Construction of a novel disulfidptosis-related lncRNAs signature for prognosis prediction and anti-tumor immunity in laryngeal squamous cell carcinoma.

Disulfidptosis, an innovative type of controlled cellular death linked to metabolic dysfunction, has garnered attention. However, there is limited knowledge regarding the involvement of disulfidptosisrelated lnRNAs (DRlncRNAs) in laryngeal squamous cell carcinoma (LSCC). The objective of our team in this study seeks to establish a DRlncRNAs signature, investigate their prognostic value in LSCC, and explore their associations with immune cell subpopulations, biological signaling pathways, and exploring implications for drug sensitivity. We accessed LSCC patients' RNA-seq data and pertinent clinical data for subsequent further analysis from The Cancer Genome Atlas (TCGA) portal. A literature search was conducted focusing on disulfidptosis-related genes. Pearson correlation coefficients were calculated to identify DRlncRNAs. Differential expression analysis of lncRNAs was performed. Utilizing univariate Cox regression analysis, we identified disulfidptosis-associated prognostic lncRNAs. The LASSO-Cox regression analysis was employed to refine this set of lncRNAs and construct a disulfidptosis-related lncRNAs signature. Various statistical techniques were employed to appraise model predictive performance. Subsequently, risk groups were stratified based on the risk score derived from the DRlncRNAs signature. The superiority of the risk score in prognostication over traditional clinicopathological features in LSCC patients was demonstrated. Evident distinctions emerged between risk groups, particularly in immune cell subpopulations like activated mast cells, eosinophils, and activated NK cells. Finally, the low-risk group demonstrated reduced IC50 values for specific chemotherapeutics like cisplatin and gemcitabine. The in vitro experiments indicated differential behavior of our DRlncRNAs. The DRlncRNAs signature can serve as a robust biomarker with the ability to predict both prognosis and therapeutic responses among patients with LSCC.

The dual effects of dexmedetomidine on intestinal barrier and intestinal motility during sepsis.

BACKGROUND: Sepsis, characterized by dysregulated host responses to infection, remains a critical global health concern, with high morbidity and mortality rates. The gastrointestinal tract assumes a pivotal role in sepsis due to its dual functionality as a protective barrier against injurious agents and as a regulator of motility. Dexmedetomidine, an α2-adrenergic agonist commonly employed in critical care settings, exhibits promise in influencing the maintenance of intestinal barrier integrity during sepsis. However, its impact on intestinal motility, a crucial component of intestinal function, remains incompletely understood. METHODS: In this study, we investigated dexmedetomidine's multifaceted effects on intestinal barrier function and motility during sepsis using both in vitro and in vivo models. Sepsis was induced in Sprague-Dawley rats via cecal ligation and puncture. Rats were treated with dexmedetomidine post-cecal ligation and puncture, and various parameters were assessed to elucidate dexmedetomidine's impact. RESULTS: Our findings revealed a dichotomous influence of dexmedetomidine on intestinal physiology. In septic rats, dexmedetomidine administration resulted in improved intestinal barrier integrity, as evidenced by reduced mucosal hyper-permeability and morphological alterations. However, a contrasting effect was observed on intestinal motility, as dexmedetomidine treatment inhibited both the frequency and amplitude of contractions in isolated intestinal strips and decreased the distance of ink migration in vivo. Additionally, dexmedetomidine suppressed the secretion of pro-motility hormones while having no influence on hormones that inhibit intestinal peristalsis. CONCLUSION: The study revealed that during sepsis, dexmedetomidine exhibited protective effects on barrier integrity, although concurrently it hindered intestinal motility, partly attributed to its modulation of pro-motility hormone secretion. These findings underscore the necessity of a comprehensive understanding of dexmedetomidine's impact on multiple facets of gastrointestinal physiology in sepsis management, offering potential implications for therapeutic strategies and patient care.

Multicomponent qualitative and quantitative analysis of Farfarae Flos in serum using UHPLC-Q TOF-MS.

Farfarae Flos is a traditional herb widely employed for treating coughs, bronchitis, and asthmatic disorders. In the current study, we utilized SWATH and IDA data acquisition modes in combination with multiple data processing techniques to identify Farfarae Flos metabolites in mice serum. A total of 56 compounds were characterized, including 31 phenolic acids, 13 flavonoids, 11 sesquiterpenoids and 1 alkaloid. Further quantitative analysis was conducted on 12 absorbed metabolites, utilizing a newly developed and rigorously validated analytical method. Our approach demonstrated an acceptable level of specificity, accuracy, precision, and stability. When applied to compare the serum of mice treated with FF, all 12 metabolites showed the highest concentration at 0.5 h. Overall, this study presented a novel strategy for unraveling the active compounds of FF via serum pharmacochemistry analysis, which made a foundation for exploring the pharmacodynamic material basis of FF.

Structural Characterization and Screening for Anti-inflammatory Activity of Polysaccharides with Different Molecular Weights from Astragali Radix.

Astragali Radix polysaccharides (APSs) exhibit a broad spectrum of biological activity, which is mainly related to immune regulation. At present, most available studies focus on total APSs or a certain component of APSs. However, structural structure study and screening for the anti-inflammatory activity of polysaccharides with different molecular weights (MW) have yet to be conducted. In this study, lipopolysaccharide (LPS)-induced RAW264.7 macrophages were used as a model to investigate the anti-inflammatory activity of APSs and its fractions. The results revealed that fraction APS-I had better anti-inflammatory effects than APS-II. After APS-Ⅰ was hydrolyzed by trifluoroacetic acid (TFA), the resulting degradation products oligosaccharides were fully methylated. These derivatized oligosaccharides were further analyzed by MALDI-TOF-MS and UPLC-Q-Exactive-MS/MS. The results showed that APS-Ⅰ was a hetero-polysaccharide with a molecular weight of about 2.0 × 106 Da, mainly consisting of glucose (46.8%) and galactose (34.4%). The degree of polymerization of Astragali Radix oligosaccharides (APOS) was 2-16. APOS were identified as 1,4-glucooligosaccharides and 1,4-galactooligosaccharides. The findings of this study lay the foundation for further elucidation of structure-function relationships of APSs and provide guidance for the development of anti-inflammatory drugs.

Intercropping with maize and sorghum-induced saikosaponin accumulation in Bupleurum chinense DC. by liquid chromatography-mass spectrometry-based metabolomics.

Bupleuri Radix is an important medicinal plant, which has been used in China and other Asian countries for thousands of years. Cultivated Bupleurum chinense DC. (B. chinense) is the main commodity of Bupleuri Radix. The benefits of intercropping with various crops for B. chinense have been recognized; however, the influence of intercropping on the chemical composition of B. chinense is still unclear yet. In this study, intercropping with sorghum and maize exhibited little effect on the root length, root diameter, and single root mass of B. chinense. Only the intercropping with sorghum increased the root length of B. chinense slightly compared to the monocropping. In addition, 200 compounds were identified by UHPLC-Q-TOF-MS, and metabolomic combined with the Venn diagram and heatmap analysis showed apparent separation between the intercropped and monocropped B. chinense samples. Intercropping with sorghum and maize could both increase the saikosaponins, fatty acyls, and organic acids in B. chinense while decreasing the phospholipids. The influence of intercropping on the saikosaponin biosynthesis was probably related with the light intensity and hormone levels in B. chinense. Moreover, we found intercropping increased the anti-inflammatory activity of B. chinense. This study provides a scientific reference for the beneficial effect of intercropping mode of B. chinense.

Systematic evaluation and meta-analysis of the effects of major dietary patterns on cognitive function in healthy adults.

PURPOSE: Evidence shows diet promotes brain health. Combining foods and nutrients may have beneficial synergistic effects, but the effects on cognitive function interventions are inconsistent. So, a meta-analysis of RCTs was conducted to examine the specific effects on cognitive function. METHODS: We searched four databases from creation to April 2023. Eligible randomized controlled trials were identified. A random-effects meta-analysis was used to combine standardized mean differences (SMD) (95% confidence intervals [CI]), and homogeneity tests for a variance were calculated. RESULTS: A total of 19 studies involving 12,119 participants were included in this systematic review. The dietary intervention group had a positive effect on overall cognitive functioning compared to the control group (SMD = 0.14, 95% CI [0.08, 0.20], P < 0.00001). The dietary intervention improved executive function, processing speed and language skills (SMD = -0.10, 95% CI [-0.17,-0.04], P = 0.002, I2 = 0%), (SMD = -0.16, 95% CI [-0.23,-0.09], P < 0.00001, I2 = 0%), (SMD = 0.10, 95% CI [0.01, 0.20], P = 0.03, I2 = 0%). The dietary intervention had no effect on delayed memory and spatial ability (SMD = 0.04, 95% CI [-0.02, 0.09], P = 0.20, I2 = 0%), (SMD = 0.08, 95% CI [-0.01, 0.16], P = 0.08, I2 = 0%). CONCLUSION: The Mediterranean diet, a diet with restricted caloric intake, a diet incorporating aerobic exercise, a low-carbohydrate diet, and a healthy lifestyle diet (increased intake of fruits and vegetables, and weight and blood pressure management) appear to have positive effects on cognitively healthy adults, as reflected in their overall cognitive, processing speed, executive, and language functions. PROSPERO REGISTRATION NUMBER: CRD42023414704.

Study on the antidepressive effects and mechanism of raw and fried Ziziphi Spinosae Semen via metabolomics and gut microbiota analysis.

Ziziphi Spinosae Semen (ZSS) and fried ZSS (FZSS) have been used for treating insomnia and depression in China. However, the potential influence of chemical variations on their efficacy remains unclear. This study demonstrated that compared with ZSS, FZSS exhibited an increase in the content of seven compounds, while the fatty oil content decreased. Both ZSS and FZSS exhibited antidepressive effects in a chronic unpredictable mild stress rat model, indicating a synergistic regulation of deficiencies in 5-hydroxytryptamine in the brain and the hyperactivation of severe peripheral inflammation. ZSS demonstrated a superior modulatory effect compared with FZSS, as indicated by integrated pharmacodynamic index, metabolic profile, and relative distance value. The potential mechanism underlying their antidepressive effects involved the modulation of gut microbiota structure to alleviate excessive inflammatory responses and imbalanced tryptophan metabolism. Correlation analysis indicated that the higher fatty oil contents should be comprehensively considered as the main reason for ZSS's superior antidepressive effects, achieved through the regulation of pyroglutamic acid levels.

Huangqin decoction attenuates spared nerve injury (SNI)-induced neuropathic pain by modulating microglial M1/M2 polarization partially mediated by intestinal nicotinamide metabolism.

BACKGROUND: The incidence of neuropathic pain is progressively increasing over time. The activation of M1-type microglia plays a crucial role in the initiation and progression of neuropathic pain. Huangqin Decoction (HQD) is traditionally used to alleviate dysentery and abdominal pain. However, it remains unclear whether HQD can effectively mitigate neuropathic pain and the underlying mechanisms. PURPOSE: The present study aims to investigate the impact of HQD on neuropathic pain induced by spared nerve injury (SNI) in mice, and to elucidate whether the analgesic effect of HQD is associated with microglia polarization. METHODS: The analgesic effect of HQD on SNI mice was investigated through assessments of mechanical pain threshold, thermal pain threshold, cold pain threshold, and motor ability. We elucidated the molecular mechanisms of HQD in alleviating SNI-induced neuropathic pain by focusing on microglia polarization and intestinal metabolite abnormalities. The expression levels of markers associated with microglia polarization (Iba-1, CD68, CD206, iNOS) was detected by immunofluorescence and Western blot, and the levels of inflammatory factors (IL-4, IL-10, IL-6, TNF-α) were assessed by ELISA. UPLC-QTOF-MS metabolomics was utilized to identify differential metabolites in the intestines of SNI mice. We screened the differential metabolites related to microglial polarization by correlation analysis, subsequently nicotinamide was selected for validation in LPS-induced BV-2 cells. RESULTS: Our findings demonstrated that HQD (20 g/kg) significantly enhanced the mechanical pain threshold, thermal pain threshold, and cold pain threshold, and protected the injured DRG neurons of SNI mice. Moreover, HQD (20 g/kg) obviously suppressed the expression of microglia M1 polarization markers (Iba-1, CD68, iNOS, IL-6, TNF-α), and promoted the expression of microglia M2 polarization markers (CD206, IL-10, IL-4) in the spinal cord of SNI mice. Additionally, HQD (20 g/kg) prominently ameliorated intestinal barrier damage by upregulating Claudin 1 and Occludin expression in the colon of SNI mice. Furthermore, HQD (20 g/kg) rectified 19 metabolite abnormalities in the intestine. Notably, nicotinamide (100 µM), an amide derivative with anti-inflammatory property, effectively suppresses microglia activation and polarization in LPS-induced BV-2 cells by downregulating IL-6 level and CD68 expression while upregulating IL-4 level and CD206 expression. CONCLUSION: In summary, HQD alleviates neuropathic pain in SNI mice by regulating the activation and polarization of microglia, partially mediated through intestinal nicotinamide metabolism.

Gastrointestinal Characteristics of Constipation from the Perspectives of Microbiome and Metabolome.

BACKGROUND: Constipation is one of the most common gastrointestinal complaints. Yet, the underlying mechanisms of constipation remain to be explored deeply. Integration of microbiome and metabolome is powerful and promising to demonstrate characteristics of constipation. AIM OF STUDY: This study aimed to characterize intestinal microbiome and metabolome of constipation. In addition, this study revealed the correlations among behaviors, intestinal microbiota, and metabolites interrupted by constipation. METHODS: Firstly, the constipation model was successfully applied. At the macro level, the ability of learning, memory, locomotor activity, and the defecation index of rats with constipation-like phenotype were characterized. At the micro-level, 16S rRNA sequencing was applied to analyze the intestinal microbiota in rats with constipation-like phenotype. 1H nuclear magnetic resonance (NMR)-based metabolomics was employed to investigate the metabolic phenotype of constipation. In addition, we constructed a correlation network, intuitively showing the correlations among behaviors, intestinal microbiota, and metabolites. RESULTS: Constipation significantly attenuated the locomotor activity, memory recognition, and frequency of defecation of rats, while increased the time of defecation. Constipation significantly changed the diversity of intestinal microbial communities, which correspondingly involved in 5 functional pathways. Besides, 28 fecal metabolites were found to be associated with constipation, among which 14 metabolites were further screened that can be used to diagnose constipation. On top of this, associated networks intuitively showed the correlations among behaviors, intestinal microbiota, and metabolites. CONCLUSIONS: The current findings are significant in terms of not only laying a foundation for understanding characteristics of constipation, but also providing accurate diagnosis and treatments of constipation clinically.

Stable Isotope Tracer Technique and Network Pharmacology to Reveal Antidepressant Targets and Active Components of Xiaoyao San.

In recent years, the research of mitochondrial dysfunction in depression has drawn the focus of researchers. Our research group previously found that Xiaoyao San (XYS) has improved the mitochondrial structure and the blocked tricarboxylic acid cycle (TCA cycle) in the hippocampal tissue of chronic unpredictable mild stress (CUMS) rats. However, the specific targets and active components of XYS remain unclear, and the potential to improve hippocampal mitochondrial TCA cycle disorder was also unexplored. In this research, a strategy to combine stable isotope-resolved metabolomics (SIRM), network pharmacology and transmission electron microscopy (TEM) was used to explore the potential, targets of action, and active components of XYS to improve hippocampal mitochondrial TCA cycle disorder of CUMS rats. The results of TEM showed that the ultrastructure of hippocampal mitochondria could be improved by XYS. A combination of SIRM and molecular docking showed that pyruvate carboxylase (PC), ATP citrate lyase (ACLK), glutamate dehydrogenase (GLDH), glutamate oxaloacetate transaminase (GOT) and pyruvate dehydrogenase (PDH) were targets of XYS to improve TCA cycle disorder. In addition, troxerutin was found to be the most potential active component of XYS to improve TCA cycle disorder. The above research results can provide new insights for the development of antidepressant drugs.

Exploration of the intestinal flora to reveal the important contribution of Radix Astragali to Huangqi Jianzhong Tang in treating chronic atrophic gastritis rats.

Radix Astragali (Huangqi in Chinese, HQ) is a commonly used Chinese herbal medicine for thousands of years. In this study, A classic prescription Huangqi Jianzhong tang (HQJZ) was selected to evaluate the important effect of HQ on rats with chronic atrophic gastritis (CAG) from the perspective of intestinal flora in cecal contents samples. Traditional pharmacological indicators, including weight change, pathological examination and biochemical indicators showed that HQ exerted favorable contribution to HQJZ against CAG, where the efficiencies of HQ and HQJZ were better than HY (HQJZ prepared without HQ). An accurate strategy was adopted to screen out the differential metabolites in the metabolomis analysis of intestinal flora in cecal contents samples based on the optimal screening factors, including VIP (importance of variables in projection), FC (fold change), AUROC (area under the receiver operating characteristic curve) and -ln(p-value), which were evaluated based on their interpreting, grouping, and predicting abilities of the performed orthogonal partial least-squares-discriminate analysis (OPLS-DA) models. Ten altered differential metabolites were obtained and associated with the intestinal flora, which HQ exerted the important metabolic contributions to HQJZ. The efficacy on the diversity of intestinal flora and their correlations with the altered metabolites further showed the important role of HQ in HQJZ composition. This work provided valuable approach for looking for potential biomarkers associated with metabolomics research with more accuracy, and provided new insights into the mechanisms to explain the efficacy of HQ contributing to HQJZ formula.

Characterization of "microbiome-metabolome-immunity" in depressed rats with divergent responses to Paroxetine.

OBJECTIVES: Selective serotonin reuptake inhibitors (SSRIs) are the first-line anti-depressants. Unfortunately, about 30 % depressed patients do not effectively respond to SSRIs. It is still unclear that the gastrointestinal characteristics of responders and non-responders, and the differences. METHODS: Herein, we characterized gut microbiome and metabolome of depressed rats with differential responses to Paroxetine (PX) by 16S rRNA sequencing and 1H NMR-based metabolomics, respectively. On top of this, we constructed both inter- and inner-layer networks, intuitively showing the correlations among behavioral indicators, immune factors, intestinal bacteria, and differential metabolites. RESULTS: Consequently, we found that depressed rats differently responded to PX, which could be divided into PX responsive (PX-R) and non-responsive (PX-N) groups. Firstly, the depressive behaviors of PX-R rats and PX-N rats significantly differed. Meanwhile, inflammatory balance was also characterized for depressed rats with different responses to PX. Overall, PX-R rats and PX-N rats exhibited differential gut microbiome and metabolome, including intestinal structures, intestinal functions, metabolic profiles, metabolites, and metabolic pathways. LIMITATIONS: Metabolites that identified by metabolomics based on 1H NMR are not comprehensive enough. CONCLUSIONS: Taken together, our study demonstrated that gut microbiome and metabolome, as well as related functions, are of significance in differential responses of depressed rats to PX, which might be novel insights in uncovering the mechanisms of differences in efficacies of antidepressants.

Development of Cyclic N,O-Aminal-Embedded Bis-tetrahydroisoquinoline Analogues as Potential DNA Alkylation Agents.

This work described a novel "functional hybrid" design for bis-tetrahydroisoquinoline (bis-THIQ) analogues as potential DNA alkylation agents by replacing the labile C21-carbinolamine on the bis-THIQ skeleton of ET-743 with a chemically stable cyclic N,O-aminal functionality. In vitro anti-proliferation evaluation has proven that it is a successful approach to deliver new bis-THIQ analogues with common cytotoxicities, among which several exhibited sub-micromolar-range IC50 against the proliferation of human cancer cell lines A549, HepG2, and MDA-MB-231, respectively.

Effects of Xiaoyao San on exercise capacity and liver mitochondrial metabolomics in rat depression model.

Objective: This study aimed to investigate the therapeutic effects of Xiaoyao San (XYS), a herbal medicine formula, on exercise capacity and liver mitochondrial metabolomics in a rat model of depression induced by chronic unpredictable mild stress (CUMS). Methods: A total of 24 male SD rats were randomly divided into four groups: control group (C), CUMS control group (M), Venlafaxine positive treatment group (V), and XYS treatment group (X). Depressive behaviour and exercise capacity of rats were assessed by body weight, sugar-water preference test, open field test, pole test, and rotarod test. The liver mitochondria metabolomics were analyzed by using liquid chromatography-mass spectrometry (LC-MS) method. TCMSP database and GeneCards database were used to screen XYS for potential targets for depression, and GO and KEGG enrichment analyses were performed. Results: Compared with C group, rats in M group showed significantly lower body weight, sugar water preference rate, number of crossing and rearing in the open field test, climbing down time in the pole test, and retention time on the rotarod test (P < 0.01). The above behaviors and exercise capacity indices were significantly modulated in rats in V and X groups compared with M group (P < 0.05, 0.01). Compared with C group, a total of 18 different metabolites were changed in the liver mitochondria of rats in M group. Nine different metabolites and six metabolic pathways were regulated in the liver mitochondria of rats in X group compared with M group. The results of network pharmacology showed that 88 intersecting targets for depression and XYS were obtained, among which 15 key targets such as IL-1ß, IL-6, and TNF were predicted to be the main differential targets for the treatment of depression. Additionally, a total of 1 553 GO signaling pathways and 181 KEGG signaling pathways were identified, and the main biological pathways were AGE-RAGE signaling pathway, HIF-1 signaling pathway, and calcium signaling pathway. Conclusion: XYS treatment could improve depressive symptoms, enhance exercise capacity, positively regulate the changes of mitochondrial metabolites and improve energy metabolism in the liver of depressed rats. These findings suggest that XYS exerts antidepressant effects through multi-target and multi-pathway.

CXCL14 as a Key Regulator of Neuronal Development: Insights from Its Receptor and Multi-Omics Analysis.

CXCL14 is not only involved in the immune process but is also closely related to neurodevelopment according to its molecular evolution. However, what role it plays in neurodevelopment remains unclear. In the present research, we found that, by crossbreeding CXCL14+/- and CXCL14-/- mice, the number of CXCL14-/- mice in their offspring was lower than the Mendelian frequency; CXCL14-/- mice had significantly fewer neurons in the external pyramidal layer of cortex than CXCL14+/- mice; and CXCL14 may be involved in synaptic plasticity, neuron projection, and chemical synaptic transmission based on analysis of human clinical transcriptome data. The expression of CXCL14 was highest at day 14.5 in the embryonic phase and after birth in the mRNA and protein levels. Therefore, we hypothesized that CXCL14 promotes the development of neurons in the somatic layer of the pyramidal cells of mice cortex on embryonic day 14.5. In order to further explore its mechanism, CXCR4 and CXCR7 were suggested as receptors by Membrane-Anchored Ligand and Receptor Yeast Two-Hybrid technology. Through metabolomic techniques, we inferred that CXCL14 promotes the development of neurons by regulating fatty acid anabolism and glycerophospholipid anabolism.

Pan-transcriptomic analysis reveals alternative splicing control of cold tolerance in rice.

Plants have evolved complex mechanisms to adapt to harsh environmental conditions. Rice (Oryza sativa) is a staple food crop that is sensitive to low temperatures. However, its cold stress responses remain poorly understood, thus limiting possibilities for crop engineering to achieve greater cold tolerance. In this study, we constructed a rice pan-transcriptome and characterized its transcriptional regulatory landscape in response to cold stress. We performed Iso-Seq and RNA-Seq of 11 rice cultivars subjected to a time-course cold treatment. Our analyses revealed that alternative splicing-regulated gene expression plays a significant role in the cold stress response. Moreover, we identified CATALASE C (OsCATC) and Os03g0701200 as candidate genes for engineering enhanced cold tolerance. Importantly, we uncovered central roles for the two serine-arginine-rich proteins OsRS33 and OsRS2Z38 in cold tolerance. Our analysis of cold tolerance and resequencing data from a diverse collection of 165 rice cultivars suggested that OsRS2Z38 may be a key selection gene in japonica domestication for cold adaptation, associated with the adaptive evolution of rice. This study systematically investigated the distribution, dynamic changes, and regulatory mechanisms of alternative splicing in rice under cold stress. Overall, our work generates a rich resource with broad implications for understanding the genetic basis of cold response mechanisms in plants.

The Beneficial Effects of Dietary Astragali Radix Are Related to the Regulation of Gut Microbiota and Its Metabolites.

Astragali Radix (AR) or its extract has been used as an herbal medicine and dietary supplement in China, Europe, and the United States. The gut microbiota could provide new insights for exploring dietary supplements' underlying mechanism on organisms. However, no reports have focused on the regulatory effect of AR on the gut microbiota as a dietary supplement. In this study, healthy ICR mice of either sex were divided into AR and control (CON) groups and given AR water extract (4.55 mg/kg·day-1) or saline by gavage for 14 days, respectively. Then 16S rRNA gene sequencing and ultra-high-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry-based fecal metabolomics were integrated to investigate the benefits of dietary AR. Weighted gene coexpression network analysis was also introduced to investigate the metabolites with highly synergistic changes. AR supplementation influenced the structure of intestinal microflora, especially enriching short-chain fatty acid-producing bacteria g_Coprobacillus, g_Prevotella, and g_Parabacteroides. AR also significantly altered the fecal metabolome, mainly related to amino acid metabolism, nucleotide metabolism, and bile acid (BA) metabolism. Moreover, the increased secondary BAs and BA-sulfates might closely relate to intestinal microflora. These findings provide valuable insights for future research of dietary AR as a functional food.

MicroRNA-483-3p Inhibitor Ameliorates Sepsis-Induced Intestinal Injury by Attenuating Cell Apoptosis and Cytotoxicity Via Regulating HIPK2.

Sepsis is a life-threatening syndrome that can result in multi-organ dysfunction. MicroRNA (miR)-483-3p was previously demonstrated to be upregulated in sepsis patients; however, its specific functions in sepsis-triggered intestinal injury remain unclarified. Human intestinal epithelial NCM460 cell line was stimulated with lipopolysaccharide (LPS) to mimic sepsis-induced intestinal injury in vitro. Terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) staining was utilized for examining cell apoptosis. Western blotting and real time quantitative polymerase chain reaction (RT-qPCR) were used for detecting molecular protein and RNA levels. LPS-induced cytotoxicity was determined by measuring concentrations of lactate dehydrogenase (LDH), diamine oxidase (DAO) and fatty acid binding protein 2 (FABP2). Luciferase reporter assay was utilized for verifying the interaction between miR-483-3p and homeodomain interacting protein kinase 2 (HIPK2). Inhibiting miR-483-3p alleviates LPS-triggered NCM460 cell apoptosis and cytotoxicity. miR-483-3p targeted HIPK2 in LPS-stimulated NCM460 cells. Knockdown of HIPK2 reversed the above effects mediated by miR-483-3p inhibitor. Inhibiting miR-483-3p ameliorates LPS-triggered apoptosis and cytotoxicity by targeting HIPK2.

Astragaloside IV Alleviates Depression in Rats by Modulating Intestinal Microbiota, T-Immune Balance, and Metabolome.

This study aims to explore the effects of Astragaloside IV (AS-IV) on abnormal behaviors, intestinal microbiota, intestinal T-immune balance, and fecal metabolism of a model of depression in rats. Herein, we integrally applied 16S rRNA sequencing, molecular biological techniques, and 1H NMR-based fecal metabolomics to demonstrate the antidepression activity of AS-IV. The results suggested that AS-IV regulated the depression-like behaviors of rats, which are presented by an increase of body weight, upregulation of sucrose preference rates, and a decrease of immobility time. Additionally, AS-IV increased the abundances of beneficial bacteria (Lactobacillus and Oscillospira) in a model of depression in rats. Moreover, AS-IV regulated significantly the imbalance of Th17/Treg cells, and the abnormal contents of both anti-inflammatory factors and pro-inflammatory factors. Besides, fecal metabolomics showed that AS-IV improved the abnormal levels of short-chain fatty acids and amino acids. Collectively, our research supplemented new data, supporting the potential of AS-IV as an effective diet or diet composition to improve depression-like behaviors, dysfunctions of microbiota, imbalance of T immune, and the abnormality of fecal metabolome. However, the causality of the other actions was not proven because of the experimental design and the methodology used. The current findings suggest that AS-IV could function as a promising diet or diet composition to alleviate depressed symptoms.

Correction: Gong et al. Neuroprotective and Cytotoxic Phthalides from Angelicae Sinensis Radix. Molecules 2016, 21, 549.

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