Evaluation on the Potential for Hepatotoxic Components from Herba Epimedii to Induce Apoptosis in HepG2 Cells and the Analysis of the Influence of Metabolism in Liver Microsomes.

The potential hepatotoxicity of Herba Epimedii is a focal point in traditional Chinese medicine security applications. As determined in our previous study, the flavonoid constituents of Herba Epimedii, sagittatoside A, icariside I, baohuoside I and icaritin, are related to the hepatotoxicity of this herb. However, the hepatotoxic mechanism of these components needs to be clarified further, and whether these components can maintain their injury action following liver metabolism needs to be confirmed. Herein, the effects of sagittatoside A, icariside I, baohuoside I and icaritin on the apoptosis of HepG2 cells and the expression of key proteins, including Bax, Bcl-2, Caspase-3 and Caspase-9, were evaluated. Moreover, with liver microsome incubation, the influences of metabolism on the apoptotic activities of these components were investigated. Then, by HPLC-MS/MS analyses, the in vitro metabolic stability of these components was determined after incubation with different kinds of liver microsomes to explain the reason for the influence. The results suggested that sagittatoside A, baohuoside I and icaritin could induce apoptosis, which is likely to be closely related to the induction of the intrinsic apoptosis pathway. After metabolic incubation, the sagittatoside A and icaritin metabolism mixture could still induce apoptosis due to less metabolic elimination, while the icariside I and baohuoside I metabolism mixtures respectively got and lost the ability to induce apoptosis, probably due to quick metabolism and metabolic transformation. The findings of this study may provide important references to explore the material basis and mechanism of the hepatotoxicity of Herba Epimedii.

Ginseng-derived nanoparticles alleviate alcohol-induced liver injury by activating the Nrf2/HO-1 signalling pathway and inhibiting the NF-κB signalling pathway in vitro and in vivo.

BACKGROUND: Previous studies have confirmed the antioxidant and anti-inflammatory effects of active ginseng components that protect against liver injury. However, ginseng-derived nanoparticles (GDNPs), low-immunogenicity nanovesicles derived from ginseng, have not been reported to be hepatoprotective. PURPOSE: In this study, we investigated whether GDNPs could attenuate alcohol-induced liver injury in LO2 cells and mice by modulating oxidative stress and inflammatory pathways, thereby advancing the theoretical basis for the development of novel pharmacological treatments. STUDY DESIGN: Alcohol was used to construct in vitro and in vivo models of alcoholic liver injury. To explore the mechanisms by which GDNPs exert their protective effects against alcoholic liver injury, we examined the expression of oxidative stress-related genes and analysed inflammatory responses in vitro and in vivo. The experimental findings were verified using network pharmacology. METHODS: The composition of the GDNPs was analysed using liquid chromatography-mass spectrometry. GDNPs were extracted and purified using differential ultracentrifugation and sucrose density gradient centrifugation. In vitro models of alcoholic liver injury were established using LO2 cells, whereas C57BL/6 J mice were used as in vivo models. Oxidative stress, inflammation, and liver injury indicators were measured using appropriate kits. Levels of proteins associated with oxidative stress and inflammation were measured via western blot, while nuclear factor erythroid2-related factor 2 (Nrf2) and NF-κB protein expression was tested using immunofluorescence, immunohistochemistry, and flow cytometry. The levels of relevant transcription factors were determined using qPCR. Experimental haematoxylin and eosin staining was used to characterise the liver histological appearance and damage in mice. Network pharmacological analysis of GDNP mRNA sequencing of GDNPs was used to predict drug targets and disease associations using TCMSP. RESULTS: GDNPs primarily included 77 compounds, including organic acids and their derivatives, amino acids and their derivatives, sugars, terpenoids, and flavonoids. GDNPs have features that allow them to be taken up by LO2 cells and promote their proliferation. In vitro data indicated that GDNPs reduced the levels of alcohol-induced reactive oxygen species by activating the Nrf2/HO-1 signalling pathway, whilst inhibiting the NF-κB pathway and thereby reducing NO, tumour necrosis factor-α, and interleukin-1ß levels to alleviate inflammation. An in vivo model showed that GDNPs improved the liver parameters and pathology in mice with alcoholic liver injury. GDNPs activate the Nrf2/HO-1/Keap1 signalling pathway in a p62-dependent manner to exert antioxidant effects. Furthermore, the TLR4/NF-κB signalling pathway was involved in the in vivo anti-inflammatory effect. Network pharmacology also confirmed that the effects of GDNPs on liver disease were associated with oxidative stress and inflammation-related targets and pathways. CONCLUSION: This study showed for the first time that GDNPs can alleviate alcohol-induced liver damage by activating the Nrf2/HO1 signalling pathway and blocking the NF-κB signalling pathway, thus lowering oxidative stress and inflammatory responses. Hereby, we present the Nrf2/HO1 and NF-κB signalling pathways as potential targets and GDNPs as a novel therapeutic approach for the management of alcohol-induced liver damage.

Haplotype-phased genome unveils the butylphthalide biosynthesis and homoploid hybrid origin of Ligusticum chuanxiong.

Butylphthalide is one of the first-line drugs for ischemic stroke therapy, while no biosynthetic enzyme for butylphthalide has been reported. Here, we present a haplotype-resolved genome of Ligusticum chuanxiong, a long-cultivated and phthalide-rich medicinal plant in Apiaceae. On the basis of comprehensive screening, four Fe(II)- and 2-oxoglutarate-dependent dioxygenases and two CYPs were mined and further biochemically verified as phthalide C-4/C-5 desaturases (P4,5Ds) that effectively promoted the forming of (S)-3-n-butylphthalide and butylidenephthalide. The substrate promiscuity and functional redundancy featured for P4,5Ds may contribute to the high phthalide diversity in L. chuanxiong. Notably, comparative genomic evidence supported L. chuanxiong as a homoploid hybrid with Ligusticum sinense as a potential parent. The two haplotypes demonstrated exceptional structure variance and diverged around 3.42 million years ago. Our study is an icebreaker for the dissection of phthalide biosynthetic pathway and reveals the hybrid origin of L. chuanxiong, which will facilitate the metabolic engineering for (S)-3-n-butylphthalide production and breeding for L. chuanxiong.

Exploring the anti-ferroptosis mechanism of Kai-Xin-San against Alzheimer's disease through integrating network pharmacology, bioinformatics, and experimental validation strategy in vivo and in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: Kai Xin San (KXS), first proposed by Sun Simiao during the Tang Dynasty, has been utilized to treat dementia by tonifying qi and dispersing phlegm. AIM OF THE STUDY: This study aimed to elucidate the mechanism by which KXS exerts its therapeutic effects on Alzheimer's disease (AD) by targeting ferroptosis, using a combination of network pharmacology, bioinformatics, and experimental validation strategies. MATERIALS AND METHODS: The active target sites and the further potential mechanisms of KXS in protecting against AD were investigated through molecular docking, molecular dynamics simulation, and network pharmacology, and combined with the validation of animal experiments. RESULTS: Computational and experimental findings provide the first indication that KXS significantly improves learning and memory defects and inhibits neuronal ferroptosis by repairing mitochondria damage and upregulating the protein expression of ferroptosis suppressor protein 1 (FSP1) in vivo APP/PS1 mice AD model. According to bioinformatics analysis, the mechanism by which KXS inhibits ferroptosis may involve SIRT1. KXS notably upregulated the mRNA and protein expression of SIRT1 in both vivo APP/PS1 mice and in vitro APP-overexpressed HT22 cells. Additionally, KXS inhibited ferroptosis induced by APP-overexpression in HT22 cells through activating the SIRT1-FSP1 signal pathway. CONCLUSIONS: Collectively, our findings suggest that KXS may inhibit neuronal ferroptosis through activating the SIRT1/FSP1 signaling pathway. This study reveals the scientific basis and underlying modern theory of replenishing qi and eliminating phlegm, which involves the inhibition of ferroptosis. Moreover, it highlights the potential application of SIRT1 or FSP1 activators in the treatment of AD and other ferroptosis-related diseases.

Ginseng-derived nanoparticles alleviate inflammatory bowel disease via the TLR4/MAPK and p62/Nrf2/Keap1 pathways.

Inflammatory bowel disease (IBD) is closely linked to the homeostasis of the intestinal environment, and exosomes can be used to treat IBD due to their high biocompatibility and ability to be effectively absorbed by the intestinal tract. However, Ginseng-derived nanoparticles (GDNPs) have not been studied in this context and their mechanism of action remains unclear. Here, we investigated GDNPs ability to mediate intercellular communication in a complex inflammatory microenvironment in order to treat IBD. We found that GDNPs scavenge reactive oxygen species from immune cells and intestinal epithelial cells, inhibit the expression of pro-inflammatory factors, promote the proliferation and differentiation of intestinal stem cells, as well as enhancing the diversity of the intestinal flora. GDNPs significantly stabilise the intestinal barrier thereby promoting tissue repair. Overall, we proved that GDNPs can ameliorate inflammation and oxidative stress in vivo and in vitro, acting on the TLR4/MAPK and p62/Keap1/Nrf2 pathways, and exerting an anti-inflammatory and antioxidant effect. GDNPs mitigated IBD in mice by reducing inflammatory factors and improving the intestinal environment. This study offers new evidence of the potential therapeutic effects of GDNPs in the context of IBD, providing the conceptual ground for an alternative therapeutic strategy.

Akebia saponin D attenuates allergic airway inflammation through AMPK activation.

Akebia saponin D (ASD) is a bioactive triterpenoid saponin extracted from Dipsacus asper Wall. ex DC.. This study aimed to investigate the effects of ASD on allergic airway inflammation. Human lung epithelial BEAS-2B cells and bone marrow-derived mast cells (BMMCs) were pretreated with ASD (50, 100 and 200 µΜ) and AMPK activator 5-aminoimidazole-4-carboxamide-1-ß-D-ribofuranoside (AICAR) (1 mM), and then stimulated with lipopolysaccharide (LPS) or IL-33. Pretreatment with ASD and AICAR significantly inhibited TNF-α and IL-6 production from BEAS-2B cells, and IL-13 production from BMMCs. Moreover, pretreatment with ASD and AICAR significantly increased p-AMPK expression in BEAS-2B cells. Inhibition of AMPK by siRNA and compound C partly abrogated the suppression effect of ASD on TNF-α, IL-6, and IL-13 production. Asthma murine model was induced by ovalbumin (OVA) challenge and treated with ASD (150 and 300 mg/kg) or AICAR (100 mg/kg). Infiltration of eosinophils, neutrophils, monocytes, and lymphocytes, and production of TNF-α, IL-6, IL-4, and IL-13 were attenuated in ASD and AICAR treated mice. Lung histopathological changes were also ameliorated after ASD and AICAR treatment. Additionally, it showed that treatment with ASD and AICAR increased p-AMPK expression in the lung tissues. In conclusion, ASD exhibited protective effects on allergic airway inflammation through the induction of AMPK activation.

LcSAO1, an Unconventional DOXB Clade 2OGD Enzyme from Ligusticum chuanxiong Catalyzes the Biosynthesis of Plant-Derived Natural Medicine Butylphthalide.

Butylphthalide, a prescription medicine recognized for its efficacy in treating ischemic strokes approved by the State Food and Drug Administration of China in 2005, is sourced from the traditional botanical remedy Ligusticum chuanxiong. While chemical synthesis offers a viable route, limitations in the production of isomeric variants with compromised bioactivity necessitate alternative strategies. Addressing this issue, biosynthesis offers a promising solution. However, the intricate in vivo pathway for butylphthalide biosynthesis remains elusive. In this study, we examined the distribution of butylphthalide across various tissues of L. chuanxiong and found a significant accumulation in the rhizome. By searching transcriptome data from different tissues of L. chuanxiong, we identified four rhizome-specific genes annotated as 2-oxoglutarate-dependent dioxygenase (2-OGDs) that emerged as promising candidates involved in butylphthalide biosynthesis. Among them, LcSAO1 demonstrates the ability to catalyze the desaturation of senkyunolide A at the C-4 and C-5 positions, yielding the production of butylphthalide. Experimental validation through transient expression assays in Nicotiana benthamiana corroborates this transformative enzymatic activity. Notably, phylogenetic analysis of LcSAO1 revealed that it belongs to the DOXB clade, which typically encompasses genes with hydroxylation activity, rather than desaturation. Further structure modelling and site-directed mutagenesis highlighted the critical roles of three amino acid residues, T98, S176, and T178, in substrate binding and enzyme activity. By unraveling the intricacies of the senkyunolide A desaturase, the penultimate step in the butylphthalide biosynthesis cascade, our findings illuminate novel avenues for advancing synthetic biology research in the realm of medicinal natural products.

Network pharmacology and molecular docking-based investigation on traditional Chinese medicine Astragalus membranaceus in oral ulcer treatment.

To analyze the mechanism of Astragalus membranaceus (AM) in molecular level in the oral ulcer (OU) treatment with reference to network pharmacology. Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform database was used in screening the AM active components and AM action targets; GeneCards database was used to screen OU targets; the common target were screened by Venny online tool; Cytoscape software was applied to construct the target gene regulation map of AM active components; STRING database was used to construct the protein-protein interaction network and the key targets were screened as per degree value; gene ontology enrichment and KEGG pathway enrichment of interactive genes were calculated through David database. There were 17 active ingredients and 429 target spots in Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform database. There are 606 target genes for OU in GeneCards database. There are 67 common targets, including 10 key targets: IL10, IL6, TNF, IL1B, CXCL8, CCL2, TLR4, IL4, ICAM1, and IFNG. It involves 30 gene ontology terms and 20 KEGG signal channels. The molecular docking results showed that quercetin and kaempferol had a good binding activity with IL6, IL1B, TNF, and CCL2. Network pharmacological analysis shows that AM can regulate multiple signal pathways through multiple targets to treat OU.

Rhizoma Atractylodis Macrocephalae-Assessing the influence of herbal processing methods and improved effects on functional dyspepsia.

Background: The unique pharmaceutical methods for the processing of botanical drugs according to the theory of traditional Chinese medicine (TCM) affect clinical syndrome differentiation and treatment. The objective of this study was to comprehensively elucidate the principles and mechanisms of an herbal processing method by investigating the alterations in the metabolites of Rhizoma Atractylodis Macrocephalae (AMR) processed by Aurantii Fructus Immaturus (AFI) decoction and to determine how these changes enhance the efficacy of aqueous extracts in treating functional dyspepsia (FD). Methods: A qualitative analysis of AMR before and after processing was conducted using UPLC-Q-TOF-MS/MS, and HPLC was employed for quantitative analysis. A predictive analysis was then conducted using a network analysis strategy to establish a botanical drug-metabolite-target-disease (BMTD) network and a protein-protein interaction (PPI) network, and the predictions were validated using an FD rat model. Results: A total of 127 metabolites were identified in the processed AMR (PAMR), and substantial changes were observed in 8 metabolites of PAMR after processing, as revealed by the quantitative analysis. The enhanced aqueous extracts of processed AMR (PAMR) demonstrate improved efficacy in treating FD, which indicates that this processing method enhances the anti-inflammatory properties and promotes gastric motility by modulating DRD2, SCF, and c-kit. However, this enhancement comes at the cost of attenuating the regulation of motilin (MTL), gastrin (GAS), acetylcholine (Ach), and acetylcholinesterase (AchE). Conclusion: Through this series of investigations, we aimed to unravel the factors influencing the efficacy of this herbal formulation in improving FD in clinical settings.

Multiomics comparison among populations of three plant sources of Amomi Fructus.

Amomi Fructus (Sharen, AF) is a traditional Chinese medicine (TCM) from three source species (or varieties), including Wurfbainia villosa var. villosa (WVV), W. villosa var. xanthioides (WVX), or W. longiligularis (WL). Among them, WVV has been transplanted from its top-geoherb region, Guangdong, to its current main production area, Yunnan, for >50 years in China. However, the genetic and transcriptomic differentiation among multiple AF source species (or varieties) and between the origin and transplanted populations of WVV is unknown. In our study, the observed overall higher expression of terpenoid biosynthesis genes in WVV than in WVX provided possible evidence for the better pharmacological effect of WVV. We also screened six candidate borneol dehydrogenases (BDHs) that potentially catalyzed borneol into camphor in WVV and functionally verified them. Highly expressed genes at the P2 stage of WVV, Wv05G1424 and Wv05G1438, were capable of catalyzing the formation of camphor from (+)-borneol, (-)-borneol and DL-isoborneol. Moreover, the BDH genes may experience independent evolution after acquiring the ancestral copies, and the following tandem duplications might account for the abundant camphor content in WVV. Furthermore, four populations of WVV, WVX, and WL are genetically differentiated, and the gene flow from WVX to WVV in Yunnan contributed to the greater genetic diversity in the introduced population (WVV-JH) than in its top-geoherb region (WVV-YC), which showed the lowest genetic diversity and might undergo genetic degradation. In addition, terpene synthesis (TPS) and BDH genes were selected among populations of multiple AF source species (or varieties) and between the top- and non-top-geoherb regions, which might explain the difference in metabolites between these populations. Our findings provide important guidance for the conservation, genetic improvement, and industrial development of the three source species (or varieties) and for identifying top-geoherbalism with molecular markers, and proper clinical application of AF.

Natural Products-Based Botanical Bactericides Discovery: Novel Abietic Acid Derivatives as Anti-Virulence Agents for Plant Disease Management.

The discovery of natural product-based pesticides is critical for agriculture. In this work, a series of novel tricyclic diterpenoid derivatives decorated with an amino alcohol moiety were elaborately prepared from natural abietic acid, and their antibacterial behavior was explored. Bioassay results indicated that compound C2 exhibited the most promising bioactivity (EC50 = 0.555 µg mL-1) against Xanthomonas oryzae pv. oryzae (Xoo), about 73 times higher than the effect of commercial thiodiazole copper (TC). Results of in vivo bioassays showed that compound C2 displayed significantly higher control of rice bacterial leaf blight (curative activity: 63.8%; protective activity: 58.4%) than TC (curative activity: 43.6%; protective activity: 40.8%), and their bioactivity could be improved maximally 16% by supplementing the auxiliaries. Antibacterial behavior suggested that compound C2 could suppress various virulence factors. Overall, these findings suggested that new botanical bactericide candidates could control intractable plant bacterial diseases by suppressing virulence factors.

KAAACI Allergic Rhinitis Guidelines: Part 2. Update in Non-pharmacological Management.

Allergic rhinitis is the most common chronic disease worldwide. Various upper airway symptoms lower quality of life, and due to the recurrent symptoms, multiple treatments are usually attempted rather than one definitive treatment. There are alternatives to medical (medication-based) and non-medical treatments. A guideline is needed to understand allergic rhinitis and develop an appropriate treatment plan. We have developed guidelines for medical treatment based on previous reports. The current guidelines herein are associated with the "KAAACI Evidence-Based Guidelines for Allergic Rhinitis in Korea, Part 1: Update in pharmacotherapy" in which we aimed to provide evidence-based recommendations for the medical treatment of allergic rhinitis. Part 2 focuses on non-pharmacological management, including allergen-specific immunotherapy, subcutaneous or sublingual immunotherapy, nasal saline irrigation, environmental management strategies, companion animal management, and nasal turbinate surgery. The evidence to support the treatment efficacy, safety, and selection has been systematically reviewed. However, larger controlled studies are needed to elevate the level of evidence to select rational non-medical therapeutic options for patients with allergic rhinitis.

Probiotic intervention benefits multiple neural behaviors in older adults with mild cognitive impairment.

Probiotic supplements were shown to improve cognitive function in Alzheimer's disease (AD) patients. However, it is still unclear whether this applies to older individuals with mild cognitive impairment (MCI). We aimed to explore the effects of probiotic supplementation on multiple neural behaviors in older adults with MCI. Forty-two MCI patients (age > 60 years) were randomly divided into two groups and consumed either probiotics (n=21) or placebo (n=21) for 12 weeks. Various scale scores, gut microbiota measures and serological indicators were recorded pre- and posttreatment. After 12 weeks of intervention, cognitive function and sleep quality were improved in the probiotic group compared with those in the control group, and the underlying mechanisms were associated with changes in the intestinal microbiota. In conclusion, our study demonstrated that probiotic treatment enhanced cognitive function and sleep quality in older MCI patients, thus providing important insights into the clinical prevention and treatment of MCI.

[Impounding Impacts of the Three Gorges Reservoir on Phytoplankton Function Groups and Its Relationship with Resource Use Efficiency].

In order to investigate the relationship between phytoplankton community functional group compositions and resource use efficiency in important tributaries of the Three Gorges Reservoir, phytoplankton and environment parameters were sampled from five tributaries, the Xiangxi River, Daning River, Meixi River, Pengxi River, and Huangjin River, in August and November, 2020. There were 119 species (variants) belonging to 62 genera and 7 phyla identified in summer, whereas 118 species (variants) belonging to 7 divisions of 58 genera were found in winter. According to Padisak's theory, all phytoplankton were divided into 25 functional groups, of which there were six important functional groups in both summer and winter:L0, H1, D, Y, MP, and P in summer and L0, H1, A, M, MP, and Y in winter. The α-diversity of the phytoplankton functional group in summer was higher than that in winter. Moreover, a higher α-diversity was also found in downstream samples relative to that in upstream samples, indicating that the community structure was more complex, and the community stability was relatively better in downstream regions of the rivers. Redundancy analysis (RDA) showed that the environment factors, i.e., ν, pH, permanganate index, WT, and RUETN, significantly affected phytoplankton functional groups (P<0.05). Variance partitioning analysis (VPA) indicated that environmental factors had a higher explanatory degree for the change in functional group composition in summer (45.23%); on the contrary, resource use efficiency had a higher explanatory degree in winter (42.33%). The linear fitted model showed that functional groups L0, H1, D, and Y showed a significant positive correlation relationship with RUETN and RUETP in summer, whereas only four functional groups (M, MP, Y, and A) had a linear relationship with RUETP, and all function groups had a good linear relationship with RUETN in winter. These results indicated that the functional groups belonging to cyanobacteria, dinoflagellates, and cryptophyta were more efficient at using limited resources in summer, whereas the diatoms had a good linear relationship with resource use efficiency and formed a dominant group in the low temperature environment of winter. These results suggest that the impounding of the Three Gorges Reservoir area can significantly change the resource use efficiency of phytoplankton, resulting in changes in the phytoplankton functional group composition and community structure.

The effect of mindfulness-based stress reduction on renal function and quality of life in uremic hemodialysis patients / 中国实用护理杂志

Objective:To construct a mindfulness-based stress reduction (MBSR) intervention program suitable for uremic hemodialysis patients, and analyze the impact of the program on renal function and quality of life in uremic hemodialysis patients.Methods:This was a randomized controlled trial. The convenience sampling method was used to select 92 uremic patients who underwent hemodialysis in the First People's Hospital of Lianyungang City from March 2018 to March 2019. They were divided into routine group (46 cases, routine care) and MBSR group (46 cases, MBSR of face-to-face guidance combined with WeChat platform supervision) by random number table method. Both groups were intervened for 8 weeks. The Chinese version of the European Five-Dimensional Scale (EQ-5D-3L) was used to evaluate the quality of life of the patients, and the quality of life of the two groups before and after the intervention was compared; and the blood creatinine (Scr) and estimated glomerular filtration rate (eGFR), urea nitrogen (BUN), cystatin C (CysC) levels of the two groups before and after the intervention were analyzed.Results:Before the intervention, there was no significant difference in the levels of Scr, eGFR, BUN, and CysC between the two groups ( P>0.05); after 8 weeks of intervention, the levels of Scr, eGFR, BUN, and CysC were (201.81±14.77) μmol/L, (35.30 ± 2.02) ml/min and (11.47 ± 2.66) mmol/L, (2.41 ± 0.28) mg/L in the MBSR group, (218.37 ± 14.90) μmol/L, (33.99 ± 1.95) ml/min, (12.50 ± 0.76) mmol/L, (2.76 ± 0.30) mg/L in the routine group, the differences were statistically significant between the two groups ( t values were 2.53-5.79, all P<0.05). Before the intervention, there was no significant difference in EQ-5D-3L scores between the two groups ( P>0.05); after 8 weeks of intervention, the pain (discomfort), anxiety (depression), Vasual Analogue Scale (VAS) scores were (1.17 ± 0.34), (1.02 ± 0.35), (88.57 ± 20.28) points in the MBSR group, and (1.46 ± 0.63), (1.30 ± 0.32), (62.69 ± 18.79) points in the routine group, the differences were statistically significant between the two groups ( t=2.75, 4.00, 6.35, all P<0.05). Scr level was negatively correlated with self-care, pain (discomfort), anxiety (depression), mobility, daily activity ability, and VAS ( r values were -0.481 - -0.214, all P<0.05); eGFR level was positively correlated with self-care, pain (discomfort), anxiety (depression), mobility, daily activity ability, and VAS ( r values were 0.199-0.492, all P<0.05). But BUN and CysC levels were not correlated with EQ-5D-3L score (all P>0.05). Conclusions:MBSR can effectively improve the renal function and quality of life of uremic hemodialysis patients, and it is worthy of clinical application.

Transcriptome analysis of sweet potato responses to potassium deficiency.

BACKGROUND: As one of three essential nutrients, potassium is regarded as a main limiting factor for growth and development in plant. Sweet potato (Ipomoea batatas L.) is one of seven major food crops grown worldwide, and is both a nutrient-rich food and a bioenergy crop. It is a typical 'K-favoring' crop, and the level of potassium ion (K+) supplementation directly influences its production. However, little is known about the transcriptional changes in sweet potato genes under low-K+ conditions. Here, we analyzed the transcriptomic profiles of sweet potato roots in response to K+ deficiency to determine the effect of low-K+ stress on this economically important crop. RESULTS: The roots of sweet potato seedlings with or without K+ treatment were harvested and used for transcriptome analyses. The results showed 559 differently expressed genes (DEGs) in low and high K+ groups. Among the DEGs, 336 were upregulated and 223 were downregulated. These DEGs were involved in transcriptional regulation, calcium binding, redox-signaling, biosynthesis, transport, and metabolic process. Further analysis revealed previously unknow genes involved in low-K+ stress, which could be investigated further to improve low K+ tolerance in plants. Confirmation of RNA-sequencing results using qRT-PCR displayed a high level of consistency between the two experiments. Analysis showed that many auxin-, ethylene- and jasmonic acid-related genes respond to K+ deficiency, suggesting that these hormones have important roles in K+ nutrient signaling in sweet potato. CONCLUSIONS: According to the transcriptome data of sweet potato, various DEGs showed transcriptional changes in response to low-K+ stress. However, the expression level of some kinases, transporters, transcription factors (TFs), hormone-related genes, and plant defense-related genes changed significantly, suggesting that they have important roles during K+ deficiency. Thus, this study identifies potential genes for genetic improvement of responses to low-K+ stress and provides valuable insight into the molecular mechanisms regulating low K+ tolerance in sweet potato. Further research is required to clarify the function of these DEGs under low-K+ stress.

Xiongshao Zhitong Recipe Attenuates Nitroglycerin-Induced Migraine-Like Behaviors via the Inhibition of Inflammation Mediated by Nitric Oxide Synthase.

Migraine is a major cause of disability worldwide, particularly in young adults and middle-aged women. Xiongshao Zhitong Recipe (XZR) is a traditional Chinese medicine prescription used for treating migraine, but its bioactive components and therapeutic mechanisms remain unclear. We aimed to confirm the therapeutic effect of XZR on migraine and to determine the possible mechanism and bioactive components of XZR. Here, a sensitive UHPLC-LTQ-Orbitrap MS assay was carried out to analyze the ingredients of XZR, and a total of 62 components were identified, including coumarins, phenolic acids, phthalides, flavonoids, and terpenoids; among them, 15 components were identified in the serum samples after XZR treatment. We established a rat model of migraine via nitroglycerin (NTG) injection. The in vivo experiments demonstrated that XZR attenuated allodynia and photophobia in rats with NTG-induced migraine, and XZR also demonstrated analgesic effects. XZR reversed the abnormal levels of nitric oxide, 5-hydroxytryptamine (5-HT), calcitonin gene-related peptide (CGRP), and substance P (SP) to normal levels. XZR also downregulated inflammatory reactions, including mast cell degranulation and serum IL-1ß, IL-6, and TNF-α levels. In terms of mechanism, we revealed that XZR treated NTG-induced migraine through the inhibition of neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS) expression in both the trigeminal nucleus caudalis (TNC) and periaqueductal gray matter (PAG), as well as the total NOS enzyme activity, which regulated the NF-κB signaling pathway. Additionally, imperatorin and xanthotoxin, two major ingredients of XZR, showed a high binding affinity to nNOS (Gly468-Leu616). In vitro, XZR, imperatorin, and xanthotoxin inhibited the nNOS expression and the NF-κB signaling pathway in lipopolysaccharide (LPS)-stimulated PC12 cells. In conclusion, we demonstrated the therapeutic effects of XZR and provided evidence that XZR played a critical anti-inflammatory role by suppressing NOS and NF-κB signaling pathway activation. Imperatorin and xanthotoxin were potential bioactive components of XZR. The findings from this study supported that XZR was a candidate herbal drug for migraine therapy.

Andrographolide suppresses breast cancer progression by modulating tumor-associated macrophage polarization through the Wnt/ß-catenin pathway.

Andrographolide(ADE) has been demonstrated to inhibit tumor growth through direct cytotoxicity on tumor cells. However, its potential activity on tumor microenvironment (TME) remains unclear. Tumor-associated macrophages (TAMs), composed mainly of M2 macrophages, are the key cells that create an immunosuppressive TME by secretion of cytokines, thus enhancing tumor progression. Re-polarized subpopulations of macrophages may represent vital new therapeutic alternatives. Our previous studies showed that ADE possessed anti-metastasis and anoikis-sensitization effects. Here, we demonstrated that ADE significantly suppressed M2-like polarization and enhanced M1-like polarization of macrophages. Moreover, ADE inhibited the migration of M2 and tube formation in HUVECs under M2 stimulation. In vivo studies showed that ADE restrained the growth of MDA-MB-231 and HCC1806 human breast tumor xenografts and 4T-1 mammary gland tumors through TAMs. Wnt5a/ß-catenin pathway and MMPs were particularly associated with ADE's regulatory mechanisms to M2 according to RNA-seq and bioinformatics analysis. Moreover， western blot also verified the expressions of these proteins were declined with ADE exposure. Among the cytokines released by M2, PDGF-AA and CCL2 were reduced. Our current findings for the first time elucidated that ADE could modulate macrophage polarization and function through Wnt5a signaling pathway, thereby playing its role in inhibition of triple-negative breast cancer.

Temporal heterogeneity of bacterial communities and their responses to Raphidiopsis raciborskii blooms.

To elucidate the interspecies connectivity between cyanobacteria and other bacteria (noncyanobacteria), microbial diversity and composition were investigated through high-throughput sequencing (HTS) in a drinking water reservoir in Chongqing city, Southwest China, during Raphidiopsis raciborskii blooms. Significant temporal changes were observed in microbial community composition during the sampling period, primarily reflected by variations in relative bacterial abundance. The modularity analysis of the network demonstrated that the bacterial community forms co-occurrence/exclusion patterns in response to variations in environmental factors. Moreover, five modules involved in the dynamic phases of the R. raciborskii bloom were categorized into the Pre-Bloom, Bloom, Post-Bloom, and Non-Bloom Groups. The reservoir was eutrophic (i.e., the average concentrations of total nitrogen (TN) and total phosphorus (TP) were 2.32 and 0.07 mg L-1, respectively) during the investigation; however, Pearson's correlation coefficient showed that R. raciborskii was not significantly correlated with nitrogen and phosphorus. However, other environmental factors, such as water temperature, pH, and the permanganate index, were positively correlated with R. raciborskii. Importantly, Proteobacteria (α-, γ-Proteobacteria), Acidobacteria, Chloroflexi, and Firmicutes were preferentially associated with increased R. raciborskii blooms. These results suggested that the transition of R. raciborskii bloom-related microbial modules and their keystone species could be crucial in the development and collapse of R. raciborskii blooms and could provide a fundamental basis for understanding the linkage between the structure and function of the microbial community during bloom dynamics.

Yinchenhao Decoction ameliorates the high-carbohydrate diet induced suppression of immune response in largemouth bass (Micropterus salmoides).

Yinchenhao Decoction (YD), a Chinese herbal medicine, has been traditionally used for treatment of metabolic liver diseases. A 10-week feeding trail was carried out to examine the effects of YD supplementation in a high carbohydrate diet (HCD) on liver histopathology, immune response, disease resistance, and expression of genes associated with endoplasmic reticulum stress, autophagy, apoptosis, necroptosis and inflammation in juvenile largemouth. A diet containing 9% carbohydrate was used as a low carbohydrate diet (LCD), and a HCD was formulated to contain 18% carbohydrate and supplemented with 0, 0.5, 1, 2 or 4% YD (HCD, HCD+0.5YD, HCD+1YD, HCD+2YD and HCD+4YD). Triplicate groups of fish (5.6 ± 0.2 g) were feed the test diets to visual satiety for 10 weeks. The highest survival rate after Nocardia seriolae challenge was recorded for the HCD+4YD group. YD application led to reduced ACP, AKP, AST and ALT activities. HCD-induced cells swelling, ruptured cell membrane, migrated nuclei and increasing inflammatory cells in hepatocytes were mitigated by YD addition. Moreover, YD decreased the expressions of pro-inflammation genes (TNF-α, IL-1ß, IL-8, hepcidin1, NF-κB, COX2, CD80 and CD83) and increased the mRNA levels of anti-inflammation genes (IL-10 and IKBα). The mode of liver cell death was preferably changed to programed apoptosis rather than uncontrolled necroptosis by application of YD in HCD. Furthermore, the expression of UPR genes (IRE1, Eif2α, ATF6, XBP1 and GRP78/Bip) and autophagy genes (LC3-2, BNIP3 and P62) was increased by YD supplementation. In summary, our results demonstrated that YD addition in HCD enhances UPR, autophagy and programed apoptosis maintaining the homeostasis, and decreases uncontrolled necroptosis and inflammation, ultimately leading to improved immune response in largemouth bass.