Efficacy of substances containing 3 types of active ingredients-saponins, flavones, and alkaloids in regulation of cytokines in autoimmune diseases a systematic review and Meta-analysis based on animal studies.

OBJECTIVE: To investigate the efficacy of substances containing 3 types of active ingredients-saponins, flavones, and alkaloids on experimental animals with autoimmune diseases (AIDs). METHODS: The protocol for this systematic review and Meta-analysis was prospectively registered with PROSPERO (CRD42023395741). Searches were conducted in the China National Knowledge Infrastructure, Wanfang, Chinese Science and Technology Journals, China Biomedical, PubMed, Cochrane Library, and Embase databases to screen for animal studies investigating the therapeutic effects of saponins, flavones, or alkaloids on autoimmune diseases; consequently, corresponding data extraction tables were prepared. Systematic Review Centre for Laboratory Animal Experimentation was used to assess the risk of methodological bias in the included literature. RevMan 5.4 was used for the Meta-analysis on the 8 serum cytokines. RESULTS: A total of 31 studies were included, all of which were randomized controlled studies. Meta-analysis indicated that substances rich in saponins, flavones, and alkaloids reduced serum levels of interleukin (IL)-1ß [standardized mean difference (SMD) = -1.94, 95% confidence interval (CI) (-2.99, -0.90), P = 0.0003], IL-6 [SMD = -1.65, 95% CI (-2.33, -0.97,) P < 0.000 01], IL-17 [SMD = -2.41, 95% CI (-3.61, -1.20), P < 0.0001], tumor necrosis factor (TNF)-α [SMD = -1.84, 95% CI (-2.61, -1.06), P < 0.0001], and interferon (IFN)-γ [SMD = -1.54, 95% CI (-2.43, -0.65), P = 0.0007], but increased serum levels of IL-4 [SMD = 1.30, 95% CI (0.15, 2.44), P = 0.03) and IL-10 [SMD = 2.05, 95% CI (1.39, 2.70), P < 0.000 01) in animal models. However, no significant regulatory effect of these three active components was observed on serum levels of IL-2 [SMD = -0.63, 95% CI (-1.82, 0.57), P = 0.30]. CONCLUTIONS: Substances containing saponins, flavones, and alkaloids regulated the changes of immune-related cytokines, it may be a novel dietary substance to relieve and control autoimmune diseases in the future.

Elevated preoperative plasma D-dimer level was an independent prognostic factor for patients with PDAC after curative resection: a retrospective analysis.

OBJECTIVE: In this study, the relationship between preoperative plasma D-dimer level and overall survival and recurrence free survival were evaluated in patients with curative resection of pancreatic ductal adenocarcinoma. METHODS: Preoperative plasma D-dimer level of 573 patients with pancreatic ductal adenocarcinoma were collected. The univariate and multivariate Cox hazard models were used to identify independent variables associated with overall survival and recurrence free survival in this study. The Kaplan-Meier method was used to evaluate overall survival and recurrence free survival, and the differences between survival curves were analyzed using the Log-rank test. Continuous variables were presented as $\overline{x}\pm s$, parametric analysis was performed using t-test. Categorical variables were analyzed by means of the chi-square or Fisher's exact test. RESULTS: Based on the analysis for the whole study, the results showed that patients in the elevated plasma D-dimer levels had a tendency to have an elder mean age (58.69 ± 8.32 years vs. 63.05 ± 8.44 years, P < 0.001), larger tumour size ≥4 cm (P = 0.006), advanced T stage (P = 0.024), N stage (P = 0.041), Tumor, Node and Metastasis (TNM) stage (P = 0.029) and postoperative complications (P = 0.042) was more likely occurred. Besides, according to the results of Cox multivariate analysis, elevated preoperative plasma D-dimer level was an independent prognostic factor not only for overall survival (Hazard Ratio (HR):1.430, 95% Confidence Interval (CI) (1.163-1.759), P = 0.001) but also for recurrence free survival (HR:1.236, 95% CI (1.018-1.500), P = 0.032). CONCLUSION: In our study, the elevated preoperative plasma D-dimer level may act as an independent prognostic factor for overall survival and recurrence free survival in patients with pancreatic ductal adenocarcinoma after curative resection. Pancreatic ductal adenocarcinoma patients with elevated preoperative plasma D-dimer level had a worse prognosis than those with normal plasma D-dimer level; and the elevated preoperative plasma D-dimer level may imply heavy tumour burden and provide supplementary information regarding disease status.

The Role of TAK1 in RANKL-Induced Osteoclastogenesis.

Bone remodelling is generally a dynamic process orchestrated by bone-resorbing osteoclasts and bone-forming osteoblasts. Osteoclasts are the only cell type capable of bone resorption to maintain bone homeostasis in the human body. However, excessive osteoclastogenesis can lead to osteolytic diseases. The receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL) has been widely considered to be an important modulator of osteoclastogenesis thereby participating in the pathogenesis of osteolytic diseases. Transforming growth factor ß-activated kinase 1 (TAK1), a member of the mitogen-activated protein kinase kinase kinase family, is an important intracellular molecule that regulates multiple signalling pathways, such as NF-κB and mitogen-activated protein kinase to mediate multiple physiological processes, including cell survival, inflammation, and tumourigenesis. Furthermore, increasing evidence has demonstrated that TAK1 is intimately involved in RANKL-induced osteoclastogenesis. Moreover, several detailed mechanisms by which TAK1 regulates RANKL-induced osteoclastogenesis have been clarified, and some potential approaches targeting TAK1 for the treatment of osteolytic diseases have emerged. In this review, we discuss how TAK1 functions in RANKL-mediated signalling pathways and highlight the significant role of TAK1 in RANKL-induced osteoclastogenesis. In addition, we discuss the potential clinical implications of TAK1 inhibitors for the treatment of osteolytic diseases.

Therapeutic Effects of CUR-Activated Human Umbilical Cord Mesenchymal Stem Cells on 1-Methyl-4-phenylpyridine-Induced Parkinson's Disease Cell Model.

The purpose of this study is to evaluate the therapeutic effects of human umbilical cord-derived mesenchymal stem cells (hUC-MSC) activated by curcumin (CUR) on PC12 cells induced by 1-methyl-4-phenylpyridinium ion (MPP+), a cell model of Parkinson's disease (PD). The supernatant of hUC-MSC and hUC-MSC activated by 5 µmol/L CUR (hUC-MSC-CUR) were collected in accordance with the same concentration. The cell proliferation and differentiation potential to dopaminergic neuronal cells and antioxidation were observed in PC12 cells after being treated with the above two supernatants and 5 µmol/L CUR. The results showed that the hUC-MSC-CUR could more obviously promote the proliferation and the expression of tyrosine hydroxylase (TH) and microtubule associated protein-2 (MAP2) and significantly decreased the expression of nitric oxide (NO) and inducible nitric oxide synthase (iNOS) in PC12 cells. Furtherly, cytokines detection gave a clue that the expression of IL-6, IL-10, and NGF was significantly higher in the group treated with the hUC-MSC-CUR compared to those of other two groups. Therefore, the hUC-MSC-CUR may be a potential strategy to promote the proliferation and differentiation of PD cell model, therefore providing new insights into a novel therapeutic approach in PD.

Effect of tumor necrosis factor-alpha on resistin expression in 3T3-L1 adipocytes and its mechanism.

In order to investigate the effect of tumor necrosis factor-alpha (TNFalpha) on resistin expression in 3T3-L1 adipocytes, and further explore its mechanisms, the differentiated 3T3-L1 adipocytes were incubated with 0, 1, 10, 100 ng/mL TNFalpha respectively for 24 h, and then the expression of resistin was determined. The differentiated 3T3-L1 adipocytes were incubated with 100 ng/ mL TNFalpha for 3, 6, 24 h respectively, and then the expression of resistin mRNA was analyzed. 3T3-L1 adipocytes were induced to differentiate into mature adipocytes. The cells were randomly divided into 4 groups for culture. In the control group, no drugs were added. Cells of TNFalpha group were treated with 100 ng/mL TNFalpha. In Ro-31-8220 group, 5 micromol/L protein kinase C inhibitor Ro-31-8220 was added. With TNFalpha+Ro-31-8220 group, 100 ng/mL TNFalpha were added 1 h after the addition of 5 micromol/L Ro-31-8220. All adipocytes were cultured for 24 h. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were employed to detect the expression of resistin gene. Our results showed that resistin protein and mRNA in 3T3-L1 adipocytes were inhibited by TNFalpha at different concentrations (P<0.01), and the inhibitory effect increased with the concentration (P<0.01). At the same concentrations, the inhibitory effect increased with time (P <0.01). Ro-31-8220 could inhibit its expression and the inhibitive effect remained unchanged with addition of TNFalpha (P>0.05). It was concluded that TNFalpha could inhibit the expression of resistin in 3T3-L1 adipocytes. The mechanism may be that the expression of resistin is partly controlled by protein kinase C signal conduction pathway.