Dendrobium officinale polysaccharide-based carrier to enhance photodynamic immunotherapy.

Photodynamic therapy (PDT) eradicates tumors via the generation of toxic reactive oxygen species (ROS) by activation of a photosensitizer (PS) with appropriate light. Local PDT toward tumors can trigger the immune response to inhibit distant tumors, but the immune response is usually insufficient. Herein, we used a biocompatible herb polysaccharide with immunomodulatory activity as the carrier of PS to enhance the immune inhibition of tumors after PDT. The Dendrobium officinale polysaccharide (DOP) is modified with hydrophobic cholesterol to serve as an amphiphilic carrier. The DOP itself can promote dendritic cell (DC) maturation. Meanwhile, TPA-3BCP are designed to be cationic aggregation-induced emission PS. The structure of one electron-donor linking to three electron-acceptors endows TPA-3BCP with high efficiency to produce ROS upon light irradiation. And the nanoparticles are designed with positively charged surfaces to capture antigens released after PDT, which can protect the antigens from degradation and improve the antigen-uptake efficiency by DCs. The combination of DOP-induced DC maturation and antigen capture-increased antigen-uptake efficiency by DCs significantly improves the immune response after DOP-based carrier-mediated PDT. Since DOP is extracted from the medicinal and edible Dendrobium officinale, the DOP-based carrier we designed is promising to be developed for enhanced photodynamic immunotherapy in clinic.

Anti-colon Cancer Effects of Dendrobium officinale Kimura & Migo Revealed by Network Pharmacology Integrated With Molecular Docking and Metabolomics Studies.

Objective: The present study aimed to investigate the potential mechanism of Dendrobium officinale (D. officinale) on colorectal cancer and the relevant targets in the pathway using a network pharmacological approach. Methods: (1) We identified the major bioactive components of D. officinale by UPLC-ESI-MS/MS and established the in-house library by using the literature mining method. (2) Target prediction was performed by SwissADME and SwissTargetPrediction. (3) A protein-protein interaction (PPI) network and component-target-pathway network (C-T-P network) were constructed. (4) The GO pathways and the KEGG pathway enrichment analysis were carried out by the Metascape database. (5) Molecular docking was performed by AutoDock software. (6) A series of experimental assays including cell proliferation, cell invasion and migration, and TUNEL staining in CRC were performed in CRC cell lines (HT-29, Lovo, SW-620, and HCT-116) to confirm the inhibitory effects of D. officinale. Results: (1) In total, 396 candidate active components of D. officinale were identified by UPLC-ESI-MS/MS and selected from the database. (2) From OMIM, GeneCards, DrugBank, and TTD databases, 1,666 gene symbols related to CRC were gathered, and (3) 34 overlapping gene symbols related to CRC and drugs were obtained. (4) These results suggested that the anti-CRC components of D. officinale were mainly apigenin, naringenin, caffeic acid, γ-linolenic acid, α-linolenic acid, cis-10-heptadecenoic acid, etc., and the core targets of action were mainly ESR1, EGFR, PTGS2, MMP9, MMP2, PPARG, etc. (5) The proliferation of muscle cells, the regulation of inflammatory response, the response of cells to organic cyclic compounds, and the apoptotic signaling pathway might serve as principal pathways for CRC treatment. (6) The reliability of some important active components and targets was further validated by molecular docking. The molecular docking analysis suggested an important role of apigenin, naringenin, PTGS2, and MMP9 in delivering the pharmacological activity of D. officinale against CRC. (7) These results of the evaluation experiment in vitro suggested that D. officinale had a strong inhibitory effect on CRC cell lines, and it exerted anti-CRC activity by activating CRC cell apoptosis and inhibiting CRC cell migration and invasion. Conclusion: This study may provide valuable insights into exploring the mechanism of action of D. officinale against CRC.

Clinical Efficacy and Safety of Human Mesenchymal Stem Cell Therapy for Degenerative Disc Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Degenerative disc disease (DDD) can cause severe low back pain, which will have a serious negative impact on the ability to perform daily tasks or activities. For the past few years, mesenchymal stem cell (MSC) transplantation has emerged as a promising strategy for the treatment of DDD. However, the clinical efficacy of MSC in the treatment of DDD still lacks clinical evidence and is controversial. We conducted a meta-analysis with randomized controlled trials (RCTs) to evaluate the clinical efficacy and safety of MSC transplantation in patients with DDD. We searched major databases using terms from the database's inception through March 2021. The Cochrane bias risk assessment tool was used to assess quality. The analysis showed that MSC therapy could decrease visual analog scale (VAS) scores (SMD = -0.50, 95%CI = -0.68 ~ -0.33, P < 0.00001) and Oswestry Disability Index (ODI) scores (SMD = -0.27, 95%CI = -0.44 ~ -0.09, P = 0.003). The outcomes with subgroup analysis showed that MSC therapy could decrease VAS scores in 3 months (P = 0.001), 6 months (P = 0.01), 12 months (P = 0.02), and ≥24 months (P = 0.002) and ODI scores in ≥24 months (P = 0.006). Pooled analysis showed that MSC therapy has a higher ratio of patients at most thresholds but particularly at the MIC (minimally important change) (P = 0.0002) and CSC (clinically significant change) (P = 0.0002) in VAS and MIC (P = 0.0005) and CSC (P = 0.001) pain responders in ODI. Adverse events (AE) of treatment-emergent adverse events (TEAE), back pain, arthralgia, and muscle spasms were not statistically significant between the two groups. However, our further statistical analysis showed that MSC therapy may induce AE of TEAE related to study treatment (OR = 3.05, 95%CI = 1.11 ~ 8.40, P = 0.03). In conclusion, this study pooled the main outcomes and showed that MSC therapy could significantly decrease VAS and ODI scores in patients with DDD. Distinctly, the findings of this meta-analysis suggest a novel therapeutic strategy for patients with chronic low back pain (LBP) and lumbar dysfunction by DDD.

The Impact of Glucagon-Like Peptide 1 Receptor Agonists on Bone Metabolism and Its Possible Mechanisms in Osteoporosis Treatment.

Diabetes mellitus and osteoporosis are closely related and have complex influencing factors. The impact of anti-diabetic drugs on bone metabolism has received more and more attention. Type 2 diabetes mellitus (T2DM) would lead to bone fragility, high risk of fracture, poor bone repair and other bone-related diseases. Furthermore, hypoglycemic drugs used to treat T2DM may have notable detrimental effects on bones. Thus, the clinically therapeutic strategy for T2DM should not only effectively control the patient's glucose levels, but also minimize the complications of bone metabolism diseases. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are novel and promising drug for the treatment of T2DM. Some studies have found that GLP-1RAs may play an anti-osteoporotic effect by controlling blood sugar levels, promoting bone formation and inhibiting bone resorption. However, in clinical practice, the specific effects of GLP-1RA on fracture risk and osteoporosis have not been clearly defined and evidenced. This review summarizes the current research findings by which GLP-1RAs treatment of diabetic osteoporosis, postmenopausal osteoporosis and glucocorticoid-induced osteoporosis and describes possible mechanisms, such as GLP-1R/MAPK signaling pathway, GLP-1R/PI3K/AKT signaling pathway and Wnt/ß-catenin pathway, that are associated with GLP-1RAs and osteoporosis. The specific role and related mechanisms of GLP-1RAs in the bone metabolism of patients with different types of osteoporosis need to be further explored and clarified.

Therapeutic Evidence of Human Mesenchymal Stem Cell Transplantation for Cerebral Palsy: A Meta-Analysis of Randomized Controlled Trials.

Cerebral palsy (CP) is a kind of movement and posture disorder syndrome in early childhood. In recent years, human mesenchymal stem cell (hMSC) transplantation has become a promising therapeutic strategy for CP. However, clinical evidence is still limited and controversial about clinical efficacy of hMSC therapy for CP. Our aim is to evaluate the efficacy and safety of hMSC transplantation for children with CP using a meta-analysis of randomized controlled trials (RCTs). We conducted a systematic literature search including Embase, PubMed, ClinicalTrials.gov, Cochrane Controlled Trials Register databases, Chinese Clinical Trial Registry, and Web of Science from building database to February 2020. We used Cochrane bias risk assessment for the included studies. The result of pooled analysis showed that hMSC therapy significantly increased gross motor function measure (GMFM) scores (standardized mean difference (SMD) = 1.10, 95%CI = 0.66-1.53, P < 0.00001, high-quality evidence) and comprehensive function assessment (CFA) (SMD = 1.30, 95%CI = 0.71-1.90, P < 0.0001, high-quality evidence) in children with CP, compared with the control group. In the subgroup analysis, the results showed that hMSC therapy significantly increased GMFM scores of 3, 6, and 12 months and CFA of 3, 6, and 12 months. Adverse event (AE) of upper respiratory infection, diarrhea, and constipation was not statistically significant between the two groups. This meta-analysis synthesized the primary outcomes and suggested that hMSC therapy is beneficial, effective, and safe in improving GMFM scores and CFA scores in children with CP. In addition, subgroup analysis showed that hMSC therapy has a lasting positive benefit for CP in 3, 6, and 12 months.

Effect of P2Y12 inhibitor monotherapy versus dual antiplatelet therapy on cardiovascular events in patients undergoing percutaneous coronary intervention: systematic review and meta-analysis.

INTRODUCTION: Clinical data on short mandatory dual antiplatelet therapy (DAPT) followed by P2Y12 inhibitor monotherapy, compared with prolonged DAPT in patients undergoing percutaneous coronary intervention (PCI) are insufficient. We aim to evaluate the effectiveness and safety of P2Y12 inhibitor monotherapy and prolonged DAPT after short mandatory DAPT on cardiovascular events in patients undergoing PCI. EVIDENCE ACQUISITION: A systematic literature search was performed in seven medical databases from building the database until July 2019. Three studies with randomized controlled trial (RCTs), totaling 21,970 patients, were included in this meta-analysis. The included studies were assessed by the Cochrane risk of bias and analyzed by Review Manager v. 5.3 software. EVIDENCE SYNTHESIS: Our result of pooled analysis showed that there was noninferior rates of in major adverse cardiac and cerebrovascular events (MACCE), stroke, myocardial infarction and cardiac death between short mandatory DAPT followed by P2Y12 inhibitor monotherapy and prolonged DAPT in patients undergoing PCI. Pooled analysis showed that short mandatory DAPT followed by P2Y12 inhibitor monotherapy could significantly reduce the risk of bleeding BARC type 2-5 (OR=0.47, 95% CI: 0.31-0.70, P=0.002), compared with prolonged DAPT in patients undergoing PCI. However, Pooled analysis showed that short mandatory DAPT followed by P2Y12 inhibitor monotherapy was not associated with BARC type 3-5, compared with prolonged DAPT. CONCLUSIONS: This meta-analysis demonstrated that short mandatory DAPT followed by P2Y12 inhibitor monotherapy compared with prolonged DAPT resulted in noninferior rates of MACCE, all-cause mortality, cardiac death, stroke, myocardial infarction and stent thrombosis. Furthermore, short mandatory DAPT followed by P2Y12 inhibitor monotherapy could significantly reduce the risk of bleeding BARC type 2-5.

Efficacy and safety of the injection of the traditional Chinese medicine salviae miltiorrhizae and ligustrazine hydrochloride for the treatment of perioperative period of fracture: A meta-analysis of randomized controlled trials.

BACKGROUND: The injection of the traditional Chinese patent medicine salviae miltiorrhizae and ligustrazine hydrochloride injection (SMLHI) has been widely used in treatment of various diseases such as angina pectoris or ischemic stroke in China. We aim to evaluate the efficacy and safety of SMLHI for the treatment of perioperative period of fracture. METHODS: A systematic literature search was performed in seven medical databases from their inception until February 2019. 16 studies with randomized controlled trials, totaling 1589 patients, were included in this meta-analysis. The included studies were assessed by the cochrane risk of bias and analyzed by Review Manager 5.3 software. RESULTS: The meta-analysis showed that SMLHI for the treatment of perioperative period of fracture was significantly better compared with the control group in terms of the total effective rate. The result showed that SMLHI could significantly reduce the risk of deep vein thrombosis and inflammatory cytokines. Furthermore, the result showed that SMLHI could significantly improve the coagulation function indexes such as prothrombin time, plasma fibrinogen and D-Dimer (P < .0001). CONCLUSIONS: This meta-analysis demonstrated that SMLHI may be more effective and safe for the treatment of perioperative period of fracture. However, further and higher quality randomized controlled trials are required to prove treatment outcome.

Network Pharmacology-Based Study on the Molecular Biological Mechanism of Action for Compound Kushen Injection in Anti-Cancer Effect.

BACKGROUND Compound Kushen injection (CKI) is a traditional Chinese medicine preparation for clinical treatment of cancer pain or treatment of various types of solid tumors. The purpose of this study was to identify the main active compounds from CKI and to investigate its anti-cancer mechanisms via drug target biological network pharmacology construction and prediction. MATERIAL AND METHODS Constituents of CKI were retrieved from Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Disease targets were collected in the Human Gene (Gene Cards) and Human Mendelian Inheritance (OMIM) databases. "Ingredients-protein targets-pathway" networks were constructed using Cytoscape. STRING database platform to construct enrichment of protein-protein interactions (PPI), related diseases and pathways network. Gene Ontology (GO) biological functions and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway of were performed to investigate by using Bioconductor tool for analysis. RESULTS The results indicated that 60 constituents of absorption, distribution, metabolism, and excretion (ADME) filtration resulted in 33 constituents exhibiting significant correlations with anti-cancer and CKI may target 113 proteins, including IL6, EGFR, CASP3, VEGFA, MYC, and ESR1. GO and KEGG enrichment analysis results show that 129 biological processes and 93 signal pathways associated with cancer. It mainly involves cancers such as prostate cancer, bladder cancer, hepatocellular carcinoma, colorectal cancer, breast cancer, etc. Active ingredients might also induce apoptosis in cancer cells via the p53 and PI3K-Akt signaling pathway mechanism. CONCLUSIONS This study was based on pharmacological networks results for the prediction of the multi-constituent, multi-target, and multi-pathway mechanisms of CKI, which might be a promising potential therapeutic and prevention candidate for anti-cancer. However, based on computer data mining and analysis, this study still needs to be further verified by in vivo/in vitro experiments, and the safety of CKI needs to be evaluated.

Are aquatic exercises efficacious in postmenopausal women with knee osteoarthritis? A meta-analysis of randomized controlled trials.

INTRODUCTION: To assess the effects of aquatic exercise in postmenopausal women with knee osteoarthritis using an up-to-date meta-analysis. EVIDENCE ACQUISITION: PubMed, Cochrane Library, Embase, Scopus, Web of Science, Google Scholar, the China National Knowledge Infrastructure (CNKI), the Chinese Biomedical Database (CBM), VIP and Wanfang database were searched systematically for randomized controlled trials (RCTs) published until July 2018. The RCTs included comparing the efficacy of aquatic exercise vs. control in postmenopausal women with knee osteoarthritis, the primary outcomes were assessed by the Western Ontario McMaster University Osteoarthritis Index (WOMAC) and the Knee injury and Osteoarthritis Outcome Score (KOOS). EVIDENCE SYNTHESIS: Six RCTs comprising 432 participants. This meta-analysis revealed that aquatic exercise could significantly relieve the symptom of postmenopausal women with knee osteoarthritis. But there was no significant difference between aquatic exercise program and control group for the improvement of pain, stiffness, function outcomes, sport, activities of daily living and quality of life. CONCLUSIONS: Contrary to prior reviews, our analysis demonstrated that aquatic exercise has no positive impact on pain physical function, stiffness, activities of daily living, sport and quality of life in elderly women with knee osteoarthritis. However, aquatic exercise could improve the symptoms of knee osteoarthritis. Further investigation is needed because of limited available data.

Traditional Chinese Medicine Yimucao Injection Combined with Western Medicine for Preventing Postpartum Hemorrhage after Cesarean Section: A Systematic Review and Meta-Analysis.

OBJECTIVE: Yimucao injection combined with several contraction uterus drugs is in use for preventing postpartum hemorrhage after cesarean section. The present study is a meta-analysis comparing the efficacy and safety of these drugs. METHODS: PubMed, Cochrane Library, Embase, the China National Knowledge Infrastructure (CNKI), the Chinese Biomedical Database (CBM), VIP, and Wanfang database were searched until June 2018. We selected RCTs of Yimucao injection combined with western medicine for preventing postpartum hemorrhage and study quality was assessed using the revised Cochrane risk of bias tool. Forty-eight RCTs are comprised of 7,330 participants. RESULTS: The overall response rate of Yimucao injection combined with western medicine as a class (OR=4.19, 95%CI=2.83, 6.20, P<0.00001) was found to be significantly improved than western medicine alone. Yimucao injection combined with western medicine group could significantly reduce blood loss in intraoperative (SMD= -1.15, 95%CI= -1.43, -0.87, P<0.00001), compared with control group. The treatment group could significantly reduce postpartum blood loss within 2 hours (SMD= -1.73, 95%CI= -2.01, -1.46, P<0.00001) and had a significantly lower blood loss within 24 hours (SMD= -1.92, 95%CI= -2.21, -1.63, P<0.00001) than control group. Additionally, in terms of the safety, Yimucao injection group reduced the risk of adverse events in the course of prevention than the western medicine group. CONCLUSIONS: This study demonstrated that Yimucao injection combined with western medicine may be more effective for preventing postpartum hemorrhage after cesarean section. However, high-quality and large multicenter randomized clinical trials will be needed to prove the consequence in the further.

The effects of litter quality and living plants on the home-field advantage of aquatic macrophyte decomposition in a eutrophic urban lake, China.

The 'home-field advantage' (HFA) hypothesis states that litter decomposes faster in its 'home' habitat, i.e., in the same habitat as the plant species from which it was derived than it does 'away' from its home, i.e., in the habitat of a different plant species. However, studies pertaining to HFA in aquatic ecosystems are relatively few. One area not well-studied is whether the presence of living plants has an effect on the HFA of aquatic macrophyte decomposition in a eutrophic lake. Here, we conducted reciprocal litter transplanting experiments, coupled with removal of living plants, between a dominant submerged macrophyte (Myriophyllum spicatum) and a floating-leaved macrophyte (Trapa natans) in a eutrophic urban lake in China, for 50 days. Test plots were created at sites by removing the dominant macrophytes from their 'home' habitats to test the effect of living plants on decomposition rates and HFA effect. The water chemistry of the two sites was not significantly different. The initial litter qualities were significantly higher in M. spicatum than in T. natans. The decomposition rates of T. natans were significantly greater in both the control and test plots in its 'home' habitat, indicating a positive HFA effect, while the decomposition rates of M. spicatum were significantly greater in the 'away' habitat compared to its 'home' habitat in all treatments, indicating a home-field disadvantage effect. The removal of living plants had a noticeable effect on the abundance of associated-macroinvertebrates, but had an inconsistent effect on decomposition rates providing conflicting evidence for HFA. In total, 10 macroinvertebrate taxa from four functional feeding groups (FFGs) were collected during the experiment. Compared to macroinvertebrate communities, microbial activities showed less correlation with decomposition rates. Our results provide evidence to suggest that decomposition-based HFA is dependent upon litter quality, habitat, and their interactions in a eutrophic urban lake.