Autophagy and pressure overload-induced cardiac hypertrophy.

Autophagy plays an important role in the pathogenesis of cardiovascular diseases. Dysregulation of autophagy may have a huge effect on cardiac hypertrophy induced by overload pressure although reports on autophagy and cardiac hypertrophy have been contradictory. Some studies showed that autophagy activation attenuated cardiac hypertrophy. However, others suggested that inhibition of autophagy would be protective. Different research models or different pathways involved could be responsible for it. Cardiac hypertrophy may be alleviated through regulation of autophagy. This review aims to highlight the pathways and therapeutic targets identified in the prevention and treatment of cardiac hypertrophy by regulating autophagy.

Bai-He-Gu-Jin-Tang formula suppresses lung cancer via AKT/GSK3ß/ß-catenin and induces autophagy via the AMPK/mTORC1/ULK1 signaling pathway.

Aims: Bai-He-Gu-Jin-Tang (BHGJT) is a classic Chinese formula used to treat lung cancer, while the underlying molecular mechanism remains obscure. The aim of the study was to investigate the molecular mechanism of BHGJT on lung cancer and demonstrate the potential for synergistic treatment combining BHGJT with conventional therapy. Methods: Cell viability assay, colony formation assay and EdU assay were used to determine the in vitro effects of BHGJT, and a subcutaneous xenograft model was used to evaluate the in vivo effect. Cell cycle analysis, apoptosis rate analysis, immunohistochemical and immunofluorescent staining, Western blot assays and network pharmacology-based analysis were used to explore the underlying mechanisms. Results: We found that BHGJT inhibited cell proliferation via a dose-dependent pathway and obviously hindered tumor growth in vivo in lung cancer. Cell cycle arrest and apoptosis were pronouncedly induced by BHGJT via dysregulation of the cell cycle regulators CDK4 and Cyclin D1 and dysregulation of apoptosis-associated proteins, such as cleaved caspase 3/9 and the BCL-2 family. Based on a network pharmacology-based analysis and experimental evidence, we demonstrated that the AKT/GSK3ß/ß-catenin signaling pathways were responsible for BHGJT-induced apoptosis in lung cancer cells. Additionally, autophagy was induced by BHGJT via the AMPK/mTORC1/ULK1 signaling pathway, and blocking autophagy with either chloroquine or a ULK1 inhibitor increased the killing efficiency of BHGJT in lung cancer cells. Conclusion: Our findings indicate that the BHGJT formula efficiently inhibits lung cancer growth and represents a potential complementary and alternative treatment for lung cancer.

Nanoscale Formulations: Incorporating Curcumin into Combination Strategies for the Treatment of Lung Cancer.

Lung cancer remains the most common cancer worldwide. Although significant advances in screening have been made and early diagnosis strategies and therapeutic regimens have been developed, the overall survival rate remains bleak. Curcumin is extracted from the rhizomes of turmeric and exhibits a wide range of biological activities. In lung cancer, evidence has shown that curcumin can markedly inhibit tumor growth, invasion and metastasis, overcome resistance to therapy, and even eliminate cancer stem cells (CSCs). Herein, the underlying molecular mechanisms of curcumin were summarized by distinct biological processes. To solve the limiting factors that curtail the clinical applications of curcumin, nanoformulations encapsulating curcumin were surveyed in detail. Nanoparticles, including liposomes, micelles, carbon nanotubes (CNTs), solid lipid nanoparticles (SLNs), nanosuspensions, and nanoemulsions, were explored as proper carriers of curcumin. Moreover, it was firmly verified that curcumin has the ability to sensitize lung cancer cells to chemotherapeutic drugs, such as cisplatin and docetaxel, and to various targeted therapies. Regarding the advantages and drawbacks of curcumin, we concluded that combination therapy based on nanoparticles would be the optimal approach to broaden the application of curcumin in the clinic in the near future.

MicroRNA-30d/JAG1 axis modulates pulmonary fibrosis through Notch signaling pathway.

Pulmonary fibrosis (PF) is a fibroproliferative disease which can finally end up fatal lung failure. PF is characterized by abnormal proliferation of fibroblast, dysregulated fibroblast differentiation to myofibroblast and disorganized collagen and extracellular matrix (ECM) production, deposition and degradation. JAG1/Notch signaling has been reported to play a key role in tissue fibrosis including PF. Herein, we confirmed the abnormal upregulation of JAG1 mRNA expression and protein levels in PF tissue specimens; JAG1 knockdown reduced TGF-ß1-induced α-SMA and Collagen I protein levels. From the aspect of miRNA regulation, we searched for candidate miRNAs which might target JAG1 to inhibit its expression. Among the selected miRNAs, miR-30d expression was downregulated in PF tissues; miR-30d overexpression attenuated TGF-ß1-induced primary normal human lung fibroblast (NHLF) proliferation, as well as α-SMA and Collagen I protein levels. Through directly binding to the 3'-UTR of JAG1, miR-30d significantly inhibited JAG1 mRNA expression and protein level. Furthermore, JAG1 overexpression partially reversed the effect of miR-30d on NHLF proliferation and α-SMA and Collagen I proteins upon TGF-ß1 stimulation; miR-30d could suppress TGF-ß1 function on NHLFs through blocking JAG1/Notch signaling. Rescuing miR-30d expression to suppress TGF-ß1-induced activation of JAG1/Notch signaling may present a promising strategy for PF treatment.

[Adjunctive treatment of axial undifferentiated spondyloarthritis by Qiangji Recipe: a clinical study].

OBJECTIVE: To evaluate the clinical efficacy and safety of Qiangji Recipe (QR) in ad- junctive treatment of axial undifferentiated spondyloarthritis (axuSpA) through a four-week open study. METHODS: Fifty-four axuSpA patients of Shen-deficiency Du-channel cold syndrome (SDDCS) in line with inclusive criteria were recruited and assigned to the treatment group and the control group according to random digit table, 27 in each group. Patients in the control group took Celecoxib Capsule (0.2 g each time, twice per day). Patients in the treatment group additionally took QR (consisting of Herba Epimedii 15 g, antler glue 15 g, Cibotium Barometz 15 g, eucommia bark 20 g, dipsacus asper 10 g, two toothed achyranthes root 15 g, drynaria 15 g, Taxillus Chinensis 20 g, ground beetle 10 g, scorpion 5 g, wild celery 10 g, notopterygium incisium 10 g, cow-fat seed 10 g, white mustard seed 6 g, and licorice root 6 g, one dose per day, twice daily). The therapeutic course for all was 4 weeks. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Bath Ankylosing Spondylitis Functional Index (BASFI), the Bath AS Metrology Index (BASMI), total body pain and spinal pain, patient and physician global assessment on a four-point scale, the Ankylosing Spondylitis Quality of Life (ASQoL), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were measured before and after 4 weeks of treatment. The primary end point in this study was the proportion of patients with a 20%improvement response accord- ing to the ASAS International Working Group Criteria (ASAS 20 responders) at week 4. RESULTS: Totally 50 patients completed this trial, 26 in the treatment group and 24 in the control group. Improvement of BASDAI, BASFI, BASMI, ASQoL, ESR, and CRP was shown in both groups after treatment. Better effect was shown in the treatment group in all indices except ESR and BASMI after treatment (P < 0.05, P < 0.01). Twenty cases (accounting for 76.92%) in the treatment group achieved ASAS 20 response at week 4, while 12 cases (accounting for 50.00%) in the control group achieved ASAS 20 response at week 4 (P < 0.05). No obvious adverse reaction occurred in the two groups. CONCLUSION: QR combined Celecoxib Capsule showed better effect in treating axuSpA patients than using Celecoxib Capsule alone.