Brucea javanica derived exosome-like nanovesicles deliver miRNAs for cancer therapy.

Triple-negative breast cancer (TNBC) is characterized by complex heterogeneity, high recurrence and metastasis rates, and short overall survival, owing to the lack of endocrine and targeted receptors, which necessitates chemotherapy as the major treatment regimen. Exosome-like nanovesicles derived from medicinal plants have shown great potential as novel biotherapeutics for cancer therapy by delivering their incorporated nucleic acids, especially microRNAs (miRNAs), to mammalian cells. In this study, we isolated exosome-like nanovesicles derived from B. javanica (BF-Exos) and investigated their influence and underlying molecular mechanisms in TNBC. We found that BF-Exos delivered 10 functional miRNAs to 4T1 cells, significantly retarding the growth and metastasis of 4T1 cells by regulating the PI3K/Akt/mTOR signaling pathway and promoting ROS/caspase-mediated apoptosis. Moreover, BF-Exos were shown to inhibit the secretion of vascular endothelial growth factor, contributing to anti-angiogenesis in the tumor microenvironment. In vivo, BF-Exos inhibited tumor growth, metastasis, and angiogenesis in breast tumor mouse models, while maintaining high biosafety. Overall, BF-Exos are considered promising nanoplatforms for the delivery of medicinal plant-derived nucleic acids, with great potential to be developed into novel biotherapeutics for the treatment of TNBC.

A review of neuroendocrine immune system abnormalities in IBS based on the brain-gut axis and research progress of acupuncture intervention.

Irritable bowel syndrome (IBS) is a common digestive disorder observed in clinics. Current studies suggest that the pathogenesis of the disease is closely related to abnormal brain-gut interactions, hypokinesia, visceral sensory hypersensitivity in the gastrointestinal tract, and alterations in the intestinal microenvironment. However, it is difficult for a single factor to explain the heterogeneity of symptoms. The Rome IV criteria emphasized the holistic biologic-psycho-social model of IBS, suggesting that symptoms of the disease are closely related to neurogastroenterology and various abnormalities in brain-gut interaction. This study comprehensively reviewed the relationship between the brain-gut axis and IBS, the structure of the brain-gut axis, and the relationship between the brain-gut axis and intestinal microenvironment, and discussed the relationship between the abnormal regulation of the nervous system, endocrine system, and immune system and the incidence of IBS on the basis of brain-gut axis. In terms of treatment, acupuncture therapy can regulate the neuroendocrine-immune system of the body and improve the intestinal microenvironment, and it has the advantages of safety, economy, and effectiveness. We study the pathogenesis of IBS from local to global and micro to macro, and review the use of acupuncture to treat the disease as a whole so as to provide new ideas for the treatment of the disease.

Efficacy of moxibustion in diarrhea-predominant irritable bowel syndrome model rats: a systematic review and meta-analysis.

Objective: To systematically evaluate the efficacy of moxibustion in diarrhea-predominant irritable bowel syndrome (IBS-D) model rats. Methods: A comprehensive search was conducted in the China National Knowledge Infrastructure, WanFang Data, VIP, PubMed, Embase, and Web of Science databases from their inception to June 30, 2023. Relevant animal experiments investigating moxibustion for treating IBS-D in model rats were included. Two independent researchers screened the literature, extracted data, and evaluated the risk of bias in the selected studies. The meta-analysis was performed using RevMan 5.3 software. Results: In total, 21 animal studies comprising 680 model rats were included. The meta-analysis results demonstrated that moxibustion enhanced the threshold capacity of the abdominal withdrawal reflex (AWR) [standardized mean difference (SMD) = 1.84; 95% confidence interval (CI): 1.09, 2.60; p < 0.00001], ameliorated the rate of loose stool (SMD = -4.03; 95% CI: -5.76, -2.30; p < 0.00001), and decreased the colon 5-hydroxytryptamine (SMD = -3.67; 95% CI: -5.33, -2.01; p < 0.00001), serum interleukin-1ß (SMD = -3.24, 95% CI: -4.06, -2.41; p < 0.00001), serum tumor necrosis factor-α (SMD = -2.35, 95% CI: -4.12, -0.58; p < 0.00001), and serum substance P (SMD = -5.14, 95% CI: -8.45, -1.83; p = 0.002) concentrations. Moxibustion did not affect the blood calcitonin gene-related peptide level compared to the blank model group (p = 0.15). Conclusion: Moxibustion modulated the brain-gut interaction, reduced visceral hypersensitivity, inhibited intestinal inflammation, and regulated the immune balance, improving the rate of loose stool and increasing the AWR threshold capacity in IBS-D model rats, achieving good analgesic and antidiarrheal effects. However, these conclusions require further validation due to limitations in the quantity and quality of the included studies.

A Comparison Study of the Effect on IBS-D Rats among Ginger-Partitioned Moxibustion, Mild Moxibustion, and Laser Moxibustion.

BACKGROUND: Diarrhea-predominant irritable bowel syndrome (IBS-D) is a functional gastrointestinal disorder that severely affects patients' life. Moxibustion is believed to be an effective way to treat IBS-D. However, the therapeutic effects and the underlying mechanisms in symptom management of IBS-D by different moxibustion therapies remain unclear. METHODS: IBS-D model rats were divided into groups and treated with ginger-partitioned moxibustion (GPM), mild moxibustion (MM), and laser moxibustion (LM) at a temperature of 43°C, respectively. The temperature curves of acupoints were recorded during interventions. The therapeutic effects were evaluated on the basis of general condition, stool, and hematoxylin-eosin staining of the colon tissue. Moreover, the expression of transient receptor potential vanilloid 1 (TRPV1) receptors in both acupoint tissue and colon tissue was analyzed by immunohistochemistry. RESULTS: After moxibustion treatment, the symptoms were improved. The expression of TRPV1 was increased in acupoint tissue and decreased in colon tissue. GPM and MM showed a more significant influence on IBS-D rats compared with LM. The temperature profile of GPM and MM was wave-like, while LM had an almost stable temperature curve. CONCLUSION: GPM, MM, and LM could improve the symptoms in IBS-D rats. Moxibustion might activate TRPV1 channels in the acupoint tissue and induce acupoint functions, which in turn inhibit the pathological activation state of the colon's TRPV1, followed by improvements in abdominal pain and diarrheal symptoms. LM with stable temperature might lead to the desensitization of TRPV1 receptors and the tolerance of acupoint. GPM and MM provided dynamic and repetitive thermal stimulations that perhaps induced acupoint sensitization to increase efficacy. Therefore, dynamic and repetitive thermal stimulation is recommended in the application of moxibustion.

High-Dose TGF-ß1 Impairs Mesenchymal Stem Cell-Mediated Bone Regeneration via Bmp2 Inhibition.

Transforming growth factor-ß1 (TGF-ß1) is a key factor in bone reconstruction. However, its pathophysiological role in non-union and bone repair remains unclear. Here we demonstrated that TGF-ß1 was highly expressed in both C57BL/6 mice where new bone formation was impaired after autologous bone marrow mesenchymal stem cell (BMMSC) implantation in non-union patients. High doses of TGF-ß1 inhibited BMMSC osteogenesis and attenuated bone regeneration in vivo. Furthermore, different TGF-ß1 levels exhibited opposite effects on osteogenic differentiation and bone healing. Mechanistically, low TGF-ß1 doses activated smad3, promoted their binding to bone morphogenetic protein 2 (Bmp2) promoter, and upregulated Bmp2 expression in BMMSCs. By contrast, Bmp2 transcription was inhibited by changing smad3 binding sites on its promoter at high TGF-ß1 levels. In addition, high TGF-ß1 doses increased tomoregulin-1 (Tmeff1) levels, resulting in the repression of Bmp2 and bone formation in mice. Treatment with the TGF-ß1 inhibitor SB431542 significantly rescued BMMSC osteogenesis and accelerated bone regeneration. Our study suggests that high-dose TGF-ß1 dampens BMMSC-mediated bone regeneration by activating canonical TGF-ß/smad3 signaling and inhibiting Bmp2 via direct and indirect mechanisms. These data collectively show a previously unrecognized mechanism of TGF-ß1 in bone repair, and TGF-ß1 is an effective therapeutic target for treating bone regeneration disability. © 2019 American Society for Bone and Mineral Research.

The protective effects of acupoint gel embedding on rats with myocardial ischemia-reperfusion injury.

AIMS: Prevention and treatment of myocardial ischemia-reperfusion (I/R) injury has for many years been a hot topic in treating ischemic heart disease. As one of the most well-known methods of complementary and alternative medicine, acupuncture has attracted increasing interest in preventing myocardial I/R injury due to its remarkable effectiveness and minimal side effect. However, traditional acupuncture approaches are limited by cumbersome execution, high labor costs and inevitable pain caused by frequent stimulation. Therefore, in this work, we aimed to develop a novel acupoint gel embedding approach and investigated its role in protecting against myocardial I/R injury in rats. MAIN METHODS: Gels were embedded at bilateral Neiguan (PC6) points of rats and their protective effects against myocardial I/R injury evaluated in terms of changes in histomorphology, myocardial enzymology, antioxidant capacity, anti-inflammatory response, and anti-apoptosis of cells. KEY FINDINGS: We found that the approach of acupoint gel embedding could significantly reduce myocardial infarcted size, repair pathological changes, mitigate oxidative stress damage and inflammatory response, as well as inhibit apoptosis of cardiomyocytes. Such cardioprotective effects were found to be associated with Notch-1/Jagged-1 signaling pathway. SIGNIFICANCE: The proposed approach of acupoint gel embedding has advantages in continuous acupoint stimulation, dosing controls, and no side effects in the course of treatment, as well as in reducing the pain caused by frequent acupuncture. It can form an alternative therapy to not only protect against myocardial I/R injury but also hold great potential in treating other diseases in the future.

Gypenoside XVII Enhances Lysosome Biogenesis and Autophagy Flux and Accelerates Autophagic Clearance of Amyloid-ß through TFEB Activation.

A strategy for activating transcription factor EB (TFEB) to restore autophagy flux may provide neuroprotection against Alzheimer's disease. Our previous study reported that gypenoside XVII (GP-17), which is a major saponin abundant in ginseng and Panax notoginseng, ameliorated amyloid-ß (Aß)25-35-induced apoptosis in PC12 cells by regulating autophagy. In the present study, we aimed to determine whether GP-17 has neuroprotective effects on PC12 cells expressing the Swedish mutant of APP695 (APP695swe) and APP/PS1 mice. We also investigated the underlying mechanism. We found that GP-17 could significantly increase Atg5 expression and the conversion of LC3-I to LC3-II in APP695 cells, which was associated with a reduction in p62 expression. GP-17 also elevated the number of LC3 puncta in APP695 cells transduced with pCMV-GFP-LC3. GP-17 promoted the autophagy-based elimination of AßPP, Aß40, and Aß42 in APP695swe cells and prevented the formation of Aß plaques in the hippocampus and cortex of APP/PS1 mice. Furthermore, spatial learning and memory deficits were cured. Atg5 knockdown could abrogate the GP-17-mediated removal of AßPP, Aß40, and Aß42 in APP695swe cells. GP-17 upregulated LAMP-1, increased LysoTracker staining, and augmented LAMP-1/LC3-II co-localization. GP-17 could release TFEB from TFEB/14-3-3 complexes, which led to TFEB nuclear translocation and the induction of autophagy and lysosome biogenesis and resulted in the amelioration of autophagy flux. The knockdown of TFEB could abolish these effects of GP-17. In summary, these results demonstrated that GP-17 conferred protective effects to the cellular and rodent models of Alzheimer's disease by activating TFEB.

[Clinical value of cupping spot effect].

The cupping spot is considered as one kind of skin change due to cupping treatment. With literature regarding cupping spot, the influencing factors and value of cupping spot in clinical diagnosis and treatment were analyzed, which could make a further exploration on the action mechanism of cupping treatment. The literature showed that the formation of cupping spot was related with cupping temperature, pressure, cup-retaining time, cupping area, individual difference and health condition, etc; cupping spot had the ability to assist diagnosis, prevent disease, cure disease and evaluate clinical efficacy. Previous studies on cupping spot have already made some progress, and played a positive significance on finding cupping rule and studying its mechanism. However, the research for this area is still in the primary stage, which needed deeper study to reveal scientific connotations of cupping spot.