SETD7 promotes metastasis of triple-negative breast cancer by YY1 lysine methylation.

Breast cancer has gradually become the predominant cause for cancer-associated death in women. The metastatic dissemination and underlying mechanisms of triple-negative breast cancer (TNBC) are not sufficiently understood. (Su(var)3-9, enhancer of zeste, Trithorax) domain-containing protein 7 (SETD7) is vital for promoting the metastasis of TNBC, as demonstrated in this study. Clinical outcomes were significantly worse in primary metastatic TNBC with upregulated SETD7. Overexpression of SETD7 in vitro and in vivo promotes migration of TNBC cells. Two highly conserved lysine (K) residues K173 and K411 of Yin Yang 1 (YY1) are methylated by SETD7. Further, we found that SETD7-mediated K173 residue methylation protects YY1 from the ubiquitin-proteasome degradation. Mechanistically, it was found that the SETD7/YY1 axis regulates epithelial-mesenchymal transition (EMT) and tumor cell migration via the ERK/MAPK pathway in TNBC. The findings indicated that TNBC metastasis is driven by a novel pathway, which may be a promising target for advanced TNBC treatment.

The Taste-Masking Mechanism of Chitosan at the Molecular Level on Bitter Drugs of Alkaloids and Flavonoid Glycosides from Traditional Chinese Medicine.

Taste masking of traditional Chinese medicines (TCMs) containing multiple bitter components remains an important challenge. In this study, berberine (BER) in alkaloids and phillyrin (PHI) in flavonoid glycosides, which are common bitter components in traditional Chinese medicines, were selected as model drugs. Chitosan (CS) was used to mask their unfriendly taste. Firstly, from the molecular level, we explained the taste-masking mechanism of CS on those two bitter components in detail. Based on those taste-masking mechanisms, the bitter taste of a mixture of BER and PHI was easily masked by CS in this work. The physicochemical characterization results showed the taste-masking compounds formed by CS with BER (named as BER/CS) and PHI (named as PHI/CS) were uneven in appearance. The drug binding efficiency of BER/CS and PHI/CS was 50.15 ± 2.63% and 67.10 ± 2.52%, respectively. The results of DSC, XRD, FTIR and molecular simulation further indicated that CS mainly masks the bitter taste by disturbing the binding site of bitter drugs and bitter receptors in the oral cavity via forming hydrogen bonds between its hydroxyl or amine groups and the nucleophilic groups of BER and PHI. The taste-masking evaluation results by the electronic tongue test confirmed the excellent taste-masking effects on alkaloids, flavonoid glycosides or a mixture of the two kinds of bitter components. The in vitro release as well as in vivo pharmacokinetic results suggested that the taste-masked compounds in this work could achieve rapid drug release in the gastric acid environment and did not influence the in vivo pharmacokinetic results of the drug. The taste-masking method in this work may have potential for the taste masking of traditional Chinese medicine compounds containing multiple bitter components.

Glycyrrhizic Acid Inhibits Core Fucosylation Modification Modulated EMT and Attenuates Bleomycin-Induced Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a fatal and incurable chronic interstitial lung disease with an unknown etiology. Recent evidence suggests that epithelial-mesenchymal transition (EMT) is one of the possible factors in the pathogenesis of pulmonary fibrosis. Glycyrrhizic acid (GA) is a natural active ingredient extracted from the root of the traditional Chinese herb licorice, which has been shown in previous studies to have the effect of alleviating lung injury. In this study, our objective was to investigate whether GA could ameliorate pulmonary fibrosis by altering EMT, as well as the therapeutic potential of changing core fucosylation (CF) to target EMT-related pathways. First, we verified that GA partially reverses EMT in a rat model of bleomycin-induced lung interstitial fibrosis, alleviating pulmonary fibrosis, and implying that GA has antifibrotic potential. Next, we discovered that GA attenuated lung interstitial fibrosis by reducing CF modifications to some extent. Interestingly, we found that GA therapy reduced the expression of phosphorylated Smad2/3 (p-Smad2/3) and ß-catenin in the EMT pathway and that GA inhibited the modification of TGF-ßR and WNT receptor proteins by CF, suggesting that GA may interfere with the EMT process by modulating TGF-ßR, WNT core fucosylation modifications to attenuate pulmonary fibrosis. In conclusion, these findings indicate that GA could be a potential therapeutic agent for IPF, and further support the idea that targeting CF alterations could be a novel technique for the treatment of diseases involving EMT.

[Chiropractic plus plum-blossom needling combined with flexibility training on attention deficit in mentally-retarded adolescents].

OBJECTIVE: To observe the clinical efficacy of chiropractic plus plum-blossom needling combined with flexibility training for attention deficit in mentally-retarded adolescents. METHODS: Thirty adolescents with mild mental retardation were randomly divided into a medical rehabilitation plus flexibility training group (10 cases, 2 cases dropped off), a flexibility training group (10 cases, 1 case dropped off) and a control group (10 cases). The patients in the flexibility training group received flexibility training, once every other day, 3 times a week for 12 weeks. The patients in the medical rehabilitation plus flexibility training group received chiropractic and plum-blossom needling at Baihui (GV 20) and Sishencong (EX-HN 1) on the basis of the treatment in the flexibility training group, once every other day, 3 times a week for 12 weeks. The patients in the control group did not receive any targeted physical training and medical rehabilitation. Tobii Pro Spectrum eye movement instrument was used to test the attention concentration (T), attention span (M), attention transfer (γ%) and attention distribution (η). RESULTS: Compared before treatment, T and M in the medical rehabilitation plus flexibility training group and the flexibility training group were increased after treatment (P<0.01, P<0.05), and γ% in the medical rehabilitation plus flexibility training group was increased after treatment (P<0.05). The increasing range of T, M and γ% in the medical rehabilitation plus flexibility training group and the flexibility training group was greater than that in the control group (P<0.01), and the increasing range of T and γ% in the medical rehabilitation plus flexibility training group was greater than that in the flexibility training group (P<0.05). CONCLUSION: The chiropractic plus plum blossom needling combined with flexibility training can improve the attention deficit in mentally-retarded adolescents.

Research on Transfer Rate of Heavy Metals and Harmful Elements in Traditional Chinese Medicine Extraction and Refining Processes and Product Health Risk Assessment.

Ramulus Mori alkaloids, also known as SangZhi alkaloids (SZ-A), is a natural medicine used for the treatment of type 2 diabetes mellitus in China. SZ-A is extracted from Morus alba L., which grows in the natural environment and may be contaminated by heavy metals and harmful elements. These contaminants can enter SZ-A products during the extraction of M. alba, thereby posing a threat to patient health. Therefore, it is necessary to formulate scientific and reasonable limits to ensure patient safety. For this purpose, in this study, we used the extraction process of SZ-A as the object of investigation and determined the content of five harmful elements: Cd, Pb, As, Hg, and Cu in the herb raw material, SZ-A product, and its intermediates obtained in different extraction steps. Next, the transfer rate of harmful elements in the extraction process was used as an indicator to evaluate the ability of different operations to remove harmful elements. Subsequently, the health risks of heavy metals and harmful elements in SZ-A were assessed. Our results demonstrated that M. alba has little risk of contamination by Hg. The cation and anion resin refining processes are the best effective method to remove Cd, Pb, and Cu from the products. However, As is not easily eliminated during the water extraction. There is as much as 87% of As transferred from the herb raw material to the water-extracted intermediate, while Cd, Pb, and Cu are rarely transferred (6% to 17%) under the same conditions. Overall, the results indicate that the regulatory standard limits for Cd, Pb, As, Hg, and Cu contained in natural medicine Ramulus Mori alkaloids are set to 1, 5, 2, 0.2, and 20 µg/g, respectively, which is the most scientific and it can guarantee the safety of patients.

The main bioactive compounds of Scutellaria baicalensis Georgi. for alleviation of inflammatory cytokines: A comprehensive review.

Scutellaria baicalensis Georgi., a plant used in traditional Chinese medicine, has multiple biological activities, including anti-inflammatory, antiviral, antitumor, antioxidant, and antibacterial effects, and can be used to treat respiratory tract infections, pneumonia, colitis, hepatitis, and allergic diseases. The main active substances of S. baicalensis, baicalein, baicalin, wogonin, wogonoside, and oroxylin A, can act directly on immune cells such as lymphocytes, macrophages, mast cells, dendritic cells, monocytes, and neutrophils, and inhibit the production of the inflammatory cytokines IL-1ß, IL-6, IL-8, and TNF-α, and other inflammatory mediators such as nitric oxide, prostaglandins, leukotrienes, and reactive oxygen species. The molecular mechanisms underlying the immunomodulatory and anti-inflammatory effects of the active compounds of S. baicalensis include downregulation of toll-like receptors, activation of the Nrf2 and PPAR signaling pathways, and inhibition of the nuclear thioredoxin system and inflammation-associated pathways such as those of MAPK, Akt, NFκB, and JAK-STAT. Given that in addition to the downregulation of cytokine production, the active constituents of S. baicalensis also have antiviral and antibacterial effects, they may be more promising candidate therapeutics for the prevention of infection-related cytokine storms than are drugs having only antimicrobial or anti-inflammatory activities.

Self-Assembled Lecithin/Chitosan Nanoparticles Based on Phospholipid Complex: A Feasible Strategy to Improve Entrapment Efficiency and Transdermal Delivery of Poorly Lipophilic Drug.

PURPOSE: Lecithin/chitosan nanoparticles have shown great promise in the transdermal delivery of therapeutic agents. Baicalein, a natural bioactive flavonoid, possesses multiple biological activities against dermatosis. However, its topical application is limited due to its inherently poor hydrophilicity and lipophilicity. In this study, the baicalein-phospholipid complex was prepared to enhance the lipophilicity of baicalein and then lecithin/chitosan nanoparticles loaded with the baicalein-phospholipid complex were developed to improve the transdermal retention and permeability of baicalein. METHODS: Lecithin/chitosan nanoparticles were prepared by the solvent-injection method and characterized in terms of particle size distribution, zeta potential, and morphology. The in vitro release, the ex vivo and in vivo permeation studies, and safety evaluation of lecithin/chitosan nanoparticles were performed to evaluate the effectiveness in enhancing transdermal retention and permeability of baicalein. RESULTS: The lecithin/chitosan nanoparticles obtained by the self-assembled interaction of chitosan and lecithin not only efficiently encapsulated the drug with high entrapment efficiency (84.5%) but also provided sustained release of baicalein without initial burst release. Importantly, analysis of the permeation profile ex vivo and in vivo demonstrated that lecithin/chitosan nanoparticles prolonged the retention of baicalein in the skin and efficiently penetrated the barrier of stratum corneum without displaying skin irritation. CONCLUSION: These results indicate the potential of drug-phospholipid complexes in enhancing the entrapment efficiency and self-assembled lecithin/chitosan nanoparticles based on phospholipid complexes in the design of a rational transdermal delivery platform to improve the efficiency of transdermal therapy by enhancing its percutaneous retention and penetration in the skin.

Biotreatment of restaurant wastewater with an oily high concentration by newly isolated bacteria from oily sludge.

High concentration restaurant oily wastewater from restaurants and food processing industries discharged into water environment usually results in environment pollution and inhibits the activity of microorganisms in biological wastewater treatment systems. In this study, 75 strains from oily sludge were isolated with oil degradation activity for edible oil-contained wastewater. Eight isolates were able to grow well in liquid cultures with edible oil as the sole carbon source and discovered with high efficient oil-degrading ability. Seven out of eight isolates were identified as Acinetobacter and one isolate as Kluyvera cryocrescens, based on their 16S rRNA gene sequences. Three highly efficient oil degrading bacteria (Acinetobacter dijkshoorniae LYC46-2, Kluyvera cryocrescens LYC50-1a and Acinetobacter pittii LYC73-4b) were selected and their degradation characteristic were examined, the results showed that the three isolates were effective under pH range from 7.0 to 10.0, and temperature from 25 to 35 °C. For degradation of 2-4% (v/v) of vegetable oil, > 85% degradation percentage were obtained within 30 h. Degradation of the higher concentration oil (6-8%, v/v) result in 50-70% degradation percentage within 72 h, and the degradation percentage for the isolated strains were decreased about 50% for the degradation of 10% oil (< 45%) compared to 2% oil. Different type of oils were also tested, > 90% of degradation percentage were obtained by the three isolates, implied that these strains are capable of removing various oils efficiently. These results suggested that Acinetobacter dijkshoorniae LYC46-2, Kluyvera cryocrescens LYC50-1a and Acinetobacter pittii LYC73-4b are potential species could be efficiently used for high concentration restaurant oily wastewater treatment and might be applicable to a wastewater treatment system for the removal of oil.

Zinc supplementation inhibits the high glucose­induced EMT of peritoneal mesothelial cells by activating the Nrf2 antioxidant pathway.

The high glucose (HG)­induced epithelial­mesenchymal transition (EMT) of peritoneal mesothelial cells (PMCs) serves an important role in peritoneal fibrosis (PF) during peritoneal dialysis. Our previous study reported that zinc (Zn) supplementation prevented the HG­induced EMT of rat PMCs in vitro. In the present study, the role of Zn in HG­induced EMT was investigated in vivo using a rat model of PF. Additionally, the molecular mechanisms underlying HG­induced EMT were studied in human PMCs (HPMCs). In the rat model of PF, HG treatment increased the glucose transfer capacity and decreased the ultrafiltration volume. Histopathological analysis revealed peritoneal thickening, increased expression of vimentin and decreased expression of E­cadherin. ZnSO4 significantly ameliorated the aforementioned changes, whereas Zn inhibition by clioquinol significantly aggravated the effects of HG on rats. The effects of Zn on HPMCs was assessed using western blot analysis, Transwell assays and flow cytometry. It was revealed that Zn also significantly suppressed the extent of the EMT, and reduced reactive oxygen species production and the migratory ability of HG­induced HPMCs, whereas Zn inhibition by N',N',N',N'­tetrakis (2­pyridylmethyl) ethylenediamine significantly potentiated the HG­induced EMT of HPMCs. HG­stimulated HPMCs exhibited increased expression of nuclear factor­like 2 (Nrf2) in the nucleus, and total cellular NAD(P)H quinone dehydrogenase 1 (NQO1) and heme oxygenase-1 (HO­1), the target proteins of the Nrf2 antioxidant pathway. Zn supplementation further promoted nuclear Nrf2 expression, and increased the expression of target proteins of the Nrf2 antioxidant pathway, whereas Zn depletion decreased nuclear Nrf2, NQO1 and HO­1 expression compared with the HG group. In conclusion, Zn supplementation was proposed to suppress the effects of HG on the EMT by stimulating the Nrf2 antioxidant pathway and subsequently reducing oxidative stress in PMCs.

Efficacy differences of electroacupuncture with single acupoint or matching acupoints for chemotherapy-induced nausea and vomiting: study protocol for a randomized controlled trial.

BACKGROUND: Previous studies have shown that acupuncture is beneficial for the alleviation of chemotherapy-induced nausea and vomiting. However, there is a lack of clinical evidence concerning the effects of acupoint-matching on chemotherapy-induced nausea and vomiting. METHODS/DESIGN: This is a parallel randomized controlled trial to evaluate the occurrence of nausea and vomiting after chemotherapy (the incidence of nausea and vomiting, frequency, VAS score, RINVR rating) as the main outcome for cancer. Quality of life, anxiety and depression scores are the secondary outcomes. Quality of life, anxiety and depression scores are the secondary phase. Use of remedy drugs, routine blood examination, and blood biochemical tests are the safety evaluation. We also compare the different effects of ST36 (single acupoint), CV12 (single acupoint), and ST36-CV12 matching groups. DISCUSSION: The results of this trial are expected to explore the effects of matching different acupoints and to offer biologic plausibility for the use of acupuncture in the treatment of chemotherapy-induced nausea and vomiting (CINV). TRIAL REGISTRATION: This trial is registered with clinicaltrials.gov NCT02195921 , The date of registration was 17 July 2014.

Identification and characterization of a phospholipid scramblase encoded by planarian Dugesia japonica.

Phospholipid scramblases (PLSCRs) are the conserved calcium-binding, type II transmembrane proteins synthesized in all eukaryotic organisms. In mammals, these proteins play essential roles in various physiological processes, especially in the immune responses. However, the existence of PLSCRs and their biological functions in planarian are still unknown at present. In this study, a new member of PLSCRs was identified in planarian Dugesia japonica (D. japonica), named DjPLSCR. The sequence analysis revealed that it contains an opening reading frame consisting of 726bp encoding a putative protein of 241 amino acids with a predicted molecular mass of ~28.7kDa and an isoelectric point of 6.21. Whole-mount in situ hybridization showed that mRNAs of DjPLSCR are predominantly expressed in adult and regenerative pharynx which is an important organ of immune system in planarians. Importantly, we found that the transcription level of DjPLSCR was significantly upregulated when planarians were stimulated with the pathogen-associated molecular patterns [polyinosinic-polycytidylic acid, lipopolysaccharide, peptidoglycan and ß-glucan], suggesting that DjPLSCR is involved in the immune response upon pathogen invasion. Our findings provide the first experimental insights into the characteristics and potential functions of PLSCR in planarians.

Acupuncture with different acupoint combinations for chemotherapy-induced nausea and vomiting: study protocol for a randomized controlled trial.

BACKGROUND: Acupuncture is beneficial for controlling chemotherapy-induced nausea and vomiting (CINV). However, the effect of different acupoint combinations on controlling CINV remains unknown. This study aims to compare the effects of distal-proximal point association and local distribution point association on controlling CINV. METHODS/DESIGN: The study is a single-center, randomized controlled trial. A total of 240 participants will be randomly divided into four groups. The control group will receive standard antiemetic only, whereas three acupuncture groups will receive four electro-acupuncture treatments once a day with the standard antiemetic. Acupuncture group I and II will receive distal-proximal point association ("Neiguan (PC6) and Zhongwan (CV12)", and "Zusanli (ST36) and CV12", respectively); Acupuncture group III will receive local distribution point association ("Shangwan (CV13) and CV12"). The primary outcome measures are the frequency and distress of nausea and vomiting. The secondary outcome measures are the grade of constipation and diarrhea, electrogastrogram, quality of life, etc. Assessment is scheduled from the day before chemotherapy to the fifth day of chemotherapy. Follow-ups are performed from the sixth day to the twenty-first day of chemotherapy. DISCUSSION: Results of this trial will help in evaluating the efficacy and safety of electro-acupuncture with different acupoint combinations in the management of CINV. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02478047 .

Effects of Tongxinluo on myocardial fibrosis in diabetic rats.

BACKGROUND: The aim of this study was to explore the effect of Tongxinluo on myocardial fibrosis in diabetic rats and its possible mechanism of action. METHODS: Diabetic rat models were established and then divided into three groups: control, diabetes, and Tongxinluo groups. Heart function and myocardial interstitial collagen volume fraction were investigated, and the protein and mRNA expression levels of transforming growth factor beta 1 (TGF-ß1), Smad3, and Smad7 were measured. RESULTS: Heart function was clearly abnormal in the diabetes group compared with that in the control group, and the collagen volume fraction and mRNA expression levels of TGF-ß1 and Smad3 were higher. However, the protein and mRNA expression levels of Smad7 were lower. In the Tongxinluo group, it was observed that these indicators were improved. CONCLUSION: Tongxinluo was effective for the prevention and treatment of myocardial fibrosis in diabetic rats. It probably mediates the expressions of TGF-ß1, Smad3, and Smad7 in rat cardiomyocytes to reduce the occurrence of myocardial fibrosis in diabetic rats.

Differential effects of variable frequencies of manual acupuncture at ST36 in rats with atropine-induced inhibition of gastric motility.

OBJECTIVE: The 'intensity-response' relationship between acupuncture stimulation and therapeutic effect is currently the focus of much research interest. The same needling manipulation with different frequencies can generate differential levels of stimulus. This study aimed to examine the effects on gastric motility induced by four twirling frequencies based on relatively standardised manual acupuncture (MA) manipulations. METHODS: Twirling manipulations at 1, 2, 3, and 4 Hz were practised before the experiments by a single operator using an MA parameter measurement device and stability was evaluated through time-frequency analysis. Forty-eight Sprague-Dawley rats were randomly divided into six groups (n=8 each): Control, Model, Model+MA (1, 2, 3, and 4 Hz). Rats in the five Model groups received injections of atropine into the tail vein to inhibit gastric motility, which was continuously recorded by a balloon in the gastric antrum. Rats in the four Model+MA groups received MA at 1, 2, 3 and 4 Hz, respectively, for 70 s and needles were retained for a further 5 min. RESULTS: The amplitude of waveforms produced by the four twirling frequencies was relatively consistent and reproducible. The gastric motility amplitude in all groups decreased after modelling (injections of atropine) (p<0.01). Twirling manipulation at 1, 2, and 3 Hz (but not 4 Hz) increased gastric motility amplitude (p<0.05). The increase in gastric motility amplitude induced by MA at 2 Hz was greater than for all other frequencies (p<0.05). CONCLUSIONS: Acupuncture at ST36 helped recover gastric motility amplitude in rats with atropine-induced gastric inhibition and the effects induced by 1-3 Hz frequency were greater than those induced by 4 Hz.

Salidroside protects against bleomycin-induced pulmonary fibrosis: activation of Nrf2-antioxidant signaling, and inhibition of NF-κB and TGF-ß1/Smad-2/-3 pathways.

Pulmonary fibrosis (PF) can severely disrupt lung function, leading to fatal consequences. Salidroside is a principal active ingredient of Rhodiola rosea and has recently been reported to protect against lung injures. The present study was aimed at exploring its therapeutic effects on PF. Lung fibrotic injuries were induced in SD rats by a single intratracheal instillation of 5 mg/kg bleomycin (BLM). Then, these rats were administrated with 50, 100, or 200 mg/kg salidroside for 28 days. BLM-triggered structure distortion, collagen overproduction, excessive inflammatory infiltration, and pro-inflammatory cytokine release, and oxidative stress damages in lung tissues were attenuated by salidroside in a dose-dependent manner. Furthermore, salidroside was noted to inhibit IκBα phosphorylation and nuclear factor kappa B (NF-κB) p65 nuclear accumulation while activating Nrf2-antioxidant signaling in BLM-treated lungs. Downregulation of E-cadherin and upregulation of vimentin, fibronectin, and α-smooth muscle actin (α-SMA) indicated an epithelial-mesenchymal transition (EMT)-like shift in BLM-treated lungs. These changes were suppressed by salidroside. The expression of TGF-ß1 and the phosphorylation of its downstream targets, Smad-2/-3, were enhanced by BLM, but weakened by salidroside. Additionally, salidroside was capable of reversing the recombinant TGF-ß1-induced EMT-like changes in alveolar epithelial cells in vitro. Our study reveals that salidroside's protective effects against fibrotic lung injuries are correlated to its anti-inflammatory, antioxidative, and antifibrotic properties.

[Expression, subcellular localization and characterization of dammarenediol-â ¡ synthase of Panax ginseng in Saccharomyces cerevisiae].

To study the expression and subcellular localization of recombinant dammarenediol-Ⅱ synthase (DS) in Saccharomyces cerevisiae, the dammarenediol-Ⅱ synthase gene ds was cloned from Panax ginseng, and the gene ds was fused with the gene of green fluorescent protein to obtain the fusion gene ds-gfp. The recombinant expression plasmids pESC-HIS-DS and pESC-HIS-DS-GFP were constructed and transformed into S. cerevisiae INVSc1 to obtain recombinant strains INVSc1-DS and INVSc1-DS-GFP. Microsomes of recombinant strains were prepared by differential centrifugation and observed by fluorescence microscope. The green fluorescence was only detected in INVSc1-DS-GFP microsomes, which indicated that DS was a membrane protein. It was also proved that dammarenediol-Ⅱ was produced from the cyclization of 2,3-oxidosqualene catalyzed by DS through in vitro enzymatic reaction. In addition, our results revealed that the fusion expression of ds with gfp significantly improved the production of dammarenediol-Ⅱ from 7.53 mg·g(-1) to 12.24 mg·g(-1). This study provides a new strategy in the optimization of the pathway of ginsenosides biosynthesis in S.cerevisiae.

Glycyrrhizic acid alleviates bleomycin-induced pulmonary fibrosis in rats.

Idiopathic pulmonary fibrosis is a progressive and lethal form of interstitial lung disease that lacks effective therapies at present. Glycyrrhizic acid (GA), a natural compound extracted from a traditional Chinese herbal medicine Glycyrrhiza glabra, was recently reported to benefit lung injury and liver fibrosis in animal models, yet whether GA has a therapeutic effect on pulmonary fibrosis is unknown. In this study, we investigated the potential therapeutic effect of GA on pulmonary fibrosis in a rat model with bleomycin (BLM)-induced pulmonary fibrosis. The results indicated that GA treatment remarkably ameliorated BLM-induced pulmonary fibrosis and attenuated BLM-induced inflammation, oxidative stress, epithelial-mesenchymal transition, and activation of transforming growth factor-beta signaling pathway in the lungs. Further, we demonstrated that GA treatment inhibited proliferation of 3T6 fibroblast cells, induced cell cycle arrest and promoted apoptosis in vitro, implying that GA-mediated suppression of fibroproliferation may contribute to the anti-fibrotic effect against BLM-induced pulmonary fibrosis. In summary, our study suggests a therapeutic potential of GA in the treatment of pulmonary fibrosis.