Astragaloside-IV promotes autophagy via the Akt/mTOR pathway to improve cellular lipid deposition.

The current study aimed to investigate the potential role of astragaloside IV (AS-IV) in improving cellular lipid deposition and its underlying mechanism. A fatty liver cell model was established by treating hepatoma cells with palmitic acid. AS-IV and SC79 were used for treatment. Oil Red O staining was applied to detect intracellular lipid deposition, and transmission electron microscopy was utilized to assess autophagosome formation. Immunofluorescence double staining was applied to determine microtubule-associated proteins 1A/1B light chain 3 (LC3) expression. Western blot analysis was performed to detect the expression of LC3, prostacyclin, Beclin-1, V-akt murine thymoma viral oncogene homolog (Akt), phosphorylated Akt, mTOR, and phosphorylated mTOR. Oil Red O staining revealed that AS-IV reduced intracellular lipid accumulation. Further, it increased autophagosome synthesis and the expression of autophagy proteins LC3 and Beclin-1 in the cells. It also reduced the phosphorylation levels of Akt and mTOR and the levels of prostacyclin. However, the effects of AS-IV decreased with SC79 treatment. In addition, LC3B + BODIPY493/503 fluorescence double staining showed that AS-IV reduced intracellular lipid deposition levels by enhancing autophagy. AS-IV can reduce lipid aggregation in fatty liver cells, which can be related to enhanced hepatocyte autophagy by inhibiting the Akt/mTOR signaling pathway.

Duhuo Jisheng Decoction regulates intracellular zinc homeostasis by enhancing autophagy via PTEN/Akt/mTOR pathway to improve knee cartilage degeneration.

BACKGROUND: Articular cartilage and cartilage matrix degradation are key pathological changes occurring in the early stage of knee osteoarthritis (KOA). However, currently, there are limited strategies for early prevention and treatment of KOA. Duhuo Jisheng Decoction (DHJSD) is a formula quoted in Bei Ji Qian jin Yao Fang, which was compiled by Sun Simiao in the Tang Dynasty of China. As a complementary therapy, it is widely used to treat early-stage KOA in China; however, its mechanism has not been completely elucidated. OBJECTIVE: This study investigated the potential role of DHJSD in preventing cartilage degradation and the underlying mechanism. METHODS: A rat model of KOA model was established via the Hulth method. Subsequently, 25 rats were randomized into sham (saline), model control (saline), high-DHJSD (1.9g/mL of DHJSD), medium-DHJSD (1.2g/mL of DHJSD), and low-DHJSD groups (0.6g/mL of DHJSD). After 4 weeks of treatment, all rats were sacrificed and the severity of the cartilage degeneration was evaluated by a series of histological methods. The autophagosome was observed using transmission electron microscopy, and the related functional proteins were detected by the western blotting and real-time polymerase chain reaction. Next, the mechanism by which DHJSD improves knee cartilage degeneration was further clarified the in vitro by gene silencing technology combined with a series of functional experiments. The proteins levels of PTEN, Akt, p-Akt, mTOR, and p-mTOR, as well as the marker proteins of autophagy and apoptosis were determined. Zinc levels in chondrocytes were determined using inductively coupled plasma mass spectrometry. RESULTS: Histopathological staining revealed that DHJSD had a protective effect on the cartilage. DHJSD increased autophagosome synthesis and the expression of autophagy proteins LC3 and Beclin-1 in chondrocytes. Moreover, it reduced the phosphorylation levels of Akt and mTOR and the levels of zinc, MMP-13, Bax, and Bcl-2. Following PTEN silencing, this DHJSD-mediated reduction in Akt and mTOR phosphorylation and Bax, Bcl-2, and zinc levels were further decreased; in addition, DHJSD-mediated increase in LC3 and Beclin-1 levels was decreased. CONCLUSION: DHJSD inhibits the Akt/mTOR signaling pathway by targeting PTEN to promote autophagy in chondrocytes, which may help reduce MMP-13 production by regulating zinc levels in chondrocytes.

Current perspectives and trends in nanoparticle drug delivery systems in breast cancer: bibliometric analysis and review.

The treatment of breast cancer (BC) is a serious challenge due to its heterogeneous nature, multidrug resistance (MDR), and limited therapeutic options. Nanoparticle-based drug delivery systems (NDDSs) represent a promising tool for overcoming toxicity and chemotherapy drug resistance in BC treatment. No bibliometric studies have yet been published on the research landscape of NDDS-based treatment of BC. In this review, we extracted data from 1,752 articles on NDDS-based treatment of BC published between 2012 and 2022 from the Web of Science Core Collection (WOSCC) database. VOSviewer, CiteSpace, and some online platforms were used for bibliometric analysis and visualization. Publication trends were initially observed: in terms of geographical distribution, China and the United States had the most papers on this subject. The highest contributing institution was Sichuan University. In terms of authorship and co-cited authorship, the most prolific author was Yu Zhang. Furthermore, Qiang Zhang and co-workers have made tremendous achievements in the field of NDDS-based BC treatment. The article titled "Nanomedicine in cancer therapy: challenges, opportunities, and clinical applications" had the most citations. The Journal of Controlled Release was one of the most active publishers in the field. "Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries" was the most cited reference. We also analysed "hot" and cutting-edge research for NDDSs in BC treatment. There were nine topic clusters: "tumour microenvironment," "nanoparticles (drug delivery)," "breast cancer/triple-negative breast cancer," "combination therapy," "drug release (pathway)," "multidrug resistance," "recent advance," "targeted drug delivery", and "cancer nanomedicine." We also reviewed the core themes of research. In summary, this article reviewed the application of NDDSs in the treatment of BC.

The effect of ultrasound-guided acupotomy and Juanbi decoction on lumbar disc herniation: A randomized controlled trial.

BACKGROUND: Acupotomy as well as Juanbi decoction has been used in the treatment of lumbar disc herniation. However, there is no study on ultrasound-guided acupotomy combined with Juanbi decoction in the treatment of lumbar disc herniation. METHOD: This study was supported by the Sichuan Provincial Administration of Traditional Chinese Medicine [grant number: 2020LC0163] and the Science and Technology Department of Sichuan Province [grant number: 2022YFS0418]. This study was 3 center, open, randomized, controlled trial, and was carried out from December 2020 to December 2022. A total of 60 eligible patients with LDH were split into group A and group B at random. The group B received Juanbi Decoction 3 times daily for 2 weeks along with an acupotomy assisted by ultrasound. The acupotomy was administered once a week. The same protocol was used with the group A, but the Juanbi Decoction was replaced with normal saline. OBSERVATION INDEX: Visual analogue scale (VAS) score on 1 day and 1 week after treatment, VAS score, Japanese orthopedic association low back pain score(JOA) rate, Oswestry Disability Index (ODI), and low back outcome scale (LBOS) at 1, 3, 6, and 12 months after treatment in 2 groups. RESULTS: There were no significant differences in general information, VAS score before treatment, JOA, ODI, and LBOS between the 2 groups (P > .05). Intra-group comparison: VAS score, JOA rate, ODI, and LBOS were compared before and after treatment in both groups, and the differences were statistically significant (P < .05). There were significant differences in VAS and LBOS between the 2 groups at 3 and 6 months after treatment, and there were statistically significant differences in ODI and JOA rates at 3, 6, and 12 months after treatment between the 2 groups. CONCLUSION: Acupotomy aided by ultrasound combined with Juanbi Decoction significantly relieves lumbar pain and can improve lumbar function in patients with LDH, and the clinical efficacy lasts for about 6 months.