Hypothalamic CRF neurons facilitate brain reward function.

Aversive stimuli activate corticotropin-releasing factor (CRF)-expressing neurons in the paraventricular nucleus of hypothalamus (PVNCRF neurons) and other brain stress systems to facilitate avoidance behaviors. Appetitive stimuli also engage the brain stress systems, but their contributions to reward-related behaviors are less well understood. Here, we show that mice work vigorously to optically activate PVNCRF neurons in an operant chamber, indicating a reinforcing nature of these neurons. The reinforcing property of these neurons is not mediated by activation of the hypothalamic-pituitary-adrenal (HPA) axis. We found that PVNCRF neurons send direct projections to the ventral tegmental area (VTA), and selective activation of these projections induced robust self-stimulation behaviors, without activation of the HPA axis. Similar to the PVNCRF cell bodies, self-stimulation of PVNCRF-VTA projection was dramatically attenuated by systemic pretreatment of CRF receptor 1 or dopamine D1 receptor (D1R) antagonist and augmented by corticosterone synthesis inhibitor metyrapone, but not altered by dopamine D2 receptor (D2R) antagonist. Furthermore, we found that activation of PVNCRF-VTA projections increased c-Fos expression in the VTA dopamine neurons and rapidly triggered dopamine release in the nucleus accumbens (NAc), and microinfusion of D1R or D2R antagonist into the NAc decreased the self-stimulation of these projections. Together, our findings reveal an unappreciated role of PVNCRF neurons and their VTA projections in driving reward-related behaviors, independent of their core neuroendocrine functions. As activation of PVNCRF neurons is the final common path for many stress systems, our study suggests a novel mechanism underlying the positive reinforcing effect of stressful stimuli.

Bioactive polysaccharides in different plant parts of Aconitum carmichaelii.

BACKGROUND: Aconitum carmichaelii is an industrially cultivated medicinal plant in China and its lateral and mother roots are used in traditional Chinese medicine due to the presence of alkaloids. However, the rootlets and aerial parts are discarded after collection of the roots, and the non-toxic polysaccharides in this plant have attracted less attention than the alkaloids and poisonous features. In this study, five neutral and 14 acidic polysaccharide fractions were isolated systematically from different plant parts of A. carmichaelii, and their structural features and bioactivity were studied and compared. RESULTS: The neutral fraction isolated from the rootlets differed from those isolated from the lateral and mother roots. It consisted of less starch and more possible mannans, galactans, and/or xyloglucans, being similar to those of the aerial parts. Pectic polysaccharides containing homogalacturonan and branched type-I rhamnogalacturonan (RG-I) were present in all plant parts of A. carmichaelii. However, more arabinogalactan (AG)-II side chains in the RG-I backbone were present in the aerial parts of the plants, while more amounts of arabinans were found in the roots. Various immunomodulatory effects were observed, determined by complement fixation activity and anti-inflammatory effects on the intestinal epithelial cells of all polysaccharide fractions. CONCLUSION: This study highlighted the diversity of polysaccharides present in A. carmichaelii, especially in the unutilized plant parts, and showed their potential medicinal value. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Mechanisms of high ammonium loading promoted phosphorus release from shallow lake sediments: A five-year large-scale experiment.

The unprecedented global increase in the anthropogenic-derived nitrogen (N) input may have profound effects on phosphorus (P) dynamics and may potentially lead to enhanced eutrophication as demonstrated in short-term mesocosm experiments. However, the role of N-influenced P release is less well studied in large-scale ecosystems. To gain more insight into ecosystem effects, we conducted a five-year large-scale experiment in ten ponds (700-1000 m2 each) with two types of sediments and five targeted total N concentrations (TN) by adding NH4Cl fertilizer (0.5, 1, 5, 10, and 25 mg N L-1). The results showed that: (ⅰ) The sediment P release increased significantly when TN exceeded 10-25 mg N L-1. (ⅱ) The most pronounced sediment P release increase occurred in summer and from sediments rich in organic matter (OMSed). (ⅲ) TN, algal biomass, fish biomass, non-algal turbidity, sediment pH, and OMSed were the dominant factors explaining the sediment P release, as suggested by piecewise structural equation modeling. We propose several mechanisms that may have stimulated P release, i.e. high ammonium input causes a stoichiometric N:P imbalance and induce alkaline phosphatase production and dissolved P uptake by phytoplankton, leading to enhanced inorganic P diffusion gradient between sediment and water; higher pelagic fish production induced by the higher phytoplankton production may have led increased sediment P resuspension through disturbance; low oxygen level in the upper sediment caused by nitrification and organic decomposition of the settled phytoplankton and, finally, long-term N application-induced sediment acidification as a net effect of ammonium hydrolysis, nitrification, denitrification; The mechanisms revealed by this study shed new light on the complex processes underlying the N-stimulated sediment P release, with implications also for the strategies used for restoring eutrophicated lakes.

Angelica sinensis aboveground part polysaccharide and its metabolite 5-MT ameliorate colitis via modulating gut microbiota and TLR4/MyD88/NF-κB pathway.

The roots of Angelica sinensis have been used in Traditional Chinese Medicine for thousands of years. However, tons of aerial parts of this herb (aboveground part) are commonly discarded during the process of root preparations. A polysaccharide (ASP-Ag-AP) in the aboveground parts of A. sinensis was isolated and preliminarily characterized as typical plant pectin. ASP-Ag-AP exhibited noticeable protective effects against dextran sodium sulfate (DSS)-induced colitis, including reduction of colonic inflammation, modulation of barrier function, and alteration of gut microbiota and serum metabolite profile. Anti-inflammatory effects of ASP-Ag-AP were observed by inhibiting TLR4/MyD88/NF-κB signaling pathway in vitro and in vivo. Additionally, the level of serum metabolite 5-methyl-dl-tryptophan (5-MT) was reduced by DSS and restored by ASP-Ag-AP, which also negatively correlated with Bacteroides, Alistipes, Staphylococcus and pro-inflammatory factors. The protection from inflammatory stress on intestinal porcine enterocytes cells (IPEC-J2) of 5-MT was observed through the inhibition of TLR4/MyD88/NF-κB pathway. Besides, 5-MT also exhibited robust anti-inflammatory effect in colitis mice with improving colitis symptoms, barrier function and gut microbiota, which was the same as presented by ASP-Ag-AP. Therefore, ASP-Ag-AP could be a promising agent for colitis prevention and 5-MT could be the signal metabolite of ASP-Ag-AP on defending against intestinal inflammatory stress.

Salvia miltiorrhiza polysaccharide and its related metabolite 5-methoxyindole-3-carboxaldehyde ameliorate experimental colitis by regulating Nrf2/Keap1 signaling pathway.

The roots of Salvia miltiorrhiza have been used in Traditional Chinese Medicine for thousands of years. However, tons of aerial parts of this plant are usually discarded in the production of roots preparation. To make better use of these plant resources, the polysaccharide isolated from the aerial part of S. miltiorrhiza was investigated for its potential protection against intestinal diseases. A pectic polysaccharide (SMAP-1) was isolated and characterized being composed of homogalacturonan as the main chain and rhamnogalacturonan type I as ramified region, with side chains including arabinans and possible arabinogalactan type I and II. SMAP-1 exhibited robust protective effects against dextran sodium sulfate (DSS)-induced colitis and restored colitis symptoms, colonic inflammation, and barrier functions. Anti-oxidative effects were also observed by up-regulating Nrf2/Keap1 signaling pathway. Additionally, the level of serum 5-methoxyindole-3-carboxaldehyde (5-MC) was restored by SMAP-1 identified in metabolomic analysis, being correlated with the aforementioned effects. Protection against oxidative stress on intestinal porcine enterocyte cells (IPEC-J2) by 5-MC was observed through the activation of Nrf2/Keap1 system, as also shown by SMAP-1. In conclusion, SMAP-1 could be a promising candidate for colitis prevention, and 5-MC could be the signal metabolite of SMAP-1 in protecting against oxidative stress in the intestine.

Application of cocrystal separation technology in the separation and purification of genistein-puerarin-daidzein ternary system / 药学学报

Cocrystal separation technology is a technology that utilizes coformers to selectively form cocrystals with target compounds and separate them from mixed systems. Our study used puerarin (PUE), daidzein (DDZ), and genistein (GEN) as model drugs, which have similar structures and are the main isoflavones in Pueraria lobata root. The separation and purification processes in the modern traditional Chinese medicine (TCM) of these three components use conventional column chromatography, recrystallization, and other technologies, which have the issues of lengthy separation cycles, high solvent consumption, and inefficient preparation. Different with existing separation technology, our team used the early-found cocrystal separation method to design a step-by-step extraction and separation experiment of GEN-PUE-DDZ ternary mixture. Caffeine and L-proline were added to the mixed system in turn, GEN-caffeine cocrystal and PUE-proline cocrystal were prepared by suspension method. The cocrystals precipitated out of the solution. The purities of the GEN-caffeine cocrystal and the PUE-proline cocrystal could achieve 93% (the purity of GEN) and 99% (the purity of PUE). Besides, the purity of DDZ could also be increased by 6.76 times. This study proposed a simple operating, low cost and wide application range separation method different from the traditional separation method and realized the separation of structurally similar chemical components in TCM, laying a foundation for the application of cocrystal technology in the separation and refining of TCM.

Pectic polysaccharides from Aconitum carmichaelii leaves protects against DSS-induced ulcerative colitis in mice through modulations of metabolism and microbiota composition.

The industrial processing of Aconitum carmichaelii roots for use in Traditional Chinese Medicine generates a high amount of waste material, especially leaves. An acidic polysaccharide fraction isolated from these unutilized leaves, AL-I, was in our previous work shown to contain pectic polysaccharides. This study aimed to investigate the protective effect of AL-I on ulcerative colitis for the possible application of A. carmichaelii leaves in the treatment of intestinal inflammatory diseases. AL-I was found to alleviate symptoms and colonic pathological injury in colitis mice, and ameliorate the levels of inflammatory indices in serum and colon. The production of short- and branched-chain fatty acids was also restored by AL-I. The observed protective effect could be due to the inhibition of NOD1 and TLR4 activation, the promotion of gene transcription of tight-junction proteins, and the modulation of gut microbiota composition like Bacteroides, Dubosiella, Alistipes and Prevotella,. A regulation of serum metabolomic profiles being relevant to the bacterial change, such as D-mannose 6-phosphate, D-erythrose 4-phosphate and uric acid, was also observed.

The comparison of preliminary structure and intestinal anti-inflammatory and anti-oxidative activities of polysaccharides from different root parts of Angelica sinensis (Oliv.) Diels.

ETHNOPHARMACOLOGICAL RELEVANCE: The root of Angelica sinensis, has been commonly used in gynecology for centuries, and is normally applied divided into different parts in various clinical applications. At present, the majority of existing studies focus on the volatile oil and ferulic acid extracted from different parts of A. sinensis, but there is a dearth of scientific information on its water-soluble polysaccharides. AIM OF THE STUDY: The structures of polysaccharides from plants, have been reported contributing to multiple pharmacological activities such as anti-oxidative, anti-inflammatory, anti-tumor and liver protection. Therefore, the focus of this study was on its anti-oxidative and anti-inflammatory activities in vitro, which would be based on the various polysaccharides with distinct structures obtained from different parts of the A. sinensis root. MATERIALS AND METHODS: Four parts of A. sinensis root were separated according to the Chinese Pharmacopoeia: head, body, tail and whole body. Crude polysaccharides were obtained by water extraction and ethanol precipitation method, and were further fractionated by DEAE Sepharose chromatographic column and gel filtration. The comparison of ASPs from different root parts were performed, including chemical compositions determined by colorimetric analysis, monosaccharide compositions measured by high performance liquid chromatography (HPLC), glycosidic linkage units determined by methylation and gas chromatography-mass spectrometry (GC-MS), organic functional groups determined by FT-IR, molecular weight (Mw) demarcated by gel permeation chromatography, and the viscosities and solubilities were measured according to method published in the previous report with minor modification. In vitro biological activities of APSs were compared on lipopolysaccharide (LPS)-induced inflammatory and oxidative stress models on IPEC-J2 cells. RESULTS: Four purified polysaccharides, ASP-H-AP, ASP-B-AP, ASP-T-AP and ASP-Hb-AP from the root of A. sinensis, were obtained, and consisted of various contents of protein and the polyphenol. They were possibly pectic polysaccharides with a long homogalacturonan region as the main backbone and ramified with rhamnogalacturonan I region, but they were differed by subregions and the relative contents of glycosidic units. The Mw of four pectic polysaccharides were ranged from 67.9-267.7 kDa. The infrared spectrum also showed that the four polysaccharide fractions contained the characteristic peaks of polysaccharides. Their distinct primary structure could lead to a variety of biological activities. In vitro biological assays suggested that four polysaccharide fractions can protect IPEC-J2 cells against the LPS-induced inflammation by down-regulating inflammation factors and related genes on IPEC-J2 cells. These polysaccharides also could alleviate oxidative stress on IPEC-J2 cells by up-regulating the gene and protein expressions of antioxidant enzymes. It was concluded that ASP-H-AP possessed better anti-inflammatory and anti-oxidative effects, while those of ASP-T-AP was relatively poor among the four polysaccharide fractions. CONCLUSION: All results indicated that the structure of pectic polysaccharides from different root parts of A. sinensis differed, which lead to their distinct anti-inflammatory and anti-oxidative activities. This may also be one of the factors why different parts of A. sinensis showed various pharmacological activities and applied independently in traditional use. In addition, it would be valuable for further studies on structure-activity relationship of polysaccharides obtained by different root parts of A. sinensis.

Anti-Dlx5 Retards the Progression of Osteoarthritis through Inhibiting Chondrocyte Hypertrophy and Apoptosis.

Osteoarthritis is a common degenerative joint disease that can cause pain and disability in patients. There is still a lack of effective treatments to improve pathological changes of osteoarthritis cartilages and reverse the progression of osteoarthritis. Our study aimed to investigate the role of Dlx5 in papain-induced osteoarthritis. Osteoarthritis was induced through intraarticular injection of papain. The pathological damage of cartilage tissues was analyzed by H&E staining. The apoptosis of cartilage tissues was detected by TUNEL assay. Immunohistochemical staining was performed to detect DLX5 and BMP-2. Western blot was performed to detect the expressions of SP7, caspase-3, and MYC. The results showed that administration of anti-Dlx5 improved pathological changes of osteoarthritis cartilages, characterized by decreased chondrocyte proliferation, chondrocyte hypertrophy, and matrix damage. Anti-Dlx5 treatment decreased the expressions of BMP-2 and SP7, which are positive regulators of chondrocyte hypertrophy. Moreover, MYC and caspase-3, the critical mediators for chondrocyte apoptosis, were both decreased after anti-Dlx5 treatment. In conclusion, anti-Dlx5 retarded the progression of osteoarthritis by downregulating chondrocyte hypertrophy and chondrocyte apoptosis-related genes. Our findings suggests that Dlx5 is a promising target for osteoarthritis treatment.

Aconitum carmichaelii Debeaux: A systematic review on traditional use, and the chemical structures and pharmacological properties of polysaccharides and phenolic compounds in the roots.

ETHNOPHARMACOLOGICAL RELEVANCE: Aconitum carmichaelii, belonging to the Ranunculaceae family, is a widely used traditional herbal plant in Asian countries, especially in China. The lateral ("Fuzi") and mother ("Chuanwu") roots are the two main plant parts used in Traditional Chinese Medicine (TCM), where they are used in the treatment of acute myocardial infarction, heart failure, rheumatoid arthritis, and as analgesics. AIM OF THE STUDY: In order to further guide the research direction and application of A. carmichaelii, this study aims to give a systematic and in-depth overview on the phytochemical and pharmacological studies of non-alkaloid natural products with focus on polysaccharides and phenolic compounds. MATERIALS AND METHODS: A comprehensive search in the literature was conducted based on the databases Google Scholar, SciFinder (American Chemical Society), Springer Link, PubMed Science, Science Direct and China National Knowledge Internet, Wanfang Data, in addition to books, doctoral and master's dissertations, and official website. The main keywords were: "Aconitum carmichaelii", "Aconiti Lateralis Radix Praeparata", "Fuzi", "Chuanwu", "Aconiti Radix", "monkshood" and "Bushi". RESULTS: A. carmichaelii is known for the use of its different root parts, including "Fuzi" and "Chuanwu". Different types of polysaccharides, both neutral and acidic, and 39 phenolic compounds like flavonoids, phenylpropanoids, lignans, neolignans, and benzoic acid derivatives have been isolated and identified from the roots. Pharmacological studies of the isolated polysaccharides have demonstrated various biological effects such as hypoglycemic, hypolipidemic, cardiovascular, immunomodulatory, anti-tumor, and neuropharmacological activities. Studies on pharmacological effects of the phenolic compounds isolated from the roots are however limited. CONCLUSIONS: This review shows that polysaccharides could be one of the active components in the roots of A. carmichaelii, and they are promising for future applications due to their pharmacological properties. In addition, polysaccharides are generally non-toxic, biocompatible, and biodegradable. This review also sheds light on new research directions for A. carmichaelii. A more detailed structural characterization of polysaccharides from different root parts of A. carmichaelii, and their structure-activity relationships are required. Additionally, their pharmacological properties as immunomodulators in the intestinal system should be investigated. Further, more knowledge about the pharmacological effects and molecular mechanisms of the phenolic compounds that have been identified are needed.

Restorative Effects of Inulin From Codonopsis pilosula on Intestinal Mucosal Immunity, Anti-Inflammatory Activity and Gut Microbiota of Immunosuppressed Mice.

An inulin (CPPF), isolated from a traditional Chinese herbal medicine Codonopsis pilosula, was characterized and demonstrated with potential prebiotic activity in vitro before. Based on its non-digested feature, the intestinal mucosa and microbiota modulatory effects in vivo on immunosuppressed mice were investigated after oral administration of 200, 100 and 50 mg/kg of CPPF for 7 days. It was demonstrated that the secretions of sIgA and mucin 2 (Muc2) in ileum were improved by CPPF, and the anti-inflammatory activities in different intestine parts were revealed. The intestine before colon could be the target active position of CPPF. As a potential prebiotic substance, a gut microbiota restorative effect was also presented by mainly modulating the relative abundance of Eubacteriales, including Oscillibacter, unidentified Ruminococcus and Lachnospiraceae after high-throughput pyrosequencing of V4 region of 16S rRNA analysis. All these results indicated that this main bioactive ingredient inulin from C. pilosula was a medicinal prebiotic with enhancing mucosal immune, anti-inflammatory and microbiota modulatory activities.

Black phosphorus-Au-thiosugar nanosheets mediated photothermal induced anti-tumor effect enhancement by promoting infiltration of NK cells in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a heterogeneous cancer required combination therapy, such as photothermal therapy and chemotherapy. In recent years, cancer immunotherapies are rapidly evolving and are some of the most promising avenues to approach malignancies. Thus, the combination of the traditional therapies and immunotherapy in one platform may improve the efficacy for HCC treatment. RESULTS: In this work, we have prepared a black phosphorus (BP)-Au-thiosugar nanosheets (BATNS), in which Au-thiosugar coating and functionalization improved the stability of both black phosphorus nanosheets (BPNS) and gold ions in different simulated physiological environments. The compression of the BATNS band gap can convert more photon energy to heat generation compared with BPNS, resulting in higher photothermal conversion efficiency. The in vitro and in vivo results also revealed a stronger reduction on the hepatocellular carcinoma of mice and prolonged survival of disease models compared with BPNS. More importantly, BATNS showed an additional immune effect by increasing local NK cell infiltration but not T cell on the liver cancer treatment, and this immune effect was caused by the thermal effect of BATNS photothermal treatment. CONCLUSIONS: The novel BATNS could improve the stability of BPNS and simultaneously combine the cancer thermotherapy and immunotherapy leaded by local NK cell infiltration, resulting in a better therapeutic efficacy on hepatocellular carcinoma. This work also provided a new path to design BP-based materials for biomedical applications.

Jiaotaiwan increased GABA level in brain and serum, improved sleep via increasing NREM sleep and REM sleep, and its component identification.

ETHNOPHARMACOLOGICAL RELEVANCE: Jiaotaiwan (JTW) is good at communicating the heart and kidney. That meets the main mechanism of insomnia in traditional Chinese medicine. But the mechanism of JTW in promoting sleep is not clear. AIM OF THE STUDY: To investigate the mechanism of JTW in promoting sleep and identify the main components. MATERIALS AND METHODS: In this study, we detected the levels of GABA in serum and brain via LC-MS/MS analysis and investigated the hypnotic effect of JTW and its role in promoting sleep via Sleep monitoring and vigilance state analysis. Further, the identification of the main components was carried out by using LC-MS/MS analysis. RESULTS: JTW could increase the GABA levels in serum, FC and BS of SDM rats. JTW reduced the amount of wakefulness, increased the time of NREM sleep and REM sleep. A total of 25 compounds were identified. CONCLUSIONS: The current work provides valuable information on the hypnotic effects of JTW and its regulatory mechanisms in promoting sleep.

Palladium cubes with Pt shell deposition for localized surface plasmon resonance enhanced photodynamic and photothermal therapy of hypoxic tumors.

Multifunctional phototherapy nanoagents for imaging-guided synergistic photothermal therapy (PTT) and photodynamic therapy (PDT) are highly desirable in the field of solid tumor therapy. Nevertheless, the tumor microenvironment (TME) inherently associated with hypoxia significantly hampers the photodynamic effect of these multifunctional nanoagents. Herein, Pd nanocubes coated with an ultrathin Pt shell were prepared and further conjugated with fluorescein labeled and thiol functionalized polyethylene glycol (FITC-PEG-SH) (denoted as Pd@Pt-PEG). The deposition of a Pt shell on Pd nanocubes not only enhances the photothermal performance, exhibiting excellent hyperthermia outcomes and impressive photothermal (PT) imaging quality, but also leads to the formation of singlet oxygen (1O2) induced by plasmonic excitation. In the meantime, the catalytic activity of the Pt layer is enhanced by electronic coupling and the plasmonic effect, which induces the decomposition of endogenous overexpressed hydrogen peroxide (H2O2) in tumors to generate O2 for conquering TME and augmenting 1O2 generation for efficacious tumor cell apoptosis. The modification of FITC-PEG-SH improves the biocompatibility and provides outstanding fluorescence (FL) imaging properties. Upon NIR laser irradiation, Pd@Pt-PEG allows in situ O2 generation and dual-mode imaging-guided synergistic PTT/PDT that effectively kills hypoxic tumor cells, which makes it a promising nanotherapeutic agent for enhanced tumor therapy.

Pectic polysaccharide from Nelumbo nucifera leaves promotes intestinal antioxidant defense in vitro and in vivo.

In this study, the Nelumbo nucifera leaf polysaccharide (NNLP) was isolated by hot water extraction and ethanol precipitation. DEAE anion exchange chromatography and gel filtration were further performed to obtained the purified fraction NNLP-I-I, the molecular weight of which was 16.4 kDa. The monosaccharide composition analysis and linkage units determination showed that the fraction NNLP-I-I was a pectic polysaccharide. In addition, the NMR spectra analysis revealed that NNLP-I-I mainly consisted of a homogalacturonan backbone and rhamnogalacturonan I, containing a long HG region and short RG-I region, with AG-II and 1-3 linked rhamnose as side chains. The biological studies demonstrated that NNLP-I-I displayed antioxidant properties through mediating the Nrf2-regulated intestinal cellular antioxidant defense, which could protect cultured intestinal cells from oxidative stress and improve the intestinal function of aged mice.

Association of tumor downstaging after neoadjuvant chemotherapy with survival in patients with locally advanced nasopharyngeal carcinoma: a retrospective cohort study.

PURPOSE: Assessing the downstaging effects of neoadjuvant chemotherapy (NACT) in patients with locally advanced nasopharyngeal carcinoma (LANPC) and predicting response to treatment remain challenging. The present study aimed to evaluate the long-term prognosis of downstaging after NACT in patients with LANPC and to investigate the prognostic value of post-NACT tumor downstaging on treatment outcomes in the era of concurrent chemoradiotherapy (CCRT). METHODS: This retrospective study included 226 patients with stage III (n = 188) and IVA (n = 38) NPC admitted to Haikou People's Hospital between 1 October 2009 and 1 October 2012. The patients were grouped as downstaging or no after NACT. Overall survival (OS), locoregional failure-free survival (LFFS), and distant failure-free survival (DFFS) were analyzed. RESULTS: Among 226 patients, 196 (86.7%) were in the downstaging group and 30 (13.3%) were in the non-downstaging group. The longest follow-up was 76 months, and the median was 45 months. The 3-year OS rates of the downstaging group and non-downstaging group were 91.0% (95% CI 0.89-0.93) and 69.5% (95% CI 0.66-0.72) (P = 0.005). The 5-year OS rates were 81.6% (95% CI 0.78-0.86) and 53.3% (95% CI 0.49-0.61) (P = 0.001). N downstaging (3-year OS, HR 0.491, 95% CI 0.221-0.881, P = 0.022; 5-year OS, HR = 0.597, 95% CI 0.378-0.878, P = 0.021) was independently associated with OS. CONCLUSION: In the treatment of LANPC, the patients with downstaging after NACT have a better prognosis than those without downstaging. This study suggests that NACT can improve the prognosis for patients with LANPC if there is downstaging.

New pectic polysaccharides from Codonopsis pilosula and Codonopsis tangshen: structural characterization and cellular antioxidant activities.

BACKGROUND: Codonopsis pilosula and Codonopsis tangshen are plants widely used in traditional Chinese medicine. Two pectic polysaccharides from the roots of C. pilosula and C. tangshen named as CPP-1 and CTP-1 were obtained by boiling water extraction and column chromatography. RESULTS: The core structures of both CPP-1 and CTP-1 comprise the long homogalacturonan region (HG) as the backbone and the rhamnogalacturonan I (RG-I) region as the side chains. CPP-1 has methyl esterified galacturonic acid units and a slightly lower molecular weight than CTP-1. Biological testing suggested that CPP-1 and CTP-1 can protect IPEC-J2 cells against the H2 O2 -induced oxidative stress by up-regulating nuclear factor-erythroid 2-related factor 2 and related genes in IPEC-J2 cells. The different antioxidative activities of polysaccharides from different source of C. pilosula may be result of differences in their structures. CONCLUSION: All of the results indicated that pectic polysaccharides CPP-1 and CTP-1 from different species of C. pilosula roots could be used as a potential natural antioxidant source. These findings will be valuable for further studies and new applications of pectin-containing health products. © 2021 Society of Chemical Industry.

Characterization of an antioxidant pectic polysaccharide from Platycodon grandiflorus.

Platycodonis Radix is widely used as homology of medicine and food in China; polysaccharides are thought to be one of its functional constituents. In this study, a pectic polysaccharide, PGP-I-I, was obtained from the root of the traditional medicine plant Platycodon grandiflorus through ion exchange chromatography and gel filtration. This was characterized being mainly composed of 1,5-α-L-arabinan and both arabinogalactan type I (AG-I) and II chains linked to rhamnogalacturonan I (RG-I) backbone linked to longer galacturonan chains. In vitro bioactivity study showed that PGP-I-I could restore the intestinal cellular antioxidant defense under the condition of hydrogen peroxide (H2O2) treatment through promoting the expressions of cellular antioxidant genes and protect against oxidative damages.

The Efficacy of Vitamin D Supplementation for Migraine: A Meta-Analysis of Randomized Controlled Studies.

INTRODUCTION: The efficacy of vitamin D for migraine remains controversial. We conduct a systematic review and meta-analysis to explore the influence of vitamin D versus placebo on treatment in migraine patients. METHODS: We search PubMed, EMbase, Web of Science, EBSCO, and Cochrane library databases through April 2020 for randomized controlled trials assessing the effect of vitamin D versus placebo on treatment efficacy in migraine patients. This meta-analysis is performed using the random-effect model. RESULTS: Five randomized controlled trials are included in the meta-analysis. Overall, compared with control group in migraine patients, vitamin D treatment is associated with substantially reduced number of headache days (standard mean difference [SMD], -0.53; 95% confidence interval [CI], -0.83 to -0.23; P = 0.0006), frequency of headache attacks (SMD, -1.09; 95% CI, -1.86 to -0.32; P = 0.006), headache severity (SMD, -0.55; 95% CI, -0.91 to -0.19; P = 0.0003), and Migraine Disability Assessment score (SMD, -0.76; 95% CI, -1.11 to -0.40; P < 0.0001). CONCLUSIONS: Vitamin D treatment is effective to alleviate migraine.

Characterization of inulin-type fructans from two species of Radix Codonopsis and their oxidative defense activation and prebiotic activities.

BACKGROUND: Codonopsis pilosula and C. tangshen are both plants widely used in traditional Chinese medicine. Polysaccharides, which are their primary active components, are thought to be important in their extensive use. In this study, two neutral polysaccharide fractions of C. pilosula (CPPN) and C. tangshen (CTPN) were obtained by fractionation on a DEAE-Sepharose column and characterized. RESULTS: It was confirmed that the neutral polymers CPPN and CTPN were ß-(2,1)-linked inulin-type fructans with non-reducing terminal glucose, and degree of polymerization (DP) of 19.6 and 25.2, respectively. The antioxidant and prebiotic activities in vitro were assayed based on IPEC-J2 cell lines and five strains of Lactobacillus. Results indicated that the effects of CPPN and CTPN were increased antioxidant defense in intestinal epithelial cells through enhanced cell viability, improved expression of total antioxidant capacity, glutathione peroxidase, superoxide dismutase and catalase, and reduced levels of malondialdehyde and lactic dehydrogenase. The prebiotic activity of CPPN and CTPN was demonstrated by the promoting effect on Lactobacillus proliferation in vitro. The different biological activities obtained between the two fractions are probably due to the different DP and thus molecular weights of CPPN and CTPN. CONCLUSION: The inulin fractions from C. pilosula and C. tangshen were natural sources of potential intestinal antioxidants as well as prebiotics, which will be valuable in further studies and new applications of inulin-containing health products. © 2020 Society of Chemical Industry.