Radix Bupleuri aqueous extract attenuates MK801-induced schizophrenia-like symptoms in mice: Participation of intestinal flora.

Schizophrenia (SCZ) is a psychotic mental disorder characterized by cognitive, behavioral, and social impairments. However, current pharmacological treatment regimens are subpar in terms of effectiveness. This study aimed to investigate the function of Radix Bupleuri aqueous extract in SCZ in mouse models. The SCZ mouse model was established by MK-801 injection and feeding of Radix Bupleuri aqueous extract or combined antibiotics. Radix Bupleuri aqueous extract significantly improved the aberrant behaviors and neuronal damage in SCZ mice, upregulated SYP and PSD-95 expression and BDNF levels in hippocampal homogenates, down-regulated DA and 5-HT levels, and suppressed microglial activation in SCZ mice. Moreover, Radix Bupleuri aqueous extract improved the integrity of the intestinal tract barrier. The 16 S rRNA sequencing of feces showed that Radix Bupleuri extract modulated the composition of gut flora. Lactobacillus abundance was decreased in SCZ mice and reversed by Radix Bupleuri aqueous extract administration which exhibited a significant negative correlation with IL-6, IL-1ß, DA, and 5-HT, and a significant positive correlation with BDNF levels in hippocampal tissues. The abundance of Parabacteroides and Alloprevotella was increased in SCZ mice. It was reversed by Radix Bupleuri aqueous extract administration, which exhibited a positive correlation with IL-6, IL-1ß, and 5-HT and a negative correlation with BDNF. In conclusion, Radix Bupleuri aqueous extract attenuates the inflammatory response in hippocampal tissues and modulates neurotransmitter levels, exerting its neuroprotective effect in SCZ. Meanwhile, the alteration of intestinal flora may be involved in this process, which is expected to be an underlying therapeutic option in treating SCZ.

The water extract of Amydrium sinense (Engl.) H. Li ameliorates Isoproterenol-induced cardiac hypertrophy through inhibiting the NF-κB signaling pathway.

OBJECTIVE: Pathologic cardiac hypertrophy (PCH) is a precursor to heart failure. Amydrium sinense (Engl.) H. Li (AS), a traditional Chinese medicinal plant, has been extensively utilized to treat chronic inflammatory diseases. However, the therapeutic effect of ASWE on PCH and its underlying mechanisms are still not fully understood. METHODS: A cardiac hypertrophy model was established by treating C57BL/6 J mice and neonatal rat cardiomyocytes (NRCMs) in vitro with isoprenaline (ISO) in this study. The antihypertrophic effects of AS water extract (ASWE) on cardiac function, histopathologic manifestations, cell surface area and expression levels of hypertrophic biomarkers were examined. Subsequently, the impact of ASWE on inflammatory factors, p65 nuclear translocation and NF-κB activation was investigated to elucidate the underlying mechanisms. RESULTS: In the present study, we observed that oral administration of ASWE effectively improved ISO-induced cardiac hypertrophy in mice, as evidenced by histopathological manifestations and the expression levels of hypertrophic markers. Furthermore, the in vitro experiments demonstrated that ASWE treatment inhibited cardiac hypertrophy and suppressed inflammation response in ISO-treated NRCMs. Mechanically, our findings provided evidence that ASWE suppressed inflammation response by repressing p65 nuclear translocation and NF-κB activation. ASWE was found to possess the capability of inhibiting inflammation response and cardiac hypertrophy induced by ISO. CONCLUSION: To sum up, ASWE treatment was shown to attenuate ISO-induced cardiac hypertrophy by inhibiting cardiac inflammation via preventing the activation of the NF-kB signaling pathway. These findings provided scientific evidence for the development of ASWE as a novel therapeutic drug for PCH treatment.

Sesamin-mediated high expression of BECN2 ameliorates cartilage endplate degeneration by reducing autophagy and inflammation.

Lumbar disc degeneration (LDD) is a prevalent clinical spinal disease characterized by the calcification and degeneration of the cartilage endplate (CEP), which significantly reduces nutrient supply to the intervertebral disc. Traditional Chinese medicine offers a conservative and effective approach for treating LDD. We aimed to investigate the molecular mechanisms underlying the therapeutic effects of Sesamin in LDD treatment. Transcriptome sequencing was used to analyze the effect of Sesamin on LPS-induced ATDC5. We explored the role of BECN2, a target gene of Sesamin, in attenuating LPS-induced degeneration of ATDC5 cells. Our results revealed the identification of 117 differentially expressed genes (DEGs), with 54 up-regulated and 63 down-regulated genes. Notably, Sesamin significantly increased the expression of BECN2 in LPS-induced ATDC5 cell degeneration. Overexpressed BECN2 enhanced cell viability and inhibited cell apoptosis in LPS-induced ATDC5 cells, while BECN2 knockdown reduced cell viability and increased apoptosis. Furthermore, BECN2 played a crucial role in attenuating chondrocyte degeneration by modulating autophagy and inflammation. Specifically, BECN2 suppressed autophagy by reducing the expression of ATG14, VPS34, and GASP1, and alleviated the inflammatory response by decreasing the expression of inflammasome proteins NLRP3, NLRC4, NLRP1, and AIM2. In vivo experiments further supported the beneficial effects of Sesamin in mitigating LDD. This study provides novel insights into the potential molecular mechanism of Sesamin in treating LDD, highlighting its ability to mediate autophagy and inflammation inhibition via targeting the BECN2. This study provides a new therapeutic strategy for the treatment of LDD, as well as a potential molecular target for LDD.

The Role of Dietary Ingredients in Mental Energy - A Scoping Review of Randomized Controlled Trials.

Low mental energy can contribute to decreased productivity, altered life balance, decreased physical performance, and ultimately affect quality of life. As such, there is a great demand for food and beverage products that positively impact mental energy. Numerous products claim to alter mental energy making continued review of the scientific evidence critical. The objective of this study was to conduct a scoping review of randomized controlled trials to evaluate the effect of 18 dietary ingredients on mental energy outcomes in adults without severe disease. Methods: A literature search, completed using PubMed, resulted in the identification of 2261 articles, 190 of which met eligibility from initial abstract review. Full-text review was completed on the 190 studies which resulted in 101 articles that fully met eligibility for inclusion in this study. The search strategy for two ingredients did not yield any eligible studies, leaving studies for 16 ingredients that were extracted and summarized by reported significantly improved outcomes for cognition, mood and perceived feelings, and sleep assessments. The preliminary results for several dietary ingredients directionally suggested a mental energy benefit (≥20% of outcomes), including ashwagandha, chamomile, dark chocolate, ginseng, green tea, lavender, lion's mane mushroom, maca, tart cherries, turmeric, and valerian root. The results of this scoping review suggest that of the 16 dietary ingredients reviewed, 11 may be promising for further exploration on their potential benefits in supporting mental energy. Given consumer demand and market growth for food and beverage products that positively impact mental energy; continued efforts in assessment method alignment and additional evaluation in well-designed trials is warranted.KEY TEACHING POINTSOf the 16 dietary ingredients reviewed, 11 (ashwagandha, chamomile, dark chocolate, ginseng, green tea, lavender, lion's mane mushroom, maca, melatonin foods, turmeric, and valerian root) may be promising for further exploration on their potential mental energy benefits.Dark chocolate, ginseng, ashwagandha, and lion's mane mushroom were the most promising ingredients for further evaluation in the cognition domain of the ingredients evaluated.Turmeric, maca, lavendar, and ashwagandha were the most promising ingredients for further evaluation in the mood and perceived feelings domain of the ingredients evaluated.Ashwagandha, chamomile, green tea, melatonin foods, valerian root were the most promising ingredients for further evaluation in the sleep domain of the ingredients evaluated.Additional, well-designed, consistent, clinical trials and systematic reviews are warranted as the challenge of heterogeneity in mental energy study design remains.

Microbial controls over soil priming effects under chronic nitrogen and phosphorus additions in subtropical forests.

The soil priming effect (PE), defined as the modification of soil organic matter decomposition by labile carbon (C) inputs, is known to influence C storage in terrestrial ecosystems. However, how chronic nutrient addition, particularly in leguminous and non-leguminous forests, will affect PE through interaction with nutrient (e.g., nitrogen and phosphorus) availability is still unclear. Therefore, we collected soils from leguminous and non-leguminous subtropical plantations across a suite of historical nutrient addition regimes. We added 13C-labeled glucose to investigate how background soil nutrient conditions and microbial communities affect priming and its potential microbial mechanisms. Glucose addition increased soil organic matter decomposition and prompted positive priming in all soils, regardless of dominant overstory tree species or fertilizer treatment. In non-leguminous soil, only combined nitrogen and phosphorus addition led to a higher positive priming than the control. Conversely, soils beneath N-fixing leguminous plants responded positively to P addition alone, as well as to joint NP addition compared to control. Using DNA stable-isotope probing, high-throughput quantitative PCR, enzyme assays and microbial C substrate utilization, we found that positive PE was associated with increased microbial C utilization, accompanied by an increase in microbial community activity, nutrient-related gene abundance, and enzyme activities. Our findings suggest that the balance between soil available N and P effects on the PE,  was dependent on rhizosphere microbial community composition. Furthermore, these findings highlight the roles of the interaction between plants and their symbiotic microbial communities in affecting soil priming and improve our understanding of the potential microbial pathways underlying soil PEs.

China's application of the One Health approach in addressing public health threats at the human-animal-environment interface: Advances and challenges.

Background: Due to emerging issues such as global climate change and zoonotic disease pandemics, the One Health approach has gained more attention since the turn of the 21st century. Although One Health thinking has deep roots and early applications in Chinese history, significant gaps exist in China's real-world implementation at the complex interface of the human-animal-environment. Methods: We abstracted the data from the global One Health index study and analysed China's performance in selected fields based on Structure-Process-Outcome model. By comparing China to the Belt & Road and G20 countries, the advances and gaps in China's One Health performance were determined and analysed. Findings: For the selected scientific fields, China generally performs better in ensuring food security and controlling antimicrobial resistance and worse in addressing climate change. Based on the SPO model, the "structure" indicators have the highest proportion (80.00%) of high ranking and the "outcome" indicators have the highest proportion (20.00%) of low ranking. When compared with Belt and Road countries, China scores above the median in almost all indicators (16 out of 18) under the selected scientific fields. When compared with G20 countries, China ranks highest in food security (scores 72.56 and ranks 6th), and lowest in climate change (48.74, 11th). Conclusion: Our results indicate that while China has made significant efforts to enhance the application of the One Health approach in national policies, it still faces challenges in translating policies into practical measures. It is recommended that a holistic One Health action framework be established for China in accordance with diverse social and cultural contexts, with a particular emphasis on overcoming data barriers and mobilizing stakeholders both domestically and globally. Implementation mechanisms, with clarified stakeholder responsibilities and incentives, should be improved along with top-level design.

RNF216 affects the stability of STAU2 in the hypothalamus.

Idiopathic hypogonadotropic hypogonadism (IHH) is a rare disease characterized by gonadal failure due to deficiency in gonadotropin-releasing hormone (GnRH) synthesis, secretion, or action. RNF216 variants have been recently identified in patients with IHH. Ring finger protein 216 (RNF216), as a ubiquitin E3 ligase, catalyzes the ubiquitination of target proteins with high specificity, which consequently modulates the stability, localization, and interaction of the target protein. In this study, we found that RNF216 interacted with Staufen2 (STAU2) and affected the stability of STAU2 through the ubiquitin-proteasome pathway. STAU2, as a double-stranded RNA-binding protein enriched in the nervous system, plays a role in RNA transport, RNA stability, translation, anchoring, and synaptic plasticity. Further, we revealed that STAU2 levels in the hypothalamus of RNF216-/- mice were increased compared with wild-type (WT) mice. The change in STAU2 protein homeostasis may affect a series of RNA cargoes. Therefore, we analyzed the changes in RNA levels in the hypothalamus of RNF216-/- mice and WT mice by RNA sequencing. We found that deletion of RNF216 led to decreased activities of the prolactin signaling pathway, neuroactive ligand-receptor interaction, GnRH signaling pathway, and ovarian steroidogenesis. The weakening of these signal pathways is likely to affect the secretion of GnRH, thereby affecting the development of gonads. Therefore, our study suggests that STAU2 may be a potential therapeutic target for IHH. Further experiments are needed to demonstrate the association between the weakening of these signaling pathways and the RNA-binding protein STAU2.

Magnesium Ascorbyl Phosphate Promotes Bone Formation Via CaMKII Signaling.

Dysregulation of bone homeostasis is closely related to the pathogenesis of osteoporosis. Suppressing bone resorption by osteoclasts to attenuate bone loss has been widely investigated, but far less effort has been poured toward promoting bone formation by osteoblasts. Here, we aimed to explore magnesium ascorbyl phosphate (MAP), a hydrophilic and stable ascorbic acid derivative, as a potential treatment option for bone loss disorder by boosting osteoblastogenesis and bone formation. We found that MAP could promote the proliferation and osteoblastic differentiation of human skeletal stem and progenitor cells (SSPCs) in vitro. Moreover, MAP supplementation by gavage could alleviate bone loss and accelerate bone defect healing through promoting bone formation. Mechanistically, we identified calcium/calmodulin-dependent serine/threonine kinase IIα (CaMKIIα) as the target of MAP, which was found to be directly bound and activated by MAP, then with a concomitant activation in the phosphorylation of ERK1/2 (extracellular regulated kinase 1/2) and CREB (cAMP-response element binding protein) as well as an elevation of C-FOS expression. Further, blocking CaMKII signaling notably abolished these effects of MAP on SSPCs and bone remodeling. Taken together, our data indicated that MAP played an important role in enhancing bone formation through the activation of CaMKII/ERK1/2/CREB/C-FOS signaling pathway and may be used as a novel therapeutic option for bone loss disorders such as osteoporosis. © 2023 American Society for Bone and Mineral Research (ASBMR).

Mechanism of electroacupuncture at acupoints of the lung meridian through PKA/PKC regulation of TRPV1 in chronic cough after lung surgery in guinea pigs.

Background: Acupuncture has achieved good results in the treatment of cough, asthma, chronic obstructive pulmonary disease (COPD) and other lung diseases, but the mechanism associated with acupuncture in the treatment of chronic cough induced by lung surgery is unknown. We investigated whether acupuncture therapy could improve the symptoms of chronic cough after lung surgery through cyclic-AMp dependent protein kinase A (PKA)/cyclic-AMp dependent protein kinase C (PKC) regulation of the transient receptor potential vanilloid-1 (TRPV1) signaling pathway. Methods: The guinea pigs were divided into 5 groups: the Sham operation Group (Sham), the Model Group (Model), the Electroacupuncture + Model Group (EA + M), the H89 + Model Group (H89 + M) and the Go6983 + Model Group (Go6983 + M). The effect of treatment was determined by measuring cough symptoms (number of coughs/cough incubation period) as the outcome criterion. The levels of inflammatory cytokines in bronchoalveolar lavage fluid (BALF) and blood were determined by enzyme-linked immunosorbent assays (ELISA). Lung tissue was stained with hematoxylin and eosin (H&E). The expression of p-PKA, p-PKC and p-TRPV1 proteins was measured by Western blotting. The mRNA levels of TRPV1, Substance P (SP), calcitonin gene-related peptide (CGRP) and neurokinin-1R (NK1R) were measured by real-time polymerase chain reaction (RT-PCR). Results: Acupuncture significantly reduced the cough frequency and prolonged the cough latency of chronic cough in guinea pigs after lung surgery. In addition, acupuncture reduced the damage to lung tissue. The levels of inflammatory cytokines decreased in all treatment groups, the expression levels of p-PKA, p-PKC and p-TRPV1 were significantly inhibited and the mRNA levels of TRPV1, SP, CGRP and NK1R decreased significantly after acupuncture treatment. Conclusions: Acupuncture therapy ameliorated chronic cough in guinea pigs after lung surgery by regulating the TRPV1 signaling pathway via PKA/PKC. Our results showed that acupuncture may be an effective treatment of chronic cough after lung surgery, and also clarified the potential mechanism, which provides a theoretical basis for the clinical treatment of patients with chronic cough after lung surgery.

Mechanism exploration of 6-Gingerol in the treatment of atherosclerosis based on network pharmacology, molecular docking and experimental validation.

BACKGROUND: The 6-Gingerol has significant anti-inflammatory, anti-oxidative and hypolipidemic activities and is widely used for treating cardiac-cerebral vascular diseases. However, the multi-target mechanism of 6-Gingerol in the treatment of atherosclerosis remains to be elucidated. METHODS: Firstly, the therapeutic actions of 6-Gingerol anti-atherosclerosis were researched based on an atherosclerotic ApoE-deficient mice model induced by high-fat feed. Then, network pharmacology and molecular docking were employed to reveal the anti-atherogenic mechanism of 6-Gingerol. Finally, the target for these predictions was validated by target protein expression assay in vitro and in vivo experiments and further correlation analysis. RESULTS: Firstly, 6-Gingerol possessed obvious anti-atherogenic activity, which was manifested by a significant reduction in the plaque area, decrease in the atherosclerosis index and vulnerability index. Secondly, based on network pharmacology, 14 predicted intersection target genes between the targets of 6-Gingerol and atherogenic-related targets were identified. The key core targets of 6-Gingerol anti-atherosclerosis were found to be TP53, RELA, BAX, BCL2, and CASP3. Lipid and atherosclerosis pathways might play a critical role in 6-Gingerol anti-atherosclerosis. Molecular docking results also further revealed that the 6-Gingerol bound well and stable to key core targets from network pharmacological predictions. Then, the experimental results in vivo and in vitro verified that the up-regulation of TP53, RELA, BAX, CASP3, and down-regulation of BCL2 from atherosclerotic ApoE-deficient mice model can be improved by 6-Gingerol intervention. Meanwhile, the correlation analysis further confirmed that 6-Gingerol anti-atherosclerosis was closely related to these targets. CONCLUSION: The 6-Gingerol can markedly improve atherosclerosis by modulating key multi-targets TP53, RELA, BAX, CASP3, and BCL2 in lipid and atherosclerosis pathways. These novel findings shed light on the anti-atherosclerosis mechanism of 6-Gingerol from the perspective of multiple targets and pathways.

Effects of dietary iron sources on growth performance, iron status, Fe-containing enzyme activity and gene expression related to iron homeostasis in tissues of weaned pigs.

The aim of this study is to evaluate the effects of dietary iron sources on growth performance, iron status and activities of Fe-containing enzymes and gene expression related to iron homeostasis in tissues of weaned pigs. A total of 480 piglets at d 28 (Duroc X Landrace) were allotted to four groups as a factorial arrangement of treatments with 30 pigs/pen (male: female = 1:1) and 4 replicate pens/treatment. The treatments for iron in the diets were: control basal diet (Con); Con + 150 mg Fe/kg as inorganic Fe (iFe); Con + 75 mg Fe/kg as inorganic Fe + 75 mg Fe/kg as organic Fe-peptide complex (iFe+oFe) and Con + 150 mg of Fe/kg as organic Fe-peptide complex (oFe). The feeding trial lasted for 36 days. There were no significant differences in final body weight, ADG, ADFI, and G/F as well as blood hemoglobin and MCHC contents between piglets fed the control and iron-supplemented groups (P > 0.05). The iron supplemented groups exhibited increased iron content in the liver, kidney and spleen as well as the CAT and SDH activities in liver compared to the control group (P < 0.05), while piglets in oFe group experienced greater Fe accumulation and activities of CAT and SDH in the liver than piglets in the iFe group. Compared with the control group, dietary supplementation of iron increased the NCOA4 mRNA expression and decreased the TfR1 mRNA expression in liver of piglets. The TfR1, NCOA4 and Ferritin mRNA expressions of bone marrow in both iFe and iFe+oFe groups were greater than both in the Con and oFe groups. These results suggest that dietary supplementation of iron does not influence the growth performance and hematological parameters in weaned pigs fed a corn-soybean meal basal diet (75.8 mg/kg) from d 28 to d 70, but increased tissue iron status and activities of Fe-containing enzymes at d 70. The addition of organic Fe-peptide complexes presents greater beneficial effects on enhancing tissue Fe accumulation and Fe-containing enzyme activities, which may be involved in different gene expression patterns related to iron intake and transport in tissues of weaned pigs.

Compound shougong powder inhibits the malignant phenotype of hepatocellular carcinoma cells by targeting the DNA damage repair pathway.

OBJECTIVES: Compound Shougong Powder (SGS), a traditional Chinese medicine formulation, has been used to treat cancer for many years with remarkable efficacy. However, the mechanisms underlying the therapeutic effect of SGS in Hepatocellular carcinoma (HCC) are not completely clear. METHODS: The survival and metastasis of HCC cells were examined by CCK-8 assay, EdU assay, Wound-healing and Transwell assay. The anti-tumour effect of SGS was studied using hoechst 33258 staining and flow cytometry. RNA sequencing was applied to detect the underlying mechanism. Comet DNA, qRT-PCR and WB experiments were performed for validation. In addition, HCC nude mouse model was constructed to detect SGS effect in vivo. KEY FINDINGS: SGS inhibited the proliferation, migration and invasion of HCC cells and induced apoptosis in vitro. In addition, SGS also suppressed tumour growth in a nude mouse model of HCC in a dose-dependent manner. RNA sequencing of the suitably treated HCC cells revealed significant changes in the expression levels of genes involved in the DNA damage repair pathway. The sequencing results were verified by Comet DNA, qRT-PCR, WB assays and molecular docking. CONCLUSIONS: Taken together, SGS inhibits the malignant phenotype of HCC cells by down-regulating DNA repair genes and consequently inducing DNA damage.

[Methodology and application of process analytical technology (PAT) for traditional Chinese medicine manufacturing:a review].

Owing to the advancement in pharmaceutical technology, traditional Chinese medicine industry has seen rapid development. Preferring conventional manufacturing mode, pharmaceutical enterprises of traditional Chinese medicine have no effective process detection tools and process control methods. As a result, the quality of the final products mainly depends on testing and the quality is inconsistent in the same batch. Process analytical technology(PAT) for traditional Chinese medicine manufacturing, as one of the key advanced manufacturing techniques, can break through the bottleneck in quality control of medicine manufacturing, thus improving the production efficiency and product quality and reducing the material and energy consumption. It is applicable to the process control and real-time release of advanced manufacturing modes such as intelligent manufacturing and continuous manufacturing. This paper summarized the general idea of PAT for traditional Chinese medicine manufacturing. Through the analysis of the characteristics and status quo of the technology, we summed up the methodology for the continuous application and improvement of PAT during the whole life-cycle of traditional Chinese medicine. The five key procedures(process understanding, process detection, process modeling, process control, and continuous improvement) were summarized, and the application was reviewed. Finally, we proposed suggestions for the technical and regulatory challenges in implementing PAT in traditional Chinese medicine industry. This paper aims to provide a reference for development and application of PAT in advanced manufacturing, intelligent manufacturing, and continuous manufacturing of traditional Chinese medicine industry.

Qingchang Mixture Prevents the Intestinal Ischemia-reperfusion Injury through TLR4/NF-kB Pathway.

OBJECT: This study aims to determine the protective effect and molecular responses of the traditional Chinese medicine Qingchang mixture on intestinal ischemia-reperfusion (IR) injury. METHODS: The rat intestinal IR model was prepared. The intestinal ischemic injury was evaluated by HE staining, biochemical assay and western blot. In addition, a human hypoxia-reoxygenation (HR) in vitro model was prepared using intestinal epithelial cells (IEC-6). The viability and apoptosis of IEC-6 cells were measured by CCK8 and apoptosis detection. TAK242 or PDTC was used as a small molecule inhibitor of TLR4 or NF-κB, respectively. RESULTS: Compared with the IR group, the pretreatment of the Qingchang mixture reduced the morphological damage, oxidative stress, inflammatory response, and barrier function damage of the small intestine tissue. IR significantly increased the expression of TLR4 and NF-κB, while the pretreatment of the Qingchang mixture inhibited the expression of TLR4 and NF-κB. Furthermore, the pretreatment of Qingchang mixture, TAK242, or PDTC effectively improved the viability and hindered apoptosis of the HR-induced IEC-6 cells. CONCLUSIONS: Traditional Chinese medicine Qingchang mixture prevents intestinal IR injury through TLR4/NF-kB pathway.

Rhubarb Peony Decoction Downregulates the Expression of c-Fos after Intestinal Epithelial Cells Hypoxia-reoxygenation Injury.

BACKGROUND: Intestinal ischemia-reperfusion (I/R) injury occurs in several clinical situations and after intestinal transplantation. This study aimed to examine the role of rhubarb peony decoction (RPD) in intestinal I/R injury. METHODS: Different concentrations of RPD were set to treat IEC-6 and Caco-2 cells. Cell proliferation and apoptosis were measured by CCK-8 and flow cytometry assays. High-throughput transcriptome sequencing was performed on IEC-6 cells treated with hypoxia-reoxygenation (HR) or HR and RPD. RESULTS: RPD treatment significantly promoted the proliferation of IEC-6 and Caco-2 cells and inhibited apoptosis. Sequencing results identified 109 significantly up-regulated genes and 36 significantly down-regulated genes in the RPD group. In addition, the results of western blot suggested that HR induced the expression of c-Fos, and the treatment of RPD prevented the HR-induced c- Fos expression. Importantly, knockdown of c-Fos rescued the HR-inhibited cell proliferation and HR-induced apoptosis. CONCLUSIONS: In conclusion, RPD was beneficial in protecting the survival of intestinal epithelial cells under HR stress. Furthermore, the increase in c-Fos expression after HR stress was closely related to the proliferation and apoptosis of intestinal epithelial cells.

Arteannuin B Enhances the Effectiveness of Cisplatin in Non-Small Cell Lung Cancer by Regulating Connexin 43 and MAPK Pathway.

Cisplatin (DDP)-based chemotherapy is the first-line regimen for advanced non-small cell lung cancer (NSCLC) patients. However, advanced NSCLC patients may have innate resistance to DDP or develop resistance during DDP treatment. We investigated a natural compound, arteannuin B (Art B), for its potential effects on DDP resistance in NSCLC. Art B was isolated from Artemisia annua by chromatographic purification and spectral elucidation. The activities of Art B on DDP-mediated effects were examined using in vitro and in vivo assays. We observed significant correlations in T stage, clinical stage, chemotherapy resistance and poor survival of NSCLC patients with low Cx43 expression. Art B enhanced the effectiveness of cisplatin by increasing Cx43 expression in normal and DDP-resistant NSCLC cells. Art B also increased DDP uptake through up-regulating Cx43. The combination of DDP and Art B showed better therapeutic effect than individual treatments both in vitro and in vivo. Art B increased intracellular Fe[Formula: see text] level, promoted calcium influx, and activated gap junction and MAPK pathways, which might contribute to Art B-mediated effects. Art B may serve as a new drug candidate to enhance the antitumor effect of DDP on NSCLC.

METTL3 antagonizes 5­FU chemotherapy and confers drug resistance in colorectal carcinoma.

Colorectal cancer (CRC) is one of top five leading causes of cancer­associated mortalities worldwide. 5­Fluorouracil (5­FU) is the first­line chemotherapeutic drug in the treatment of CRC; however, its antineoplastic efficiency is limited due to acquired drug resistance. The regulatory mechanism underlying 5­FU chemotherapeutic response and drug resistance in CRC remains largely unknown. The present study identified that silencing of methyltransferase­like 3 (METTL3) suppressed the proliferation and migration of CRC HCT­8 cells. Using cell survival assays, flow cytometric and colony formation analyses, it was revealed that inhibition of METTL3 sensitized HCT­8 cells to 5­FU by enhancing DNA damage and inducing apoptosis in HCT­8 cells under 5­FU treatment. Furthermore, the expression of METTL3 was upregulated in 5­FU­resistant CRC cells (HCT­8R), which contributed to drug resistance through regulation of RAD51 associated Protein 1 (RAD51AP1) expression. Western blotting, immunofluorescence staining and drug sensitivity assays demonstrated that knockdown of METTL3 augmented 5­FU­induced DNA damage and overcame 5­FU­resistance in HCT­8R cells, which could be mimicked by inhibition of RAD51AP1. The present study revealed that the METTL3/RAD51AP1 axis plays an important role in the acquisition of 5­FU resistance in CRC, and targeting METTL3/RAD51AP1 may be a promising adjuvant therapeutic strategy for patients with CRC, particularly for those with 5­FU­resistant CRC.

Root stoichiometry explains wheat endophytes and their link with crop production after four decades of fertilization.

Fertilization can impact root endophytic microbiomes and food production. However, the impacts of decades of continued fertilization on root microbiomes, and their link with ongoing crop production, remain poorly understood. Here, we used a four decade-long fertilization experiment, including contrasting types of organic and inorganic fertilization, to investigate the effects of long-term fertilization on multi-kingdom root endophytic microbiomes, including keystone species (modules within microbial networks), and their indirect associations with the production of wheat, which is one of the most important crops worldwide. We found that long-term inorganic (nitrogen, phosphorus, potassium (NPK)) and organic (NPK with straw (NPKS) and NPK with cow manure (NPKM)) fertilization had significant impacts on the community composition of endophytic arbuscular mycorrhizal fungi (AMF), bacteria, and non-mycorrhizal fungi. In addition, compared with NPK fertilization, NPKS and NPKM amendments significantly decreased the microbial network complexity, which was associated with changes in the root iron content. Finally, we identified an important subset of keystone root endophyte species within the microbial network (Module #2), which was positively correlated with wheat yield, and affected by changes in root carbon to phosphorus ratio. This study provides evidence that long-term fertilization can affect keystone root endophytic species in the root microbiome, with implications for food security in an over-fertilized world.

[Granulation of Yangxue Qingnao Granules in fluidized bed based on near-infrared spectroscopy].

To realize the real-time monitoring of the production process of Yangxue Qingnao Granules and improve the inter-batch consistency of granule quality in the granulation process, this study established a near-infrared quantitative prediction model of moisture, particle size, bulk density, and angle of repose in the fluidized bed granulation process of Yangxue Qingnao Granules based on near-infrared spectroscopy(NIRS). The near-infrared spectra were collected from 355 samples in 12 batches in the granulation process by integrating the sphere detection module of the near-infrared spectrometer. In combination with the pretreatment methods such as the first derivative, multiplicative scatter correction(MSC), and standard normal variate(SNV), the model was established by partial least squares(PLS) regression. The root mean square error of prediction(RMSEP) of moisture was 0.347 and R_P~2 was 0.935. The RMSEP of the D_(50) particle size model was 38.4 and R_P~2 was 0.980. The RMSEPs of bulk density and angle of repose were 0.018 8 and 0.879, with R_P~2 of 0.085 9 and 0.958. The results showed that the prediction of the PLS quantitative model combined with NIRS was accurate, and this model can be applied to the monitoring of key quality attributes in the fluidized bed granulation of Chinese medicinal granules in the production scale.

[Research on batch-to-batch quality control of compound Danshen extract based on physical characterization and multivariate statistical analysis].

Physical attributes of Chinese herbal extracts are determined by their chemical components, and the physical and chemical attributes jointly affect the preparation process performance and the final product quality. Therefore, in order to improve the quality control of Chinese herbal extracts, we should comprehensively study the batch-to-batch consistency of physical and chemical attributes as well as the correlations between them. This paper first explored the physical attributes affecting the preparation process performance of the compound Danshen extract and developed a method for characterizing the texture attributes. With such main chemical components as water, phenolic acids, saponins, and saccharides and texture, rheology, and other physical attributes taken into consideration, the batch-to-batch quality fluctuation of products from different production lines and time was analyzed by principal components analysis(PCA). Finally, the correlation and partial least squares(PLS) analysis was conducted, and the regression equation was established. The fitting result of the PLS model for dynamic viscosity was satisfying(R~2Y=0.857, Q~2=0.793), suggesting that the chemical components could be adjusted by the component transfer rate in the extraction process, the impurity removal rate in the alcohol precipitation process, and the water retention rate of the concentration process to meet the control of the extract dynamic viscosity. This study clarified the correlations between physical and chemical attributes of the compound Danshen extract and established a method for controlling its physical attributes based on process regulation, which would provide reference for improving the quality control of Chinese herbal extracts.