Qingfei xieding prescription ameliorates mitochondrial DNA-initiated inflammation in bleomycin-induced pulmonary fibrosis through activating autophagy.

ETHNOPHARMACOLOGICAL RELEVANCE: Qingfei Xieding prescription was gradually refined and produced by Hangzhou Red Cross Hospital. The raw material includes Ephedra sinica Stapf, Morus alba L., Bombyx Batryticatus, Gypsum Fibrosum, Prunus armeniaca L. var. ansu Maxim., Houttuynia cordata Thunb. , Pueraria edulis Pamp. Paeonia L., Scutellaria baicalensis Georgi and Anemarrhena asphodeloides Bge. It is effective in clinical adjuvant treatment of patients with pulmonary diseases. AIM OF THE STUDY: To explore the efficacy and underlying mechanism of Qingfei Xieding (QF) in the treatment of bleomycin-induced mouse model. MATERIALS AND METHODS: TGF-ß induced fibrotic phenotype in vitro. Bleomycin injection induced lung tissue fibrosis mouse model in vivo. Flow cytometry was used to detect apoptosis, cellular ROS and lipid oxidation. Mitochondria substructure was observed by transmission electron microscopy. Autophagolysosome and nuclear entry of P65 were monitored by immunofluorescence. Quantitative real-time PCR was performed to detect the transcription of genes associated with mtDNA-cGAS-STING pathway and subsequent inflammatory signaling activation. RESULTS: TGF-ß induced the expression of α-SMA and Collagen I, inhibited cell viability in lung epithelial MLE-12 cells that was reversed by QF-containing serum. TGF-ß-mediated downregulation in autophagy, upregulation in lipid oxidation and ROS contents, and mitochondrial damage were rescued by QF-containing serum treatment, but CQ exposure, an autophagy inhibitor, prevented the protective role of QF. In addition to that, the decreased autophagolysosome in TGF-ß-exposed MLE-12 cells was reversed by QF and restored to low level in the combination treatment of QF and CQ. Mechanistically, QF-containing serum treatment significantly inhibited mtDNA-cGAS-STING pathway and subsequent inflammatory signaling in TGF-ß-challenged cells, which were abolished by CQ-mediated autophagy inhibition. In bleomycin-induced mouse model, QF ameliorated pulmonary fibrosis, reduced mortality, re-activated autophagy in lung tissues and restrained mtDNA-cGAS-STING inflammation pathway. However, the protective effects of QF in bleomycin-induced model mice were also abrogated by CQ. CONCLUSION: QF alleviated bleomycin-induced pulmonary fibrosis by activating autophagy, inhibiting mtDNA-cGAS-STING pathway-mediated inflammation. This research recognizes the protection role of QF on bleomycin-induced mouse model, and offers evidence for the potentiality of QF in clinical application for pulmonary fibrosis treatment.

Potential Mechanisms of Action of Chinese Patent Medicines for COVID-19: A Review.

Coronavirus disease 2019 (COVID-19) is an emergent infectious pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is highly contagious and pathogenic. COVID-19 has rapidly swept across the world since it was first discovered in December 2019 and has drawn significant attention worldwide. During the early stages of the outbreak in China, traditional Chinese medicines (TCMs) were involved in the whole treatment process. As an indispensable part of TCM, Chinese patent medicines (CPMs) played an irreplaceable role in the prevention and treatment of this epidemic. Their use has achieved remarkable therapeutic efficacy during the period of medical observation and clinical treatment of mild, moderate, severe, and critical cases and during convalescence. In order to better propagate and make full use of the benefits of TCM in the treatment of COVID-19, this review will summarize the potential target of SARS-CoV-2 as well as the theoretical basis and clinical efficacy of recommended 22 CPMs by the National Health Commission and the Administration of TCM and local provinces or cities in the treatment of COVID-19. Additionally, the study will further analyze the drug composition, potential active ingredients, potential targets, regulated signaling pathways, and possible mechanisms for COVID-19 through anti-inflammatory and immunoregulation, antiviral, improve lung injury, antipyretic and organ protection to provide meaningful information about the clinical application of CPMs.

Astragalus polysaccharides inhibit ovarian cancer cell growth via microRNA-27a/FBXW7 signaling pathway.

Astragalus polysaccharide (APS), a natural antioxidant found in Astragalus membranaceus emerging as a novel anticancer agent, exerts antiproliferative and pro-apoptotic activity in various cancer cell types, but its effect on ovarian cancer (OC) remains unknown. In the present study, we tried to elucidate the role and mechanism of APS in OC cells. Our results showed that APS treatment suppressed the proliferation and induced apoptosis in OC cells. Afterward, the microRNA (miRNA) profiles in APS-treated cells were determined by a microarray assay, and whether APS affected OV-90 cells through regulation of miRNA was determined. Among these aberrant miRNAs, miR-27a was selected for further study as its oncogenic roles in various human cancers. Moreover, we found overexpression of miR-27a reversed the antiproliferation and pro-apoptotic effects of APS on OC cells. F-box and WD-40 domain protein 7 (FBXW7), a classical tumor suppressor, was found directly targeted by miR-27a and its translation was suppressed by miR-27a in OC cells. Finally, it was also observed that knockdown of FBXW7 by si-FBXW7 reversed the tumor suppressive activity of APS in OC cells, which is similar to the effects of miR-27a overexpression. Our findings demonstrate that APS can suppress OC cell growth in vitro via miR-27a/FBXW7 axis, and this observation reveals the therapeutic potential of APS for treatment of OC.

Bacteria-induced aggregation of bioorthogonal gold nanoparticles for SERS imaging and enhanced photothermal ablation of Gram-positive bacteria.

The challenge in antimicrobial photothermal therapy (PTT) is to develop strategies for decreasing the damage to cells and increasing the antibacterial efficiency. Herein, we report a novel theranostic strategy based on bacteria-induced gold nanoparticle (GNP) aggregation, in which GNPs in situ aggregated on the bacterial surface via specific targeting of vancomycin and bioorthogonal cycloaddition. Plasmonic coupling between adjacent GNPs exhibited a strong "hot spot" effect, enabling effective surface enhanced Raman scattering (SERS) imaging of bacterial pathogens. More importantly, in situ aggregation of GNPs showed strong NIR adsorption and high photothermal conversion, allowing enhanced photokilling activity against Gram-positive bacteria. In the absence of bacterial strains, GNPs were dispersed and showed a very low photothermal effect, minimizing the side effects towards surrounding healthy tissues. Given the above advantages, the bioorthogonal theranostic strategy developed in this study may find potential applications in treating bacterial infection and even multidrug-resistant bacteria.

[Preparation and antitumor effects of tanshinone â ¡A loaded albumin nanoparticles].

In this study, the tanshinone ⅡA loaded albumin nanoparticles were prepared by high pressure homogenization method. The formulation was optimized by central composite design-response surface method (CCD-RSM), with the particle size, encapsulation efficiency, and drug loading as indexes to investigate their in vitro anti-tumor effect. The results showed that the prepared nanoparticles had uniformly spherical morphology and uniform particle size distribution. The average particle size, encapsulation efficiency and drug loading of nanoparticles were about (175.7± 3.07) nm, 90.8%±1.47% and 5.52%±0.09%, respectively. Tanshinone ⅡA loaded albumin nanoparticles showed a more powerful antitumor effect than free tanshinone ⅡA for human promyelocytic leukemia NB4 cells. The preparation method of the drug-loaded albumin nanoparticles was simple and easy, and can significantly improve the solubility of tanshinone ⅡA, so it was helpful to extend its application in therapies against hematological malignancies.

[Treatment Ideas and Methods for Treating Breast Cancer Guided by Molecular Classification].

The gene types of breast cancer can be classified into three types according to its molecules: Luminal type A, Luminal type B, HER-2-positive type, triple negative type. Authors combined pathological characteristics of breast cancer, biological characteristics, and comprehensive treatment, used syndrome typing based medication, and explored treatment meticulous ideas and methods of "treating the same disease with different methods" as well as "different treatment methods in accordance with patients individually".

Encapsulation of iron in liposomes significantly improved the efficiency of iron supplementation in strenuously exercised rats.

To investigate the effect of iron liposome supplementation, a rat model of exercise-associated anemia was established by subjecting the animals to high-intensity running exercises for 4 weeks. Rats with confirmed anemia were strenuously exercised for another 2 weeks while receiving iron supplements by intragastric administration of ferric ammonium citrate (FAC) liposomes or heme iron liposomes. Control groups were administered equivalent amounts of FAC, heme iron, or blank liposomes. Subsequently, complete blood count (CBC), serum iron, and liver iron levels were tested to determine the efficiency of iron liposomes in relieving anemia. Superoxide dismutase (SOD) and malonyldialdehyde (MDA) were also detected to determine potential side effects of iron supplementation. The CBC, as well as serum iron and liver iron contents, significantly increased and reached much higher levels in anemic rats treated with iron liposomes, compared with those of control groups. The increase of SOD and decrease of MDA levels were also observed after supplementation with iron liposomes. These results demonstrate that iron liposomes can efficiently relieve the iron deficiency in strenuously exercised rats and may potentially be used as a supplement for the treatment of exercise-associated iron deficiency anemia with minimal side effects.

[Study on absorption kinetics of betulic acid in rat's intestines].

OBJECTIVE: To establish a HPLC-DAD method for determining concentrations of betulic acid and phenol red in intestinal circulation liquid, and probe into the absorption kinetic characteristics of betulic acid at different intestine segments in rats and the effect of different drug concentrations on absorption. METHOD: The rat intestinal absorption model was established to detect the impact of absorption site, drug concentration and pH value on drug absorption. RESULT: Within the range from 75-125 mg x L(-1), the absorption rate and the quality concentration of betulic acid had a linear relation, with Ka value keeping unchanged. The absorption rate for each intestinal segment showed no remarkable difference, with Ka values in duodenum, jejunum, ileum and colon being (0.151 +/- 0.0049), (0.159 +/- 0.0056), (0.156 +/- 6.0083), (0.149 +/- 0.0041) h(-1), respectively. CONCLUSION: Betulic acid is proved to be well absorbed in intestines marked by no specific absorption site in the intestine. The absorption mechanism of the drug conforms to passive transport mechanism and first-order kinetics. The bioavailability of betulic acid preparation can be increased by enhancing the dissolution rate and the solubility.

Hydrodynamic delivery of chitosan-folate-DNA nanoparticles in rats with adjuvant-induced arthritis.

50 kDa chitosan was conjugated with folate, a specific tissue-targeting ligand. Nanoparticles such as chitosan-DNA and folate-chitosan-DNA were prepared by coacervation process. The hydrodynamic intravenous injection of nanoparticles was performed in the right posterior paw in normal and arthritic rats. Our results demonstrated that the fluorescence intensity of DsRed detected was 5 to 12 times more in the right soleus muscle and in the right gastro muscle than other tissue sections. ß-galactosidase gene expression with X-gal substrate and folate-chitosan-plasmid nanoparticles showed best coloration in the soleus muscle. Treated arthritic animals also showed a significant decrease in paw swelling and IL-1ß and PGE2 concentration in serum compared to untreated rats. This study demonstrated that a nonviral gene therapeutic approach using hydrodynamic delivery could help transfect more efficiently folate-chitosan-DNA nanoparticles in vitro/in vivo and could decrease inflammation in arthritic rats.

Bone-protective effects of nonviral gene therapy with folate-chitosan DNA nanoparticle containing interleukin-1 receptor antagonist gene in rats with adjuvant-induced arthritis.

Interleukin-1 receptor antagonist (IL-1Ra), is a natural blocker of the inflammatory cytokine interleukin-1. Using a rat adjuvant-induced arthritis (AIA) model of rheumatoid arthritis (RA), we examined the protective effects of IL-1Ra in bone metabolism in vivo after folate-mediated nonviral gene delivery. We detected secreted human IL-1Ra protein in serum and cultured primary osteoblasts of rats that were treated with chitosan-IL-1Ra and folate-IL-1Ra-chitosan nanoparticles, respectively. In vivo, IL-1Ra gene delivery significantly reverted alterations in bone turnover observed in arthritic animals by modulating the level of osteocalcin (OC) as well as the activities of alkaline phosphatase and tartrate-resistant acid phosphatase. The protective effects of these nanoparticles were evident from the decrease in the expression levels of interleukine-1beta and prostaglandin E(2) as well as osteoclast number and other histopathological findings. Compared to naked DNA and chitosan-DNA, folate-chitosan-DNA nanoparticles were less cytotoxic and enhanced IL-1Ra protein synthesis in vitro and offered a better protection against inflammation and abnormal bone metabolism in vivo. Nonviral gene therapy with folate-chitosan-DNA nanoparticles containing the IL-1 Ra gene seemed to protect against bone damage and inflammation in rat adjuvant-induced arthritis model.