Alginate oligosaccharide assimilation by gut microorganisms and the potential role in gut inflammation alleviation.

Dietary fiber metabolism by gut microorganisms plays important roles in host physiology and health. Alginate, the major dietary fiber of daily diet seaweeds, is drawing more attention because of multiple biological activities. To advance the understanding of alginate assimilation mechanism in the gut, we show the presence of unsaturated alginate oligosaccharides (uAOS)-specific alginate utilization loci (AUL) in human gut microbiome. As a representative example, a working model of the AUL from the gut microorganism Bacteroides clarus was reconstructed from biochemistry and transcriptome data. The fermentation of resulting monosaccharides through Entner-Doudoroff pathway tunes the metabolism of short-chain fatty acids and amino acids. Furthermore, we show that uAOS feeding protects the mice against dextran sulfate sodium-induced acute colitis probably by remodeling gut microbiota and metabolome. IMPORTANCE: Alginate has been included in traditional Chinese medicine and daily diet for centuries. Recently discovered biological activities suggested that alginate-derived alginate oligosaccharides (AOS) might be an active ingredient in traditional Chinese medicine, but how these AOS are metabolized in the gut and how it affects health need more information. The study on the working mechanism of alginate utilization loci (AUL) by the gut microorganism uncovers the role of unsaturated alginate oligosaccharides (uAOS) assimilation in tuning short-chain fatty acids and amino acids metabolism and demonstrates that uAOS metabolism by gut microorganisms results in a variation of cell metabolites, which potentially contributes to the physiology and health of gut.

Acetylation of homogalacturonan and rhamnogalacturonan-I is catalyzed by a suite of trichome birefringence-like proteins.

Plant cell wall polysaccharides, including xylan, mannan, xyloglucan, and pectins, are often acetylated and members of the domain of unknown function 231 (DUF231)/trichome birefringence-like (TBL) family have been shown to be O-acetyltransferases mediating the acetylation of xylan, mannan, and xyloglucan. However, little is known about the O-acetyltransferases responsible for pectin acetylation. In this report, we biochemically characterized a suite of Arabidopsis DUF231/TBL proteins for their roles in pectin acetylation. We generated 24 TBL recombinant proteins in mammalian cells and demonstrated that 10 of them were able to transfer acetyl groups from acetyl-CoA onto the pectins homogalacturonan (HG) or rhamnogalacturonan-I (RG-I), and thus were named pectin O-acetyltransferase 1 to 10 (POAT1 to 10). It was found that POAT2,4,9,10 specifically acetylated HG and POAT5,6 acetylated RG-I, whereas POAT1,3,7,8 could act on both HG and RG-I. The acetylation of HG and RG-I by POATs was further corroborated by hydrolysis with pectin acetylesterases and by nuclear magnetic resonance spectroscopy. In addition, mutations of the conserved GDS and DXXH motifs in POAT3 and POAT8 were shown to lead to a loss of their ability to acetylate HG and RG-I. Furthermore, simultaneous RNA interference downregulation of POAT1,3,6,7,8 resulted in reduced cell expansion, impaired plant growth, and decreased pectin acetylation. Together, our findings indicate that these POATs are pectin O-acetyltransferases involved in acetylation of the pectin polysaccharides HG and RG-I.

An artificial intelligence prediction model outperforms conventional guidelines in predicting lymph node metastasis of T1 colorectal cancer.

Background: According to guidelines, a lot of patients with T1 colorectal cancers (CRCs) undergo additional surgery with lymph node dissection after being treated by endoscopic resection (ER) despite the low incidence of lymph node metastasis (LNM). Aim: The aim of this study was to develop an artificial intelligence (AI) model to more effectively identify T1 CRCs at risk for LNM and reduce the rate of unnecessary additional surgery. Methods: We retrospectively analyzed 651 patients with T1 CRCs. The patient cohort was randomly divided into a training set (546 patients) and a test set (105 patients) (ratio 5:1), and a classification and regression tree (CART) algorithm was trained on the training set to develop a predictive AI model for LNM. The model used 12 clinicopathological factors to predict positivity or negativity for LNM. To compare the performance of the AI model with the conventional guidelines, the test set was evaluated according to the Japanese Society for Cancer of the Colon and Rectum (JSCCR) and National Comprehensive Cancer Network (NCCN) guidelines. Finally, we tested the performance of the AI model using the test set and compared it with the JSCCR and NCCN guidelines. Results: The AI model had better predictive performance (AUC=0.960) than the JSCCR (AUC=0.588) and NCCN guidelines (AUC=0.850). The specificity (85.8% vs. 17.5%, p<0.001), balanced accuracy (92.9% vs. 58.7%, p=0.001), and the positive predictive value (36.3% vs. 9.0%, p=0.001) of the AI model were significantly better than those of the JSCCR guidelines and reduced the percentage of the high-risk group for LNM from 83.8% (JSCCR) to 20.9%. The specificity of the AI model was higher than that of the NCCN guidelines (85.8% vs. 82.4%, p=0.557), but there was no significant difference between the two. The sensitivity of the NCCN guidelines was lower than that of our AI model (87.5% vs. 100%, p=0.301), and according to the NCCN guidelines, 1.2% of the 105 test set patients had missed diagnoses. Conclusion: The AI model has better performance than conventional guidelines for predicting LNM in T1 CRCs and therefore could significantly reduce unnecessary additional surgery.

Protein Profiling of Aedes aegypti Treated with Streptomyces sp. KSF103 Ethyl Acetate Extract Reveals Potential Insecticidal Targets and Metabolic Pathways.

The insecticidal activity of Streptomyces sp. KSF103 ethyl acetate (EA) extract against mosquitoes is known; however, the underlying mechanism behind this activity remains elusive. In this study, liquid chromatography with tandem mass spectrometry (LC-MS/MS) was employed to investigate changes in the protein profile of Aedes aegypti larvae and adults treated with lethal concentrations of 50 (LC50) EA extract. By comparing the treated and untreated mosquitoes, this study aimed to identify proteins or pathways that exhibit alterations, potentially serving as targets for future insecticide development. Treatment with a lethal concentration of EA extract upregulated 15 proteins in larvae, while in adults, 16 proteins were upregulated, and two proteins were downregulated. These proteins were associated with metabolism, protein regulation/degradation, energy production, cellular organization and structure, enzyme activity, and catalysis, as well as calcium ion transport and homeostasis. Notably, ATP synthase, fructose-bisphosphate aldolase (FBA), and ATP citrate synthase were significantly expressed in both groups. Gene ontology analysis indicated a focus on energy metabolic processes. Molecular docking revealed a strong interaction between dodemorph, selagine (compounds from the EA extract), and FBA, suggesting FBA as a potential protein target for insecticide development. Further studies such as Western blot and transcriptomic analyses are warranted to validate the findings.

Freeze-drying pretreatment of watermelon peel to improve the efficiency of pectin extraction: RSM optimization, extraction mechanism, and characterization.

This study assessed the processing parameters and mechanism of pectin extraction and pectin qualities from freeze-dried (FD) pretreatment watermelon peel. The optimal extraction conditions for the highest pectin yield (21.83 %) were a liquid/solid ratio (w/w) of 29, pH of 1.8, ultrasonic power of 573 W, and ultrasonic time of 43 min. Compared to hot-air dried (HD) method, the extraction of pectin from FD watermelon peel was facilitated by the increased cross-sectional areas of cells, transfer rate of extracting solution, mass transfer rate, and reduced rehydration time during the extraction. HD pectin (HDP) exhibited browning, whereas FD pectin (FDP) displayed bright brownish-yellow coloration. Furthermore, the L* value of pectin from FDP was significantly higher and a* and b* values were significantly lower than pectin from HDP (P < 0.05). Additionally, the moisture, ash and protein contents of FDP were significantly higher than those in HDP (P < 0.05). Structural characterization demonstrated FDP as a low-methoxy acetylated pectin, with significantly lower degree of methoxylation and molecular weight compared to that of HDP (P < 0.05). Besides, FDP demonstrated significantly superior emulsification performance compared to HDP (P < 0.05). These findings suggest FD as a potent, efficient, and time-saving technology for drying fresh watermelon peel for pectin preparation.

Active film preparation using pectin and polyphenols of watermelon peel and its applications for super-chilled storage of chilled mutton.

We investigated the effect of active packaging films prepared by pectin (WMP) and polyphenols (WME) obtained from watermelon peel on the quality of chilled mutton during super-chilled storage. The addition of WME created new chemical and hydrogen bonds in film. Furthermore, an appropriate amount of WME (≤1.5%) was evenly distributed throughout the film matrix, improving barrier properties, mechanical properties, thermal stability, and light transmittance of the film. An assessment of the meat quality showed that the pH, L*, b*, thiobarbituric acid reactive substances (TBARs), total volatile basic nitrogen (TVB-N), and total bacterial count (TCA) of super-chilled + film group were significantly lower, whereas shear force and a* value were significantly higher (P < 0.05) than other groups. The WMP/WME film has dense microstructure and excellent mechanical properties after storage. Pectin and polyphenols obtained from watermelon peel have good potential as a novel packaging material for chilled mutton during super-chilled storage.

Insecticidal activities of Streptomyces sp. KSF103 ethyl acetate extract against medically important mosquitoes and non-target organisms.

A potentially novel actinobacterium isolated from forest soil, Streptomyces sp. KSF103 was evaluated for its insecticidal effect against several mosquito species namely Aedes aegypti, Aedes albopictus, Anopheles cracens and Culex quinquefasciatus. Mosquito larvae and adults were exposed to various concentrations of the ethyl acetate (EA) extract for 24 h. Considerable mortality was evident after the EA extract treatment for all four important vector mosquitoes. Larvicidal activity of the EA extract resulted in LC50 at 0.045 mg/mL and LC90 at 0.080 mg/mL for Ae. aegypti; LC50 at 0.060 mg/mL and LC90 at 0.247 mg/mL for Ae. albopictus; LC50 at 2.141 mg/mL and LC90 at 6.345 mg/mL for An. cracens; and LC50 at 0.272 mg/mL and LC90 at 0.980 mg/mL for Cx. quinquefasciatus. In adulticidal tests, the EA extract was the most toxic to Ae. albopictus adults (LD50 = 2.445 mg/mL; LD90 = 20.004 mg/mL), followed by An. cracens (LD50 = 5.121 mg/mL; LD90 = 147.854 mg/mL) and then Ae. aegypti (LD50 = 28.873 mg/mL; LD90 = 274.823 mg/mL). Additionally, the EA extract exhibited ovicidal activity against Ae. aegypti (LC50 = 0.715 mg/mL; LC90 = 6.956 mg/mL), Ae. albopictus (LC50 = 0.715 mg/mL; LC90 = 6.956 mg/mL), and An. cracens (LC50 = 0.715 mg/mL; LC90 = 6.956 mg/mL), evaluated up to 168 h post-treatment. It displayed no toxicity on the freshwater microalga Chlorella sp. Beijerinck UMACC 313, marine microalga Chlorella sp. Beijerinck UMACC 258 and the ant Odontoponera denticulata. In conclusion, the EA extract showed promising larvicidal, adulticidal and ovicidal activity against Ae. aegypti, Ae. albopictus, An. cracens, and Cx. quinquefasciatus (larvae only). The results suggest that the EA extract of Streptomyces sp. KSF103 has the potential to be used as an environmental-friendly approach in mosquito control. The current study would serve as an initial step toward complementing microbe-based bioinsecticides for synthetic insecticides against medically important mosquitoes.

Effects of Dietary Selenium and Oxidized Fish Oils on Intestinal Lipid Metabolism and Antioxidant Responses of Yellow Catfish Pelteobagrus fulvidraco.

Currently, the effect of selenium and oxidized fish oil interactions on the intestinal lipid metabolism and antioxidant responses of fish remains unknown. Herein, yellow catfish Pelteobagrus fulvidraco (weight: 3.99 ± 0.01 g) were used as experimental animals and were fed four diets: an adequate amount of selenium (0.25 mg kg-1) with fresh fish oil (A-Se+FFO), an adequate amount of selenium with oxidized fish oil (A-Se+OFO), a high amount of selenium (0.50 mg kg-1) with fresh fish oil (H-Se+FFO), and a high amount of selenium with oxidized fish oil (H-Se+OFO). The feeding experiment was conducted for 10 weeks. The results showed that selenium supplementation alleviated the intestinal tissue damage and reduced the lipid accumulation that was induced by oxidized fish oils. Meanwhile, we also found that 0.50 mg kg-1 selenium reduced the oxidative stress that is caused by oxidized fish oils through increasing the GSH and the activity and mRNA expression of antioxidant enzymes. Dietary selenium and oxidized fish oils also affected the mRNA expression of intestinal selenoproteins including selenow2a, selenop2, and selenot2. Mechanistically, Se and oxidized eicosapentaenoic acid (oxEPA) influenced the GSH content by affecting the DNA binding ability of activating transcription factor (ATF) 3 to the slc7a11 promoter. For the first time, our results suggested that selenium alleviated the oxidized fish oil-induced intestinal lipid deposition and the oxidative stress of the fish. We also elucidated the novel mechanism of selenium increasing the GSH content by affecting the interaction of ATF3 and the slc7a11 promoter.

Identification of biomarkers, immune infiltration landscape, and treatment targets of ischemia-reperfusion acute kidney injury at an early stage by bioinformatics methods.

BACKGROUND: Mechanisms underlying ischemia/reperfusion injury-acute kidney injury (IRI-AKI) are not fully elucidated. We conducted an integrative analysis of IRI-AKI by bioinformatics methods. METHODS: We screened gene expression profiles of the IRI-AKI at early phase from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified and enrichment pathways were conducted based on gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) database, and Gene set enrichment analysis (GSEA). Immune cell infiltration analysis was performed to reveal the change of the microenvironment cell types. We constructed protein-protein interaction (PPI), and Cytoscape with plug-ins to find hub genes and modules. We performed robust rank aggregation (RRA) to combine DEGs and analyzed the target genes for miRNA/transcription factor (TF) and drug-gene interaction networks. RESULTS: A total of 239 and 384 DEGs were identified in GSE87024 and GSE34351 separately, with the 73 common DEGs. Enrichment analysis revealed that the significant pathways involve mitogen-activated protein kinase (MAPK) signaling, interleukin-17, and tumor necrosis factor (TNF) signaling pathway, etc. RRA analysis detected a total of 27 common DEGs. Immune cell infiltration analysis showed the plasma cells reduced and T cells increased in IRI-AKI. We identified JUN, ATF3, FOS, EGR1, HMOX1, DDIT3, JUNB, NFKBIZ, PPP1R15A, CXCL1, ATF4, and HSPA1B as hub genes. The target genes interacted with 23 miRNAs and 116 drugs or molecular compounds such as curcumin, staurosporine, and deferoxamine. CONCLUSION: Our study first focused on the early IRI-AKI adopting RRA analysis to combine DEGs in different datasets. We identified significant biomarkers and crucial pathways involved in IRI-AKI and first construct the immune landscape and detected the potential therapeutic targets of the IRI-AKI by drug-gene network.

HSF1-SELENOS pathway mediated dietary inorganic Se-induced lipogenesis via the up-regulation of PPARγ expression in yellow catfish.

At present, studies involved in the effects of dietary Se sources on lipid metabolism were very scarce and the underlying mechanism remains unknown. Previous studies reported that dietary Se sources differentially affected selenoprotein S (SELENOS) expression and SELENOS affected lipid metabolism via the inositol-requiring enzyme 1α (IRE1α)- spliced X-box binding protein 1 (XBP1s) pathway. Thus, we used yellow catfish as an experimental model to explore whether dietary selenium sources affected the hepatic lipid metabolism, and further determined the role of SELENOS-IRE1α-XBP1s pathway in dietary selenium sources affecting hepatic lipid metabolism. Compared with the selenomethionine (S-M) group, sodium selenite (SS) group possessed higher liver triglycerides (TGs) (34.7%), lipogenic enzyme activities (57.9-70.6%), and lower antioxidant enzyme activities (23.3-35.5%), increased protein levels of heat shock transcription factor 1 (HSF1) and SELENOS (1.17-fold and 47.4%, respectively), and XBP1s- peroxisome proliferators-activated receptor γ (PPARγ) pathway. Blocking SELENOS and PPARγ by RNA interference demonstrated that the SELENOS/XBP1s/PPARγ axis was critical for S-S-induced lipid accumulation. Moreover, S-S-induced upregulation of SELENOS was via the increased DNA binding capacity of HSF1 to SELENOS promoter, which activated the XBP1s/PPARγ pathway and promoted lipogenesis and lipid accumulation. XBP1s is required for S-S-induced upregulation of PPARγ expression. Our finding elucidated the mechanism of dietary Se sources affecting the lipid metabolism in the liver of yellow catfish and demonstrated novel function of SELENOS in metabolic regulation. Our study also suggested that seleno-methionine was a better Se source than selenite against abnormal lipid deposition in the liver of yellow catfish.

Cell wall biology of the moss Physcomitrium patens.

The moss Physcomitrium (previously Physcomitrella) patens is a non-vascular plant belonging to the bryophytes that has been used as a model species to study the evolution of plant cell wall structure and biosynthesis. Here, we present an updated review of the cell wall biology of P. patens. Immunocytochemical and structural studies have shown that the cell walls of P. patens mainly contain cellulose, hemicelluloses (xyloglucan, xylan, glucomannan, and arabinoglucan), pectin, and glycoproteins, and their abundance varies among different cell types and at different plant developmental stages. Genetic and biochemical analyses have revealed that a number of genes involved in cell wall biosynthesis are functionally conserved between P. patens and vascular plants, indicating that the common ancestor of mosses and vascular plants had already acquired most of the biosynthetic machinery to make various cell wall polymers. Although P. patens does not synthesize lignin, homologs of the phenylpropanoid biosynthetic pathway genes exist in P. patens and they play an essential role in the production of caffeate derivatives for cuticle formation. Further genetic and biochemical dissection of cell wall biosynthetic genes in P. patens promises to provide additional insights into the evolutionary history of plant cell wall structure and biosynthesis.

Streptomyces derivatives as an insecticide: Current perspectives, challenges and future research needs for mosquito control.

The pervasiveness of arboviruses in wreaking havoc on public health has lingered on international health agendas. A scarcity of mosquito-borne disease vaccines and therapies demands prompt attention, as billions of people worldwide are at risk of infections. It is widely known that vector control continues, and in some diseases, remains the only resort in suppressing disease transmissions we presently possess at its disposal. But the use of commercial insecticides is being crippled by the widespread insecticide resistance, which greatly menaces their efficacies, toxicological repercussions such as environmental pollution and human health risk. Rather, an environmentally benign technique of employing Streptomyces isolates from settings such as terrestrial soils, marine sediments, and mangrove soils for Culicidae management has recently received a lot of positive attention. Streptomyces' capacities to produce a wide range of bioactive secondary metabolites that contribute to pharmaceutical, agricultural and veterinarian, Streptomyces-derived bioactive compounds are increasingly being considered for use in vector control. Herein, we compiled all of the available datasets on the effectiveness of Streptomyces-derived compounds against major mosquito vectors of medical importance. Aedes, Anopheles, and Culex are used to assess the toxicity of crude extracts or fractions. This paper reviewed the promising ovicidal, larvicidal, and pupacidal effects of different Streptomyces strains. Notably, no research into the adulticidal effect of Streptomyces-derived compounds has yet been done. Aside from the genetic makeup, the production of secondary metabolites from Streptomyces depends on the growing conditions. And that, to optimise the maximum yield of highly potent bioactive compounds being extracted, solvents' choice is of paramount importance. Thus, both cultivation parameters and the choice of organic solvents for secondary metabolites extraction will be discussed. Furthermore, biases derived from different studies have implied the need for standardizing experimental procedures. While entomological data should be collected consistently across all studies to expedite evidence-based policymaking of bioinsecticides, the quality of data from vector control interventions - particularly the experimental design, execution, analysis, and presentation of results of vector control studies - will be thoroughly reviewed. Lastly, to promote consistency and reliability, these knowledge gaps are identified, along with a discussion of current perspectives on vector control, global bioinsecticide trends, challenges on commercializing bioinsecticides and future research needs.

The Influence of Stomach Back-Shu and Front-Mu Points on Insular Functional Connectivity in Functional Dyspepsia Rat Models.

Functional Dyspepsia (FD) is a common functional gastrointestinal disease, which can reduce the quality of life in patients. Prior research has indicated that insula is closely related to FD and that acupuncture can regulate the functional connectivity (FC) of FD. Therefore, we hypothesized that acupuncture on FD was effected through the insular pathway. To test our hypothesis, we performed electroacupuncture (EA) on FD rat models and then examined the FC between insula and other brain regions through resting-state functional magnetic resonance imaging (rs-fMRI). Seven-day-old male infant Sprague-Dawley (SD) rats were randomly divided into control group, FD model group, and FD acupuncture group, with twelve rats per group (n = 36). Upon establishing successful models, the FD acupuncture group was subjected to EA intervention using Stomach back-shu (BL-21) and front-mu (RN-12) points for ten consecutive days for durations of 20 minutes each day. After intervention, each group was subject to rs-fMRI. The digital image data obtained were analyzed using FC analysis methods. Subsequently, gastric ligation was performed to measure gastric emptying rates. Before EA intervention, the FD model group exhibited decreased functional connections between the insula and a number of brain regions. After EA intervention, FD acupuncture group exhibited increasing FC between insula and regions when compared to the FD model group, such as the primary somatosensory cortex (S1), hippocampal CA3 (CA3), polymorphic layer of dentate gyrus (PoDG), caudate putamen (CPu), and oral pontine reticular nuclei (PnO) (P < 0.05); decreasing FC was also exhibited between insula and regions such as the bilateral primary and secondary motor cortexes (M1/2), paraventricular hypothalamic nucleus (PVA), and limbic cortex (LC). These findings indicate that the effective treatment of FD using EA may be through regulating the abnormal FC between insula and several brain regions, in particular CA3, PoDG, and PVA.

Brain structural alterations in MDD patients with gastrointestinal symptoms: Evidence from the REST-meta-MDD project.

OBJECTIVE: While gastrointestinal (GI) symptoms are very common in patients with major depressive disorder (MDD), few studies have investigated the neural basis behind these symptoms. In this study, we sought to elucidate the neural basis of GI symptoms in MDD patients by analyzing the changes in regional gray matter volume (GMV) and gray matter density (GMD) in brain structure. METHOD: Subjects were recruited from 13 clinical centers and categorized into three groups, each of which is based on the presence or absence of GI symptoms: the GI symptoms group (MDD patients with at least one GI symptom), the non-GI symptoms group (MDD patients without any GI symptoms), and the healthy control group (HCs). Structural magnetic resonance images (MRI) were collected of 335 patients in the GI symptoms group, 149 patients in the non-GI symptoms group, and 446 patients in the healthy control group. The 17-item Hamilton Depression Rating Scale (HAMD-17) was administered to all patients. Correlation analysis and logistic regression analysis were used to determine if there was a correlation between the altered brain regions and the clinical symptoms. RESULTS: There were significantly higher HAMD-17 scores in the GI symptoms group than that of the non-GI symptoms group (P < 0.001). Both GMV and GMD were significant different among the three groups for the bilateral superior temporal gyrus, bilateral middle temporal gyrus, left lingual gyrus, bilateral caudate nucleus, right Fusiform gyrus and bilateral Thalamus (GRF correction, cluster-P < 0.01, voxel-P < 0.001). Compared to the HC group, the GI symptoms group demonstrated increased GMV and GMD in the bilateral superior temporal gyrus, and the non-GI symptoms group demonstrated an increased GMV and GMD in the right superior temporal gyrus, right fusiform gyrus and decreased GMV in the right Caudate nucleus (GRF correction, cluster-P < 0.01, voxel-P < 0.001). Compared to the non-GI symptoms group, the GI symptoms group demonstrated significantly increased GMV and GMD in the bilateral thalamus, as well as decreased GMV in the bilateral superior temporal gyrus and bilateral insula lobe (GRF correction, cluster-P < 0.01, voxel-P < 0.001). While these changed brain areas had significantly association with GI symptoms (P < 0.001), they were not correlated with depressive symptoms (P > 0.05). Risk factors for gastrointestinal symptoms in MDD patients (p < 0.05) included age, increased GMD in the right thalamus, and decreased GMV in the bilateral superior temporal gyrus and left Insula lobe. CONCLUSION: MDD patients with GI symptoms have more severe depressive symptoms. MDD patients with GI symptoms exhibited larger GMV and GMD in the bilateral thalamus, and smaller GMV in the bilateral superior temporal gyrus and bilateral insula lobe that were correlated with GI symptoms, and some of them and age may contribute to the presence of GI symptoms in MDD patients.

Combining 1H-NMR-based metabonomics and network pharmacology to dissect the mechanism of antidepression effect of Milletia speciosa Champ on mouse with chronic unpredictable mild stress-induced depression.

OBJECTIVES: Milletia speciosa Champ (MS), a traditional Chinese medicine, has the abilities of antistress, antifatigue, anti-oxidation and so on. In our previous study, MS was found to antidepression while the underlying mechanism of which needs further elucidation. METHODS: Here, a proton nuclear magnetic resonance (1H-NMR)-based metabonomics combined network pharmacology research approach was performed to investigate the antidepressive mechanism of MS act on mouse with chronic unpredictable mild stress-induced depression. KEY FINDINGS: Results showed that MS could alleviate the ethology of depression (including sucrose preference degree, crossing lattice numbers and stand-up times) and disordered biochemical parameters (5-hydroxytryptamine, norepinephrine and brain-derived neurotrophic factor). Metabonomics study and network pharmacology analysis showed that MS might improve depression through synergistically regulating five targets including Maoa, Maob, Ache, Ido1 and Comt, and three metabolic pathways such as tryptophan metabolism, synthesis of neurotransmitter and phospholipid metabolism. CONCLUSIONS: This study for the first time preliminary clarified the potential antidepressive mechanism of MS and provided theoretical basis for developing MS into novel effective antidepressant.

A pH-sensitive oxidized-dextran based double drug-loaded hydrogel with high antibacterial properties.

Delayed healing or non-healing of wounds caused by bacterial infection is still a difficult medical problem. Nowadays, the topical application of antibiotics is a common treatment for infections. However, subinhibitory concentrations or high dose of antibiotics leads to the antibacterial effect counterproductive. So it's necessary to put forward an on-demand drug delivery to solve this tough issue. In this paper, a pH-responsive hydrogel was prepared by oxidized dextran (Dex-CHO), sulfadiazine (SD) and tobramycin (TOB). The hydrogel was designed by the environment in the early immature stage of biofilm (pH 5.0). Schiff bases can release drugs in slightly acidic environment. The hydrogel showed injectable, pH-sensitive drug release, and great biocompatibility. Released SD and TOB exhibited a synergistic effect therefore the hydrogel showed high antibacterial activity. This study provides an easy and promising strategy to develop smart hydrogels that aim at topical administration of antibiotics and come up with a new treatment of local bacterial infections.

Antitumor effects of different Ganoderma lucidum spore powder in cell- and zebrafish-based bioassays.

OBJECTIVE: Ganoderma lucidum spore (GLS) is gaining recognition as a medicinal part of G. lucidum and has been reported to possess various pharmacological properties, such as antitumor activity. In this work, wall-broken GLS powder (BGLSP) and wall-removed GLS powder (RGLSP), two kinds of GLS powder with different manufacturing techniques, were compared in terms of contents of active constituents and in vivo and in vitro antitumor effects. METHODS: The ultraviolet and visible spectrophotometry method was used to determine the contents of polysaccharides and total triterpenoids in BGLSP and RGLSP. Seventeen individual triterpenoids were further quantified using ultra-high-performance liquid chromatography and quantitative analysis of multi-components by single marker. The antitumor effects of BGLSP and RGLSP were evaluated using in vitro cell viability assay against human gastric carcinoma SGC-7901, lung carcinoma A549 and lymphoma Ramos and further validated by in vivo zebrafish xenograft models with transplanted SGC-7901, A549 and Ramos. RESULTS: The results showed that the contents of polysaccharides, total triterpenoids and individual triterpenoids of RGLSP were significantly higher than those of BGLSP. Although both BGLSP and RGLSP inhibited the three tumor cell lines in vitro in a dose-dependent manner, the inhibitory effects of RGLSP were much better than those of BGLSP. In the in vivo zebrafish assay, RGLSP exhibited more potent inhibitory activities against tumors transplanted into the zebrafish compared with BGLSP, and the inhibition rates of RGLSP reached approximately 78%, 31% and 83% on SGC-7901, A549 and Ramos, respectively. CONCLUSION: The results indicated that the antitumor effects of GLS were positively correlated with the contents of the polysaccharides and triterpenoids and demonstrated that the wall-removing manufacturing technique could significantly improve the levels of active constituents, and thereby enhance the antitumor activity.

Efficacy of Acupuncture Treatment of Migraine Delivered by Senior or Junior Acupuncturists: Study Protocol for a Randomized Controlled Trial.

INTRODUCTION: Acupuncture is an efficacious and safe treatment choice for migraine prevention. Results from clinical trials have shown that non-specific effects play an important role in acupuncture's efficacy. To date, however, there is no evidence available quantitatively evaluating the effect of non-specific effects, such as patients' expectations and beliefs for acupuncturists, on acupuncture efficacy, necessitating further exploration. METHODS: A total of 156 patients with migraine without aura (MwoA) will be randomized to either junior or senior acupuncturist group, at a ratio of 1:1. The study will last 24 weeks, for each patient, comprising baseline, treatment, and follow-up phases lasting 4, 8, and 12 weeks, respectively. All patients will undergo 12 sections of acupuncture treatment delivered by either a junior or senior acupuncturist following the same acupuncture prescription and manipulation. The primary outcomes will be changes in the number of migraine days and frequency of attacks per 4 weeks cycle, relative to the baseline. Secondary outcomes will include severity of headache pain, quality of life, anxiety/depression levels, and use of non-steroidal anti-inflammatory drugs (NSAIDs) per 4 weeks cycle, compared to the baseline, as well as adverse events and rate of positive response to treatment. Prior to randomization of patients into junior or senior acupuncturist groups, the Acupuncture Expectations Evaluation Scale (AES) will be used to evaluate their expectations and belief with regards to acupuncture efficacy delivered by senior or junior acupuncturists. DISCUSSION: Results from this clinical randomized controlled trial will help to quantitatively evaluate the extent of the effect of acupuncture treatment delivered by a senior or junior acupuncturist (high relative to low expectations) in migraine patients. ETHICS AND DISSEMINATION: This trial has been approved by the Institutional Review Boards and Ethics Committees of Hospital of Chengdu University of Traditional Chinese Medicine (Approval No. 2020KL-058).

1H NMR-based urinary metabonomic study of the antidiabetic effects of Rubus Suavissimus S. Lee in STZ-induced T1DM rats.

Long-term hyperglycemia associated with diabetes mellitus (DM) causes damage to various organs and tissues, including the eyes, kidneys, heart, blood vessels and nerves. Rubus Suavissimus S. Lee (RS), a shrub whose leaves are used in traditional Chinese medicine (TCM), has been shown to exert hypoglycemic effects in DM patients. However, the underlying mechanism is unclear. This was investigated in the present study in a rat model of streptozotocin-induced type 1 diabetes mellitus (T1DM) by 1H NMR analysis. We identify 9 metabolites whose levels were altered in T1DM rats compared to control rats, namely, lactate, acetate, pyruvate, succinate, 2-oxoglutarate, citrate, creatinine, allantoin, and hippurate, which are mostly related to glycolysis/gluconeogenesis, pyruvate metabolism, TCA cycle, and other metabolism. The observed pathologic changes in the levels of these metabolites in T1DM rats were reversed by treatment with RS. Thus, RS exerts effects in T1DM rats by regulating the three abnormal metabolic pathways synergistically. These findings provide supporting evidence for the therapeutic efficacy of this TCM formulation in the treatment of DM.

Epigastric pain syndrome: What can traditional Chinese medicine do? A randomized controlled trial of Biling Weitong Granules.

BACKGROUND: Recent research suggests that although prokinetic agents, acid suppressors, and radical treatment for Helicobacter pylori infection may be effective in patients with functional dyspepsia (FD), a large proportion of patients still fail to respond to these treatments or may suffer from severe adverse reactions. Many traditional Chinese medicinal herbs can regulate the status of the entire body and have special advantages in the treatment of functional diseases. The present study was designed to verify the efficacy of Biling Weitong Granules (BLWTG), a traditional Chinese medicinal herbal compound formula, in alleviating epigastric pain syndrome (EPS) in FD patients, in an attempt to provide an effective prescription for the clinical treatment of this disease. AIM: To evaluate the clinical efficacy and safety of BLWTG in treating EPS in patients with FD. METHODS: In this multicenter, stratified, randomized, double-blind, placebo-controlled, parallel group clinical trial, eligible patients were randomized into the BLWTG and placebo groups who were treated for 6 wk. Efficacy indicators including the severity and frequency of EPS and the time to pain resolution and safety indicators including adverse events were observed and compared. RESULTS: The baseline demographic data and clinical characteristics, such as epigastric pain symptoms, pain intensity, and frequency of attacks, were matched between the two groups before randomization. After 6 wk of treatment and after the center effect was eliminated, the epigastric pain was significantly improved in 28.33% and 85.59% of the patients in the placebo and BLWTG groups, respectively (P < 0.05). At 6 wk, the resolution rate of epigastric pain was 15% and 69.49% in the placebo and BLWTG groups, respectively (P < 0.05). The differences of total FD clinical score between these two groups were significant (P < 0.05) at 2, 4, and 6 wk (P < 0.05). The scores of each item and the total score in the Functional Digestive Disorders Quality of Life Questionnaire showed significant differences between the two groups at 6 wk after both the center and interaction effects were eliminated (P < 0.05). There was no significant difference in the incidence of adverse events between the two groups, and no serious adverse event was noted during the observation. CONCLUSION: Compared with placebo, BLWTG markedly improved EPS in FD patients without causing serious adverse reactions.