Novel inhalation therapy in pulmonary fibrosis: principles, applications and prospects.

Pulmonary fibrosis (PF) threatens millions of people worldwide with its irreversible progression. Although the underlying pathogenesis of PF is not fully understood, there is evidence to suggest that the disease can be blocked at various stages. Inhalation therapy has been applied for lung diseases such as asthma and chronic obstructive pulmonary disease, and its application for treating PF is currently under consideration. New techniques in inhalation therapy, such as the application of microparticles and nanoparticles, traditional Chinese medicine monomers, gene therapy, inhibitors, or agonists of signaling pathways, extracellular vesicle interventions, and other specific drugs, are effective in treating PF. However, the safety and effectiveness of these therapeutic techniques are influenced by the properties of inhaled particles, biological and pathological barriers, and the type of inhalation device used. This review provides a comprehensive overview of the pharmacological, pharmaceutical, technical, preclinical, and clinical experimental aspects of novel inhalation therapy for treating PF and focus on therapeutic methods that significantly improve existing technologies or expand the range of drugs that can be administered via inhalation. Although inhalation therapy for PF has some limitations, the advantages are significant, and further research and innovation about new inhalation techniques and drugs are encouraged.

Traditional Chinese medicine inspired dual-drugs loaded inhalable nano-therapeutics alleviated idiopathic pulmonary fibrosis by targeting early inflammation and late fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a highly debilitating and fatal chronic lung disease that is difficult to cure clinically. IPF is characterized by a gradual decline in lung function, which leads to respiratory failure and severely affects patient quality of life and survival. Oxidative stress and chronic inflammation are believed to be important pathological mechanisms underlying the onset and progression of IPF, and the vicious cycle of NOX4-derived ROS, NLRP3 inflammasome activation, and p38 MAPK in pulmonary fibrogenesis explains the ineffectiveness of single-target or single-drug interventions. In this study, we combined astragaloside IV (AS-IV) and ligustrazine (LIG) based on the fundamental theory of traditional Chinese medicine (TCM) of "tonifying qi and activating blood" and loaded these drugs onto nanoparticles (AS_LIG@PPGC NPs) that were inhalable and could penetrate the mucosal barrier. Our results suggested that inhalation of AS_LIG@PPGC NPs significantly improved bleomycin-induced lung injury and fibrosis by regulating the NOX4-ROS-p38 MAPK and NOX4-NLRP3 pathways to treat and prevent IPF. This study not only demonstrated the superiority, feasibility, and safety of inhalation therapy for IPF intervention but also confirmed that breaking the vicious cycle of ROS and the NLRP3 inflammasome is a promising strategy for the successful treatment of IPF. Moreover, this successful nanoplatform is a good example of the integration of TCM and modern medicine.

Modified Guo-Min decoction ameliorates PM2.5-induced lung injury by inhibition of PI3K-AKT and MAPK signaling pathways.

BACKGROUND/PURPOSE: Exposure to particles with an aerodynamic diameter of ≤2.5 µm (PM2.5) increased various lung diseases, which lack effective treatment. Massive evidence links PM2.5 to the development of allergic lung diseases like asthma. Modified Guo-Min Decoction (MGMD) is a traditional Chinese formula for allergic diseases. However, whether MGMD could improve PM2.5-induced lung injury and the underlying mechanism remain unclear and we aimed to explore. STUDY DESIGN/METHODS: Male Wistar rats (200-220 g) were intratracheally instilled of PM2.5 suspension daily for 4 weeks to establish PM2.5-induced lung injury model. MGMD (2.1 g/kg) treatment by gavage was started 1 week before, at the same time or 1 week after the instillation of PM2.5 suspension, namely the pre-, sync- or post-administration groups. HE and Masson staining were used to observe morphological changes. Immunohistochemistry staining was used to detect macrophage and neutrophil infiltration. The levels of inflammatory cytokines in the bronchoalveolar lavage fluid were detected by ELISA. The main components of MGMD were detected by UHPLC-LTQ-Orbitrap MSn. Network pharmacology was used to identify the key targets mediating the effect of MGMD in treating PM2.5-induced lung injury. Changes in the expression of target proteins were examined by western blot. In-vitro experiments were carried out in Beas2b cells to evaluate the protective effect and mechanism of MGMD against PM2.5 induced injury. RESULTS: Exposure to PM2.5 suspension resulted in disarrangement of tracheal epithelium, neutrophil and M1 macrophage infiltration and collagen deposition, and significantly increased IgE, IL-1ß and IL-17 secretion and NLRP3 expression, which were inhibited by MDMD treatment and pre-MGMD treatment showed the best effect. By UHPLC-LTQ-Orbitrap MSn, 46 main compounds were identified in MGMD. Using network pharmacology approach, we found MGMD attenuate PM2.5-induced lung damage by targeting 216 genes, and PPI network, GO and KEGG analysis all indicated that PI3K-AKT and MAPK pathways were important. Western blot showed that PM2.5 suspension exposure increased PI3K, AKT, ERK and JNK phosphorylation, which were reversed by MGMD intervention significantly. In vitro, the viability of Beas2b cells was significantly decreased after PM2.5 suspension exposure, and was obviously upregulated after MGMD-containing serum or LY294002 treatment. CONCLUSION: The present study demonstrated that MGMD could improve PM2.5-induced lung injury through reducing inflammation and pulmonary fibrosis, which was probably mediated by inhibition of the PI3K-AKT and MAPK signaling pathways, and NLRP3 inflammasome. The results of this study support and provide scientific evidence for the clinical application of MGMD on PM2.5-induced lung injury. Pre-treatment, sync-treatment, and post-treatment is the highlight of this study.

Bu-Fei Yi-Shen Granules Reduce Acute Exacerbations in Patients with GOLD 3-4 COPD: A Randomized Controlled Trial.

Purpose: Chronic obstructive pulmonary disease (COPD) is a disease characterized by frequent acute exacerbations (AEs), especially in severe and very severe cases. We aimed to evaluate the efficacy and safety of Bu-fei Yi-shen granules (BYGs) for COPD. Patients and Methods: We conducted a multicenter, randomized, double-blinded, placebo-controlled trial of 348 COPD patients with GOLD 3-4 COPD. The patients were randomly assigned into experimental or control groups in a 1:1 ratio. Patients in the experimental group were prescribed BYG, while those in the control group were administered a placebo, orally, twice daily, with 5 days on and 2 days off per week for 52 weeks. The outcomes included AEs, pulmonary function, clinical signs and symptoms, dyspnea scores (mMRC), quality of life scores, and a 6-minute walk test (6MWT). Results: A total of 280 patients completed the trial, including 135 patients in the experimental group and 145 in the control group. Compared to the control group, significant differences were observed in frequencies of AEs (mean difference: -0.35; 95% CI: -0.61, -0.10; P = 0.006) and AE-related hospitalizations (-0.18; 95% CI: -0.36, -0.01; P = 0.04), 6MWD (40.93 m; 95% CI: 32.03, 49.83; P < 0.001), mMRC (-0.57; 95% CI: -0.76, -0.37; P < 0.001), total symptoms (-2.18; 95% CI: -2.84, -1.53; P < 0.001), SF-36 (11.60; 95% CI: 8.23, 14.97; P < 0.001), and mCOPD-PRO (-0.45; 95% CI: -0.57, -0.33; P < 0.001) after treatment. However, there were no significant differences in mortality, pulmonary function, and mESQ-PRO scores (P > 0.05). No obvious adverse events were observed. Conclusion: BYG, as compared to a placebo, could significantly reduce the frequencies of AEs and AE-related hospitalizations for GOLD 3-4 COPD patients. Clinical symptoms, treatment satisfaction, quality of life, and exercise capacity improved. There was no significant improvement in mortality and pulmonary function.

Mechanical thrombectomy combined with intravenous thrombolysis for acute ischemic stroke: a systematic review and meta-analyses.

To assess the clinical value of mechanical thrombectomy (MT) combined with intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) by comparing it with the MT alone. In this study, we conducted a comprehensive meta-analysis of both observational and randomized controlled studies (RCTs) to investigate various outcomes. Our search for relevant studies was conducted between January 2011 and June 2022 in four major databases: PubMed, Embase, WOS, and Cochrane Library. We collected data on several outcomes, including functional independence (FI; defined as modified Rankin Scale score of 0 to 2), excellent outcomes (mRS 0-1), successful recanalization (SR), symptomatic intracerebral hemorrhage (sICH), any intracerebral hemorrhage (aICH), and mortality at three months or discharge. The primary efficacy outcome and safety outcome were FI and sICH, respectively, whereas excellent outcomes and SR were considered secondary efficacy outcomes. Additionally, mortality and aICH were analyzed as secondary safety outcomes. We employed the Mantel-Haenszel fixed-effects model for RCTs when I2 < 50%, otherwise the random-effects model was utilized. For observational studies and subgroup analyses, we used the random-effects model to minimize potential bias. A total of 55 eligible studies (nine RCTs and 46 observational studies) were included. For RCTs, the MT + IVT group was superior in FI (OR: 1.27, 95% CI: 1.11-1.46), excellent outcomes (OR: 1.21, 95% CI: 1.03-1.43), SR (OR: 1.23, 95% CI: 1.05-1.45), mortality (OR: 0.72, 95% CI: 0.54-0.97) in crude analyses. In adjusted analyses, the MT + IVT group reduced the risk of mortality (OR: 0.65, 95% CI: 0.49-0.88). However, the difference in FI between the MT + IVT group and the MT alone group was not significant (OR: 1.17, 95% CI: 0.99-1.38, Fig. 3a). For observational studies, the results of FI (OR: 1.34, 95% CI: 1.16-1.33), excellent outcomes (OR: 1.30, 95% CI: 1.09-1.54), SR (OR: 1.23, 95% CI: 1.05-1.44), mortality (OR: 0.70, 95% CI: 0.64-0.77) in the MT + IVT group were better. Additionally, the MT + IVT group increased the risk of hemorrhagic transformation (HT) including sICH (OR: 1.16, 95% CI: 1.11-1.21) and aICH (OR: 1.24, 95% CI: 1.05-1.46) in crude analyses. In adjusted analyses, significant better outcomes were seen in the MT + IVT group on FI (OR: 1.36, 95% CI: 1.21-1.52), excellent outcomes (OR: 1.49, 95% CI: 1.26-1.75), and mortality (OR: 0.73, 95% CI: 0.56-0.94). The MT + IVT therapy did improve the prognosis for AIS patients and did not increase the risk of HT compared with MT alone therapy.

Network Pharmacology Prediction and Experimental Validation of Trichosanthes-Fritillaria thunbergii Action Mechanism Against Lung Adenocarcinoma.

We aimed to study the mechanism of Trichosanthes-Fritillaria thunbergii in treating lung adenocarcinoma (LUAD) based on network pharmacology and experimental verification. The effective components and potential targets of Trichosanthis and Fritillaria thunbergii were collected by high-throughput experiment and reference-guided (HERB) database of traditional Chinese medicine and a similarity ensemble approach (SEA) database, and the LUAD-related targets were queried by the GeneCards and Online Mendelian Inheritance in Man (OMIM) databases. A drug-component-disease-target network was constructed by Cytoscape software. Protein-protein interaction (PPI) network, gene ontology (GO) function, and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses were conducted to obtain core targets and key pathways. An aqueous extract of Trichosanthes-Fritillaria thunbergii and A549 cells were used for the subsequent experimental validation. Through the HERB database and literature search, 31 effective compounds and 157 potential target genes of Trichosanthes-Fritillaria thunbergii were screened, of which 144 were regulatory targets of Trichosanthes-Fritillaria thunbergii in the treatment of lung adenocarcinoma. The GO functional enrichment analysis showed that the mechanism of action of Trichosanthes-Fritillaria thunbergii against lung adenocarcinoma is mainly protein phosphorylation. The KEGG pathway enrichment analysis suggested that the treatment of lung adenocarcinoma by Trichosanthes-Fritillaria thunbergii mainly involves the PI3K/AKT signaling pathway. The experimental validation showed that an aqueous extract of Trichosanthes-Fritillaria thunbergii could inhibit the proliferation of A549 cells and the phosphorylation of AKT. Through network pharmacology and experimental validation, it was verified that the PI3K/AKT signaling pathway plays a vital role in the action of Trichosanthes-Fritillaria thunbergii in treating lung adenocarcinoma.

Systematic Pharmacology-Based Strategy to Explore the Mechanism of Bufei Huoxue Capsule in the Treatment of Chronic Obstructive Pulmonary Disease.

Objective: To explore the effects and mechanisms of Bufei Huoxue Capsule (BHC) on chronic obstructive pulmonary disease (COPD) based on network pharmacology. Methods: The effective components and related targets of BHC were collected by searching TCMSP, HERB, and ETCM databases, after which the related targets of COPD were obtained on GeneCards and OMIM databases. The common targets were imported into the STRING database and Cytoscape database to construct a target interaction network and screen core targets. Next, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on the Metascape platform. According to the prediction results of network pharmacology, the action mechanism was further examined in an animal model of COPD. The pathological changes of lung tissue were observed by HE staining; goblet cells and mucus secretion in lung tissue were observed by AB-PAS staining, airway collagen deposition was observed by Masson staining, and the expression of NE, TGF-ß1, P-EGFR/EGFR, P-ERK1/2/ERK1/2, P-JNK/JNK, and P-P38/P38MAPK protein was detected by Western blot analysis. Results: A total of 379 targets related to BHC and 7391 targets related to COPD were obtained, including 313 potential targets of BHC in treating chronic obstructive pulmonary disease, with JUN, AKT1, TNF, IL6, EGFR, MAPK1, and MAPK14 as the core targets. Through enrichment analysis, BHC may interfere with COPD by regulating the MAPK signal pathway, HIF-1 signal pathway, NF-κB signal pathway, cAMP signal pathway, cGMP-PKG signal pathway, and so on. Animal experiments showed that the BHC could reduce airway inflammatory cell infiltration, inhibit airway epithelial goblet cell proliferation, reduce mucus secretion, and improve small airway collagen fiber deposition in COPD model rats. Besides, BHC could downregulate the protein expression of NE, TGF-ß1, P-EGFR, P-ERK1/2, and P-P38MAPK. Conclusion: BHC can reduce airway inflammation, inhibit mucus hypersecretion, and improve airway remodeling by regulating the MAPK signal transduction pathway.

Pharmacological Mechanisms Underlying the Anti-asthmatic Effects of Modified Guomin Decoction Determined by Network Pharmacology and Molecular Docking.

BACKGROUND: Asthma is a chronic inflammatory disease characterized by Th2-predominant inflammation and airway remodeling. Modified Guo Min decoction (MGMD) has been an extensive practical strategy for allergic disorders in China. Although its potential anti-asthmatic activity has been reported, the exact mechanism of action of MGMD in asthma remains unexplored. METHODS: Network pharmacology approach was employed to predict the active components, potential targets, and molecular mechanism of MGMD for asthma treatment, including drug-likeness evaluation, oral bioavailability prediction, protein-protein interaction (PPI) network construction and analysis, Gene Ontology (GO) terms, and Reactome pathway annotation. Molecular docking was carried out to investigate interactions between active compounds and potential targets. RESULTS: A total of 92 active compounds and 72 anti-asthma targets of MGMD were selected for analysis. The GO enrichment analysis results indicated that the anti-asthmatic targets of MGMD mainly participate in inflammatory and in airway remolding processes. The Reactome pathway analysis showed that MGMD prevents asthma mainly through regulation of the IL-4 and IL-13 signaling and the specialized pro-resolving mediators (SPMs) biosynthesis. Molecular docking results suggest that each bioactive compounds (quercetin, wogonin, luteolin, naringenin, and kaempferol) is capable to bind with STAT3, PTGS2, JUN, VEGFA, EGFR, and ALOX5. CONCLUSION: This study revealed the active ingredients and potential molecular mechanism by which MGMD treatment is effective against airway inflammation and remodeling in asthma through regulating IL-4 and IL-13 signaling and SPMs biosynthesis.

Hydroxyl safflower yellow A regulates the tumor immune microenvironment to produce an anticancer effect in a mouse model of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a serious threat to human health. Chemotherapy drugs such as cisplatin are widely used in cancer treatment, but can cause severe side effects. Hydroxyl safflower yellow A (HSYA) is a water-soluble chalcone glycoside substance extracted from safflowers (Carthamus tinctorius L.) that has been reported to inhibit tumor growth with few side effects. The tumor immune microenvironment is crucial for the proliferation and invasiveness of tumor cells, and it is mediated by forkhead box P3-positive (FOXP3+) regulatory T cells (Tregs) and retinoic acid receptor-related orphan receptor-γ (RORγ)-expressing Th17 cells. FOXP3+ Tregs inhibit immunoreaction and FOXP3 is a key indicator of Tregs. RORγ isoform 2, also known as RORγt, is an important transcription factor in Th17 cells that may promote cancer progression. In the present study, the antitumor effect of HSYA on HCC was investigated, as well as its impact on the tumor immune microenvironment. Following the establishment of a mouse model for HCC, hematoxylin and eosin staining were performed to observe histological changes in liver tumors, and the spleen and thymus were weighed to calculate the spleen and thymus indexes. The proportion of FOXP3+ Tregs in the spleen was determined by flow cytometry, and expression levels of Foxp3 and Rorγt were examined by reverse transcription-quantitative polymerase chain reaction and western blot analysis. The results of the present study showed that cisplatin inhibited tumor growth, caused weight loss and reduced the immunoreactivity of the mice. HSYA inhibited tumor growth without causing significant weight loss. The proportion of FOXP3-expressing Tregs in the spleen and the expression of Foxp3 and Rorγt mRNA decreased following treatment with certain doses of HSYA. In conclusion, HSYA inhibited tumor growth without detrimental effects on the weight of the mice, indicating that HSYA may be suitable as a novel therapy for HCC patients.

Louqin Zhisou Decoction Inhibits Mucus Hypersecretion for Acute Exacerbation of Chronic Obstructive Pulmonary Disease Rats by Suppressing EGFR-PI3K-AKT Signaling Pathway and Restoring Th17/Treg Balance.

Airway mucus hypersecretion is the main pathogenic factor in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and the control of mucus secretion is closely associated with survival. Louqin Zhisou decoction (LQZS) has been found to improve lung function and reduce sputum in AECOPD patients, but the mechanism remains unclear. This study aimed to explore the mechanism of LQZS against mucus hypersecretion in lung tissues of rat AECOPD model. Wistar rats were used to establish AECOPD model by intratracheal instillation of LPS in combination with the continuous cigarette smoking. Rats were administrated LQZS/clarithromycin (CAM)/distilled water via gavage every day and all rats were sacrificed after 30 days. BALF and lung tissues were obtained. Lung morphology, cytokines levels, MUC5AC mRNA transcription and protein expression, phosphorylation of the EGFR-PI3K-AKT signaling pathway, and molecules involved in Th17/Treg balance were evaluated. The results demonstrated that LQZS protected rats from decline in pulmonary function and ameliorated lung injury. LQZS treatment decreased the number of goblet cells in airway and suppressed MUC5AC mRNA and protein expression of lung tissues. Furthermore, LQZS attenuated the level of phospho-EGFR, phospho-PI3K and phospho-AKT in AECOPD rats. In addition, LQZS could inhibit the production of proinflammatory cytokines in BALF, including IL-6 and IL-17A and downregulate the secretion of NE and MCP-1, indicating that LQZS could limit inflammatory responses in AECOPD. Moreover, LQZS reversed RORγt and Foxp3 expression, the key transcription factors of Th17 and Treg, respectively. In conclusion, this research demonstrated the inhibitory effects of LQZS against mucus hypersecretion in AECOPD via suppressing EGFR-PI3K-AKT signaling pathway and restoring Th17/Treg balance.

[Expert consensus statement on Pudilan Xiaoyan Oral Liquid in clinical practice].

Pudilan Xiaoyan Oral Liquid has effects in clearing away heat and detoxifying,and is used to treat pharynx and throat swelling caused by the syndrome of excessive heat and toxin accumulation. Its efficacy is to relieve swelling and pain( redness,swelling and hot pain). It is included in the Chinese Pharmacopoeia of 2015 Edition,and has been listed in provincial health insurance directories of Shaanxi,Jiangsu,Liaoning,Hunan,Tianjin,Xinjiang and Hebei. It has been recommended by health departments of Beijing,Chongqing and other provinces as a preferred drug for the prevention and treatment of H1 N1 and HFMD,and listed in the diagnosis and Treatment Guide of HFMD by the Ministry of Health,the Clinical Application Guide of Chinese Patent Medicine edited by the Lung Department Disease Branch of China Association of Chinese Medicine,and the Clinical Practice Guide of Single Administration/Combined Administration of Antibiotics in Treatment of Common Infectious Diseases by China Association of Chinese Medicine. To further improve the clinician's understanding of drugs and better guide the rational clinical application,we invited front-line clinical experts from respiratory department,infectious department and dermatology of traditional Chinese and Western medicine to develop and compile the expert consensus. The consensus fully considered the clinical evidence and the expert clinical experience to give recommendations for clinical problems with evidence support and consensus suggestions for clinical problems without evidence support by the nominal group method.This consensus is based on clinical research evidence and expert experience in a simple and clear format,which provides a preliminary reference for the clinical use of the drug.

Evaluation on clinical efficacy of Fuzheng Jiedu Huayu Decoction combined with antibiotics in the treatment of pneumonia in the elderly - A multi-center, double-blind, parallel, randomized controlled trial.

OBJECTIVE: To evaluate the efficacy and safety of Fuzheng Jiedu Huayu Decoction (FJHD) in treating pneumonia in the elderly. METHODS: Adopting a multi-center, double-blind, parallel, randomized controlled trial, 284 elderly pneumonia patients were enrolled and randomly allocated to the standard treatment with FJHD (treatment group, TG) and the standard treatment with placebo group (control group, CG). Efficacy and safety was evaluated through mortality rate, curative rate, symptom improvement, chest X-ray (CXR) lesion absorption, arterial blood gas (ABG), peripheral blood leukocyte count (PBLC) and adverse events. RESULTS: There was no significant difference in mortality rate between both groups (P > 0.05). TG significantly enhanced the curative rate of a 2-week treatment course (P < 0.05). Compared with CG, TG significantly decreased the expectoration score during the first and second week of treatment (P < 0.05). During the first week, improvement in expectoration was conducive to airway patency. During the second week, wheezing, shortness of breath and other symptoms were also significantly improved. During the third week, body temperature was stable. TG improved lesion absorption with Pneumonia Severity Index (PSI) class II (P < 0.05) and SMART-COP score 1 (P < 0.05). TG significantly decreased the arterial carbon dioxide partial pressure after a 1-week treatment. There were no serious adverse events in TG. CONCLUSION: Standard anti-infection treatment with FJHD is a safe and reliable method of treating elderly patients with pneumonia, improving the curative effect after a 2-week treatment course, ameliorating expectoration and promoting the absorption of pneumonia lesions.

Hydroxysafflor-Yellow A Induces Human Gastric Carcinoma BGC-823 Cell Apoptosis by Activating Peroxisome Proliferator-Activated Receptor Gamma (PPARγ).

BACKGROUND Anti-tumor properties of hydroxysafflor-yellow A (HSYA) have been recently revealed, as a series of apoptotic factors were confirmed to be regulated by HSYA and associated with peroxisome proliferator-activated receptor Gamma (PPARγ). In this study, we investigated the cell apoptosis mechanism of HSYA via activated PPARγ signal in human gastric carcinoma cells. MATERIAL AND METHODS BGC-823 cells were cultured and divided into 5 independent groups: Tumor, HSYA, HSYA+PPARγ inhibitor (GW9662), and PPARg agonist (RGZ), RGZ+GW9662. Cell proliferative activity was measured by MTT. Apoptosis and cell cycle were detected by flow cytometry. The nuclear translocation of PPARγ was detected by immunofluorescence staining chemistry, and mRNA levels of PPARγ and caspase-3 were measured by real-time qPCR. RESULTS Compared to the RGZ group, the HSYA group (100 µM) showed a similar inhibitory effect on the proliferation process of BGC-823 cells, inducing their apoptosis. As a result, the transition of BGC-823 cells from G0/G1 phase to S phase was blocked. HSYA was also found to promote the nuclear translocation of PPARγ, leading to increased expression of PPARγ and caspase-3. The regulatory effect of HSYA on BGC-823 cells could be further inhibited by PPARγ inhibitor in group GW9662. CONCLUSIONS We report the inhibitory effect of HSYA on the proliferation of BGC-823 cells, which results in activating PPARg-dependent cell cycle blocking and cell apoptosis, suggesting that PPARg is a specific type of HSYA that can induce apoptosis of BGC-823 cells.

Activation and Migration of Adventitial Fibroblasts Contributes to Vascular Remodeling.

The rat carotid artery balloon injury model was used to prove the activation and migration of adventitial fibroblasts. We found that at day 7 after injury, adventitial fibroblasts proliferated, transformed into myofibroblasts under transmission electron microscopy in the model group. Simultaneously, we proved that the adventitial cells migrated to the media and intima on seventh day after injury by directly labeled the adventitial cells by the in vivo gene transfer technique. Moreover, we captured the precise moment when the adventitial fibroblasts migrated from the adventitia to the media through the external elastic plate under transmission electron microscope. This study provides direct evidences that adventitial fibroblasts activate and migrate to the media and intima, then actively take part in revascularization. Anat Rec, 301:1216-1223, 2018. © 2018 Wiley Periodicals, Inc.

Lovastatin induces neuroprotection by inhibiting inflammatory cytokines in 6-hydroxydopamine treated microglia cells.

PURPOSE/AIM: This study aims to investigate the impact of lovastatin on neuroinflammation in 6-OHDA-treated microglia cells. MATERIALS AND METHODS: 6-Hydroxydopamine (6-OHDA)-treated microglia cells were used to investigate the neuroprotective nature of lovastatin. After incubation with 6-OHDA and/or lovastatin for 24 h, test kits were used to detect the levels of LDH and glutamate, which were released from PC12 cells exposed to different culture media. The mRNA levels of TNF-α, IL-6 and IL-1ß were determined by RT-PCR and the protein levels were analyzed by Western blot. RESULTS: LDH and glutamate levels in 6-OHDA-incubated PC12 cells increased, when compared with those in the controls, while incubation with lovastatin inhibited this elevation. The expression levels of TNF-α IL-6 and IL-1ß were significantly upregulated after treatment with 6-OHDA. The 6-OHDA-stimulated mRNA and protein levels of TNF-α IL-6 and IL-1ß were reduced by lovastatin. CONCLUSIONS: Our results suggest that Lovastatin is able to induce neuroprotection by inhibiting inflammatory cytokines. The data provide direct evidence of the potential application of lovastatin for the treatment of neuroinflammatory diseases.

[Correlation between essential elements of Chinese medicine syndrome and the lung function in patients with acute aggravating chronic obstructive pulmonary disease].

OBJECTIVE: To study the correlation between essential elements of Chinese medicine syndrome (EECMS) and the lung function in patients with acute aggravating chronic obstructive pulmonary disease (AACOPD). METHODS: Adopting clinical epidemiological method, the Chinese medicine syndrome of 199 AACOPD patients with various grades of the lung function was differentiated, and EECMS in them were picked up, summarized and analyzed statistically. RESULTS: Along with the deteriorating of the lung ventilation, the EECMS of disease-position was progressed correspondingly, i.e. in patients with lung function of grade I, disease was positioned mainly on Fei (88.89%); in patients of grade II, on Fei-Shen (25.97%), Fei-Pi (9.09%), and Fei-Gan (3.90%); in those of grade III, on Fei-Shen (51.32%), Fei-Pi (7.89%), Fei-Pi-Shen (19.74%), and Fei-Pi-Shen-Xin (2.63%); in those of grade IV: on Fei-Shen (56.76%), Fei-Pi-Shen (27.03%). The EECMS of disease-property was also progressed, that for excessive syndromes were disposed as: grade I - II, phlegm (23.76%); grade III: phlegm-heat (30.26%), phlegm-stasis (15.79%), and phlegm-retention (9.21%); grade IV: phlegm-stasis (24.32%), phlegm-heat-stasis (29.73%), phlegm-retention-stasis (2.70%); and for deficiency syndromes were arranged as qi-deficiency --> qi-yin deficiency --> qi-yang deficiency --> qi-yin-yang deficiency. CONCLUSION: The lung function could be taken as the objective and quantitative index for the progression of Chinese medicine syndromes in patients with AACOPD.

[Effect of TCM therapy by principle for nourishing Qi, activating blood circulation and resolving phlegm on quality of life of patients with chronic obstructive pulmonary disease].

OBJECTIVE: To observe the effect of TCM therapy, by principle for nourishing Qi, activating blood circulation and resolving phlegm, on quality of life of patients with chronic obstructive pulmonary disease (COPD). METHODS: Seventy-two COPD patients with Qi-deficiency, blood stasis and phlegm retention syndrome were randomly divided into two groups. Thirty-five patients in the treated group were treated with the integrative traditional and Western medicine, that is, conventional Western medicine combined with Chinese compound recipe prescribed based on the principle of nourishing Qi, activating blood circulation and resolving phlegm, or with Feikang granule and Bailing capsule, while 37 in the control group was treated with conventional Western medicine alone. The clinical efficacy was evaluated by assessment software of COPD quality of life after patients were treated for 3 months. RESULTS: The clinical efficacy in the treated group was superior to that in the control group, showing significant difference (P < 0.01). CONCLUSION: Compound recipe prescribed according to the therapeutic principle for nourishing Qi, activating blood circulation and resolving phlegm can improve the symptoms of patients with COPD at stable stage, elevate their quality of life.