Whole-protein enteral nutrition formula supplementation reduces Escherichia and improves intestinal barrier function in HIV-infected immunological nonresponders.

People living with human immunodeficiency virus (PLWH) have persistent malnutrition, intestinal barrier dysfunction, and gut microbial imbalance. The interplay between gut microbiota and nutrients is involved in the immune reconstitution of PLWH. To evaluate the effects of whole-protein enteral nutrition formula supplementation on T-cell levels, intestinal barrier function, nutritional status, and gut microbiota composition in human immunodeficiency virus (HIV)-infected immunological nonresponders (INRs) who failed to normalize CD4+ T-cell counts, with a number <350 cells/µL, a pilot study was carried out in 13 HIV-infected INRs undergoing antiretroviral therapy who received a 3-month phase supplementation of 200 mL/200 kcal/45 g whole-protein enteral nutrition formula once daily. Our primary endpoint was increased CD4+ T-cell counts. Secondary outcome parameters were changes in intestinal barrier function, nutritional status, and gut microbiota composition. We showed that CD4+ T-cell counts of HIV-infected INRs increased significantly after the 3-month supplementation. Dietary supplementation for 3 months improved the intestinal barrier function and nutritional status of HIV-infected INRs. Furthermore, the enteral nutrition formula significantly decreased the relative abundance of Escherichia at the genus level and increased the alpha diversity of gut microbiota in HIV-infected INRs. The findings demonstrated that the whole-protein enteral nutrition formula aids in reducing Escherichia and improving intestinal barrier function in HIV-infected INRs. This study provides insight into the role of nutrients in the improvement of immune reconstitution in HIV-infected INRs. This study is registered in the Chinese Clinical Trial Registry (Document No. ChiCTR2000037839; http://www.chictr.org.cn/index.aspx).

Blue LED light promoting the growth, accumulation of high-value isoflavonoids and astragalosides, antioxidant response, and biosynthesis gene expression in Astragalus membranaceus (Fisch.) Bunge hairy root cultures.

The root of Astragalus membranaceus (Fisch.) Bunge is one of the most frequently used herbs in traditional Chinese medicine (TCM) formulae for fighting COVID-19 infections, due to the presence of isoflavonoids and astragalosides associated with antiviral and immune-enhancing activities. For the first time, the exposure of A. membranaceus hairy root cultures (AMHRCs) to different colors of LED lights i.e., red, green, blue, red/green/blue (1/1/1, RGB), and white, was conducted to promote the root growth and accumulation of isoflavonoids and astragalosides. LED light treatment regardless of colors was found beneficial for root growth, which might be a result of the formation of more root hairs upon light stimulation. Blue LED light was found most effective for enhancing phytochemical accumulation. Results showed that the productivity of root biomass in blue-light grown AMHRCs with an initial inoculum size of 0.6% for 55 days was 1.40-fold higher than that in dark (control), and yields of high-value isoflavonoids and astragalosides including calycosin, formononetin, astragaloside IV, and astragaloside I increased by 3.17-fold, 2.66-fold, 1.78-fold, and 1.52-fold relative to control, respectively. Moreover, the photooxidative stress together with transcriptional activation of biosynthesis genes might contribute to the enhanced accumulation of isoflavonoids and astragalosides in blue-light grown AMHRCs. Overall, this work offered a feasible approach for obtaining higher yields of root biomass and medicinally important compounds in AMHRCs via the simple supplementation of blue LED light, which made blue-light grown AMHRCs industrially attractive as plant factory in controlled growing systems. Supplementary Information: The online version contains supplementary material available at 10.1007/s11240-023-02486-7.

[Effect of transcutaneous auricular vagus nerve stimulation on functional connectivity in the related brain regions of patients with depression based on the resting-state fMRI].

OBJECTIVE: To explore the brain effect mechanism and the correlation between brain functional imaging and cognitive function in treatment of depressive disorder (DD) with transcutaneous auricular vagus nerve stimulation (taVNS) based on the resting-state functional magenetic reasonance imaging (rs-fMRI). METHODS: Thirty-two DD patients were included in a depression group and 32 subjects of healthy condition were enrolled in a normal group. In the depression group, the taVNS was applied to bilateral Xin (CO15) and Shen (CO10), at disperse-dense wave, 4 Hz/20 Hz in frequency and current intensity ≤20 mA depending on patient's tolerance, 30 min each time, twice daily. The duration of treatment consisted of 8 weeks. The patients of two groups were undertaken rs-fMRI scanning. The scores of Hamilton depression scale (HAMD), Hamilton anxiety scale (HAMA) and Wisconsin card sorting test (WCST) were observed in the normal group at baseline and the depression group before and after treatment separately. The differential brain regions were observed before and after treatment in the two groups and the value of degree centrality (DC) of fMRI was obtained. Their correlation was analyzed in terms of HAMD, HAMA and WCST scores. RESULTS: The scores of HAMD and HAMA in the depression group were all higher than those in the normal group (P<0.05). After treatment, the scores of HAMD and HAMA were lower than those before treatment in the depression group; the scores of total responses, response errors and perseverative errors of WCST were all lower than those before treatment (P<0.05). The brain regions with significant differences included the left inferior temporal gyrus, the left cerebellar peduncles region 1, the left insula, the right putamen, the bilateral supplementary motor area and the right middle frontal gyrus. After treatment, the value of DC in left supplementary motor area was negatively correlated to HAMD and HAMA scores respectively (r=-0.324, P=0.012; r=-0.310, P=0.015); the value of DC in left cerebellar peduncles region 1 was negatively correlated to the total responses of WCST (r=-0.322, P=0.013), and the left insula was positively correlated to the total responses of WCST (r=0.271, P=0.036). CONCLUSION: The taVNS can modulate the intensity of the functional activities of some brain regions so as to relieve depressive symptoms and improve cognitive function.

Exogenous gibberellic acid shortening after-ripening process and promoting seed germination in a medicinal plant Panax notoginseng.

BACKGROUND: Panax notoginseng (Burk) F.H. Chen is an essential plant in the family of Araliaceae. Its seeds are classified as a type of morphophysiological dormancy (MPD), and are characterized by recalcitrance during the after-ripening process. However, it is not clear about the molecular mechanism on the after-ripening in recalcitrant seeds. RESULTS: In this study, exogenous supply of gibberellic acid (GA3) with different concentrations shortened after-ripening process and promoted the germination of P. notoginseng seeds. Among the identified plant hormone metabolites, exogenous GA3 results in an increased level of endogenous hormone GA3 through permeation. A total of 2971 and 9827 differentially expressed genes (DEGs) were identified in response to 50 mg L-1 GA3 (LG) and 500 mg L-1 GA3 (HG) treatment, respectively, and the plant hormone signal and related metabolic pathways regulated by GA3 was significantly enriched. Weighted gene co-expression network analysis (WGCNA) revealed that GA3 treatment enhances GA biosynthesis and accumulation, while inhibiting the gene expression related to ABA signal transduction. This effect was associated with higher expression of crucial seed embryo development and cell wall loosening genes, Leafy Contyledon1 (LEC1), Late Embryogenesis Abundant (LEA), expansins (EXP) and Pectinesterase (PME). CONCLUSIONS: Exogenous GA3 application promotes germination and shorts the after-ripening process of P. notoginseng seeds by increasing GA3 contents through permeation. Furthermore, the altered ratio of GA and ABA contributes to the development of the embryo, breaks the mechanical constraints of the seed coat and promotes the protrusion of the radicle in recalcitrant P. notoginseng seeds. These findings improve our knowledge of the contribution of GA to regulating the dormancy of MPD seeds during the after-ripening process, and provide new theoretical guidance for the application of recalcitrant seeds in agricultural production and storage.

Efficacy of Faecal Microbiota Transplantation for the Treatment of Autism in Children: Meta-Analysis of Randomised Controlled Trials.

Objective: Evidence-based research methods were applied to assess the efficacy of faecal microbiota transplantation (FMT) for the treatment of autism in children. Methods: We searched the Chinese Biomedical Literature, CNKI, Wanfang, PubMed, Embase, Web of Science, and the Cochrane Library databases to collect randomised controlled trials on faecal microbiota transplantation for the treatment of autism in children. The search included studies published from the creation of the respective database to 5 April 2022. Literature screening, data extraction, and quality evaluation were implemented by three investigators according to the inclusion and exclusion criteria. The meta-analysis was performed using the RevMan 5.1 software. Results: Nine studies with population-based subjects and four studies with animal-based subjects were included. Five papers were screened for the meta-analysis. The results showed that FMT markedly reduced Autism Behaviour Checklist (ABC) scores in children with autism spectrum disorder (weighted mean difference (WMD) = -14.96; 95% confidence intervals (CI), -21.68 to -8.24; P < 0.001; I 2 = 0%). FMT also reduced Childhood Autism Rating Scale (CARS) scores (WMD = -6.95; 95% CI, -8.76 to -5.14; P < 0.001; I 2 = 28.1%). Conclusion: Our results indicate that FMT can benefit children with autism by reducing ABC and CARS scores, but more high-quality studies are needed to verify these results.

Effect of transcutaneous auricular vagus nerve stimulation on functional connectivity in the related brain regions of patients with depression based on the resting-state fMRI / 中国针灸

OBJECTIVE@#To explore the brain effect mechanism and the correlation between brain functional imaging and cognitive function in treatment of depressive disorder (DD) with transcutaneous auricular vagus nerve stimulation (taVNS) based on the resting-state functional magenetic reasonance imaging (rs-fMRI).@*METHODS@#Thirty-two DD patients were included in a depression group and 32 subjects of healthy condition were enrolled in a normal group. In the depression group, the taVNS was applied to bilateral Xin (CO15) and Shen (CO10), at disperse-dense wave, 4 Hz/20 Hz in frequency and current intensity ≤20 mA depending on patient's tolerance, 30 min each time, twice daily. The duration of treatment consisted of 8 weeks. The patients of two groups were undertaken rs-fMRI scanning. The scores of Hamilton depression scale (HAMD), Hamilton anxiety scale (HAMA) and Wisconsin card sorting test (WCST) were observed in the normal group at baseline and the depression group before and after treatment separately. The differential brain regions were observed before and after treatment in the two groups and the value of degree centrality (DC) of fMRI was obtained. Their correlation was analyzed in terms of HAMD, HAMA and WCST scores.@*RESULTS@#The scores of HAMD and HAMA in the depression group were all higher than those in the normal group (P<0.05). After treatment, the scores of HAMD and HAMA were lower than those before treatment in the depression group; the scores of total responses, response errors and perseverative errors of WCST were all lower than those before treatment (P<0.05). The brain regions with significant differences included the left inferior temporal gyrus, the left cerebellar peduncles region 1, the left insula, the right putamen, the bilateral supplementary motor area and the right middle frontal gyrus. After treatment, the value of DC in left supplementary motor area was negatively correlated to HAMD and HAMA scores respectively (r=-0.324, P=0.012; r=-0.310, P=0.015); the value of DC in left cerebellar peduncles region 1 was negatively correlated to the total responses of WCST (r=-0.322, P=0.013), and the left insula was positively correlated to the total responses of WCST (r=0.271, P=0.036).@*CONCLUSION@#The taVNS can modulate the intensity of the functional activities of some brain regions so as to relieve depressive symptoms and improve cognitive function.

Health-Promoting Phenolic Compound Accumulation, Antioxidant Response, Endogenous Salicylic Acid Generation, and Biosynthesis Gene Expression in Germinated Pigeon Pea Seeds Treated with UV-B Radiation.

Germinated pigeon pea seeds (GPPSs) are good dietary supplements with satisfactory nutritional and medicinal values. In this study, UV-B treatment was used to promote the accumulation of health-promoting phenolic compounds (10 flavonoids and 1 stilbene) in GPPS. The total yield of 11 phenolic compounds (235 839.76 ± 17 118.24 ng/g DW) significantly improved (2.53-fold increase) in GPPSs exposed to UV-B radiation (3 W/m2) for 8 h, whereas free amino acid and reducing sugar contents exhibited a decreasing tendency during UV-B exposure. Meanwhile, the positive response in the antioxidant activities of enzymes and nonenzymatic extracts was noticed in UV-B-treated GPPSs. Moreover, UV-B radiation could cause tissue damages in hypocotyls and cotyledons of the GPPSs and enhance the generation of endogenous salicylic acid, thus activating the expression of biosynthesis genes (especially CHS and STS1). Overall, the simple UV-B supplementation strategy makes GPPSs more attractive as functional foods/nutraceuticals in diet for promoting human health.

Identification of two UDP-glycosyltransferases involved in the main oleanane-type ginsenosides in Panax japonicus var. major.

MAIN CONCLUSION: Two UDP-glycosyltransferases from Panax japonicus var. major were identified, and the biosynthetic pathways of three oleanane-type ginsenosides (chikusetsusaponin IVa, ginsenoside Ro, zingibroside R1) were elucidated. Chikusetsusaponin IVa and ginsenoside Ro are primary active components formed by stepwise glycosylation of oleanolic acid in five medicinal plants of the genus Panax. However, the key UDP-glycosyltransferases (UGTs) in the biosynthetic pathway of chikusetsusaponin IVa and ginsenoside Ro are still unclear. In this study, two UGTs (PjmUGT1 and PjmUGT2) from Panax japonicus var. major involved in the biosynthesis of chikusetsusaponin IVa and ginsenoside Ro were identified based on bioinformatics analysis, heterologous expression and enzyme assays. The results show that PjmUGT1 can transfer a glucose moiety to the C-28 carboxyl groups of oleanolic acid 3-O-ß-D-glucuronide and zingibroside R1 to form chikusetsusaponin IVa and ginsenoside Ro, respectively. Meanwhile, PjmUGT2 can transfer a glucose moiety to oleanolic acid 3-O-ß-D-glucuronide and chikusetsusaponin IVa to form zingibroside R1 and ginsenoside Ro. This work uncovered the biosynthetic mechanism of chikusetsusaponin IVa and ginsenoside Ro, providing the rational production of valuable saponins through synthetic biology strategy.

A comprehensive study of three species of Paeonia stem and leaf phytochemicals, and their antioxidant activities.

ETHNOPHARMACOLOGICAL RELEVANCE: Paeonia plants have been widely used as traditional Chinese medicinal materials for more than 2,000 years in the treatment of cardiovascular, extravasated blood and female genital diseases; paeoniflorin and paeonol have been implicated as the plants' primary active ingredients. AIM OF THE STUDY: Previous studies have been singularly focused on the chemical constituents and content variation of the Paeonia roots in the advancement of traditional Chinese medicine, with the plants' stems and leaves considered useless. This study aims to explore the chemical constituents, content variation, and antioxidant capacity in Paeonia stems and leaves for the future utilization of traditional Chinese medicine, given that current practices of digging and trade endanger Paeonia in the wild. MATERIALS AND METHODS: Herein, secondary metabolites from the stems and leaves from six developmental stages of the annual growth cycle of Paeonia ostii T. Hong & J. X. Zhang, P. 'Hexie', and P. lactiflora Pall. were qualitatively and quantitatively analyzed via high-performance liquid chromatography with a diode array detector (HPLC-DAD) and high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS). Antioxidant capacity at each stage was also evaluated by various free radical scavenging assays. RESULTS: A total of 24 metabolites were detected and identified, including 5 monoterpene glycosides, 4 tannins, 5 phenols, 9 flavonoids, and paeonol. Excepting paeonol and the phenols, the levels of each metabolite category were significantly higher in the leaves than the stems during all developmental stages. The paeoniflorin content in the P. ostii leaves was the highest during the first developmental stage and higher than the standards of the Chinese Pharmacopoeia, suggesting it to be the optimal harvesting stage for medicinal uses. Notably, the antioxidant capacity of the leaves was significantly greater than in the stems, particularly for the leaves of P. 'Hexie'. CONCLUSION: Our study indicates that the leaves of P. 'Hexie' have the potential to be a worthy medicinal substitute to Paeonia roots due to their high monoterpene glycosides, phenols, and flavonoids as well as their strong antioxidant capacity. Further, this study provides a theoretical basis for the development and utilization of non-root Paeonia plant sections as medicinal plant resources.

Simultaneous quantification of eleven bioactive phenolic compounds in pigeon pea natural resources and in vitro cultures by ultra-high performance liquid chromatography coupled with triple quadrupole mass spectrometry (UPLC-QqQ-MS/MS).

Bioactive phenolics primarily contribute to versatile health benefits of pigeon pea. For the first time, an UPLC-QqQ-MS/MS method was developed for the quantitative analysis of eleven bioactive phenolic compounds in pigeon pea natural resources (seeds, leaves, and roots) and in vitro cultures (calli and hairy roots). The proposed method could be achieved within 6 min of running time, and displayed the satisfactory linearity, sensitivity, precision, accuracy, and stability. According to analytical results, the distribution of eleven target compounds in different organs of pigeon pea was clarified. Also, it was surprisingly found that pigeon pea in vitro cultures exhibited superiority in contents of genistin and cajaninstilbene acid as compared with natural resources. Overall, the present work provided a rapid and sensitive analysis approach, which could be useful not only for quality control of pigeon pea natural resources, but also for applicability and safety evaluation of pigeon pea in vitro cultures.

Engineering CrtW and CrtZ for improving biosynthesis of astaxanthin in Escherichia coli.

This study engineered ß-carotene ketolase CrtW and ß-carotene hydroxylase CrtZ to improve biosynthesis of astaxanthin in Escherichia coli. Firstly, crtW was randomly mutated to increase CrtW activities on conversion from ß-carotene to astaxanthin. A crtW* mutant with A6T, T105A and L239M mutations has improved 5.35-fold astaxanthin production compared with the wild-type control. Secondly, the expression levels of crtW* and crtZ on chromosomal were balanced by simultaneous modulation RBS regions of their genes using RBS library. The strain RBS54 selected from RBS library, directed the pathway exclusively towards the desired product astaxanthin as predominant carotenoid (99%). Lastly, the number of chromosomal copies of the balanced crtW-crtZ cassette from RBS54 was increased using a Cre-loxP based technique, and a strain with 30 copies of the crtW*-crtZ cassette was selected. This final strain DL-A008 had a 9.8-fold increase of astaxanthin production compared with the wild-type control. Fed-batch fermentation showed that DL-A008 produced astaxanthin as predominant carotenoid (99%) with a specific titer of 0.88 g·L-1 without addition of inducer. In conclusion, through constructing crtW mutation, balancing the expression levels between crtW* and crtZ, and increasing the copy number of the balanced crtW*-crtZ cassette, the activities of ß-carotene ketolase and ß-carotene hydroxylase were improved for conversion of ß-carotene to astaxanthin with higher efficiency. The series of conventional and novel metabolic engineering strategies were designed and applied to construct the astaxanthin hetero-producer strain of E. coli, possibly offering a general approach for the construction of stable hetero-producer strains for other natural products.

Effective Production of Phenolic Compounds with Health Benefits in Pigeon Pea [Cajanus cajan (L.) Millsp.] Hairy Root Cultures.

Phenolic compounds in pigeon pea possess various biological properties beneficial to human health. In this study, pigeon pea hairy root cultures (PPHRCs) were developed as an effective in vitro platform for the production of phenolic compounds. A high-productive hairy root line was screened and characterized, and its culture conditions were optimized in terms of biomass productivity and phenolic yield. The comparative profiling of 10 phenolic compounds in PPHRCs and pigeon pea natural resources (seeds, leaves, and roots) was achieved by ultra-high-performance liquid chromatography-tandem mass spectrometry analysis. The total phenolic yield in PPHRCs (3278.44 µg/g) was much higher than those in seeds (68.86 µg/g) and roots (846.03 µg/g), and comparable to leaves (3379.49 µg/g). Notably, PPHRCs exhibited superiority in the yield of the most important health-promoting compound cajaninstilbene acid (2996.23 µg/g) against natural resources (4.42-2293.31 µg/g). Overall, PPHRCs could serve as promising potential alternative sources for the production of phenolic compounds with nutraceutical/medicinal values.

Baicalin Is Curative Against Rotavirus Damp Heat Diarrhea by Tuning Colonic Mucosal Barrier and Lung Immune Function.

BACKGROUND: Previous studies have indicated that rotavirus (RV) is a causative factor for diarrhea and gastroenteritis in pediatric and neonatal settings. Baicalin has many functions, including antibacterial, antiinflammatory, and antihypertensive activities. However, the immunological mechanism of RV-induced diarrhea with heat-dampness syndrome (RV-DH) remains unclear. AIMS: The aim of this study is to explore the role of baicalin in RV-DH diarrhea and its underlying mechanism. METHODS: A mouse model of pediatric RV-DH diarrhea was established and treated with baicalin. The concentrations of cytokines were detected by enzyme-linked immunosorbent assay. Messenger RNA (mRNA) expression levels were detected by quantitative real-time polymerase chain reaction (qRT-PCR), while protein expression levels were determined by Western blotting and immunohistochemistry. Flow cytometry was used to detect the frequency of lymphocytes. RESULTS: The concentrations of interleukin-1ß (IL-1ß), IL-2, IL-6, IL-8, RVvb, and secretory immunoglobulin A (SIgA) in bronchoalveolar lavage fluid (BALF) and colonic mucosa were significantly increased in the RV-DH group. Decreased expression of occludin, claudin-1, and zonula occludens-1 (ZO-1) indicated loss of tight junction function and disturbances in intestinal mucosal permeability in the RV-DH group. Flow cytometry analysis showed a high rate of CD8+ lymphocytes and low amount of CD4+ lymphocytes in the RV-DH group. Treatment of RV-DH mice with baicalin significantly reduced the duration of diarrhea and ameliorated the symptoms and pathological and immunological changes. Furthermore, baicalin inhibited STAT1 and activated STAT3 signaling pathways. CONCLUSIONS: These findings indicate the curative and immunoregulatory properties of baicalin and have direct practical and clinical relevance for the treatment of RV-DH enteritis in humans.

Effect of Moringa oleifera supplementation on productive performance, colostrum composition and serum biochemical indexes of sow.

Moringa oleifera has been considered as a potential functional feed or food, since it contains multiple components beneficial to animal and human. However, little is known about the effects of Moringa oleifera supplementation on productive performances in sows. In the current study, the results showed that dietary Moringa oleifera significantly decreased the farrowing length and the number of stillborn (p < .05), while had an increasing trend in the number of live-born (0.05 < p < .10). Furthermore, 8% Moringa oleifera supplementation significantly elevated protein levels in the colostrum (p < .05); 4% Moringa oleifera lowed serum urea nitrogen of sows after 90 days of gestation (p < .05) and significantly decreased serum glucose on 10 days of lactation (p < .05). Both groups showed significant elevation in serum T-AOC activity (p < .05). The serum malondialdehyde (MDA) of sows declined significantly in 4% Moringa oleifera addition group (p < .05). 8% Moringa oleifera meal significantly elevated serum CAT activity after 60 days of gestation (p < .05), while decreased the serum MDA level and increased the serum GSH-Px activity of sows at 10 days of lactation (p < .05). Of piglets, both two dosages of Moringa oleifera supplementation essentially reduced the serum urea nitrogen (p < .05), and 4% Moringa oleifera meal increased serum total protein (p < .05). In addition, piglets that received 8% Moringa oleifera had the highest serum CAT and SOD activities among all groups (p < .05). The present study indicated that Moringa oleifera supplementation could enhance the reproduction performances, elevate protein levels in the colostrum and improve the serum antioxidant indices in both sows and piglets.

Anti-oxidation and Anti-inflammatory Effect of Yixinshu Capsule in Treatment of Qi-Yin Deficiency in Viral Myocarditis / 中国实验方剂学杂志

Objective:To discuss the clinical efficacy of Yixinshu capsule for viral myocarditis (VMC) with deficiency of Qi and Yin, and to investigate its antioxidant and anti-inflammatory effect. Method:One hundred and thirty-two patients were randomly divided into control group (66 cases) and observation group (66 cases) by random number table. Patients in two group got comprehensive treatment of Western medicine, i.e. intravenous drip of creatine phosphate injection for 14 days, 1 g/time, 1 time/day. Coenzyme Q10 capsule, 1 grain/time, 3 times/day after meals. Trimetazidine dihydrochloride tablets, 1 tablet/time, 3 times/day during meals. And critically ill patients got intravenous drip of dexamethasone sodium phosphate injection for 14 days, 10-20 mg/time, 1 time/day. The control group took Wenxin granules orally,One bag at a time,3 times/day. Patients in observation group additionally got Yixinshu capsule, 3 grains/time, 3 times/days. The courses of treatment were 8 weeks in both groups. The serum troponin I (cTnI) and creatine phosphokinase (CK-MB) were monitored, and after treatment, the recovery rates of cTnI, CK-MB were recorded. Before and after treatment, the electrocardiogram was observed and the recovery rate after treatment was recorded. Before and after treatment, the scores of deficiency of Qi and Yin were graded, and levels of creatine phosphokinase (CPK), hydroxybutyrate dehydrogenase (HBDH), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), interferon-γ (IFN-γ), interleukin-10 (IL-10), IL-17 and IL-35 were detected. Echocardiography, left ventricular ejection fraction (LVEF), cardiac index (CI), and maximum velocity values between early and late diastolic (E/A) were detected. Result:In the analysis of rank sum test, clinical efficacy in observation group was better than that in control group (Z=2.151, P<0.05). Recovery rates of cTnI, CK-MB and electrocardiogram in observation group were 82.26% (51/62), 90.32% (56/62) and 80.65% (50/62), higher than 65.00% (39/60), 73.33% (44/60) and 63.33% (38/60) in control group (P<0.05). Levels of serum cTnI, CK-MB, CPK, HBDH, LDH, AST, MDA, IFN-γ and IL-17 were lower than those in control group (P<0.01), while levels of LVEF, CI, E/A, SOD, GSH-Px, IL-10 and IL-35 were higher than those in control group (P<0.01). Conclusion:On the basis of comprehensive anti-infection treatment, Yixinshu capsule can additional protect myocardium by anti-inflammatory and antioxidant effect, reduce myocardial enzyme, promote the recovery of ECG and cardiac enzyme, improve cardiac function and improve the effect of clinical treatment.

Succinate induces skeletal muscle fiber remodeling via SUNCR1 signaling.

The conversion of skeletal muscle fiber from fast twitch to slow-twitch is important for sustained and tonic contractile events, maintenance of energy homeostasis, and the alleviation of fatigue. Skeletal muscle remodeling is effectively induced by endurance or aerobic exercise, which also generates several tricarboxylic acid (TCA) cycle intermediates, including succinate. However, whether succinate regulates muscle fiber-type transitions remains unclear. Here, we found that dietary succinate supplementation increased endurance exercise ability, myosin heavy chain I expression, aerobic enzyme activity, oxygen consumption, and mitochondrial biogenesis in mouse skeletal muscle. By contrast, succinate decreased lactate dehydrogenase activity, lactate production, and myosin heavy chain IIb expression. Further, by using pharmacological or genetic loss-of-function models generated by phospholipase Cß antagonists, SUNCR1 global knockout, or SUNCR1 gastrocnemius-specific knockdown, we found that the effects of succinate on skeletal muscle fiber-type remodeling are mediated by SUNCR1 and its downstream calcium/NFAT signaling pathway. In summary, our results demonstrate succinate induces transition of skeletal muscle fiber via SUNCR1 signaling pathway. These findings suggest the potential beneficial use of succinate-based compounds in both athletic and sedentary populations.

Transcriptome analysis of Panax zingiberensis identifies genes encoding oleanolic acid glucuronosyltransferase involved in the biosynthesis of oleanane-type ginsenosides.

MAIN CONCLUSION: Oleanolic acid glucuronosyltransferase (OAGT) genes synthesizing the direct precursor of oleanane-type ginsenosides were discovered. The four recombinant proteins of OAGT were able to transfer glucuronic acid at C-3 of oleanolic acid that yields oleanolic acid 3-O-ß-glucuronide. Ginsenosides are the primary active components in the genus Panax, and great efforts have been made to elucidate the mechanisms underlying dammarane-type ginsenoside biosynthesis. However, there is limited information on oleanane-type ginsenosides. Here, high-performance liquid chromatography analysis demonstrated that oleanane-type ginsenosides (particularly ginsenoside Ro and chikusetsusaponin IV and IVa) are the abundant ginsenosides in Panax zingiberensis, an extremely endangered Panax species in southwest China. These ginsenosides are derived from oleanolic acid 3-O-ß-glucuronide, which may be formed from oleanolic acid catalyzed by an unknown oleanolic acid glucuronosyltransferase (OAGT). Transcriptomic analysis of leaves, stems, main roots, and fibrous roots of P. zingiberensis was performed, and a total of 46,098 unigenes were obtained, including all the identified homologous genes involved in ginsenoside biosynthesis. The most upstream genes were highly expressed in the leaves, and the UDP-glucosyltransferase genes were highly expressed in the roots. This finding indicated that the precursors of ginsenosides are mainly synthesized in the leaves and transported to different parts for the formation of particular ginsenosides. For the first time, enzyme activity assay characterized four genes (three from P. zingiberensis and one from P. japonicus var. major, another Panax species with oleanane-type ginsenosides) encoding OAGT, which particularly transfer glucuronic acid at C-3 of oleanolic acid to form oleanolic acid 3-O-ß-glucuronide. Taken together, our study provides valuable genetic information for P. zingiberensis and the genes responsible for synthesizing the direct precursor of oleanane-type ginsenosides.

Fatty Acid Composition, Phytochemistry, Antioxidant Activity on Seed Coat and Kernel of Paeonia ostii from Main Geographic Production Areas.

Paeonia ostii is an important woody oil plant cultivated in China on a large scale. Its seed oil is enriched with unsaturated fatty acids and a high content of alpha-linolenic acid (ALA), which are beneficial to human health. The aim of this research is to determine the qualitative traits characteristic of P. ostii seed from various production areas in China. In this study, seed quality traits were evaluated on the basis of proximate composition, content of fatty acids, tocopherol, secondary metabolites, and the antioxidant activity of seed coat (PSC) and kernel (PSK). A high content of total fatty acids (298.89-399.34 mg g-1), crude protein (16.91%-22.73%), and total tocopherols (167.83-276.70 µg g-1) were obtained from PSK. Significant differences were found in the content of palmitic acids (11.31-14.27 mg g-1), stearic acids (2.42-4.24 mg g-1), oleic acids (111.25-157.63 mg g-1), linoleic acids (54.39-83.59 mg g-1), and ALA (99.85-144.71 mg g-1) in the 11 main production areas. Eight and seventeen compounds were detected in PSC and PSK, respectively. A significantly higher content of total phenols was observed in PSC (139.49 mg g-1) compared with PSK (3.04 mg g-1), which was positively related to antioxidant activity. This study indicates that seeds of P. ostii would be a good source of valuable oil and provides a basis for seed quality evaluation for the production of edible oil and potential ALA supplements from the promising woody oil plant.

New azaphilones and tremulane sesquiterpene from endophytic Nigrospora oryzae cocultured with Irpex lacteus.

Five new metabolites belonging to two backbones of pulvilloric acid-type azaphilone and tremulane sesquiterpene were obtained and their structures were determined by spectral analysis. Based on the biogenesis analysis, tremulane sesquiterpenes were obtained from Irpex lacteus by the stimulation of mixed-culture. The antifungal selectivities of metabolites produced by fungus against their co-culture fungus and common pathogens, exhibited competitive interaction of this mix-culture. The tremulane sesquiterpene conocenol B produced by I. lacteus through the induction of Nigrospora oryzae showed selectivity of anti-fungal activity against its co-culture fungus, N. oryzae, with MICs at 16 µg/mL and 128 µg/mL against I. lacteus. The fungus can metabolize these new compounds to inhibit the growth of co-culture fungus while not inhibiting its own growth. Compound 5 was active against acetylcholinesterase (AChE) with a ratio of 35% at the concentration of 50 µM.

Effect of parenteral glutamine supplementation combined with enteral nutrition on Hsp90 expression and Peyer's patch apoptosis in severely burned rats.

OBJECTIVES: The aim of this study was to investigate the effects of parenteral glutamine (GLN) supplementation combined with enteral nutrition (EN) on heat shock protein (Hsp) 90 expression and Peyer's patch (PP) apoptosis in severely burned rats. METHODS: Male Sprague-Dawley (SD) rats were randomly assigned to four groups: Sham burn + EN + GLN-free amino acid (AA; n = 10), sham burn + EN + GLN (n = 10), burn + EN + AA (n = 10), and burn + EN + GLN (n = 10). Two hours after a 30% total body surface area (TBSA), full-thickness scald burn injury on the back, burned rats in two of the experimental groups (burn + EN + AA and burn + EN + GLN groups) were fed with a conventional EN solution by oral gavage for 7 d. Simultaneously, rats in the burn + EN + GLN group were given 0.35 g GLN/kg body weight/d once via a tail vein injection for 7 d and rats in the burn + EN + AA group were administered isocaloric/isonitrogenous GLN-free amino acid solution (Tyrosine) for comparison. Rats in two sham burn control groups (sham burn + EN + AA and sham burn + EN + GLN groups) were treated in the same manner except for the burn injury. All rats in the four groups were given 175 kcal/kg body wt/d. There was isonitrogenous, isovolumic, and isocaloric intake among the four groups. At the end of the seventh day after completion of the nutritional program, all rats were anesthetized and samples were collected for further analysis. PP apoptosis was measured by terminal deoxyuridine nick-end labeling (TUNEL). The expression of Hsp90 in PPs was analyzed by western blotting. Caspase-3 activity of PPs was also assessed. Levels of proinflammatory cytokines of gut tissues were evaluated by enzyme-linked immunosorbent assay (ELISA). The intestinal immunoglobulin A (IgA) content was also determined by ELISA. RESULTS: The results revealed that intestinal IgA content in rats of the burn + EN + GLN group were significantly increased compared with those in the burn + EN + AA group (P < 0.05). The expression of Hsp90 of PPs in rats in the burn + EN + GLN group was significantly upregulated compared with those in the burn + EN + AA group (P < 0.05). On the other hand, levels of proinflammatory cytokines of gut tissues, caspase-3 activity, and the number of TUNEL-stained cells of PPs in rats of the burn + EN + GLN group were markedly decreased compared with those of the burn + EN + AA group (P < 0.05). CONCLUSIONS: The results of this study show that parenteral glutamine supplementation combined with EN may upregulate the expression of Hsp90, reduce caspase-3 activity, lessen the release of proinflammatory cytokines, attenuate PP apoptosis, and improve intestinal IgA response in burned rats. Clinically, therapeutic efforts to improve intestinal immunity may contribute to a favorable outcome in severely burned patients.