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The steamed Panax ginsengC. A. Mey., Panax notoginseng(Burk.) F. H. Chen, and Panax quinquefoliumL. not only facilitate storage, but also increase the content of rare saponins and enhance their clinical application value. The traditional steaming process has high energy consumption, low efficiency, and lacks standardized operating procedures and unified standards. This paper retrieves the research literature on the steaming process parameters, rare saponin increments, and efficacy enhancement results of ginseng plants. By summarizing the effects of different steaming processes on rare saponins and pharmacodynamics in P. ginseng, P. notoginsengand P. quinquefolium, we explored new steaming methods and established a new quality evaluation system to provide guarantee for the effectiveness and safety of clinical medication and provide scientific basis for its rational use.

Jiaogulan (Gynostemma pentaphyllum) tea is a functional food that is commercially available worldwide. Gypensapogenin I (Gyp I), which is a natural damarane-type saponin, was obtained from the hydrolysates of total gypenosides. The present research was performed to investigate the potential antiproliferation effect of Gyp I in MDA-MB-231 cells and the underlying mechanisms. Here, we found that Gyp I attenuated survival, inhibited proliferation, and induced apoptosis in MDA-MB-231 cells. Target prediction by binding molecule docking and western blot assays confirmed the mechanism by which Gyp I inhibited the proliferation of breast cancer cells via the AKT/GSK3β/β-catenin signaling pathway. We also showed that Gyp I exhibited superior in vivo efficacy that was dose dependent. Tumor tissue transcriptome analysis indicated that Gyp I could decrease the expression levels of NOTCH1and HES1, which was in contrast to the effect on MAMLand NUMBL, indicating that our compound hindered the activation of the Notch-1 signaling pathway. In summary, we report for the first time that Gyp I shows excellent anti-breast cancer activity in vivo and in vitro and that its pathway of action is related to the AKT/GSK3β/β-catenin and Notch-1 signaling pathways. Therefore, Jiaogulan tea can not only be used as a health food but also possesses the possibility to treat triple-negative breast cancer (TNBC).

Anti-inflammatory drugs targeting inflammatory bowel disease (IBD) have attracted considerable attention but still face low therapeutic outcomes and frequent side effects. Astaxanthin (ATX), a natural ketone, possesses potent antioxidant and anti-inflammatory properties. However, it faces problems such as poor water solubility, photothermal instability, and low bioavailability. Here, we employed a supramolecular encapsulation strategy to create a nanoscale oral delivery system for ATX (referred to as FC-ATX NPs) by coupling fucoidan (FUC) with chitosan oligosaccharides (COS). The obtained FC-ATX NPs exhibited a particular “bean pod” structure with uniform size, good encapsulation efficiency, excellent physical and chemical stability, pH-triggered intestinal targeted slow-release properties, and potent antioxidant capacity. In vitrocell culture experiments showed that FC-ATX NPs promoted cellular uptake and scavenged excessive intracellular reactive oxygen species (ROS). In mouse models of colitis, FC-ATX NPs enhanced the drug absorption of intestinal epithelial cells and effectively accumulated at the site of inflammation. This work provides an efficient approach to enhance the bioavailability of ATX and has excellent application potential as an oral targeted delivery system for colitis therapy.

Levodopa-induced dyskinesia (LID) is an intractable motor complication arising in Parkinson’s disease with the progression of disease and chronic treatment of levodopa. However, the specific cell assemblies mediating dyskinesia have not been fully elucidated. Here, we utilize the activity-dependent tool to identify three brain regions (globus pallidus external segment [GPe], parafascicular thalamic nucleus, and subthalamic nucleus) that specifically contain dyskinesia-activated ensembles. An intensity-dependent hyperactivity in the dyskinesia-activated subpopulation in GPe (GPeTRAPed in LID) is observed during dyskinesia. Optogenetic inhibition of GPeTRAPed in LIDsignificantly ameliorates LID, whereas reactivation of GPeTRAPed in LIDevokes dyskinetic behavior in the levodopa-off state. Simultaneous chemogenetic reactivation of GPeTRAPed in LIDand another previously reported ensemble in striatum fully reproduces the dyskinesia induced by high-dose levodopa. Finally, we characterize GPeTRAPed in LIDas a subset of prototypic neurons in GPe. These findings provide theoretical foundations for precision medication and modulation of LID in the future.

Parkinson’s disease with mild cognitive impairment (PD-MCI) or dementia (PDD) has been shown to be correlated with poor quality of life (QoL). The association between specific cognitive domains and QoL is less clear. To determine how the cognitive domains affect QoL in different cognitive states in PD. We recruited 600 PD patients, including 185 PD patients with normal cognition (PD-NC), 336 PD-MCI patients, and 79 PDD patients. All patients underwent a scale-based assessment (PDQ-39) for QoL, as well as clinical evaluations and neuropsychological tests. Compared to PD-NC group, QoL became more impaired in the PD-MCI and PDD groups. Generalized linear model revealed that no neuropsychological test was significantly associated with QoL in PD-NC group; neuropsychological tests in attention and language domains were significantly associated with QoL in PD-MCI patients; neuropsychological tests in memory and language domains were significantly associated with QoL in PDD patients. Cognitive domains contribute differently to QoL in PD. These findings may prompt clinicians to target specific cognitive domains for improving QoL in the PD patients.

Adaptation to endoplasmic reticulum (ER) stress has been indicated as a driver of malignancy and resistance to therapy in human melanoma. However, the relationship between cancer stem cells and adaptation to ER stress remains unclear. Here, we show that the ratio of cancer stem cells is increased in ER stress-resistant melanoma cells, which inhibit ER stress-induced apoptosis and promote tumorigenesis. Further mechanistic studies showed that HOXB9 triggered by ER stress favors cancer stem cell self-renewal and enhances ER stress resistance. HOXB9 directly binds to the promoter of microRNA-765 and facilitates its transcription, which in turn targets FOXA2, resulting in a FOXA2 decrease and cancer stem cell increase. Additionally, an increase in HOXB9 promotes melanoma growth and inhibits cell apoptosis in a mouse xenograft model. Elevated HOXB9 is found in human melanoma tissues, which is associated with microRNA-765 up-regulation and FOXA2 decreases. Thus, our data showed that the HOXB9-dependent, microRNA-765–mediated FOXA2 pathway contributes to the survival of melanoma under ER stress by maintaining the properties of cancer stem cells.

Intestinal epithelial cells can respond to certain bacteria by producing an array of cytokines and chemokines which are associated with host immune responses. Lactobacillus acidophilus NCFM is a characterized probiotic, originally isolated from human feces. This study aimed to test the ability of L. acidophilus NCFM to stimulate cytokine and chemokine production in intestinal epithelial cells and to elucidate the mechanisms involved in their upregulation. In experiments using intestinal epithelial cell lines and mouse models, we observed that L. acidophilus NCFM could rapidly but transiently upregulate a number of effector genes encoding cytokines and chemokines such as interleukin 1α (IL-1α), IL-1β, CCL2, and CCL20 and that cytokines showed lower expression levels with L. acidophilus NCFM treatment than chemokines. Moreover, L. acidophilus NCFM could activate a pathogen-associated molecular pattern receptor, Toll-like receptor 2 (TLR2), in intestinal epithelial cell lines. The phosphorylation of NF-κB p65 and p38 mitogen-activated protein kinase (MAPK) in intestinal epithelial cell lines was also enhanced by L. acidophilus NCFM. Furthermore, inhibitors of NF-κB (pyrrolidine dithiocarbamate [PDTC]) and p38 MAPK (SB203580) significantly reduced cytokine and chemokine production in the intestinal epithelial cell lines stimulated by L. acidophilus NCFM, suggesting that both NF-κB and p38 MAPK signaling pathways were important for the production of cytokines and chemokines induced by L. acidophilus NCFM.

ABSTRACTIntestinal epithelial cells can respond to certain bacteria by producing an array of cytokines and chemokines which are associated with host immune responses. Lactobacillus acidophilusNCFM is a characterized probiotic, originally isolated from human feces. This study aimed to test the ability of L. acidophilusNCFM to stimulate cytokine and chemokine production in intestinal epithelial cells and to elucidate the mechanisms involved in their upregulation. In experiments using intestinal epithelial cell lines and mouse models, we observed that L. acidophilusNCFM could rapidly but transiently upregulate a number of effector genes encoding cytokines and chemokines such as interleukin 1a (IL-1a), IL-1ß, CCL2, and CCL20 and that cytokines showed lower expression levels with L. acidophilusNCFM treatment than chemokines. Moreover, L. acidophilusNCFM could activate a pathogen-associated molecular pattern receptor, Toll-like receptor 2 (TLR2), in intestinal epithelial cell lines. The phosphorylation of NF-?B p65 and p38 mitogen-activated protein kinase (MAPK) in intestinal epithelial cell lines was also enhanced by L. acidophilusNCFM. Furthermore, inhibitors of NF-?B (pyrrolidine dithiocarbamate [PDTC]) and p38 MAPK (SB203580) significantly reduced cytokine and chemokine production in the intestinal epithelial cell lines stimulated by L. acidophilusNCFM, suggesting that both NF-?B and p38 MAPK signaling pathways were important for the production of cytokines and chemokines induced by L. acidophilusNCFM.

Purpose:The purpose of this study was to evaluate the effect of various media on the color stability of compomer and to compare these results to those of other materials that could be used in similar clinical circumstances.

Abstract: The comparative study of organic matter in carbonate rocks and argillaceous rocks from the same horizon indicates that the organic thermal maturities of carbonate rocks are much lower than those of argillaceous rocks. And extensive analysis of extracted and inclused organic matter from the same sample shows that inclused organic matter is different from extracted organic matter, and the thermal maturity of the former is usually lower than that of the latter in terms of biomarker structural parameters. It seems that carbonate minerals could preserve organic matter and retard organic maturation. The inclused organic matter, abundant in most carbonate rocks, will be released from minerals and transformed into oil and gas during the high thermal maturity stage.