-pulmonary fibrosis effect. Meanwhile, network topology analysis showed that OPD had the greatest relationship with mitophagy. Animal experiments showed that OPD could relieve pulmonary fibrosis and reduce collagen deposition in mice. At the same time, the detection of mitophagy related proteins showed that the compound could increase the expression of PINK1 and Parkin proteins, reduce the content of P62 protein in lung tissue, and reduce the intracellular ROS level. Conclusions OPD can improve mitochondrial function and play an anti-pulmonary fibrosis role by promoting PINKl/Parkin dependent mitophagy in lung tissue.
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Aim To explore the effect of Taohong Siwu Decoction on apoptosis and EMT of pulmonary fibrosis model rats by JAK2/STAT3 signaling pathway. Methods Forty SD rats were randomly divided into control group, model group, methylprednisolone group, Taohong Siwu Decoction low-concentration, high-concentration group respectively, with eight cases in each group. The intratracheal injection of bleomycin was applied to induce IPF rat models. HE and Masson staining were performed to observe the pathological changes of lung tissues in each group. ELISA was used to detect the contents of TNF-α, MMP-7 and TGFβ-l in serum of rats. Immunohistochemistry and Western blot were applied to detect the protein expression of JAK2, pJAK2, STAT3, p-STAT3, E-cadherin, α-SMA in lung tissues. RT-PCR was applied to detect the expression of JAK2, STAT3, Bcl2 and Bax genes in lung tissues. Results Compared with control group, the degree of alveolar inflammation and fibrosis degree, the contents of TNF-α, MMP-7 and TGFβ-1 in serum, the levels of JAK2, p-JAK2, STAT3, p-STAT3, α-SMA protein expression, JAK2, STAT3, Bax gene expression were up-regulated, and the levels of Bcl-2 gene and E-cadherin protein expression were down-regulated in lung tissues. Compared with model group, the degree of alveolar inflammation and fibrosis, the contents of TNF-α, MMP-7 and TGFβ-1 in serum, the levels of JAK2, p-JAK2, STAT3, p-STAT3, α-SMA protein expression, JAK2, STAT3 and Bax gene expression were reduced, while the levels of Bcl-2 gene and E-cadherin protein expression were elevated in Taohong Siwu Decoction high-concentration group. Conclusions Taohong Siwu Decoction may regulate JAK2/STAT3 signaling pathway, down-regulate Bax, α-SMA and up-regulate Bcl-2, E-cadherin expression to induce apoptosis and EMT in rat model of pulmonary fibrosis, thus playing an anti-pulmonary fibrosis role.
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Abstract Background Bleomycin is a chemotherapeutical drug used to treat several neoplasias, including non-melanoma skin cancer; it is effective in the treatment of basal cell carcinoma (BCC) via intralesional infiltration. Transdermal drug delivery, which includes technologies such as CO2 Laser, Dermapen, Dermaroller and MMP®, delivers the desired medication to treat skin neoplasias and also acts in skin rejuvenation. Objective To treat BCC lesions using bleomycin via MMP®. Methods Ninety-eight BCC lesions in different anatomical areas were treated using MMP® technology to administer and uniformly distribute bleomycin throughout the lesion and in the established safety margin. Results The cure rate after six months was 96.94%; and recurrences were not associated with lesion size and/or depth. Adverse effects were the expected ones. Study limitations The follow-up time was only six months. Conclusion This therapeutic route showed to be promising and effective.
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Abstract Objective At present, bleomycin has been widely used in the treatment of Lymphatic Malformations (LMs). This study aims to perform a meta-analysis to investigate the effectiveness and influencing factors of bleomycin in the treatment of LMs. Methods We conducted a systematic review and meta-analysis to clarify the relationship between bleomycin and LMs. PubMed, ISI Web of Science and MEDLINE were searched. Results A total of 21 studies (including 428 cases) about bleomycin sclerotherapy for LMs were included in the current meta-analyses. We calculated pooled effective rate and 95% Confidence Interval (95% CI) using random effects model to evaluate the relations between bleomycin and LMs. The results suggested that the effective rate of bleomycin was the combined effective rate was 84.0% (95% CI 0.81‒0.87) and ranged from 39% (95% CI 0.22‒0.56) to 94% (95% CI 0.87-1.02). The heterogeneity among the studies was substantial (I2 = 61.7%, p = 0.000). In subgroup analyses, it was observed that among retrospective study and prospective study, the estimated effective rate was 80.0% (95% CI 0.76‒0.84) and 91.0% (95% CI 0.85‒0.97), respectively. In terms of the dosage, the combined effective rates of weight-based group and fixed-dose group were 86% (95% CI 0.83‒0.90) and 74.0% (95% CI 0.66‒0.82), respectively. There was no significant publication bias in Egger's test (p = 0.059, 95% CI −3.81 to 0.082), but Begg's test did (p = 0.023), and the funnel plot is asymmetric. Conclusion Our study suggested that bleomycin was safe and effective in the treatment of LMs and was primarily dose dependent.
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Las malformaciones linfáticas y su manejo no han sido bien descritas en República Dominicana. Es por ello, que el objetivo de este artículo es la presentación de tres casos, con diferentes patrones y necesidades de tratamiento, de modo que sirva como referencia para trabajadores de la salud en países en vías de desarrollo.
Lymphatic malformations and its management are not well described in the Dominican Republic. That is why this article's objective is to present 3 cases, with different patterns and treatment needs, so it will work as a reference for healthcare workers in developing countries.
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Humans , Male , Female , Child , Lymphangioma, Cystic , Sclerotherapy , SirolimusABSTRACT
Summary@#Flagellate erythema is characterized by “whiplike’’ linear streaks, usually following bleomycin chemotherapy or is associated with consumption of shiitake mushrooms, dermatomyositis, adult onset still disease as well as human immunodeficiency disease. Here, we describe a case of bleomycin-induced flagellate erythema in a patient with Hodgkin lymphoma.
ABSTRACT
The cell cycle inhibitor P21 has been implicated in cell senescence and plays an important role in the injury-repair process following lung injury. Pulmonary fibrosis (PF) is a fibrotic lung disorder characterized by cell senescence in lung alveolar epithelial cells. In this study, we report that P21 expression was increased in alveolar epithelial type 2 cells (AEC2s) in a time-dependent manner following multiple bleomycin-induced PF. Repeated injury of AEC2s resulted in telomere shortening and triggered P21-dependent cell senescence. AEC2s with elevated expression of P21 lost their self-renewal and differentiation abilities. In particular, elevated P21 not only induced cell cycle arrest in AEC2s but also bound to P300 and β-catenin and inhibited AEC2 differentiation by disturbing the P300-β-catenin interaction. Meanwhile, senescent AEC2s triggered myofibroblast activation by releasing profibrotic cytokines. Knockdown of P21 restored AEC2-mediated lung alveolar regeneration in mice with chronic PF. The results of our study reveal a mechanism of P21-mediated lung regeneration failure during PF development, which suggests a potential strategy for the treatment of fibrotic lung diseases.