New cassane-type alkaloids and diterpenoids from the pericarps of Caesalpinia bonduc.

The phytochemical investigation of the pericarps of Caesalpinia bonduc led to the isolation and identification of five new cassane-type alkaloids: caesalminines C - G (1-5) and six new diterpenoids: caesalbonducin K - P (6-11), along with seven known compounds (12-18). Compounds 1-5 were identified as a group of rare alkaloids possessing a tetracyclic cassane-type diterpenoid skeleton with a lactam D-ring instead of a typical furan or lactone moiety. The structures of 1-11 were elucidated on the basis of 1D and 2D NMR including HSQC, HMBC, COSY and NOESY, and other spectroscopic analyses. The cytotoxic activities of the isolated compounds were evaluated in the A431, A549 and U87MG cancer cell lines.

Efficacy and safety of the Chinese herbal medicine Xiao Yao San for treating anxiety: a systematic review with meta-analysis and trial sequential analysis.

Introduction: The effectiveness and safety of the Chinese herbal medicine (CHM) Xiao Yao San (XYS) used for treating anxiety disorders are still unknown. Thus, we conducted this systematic review with meta-analysis and trial sequential analysis (TSA) to determine its safety and efficacy. Methods: We searched 12 databases for relevant studies from the inception of each database till 10 August 2023. We selected randomized controlled trials to compare the efficacy and safety of XYS (including XYS only and XYS + anxiolytics) to those of anxiolytics in patients with anxiety. Results: We found 14 trials with 1,256 patients in total that met the requirements for inclusion. We assessed the majority of studies (8 out of 14) as being at high risk of bias; 6 were assessed as having a moderate risk of bias. Three trials compared oral XYS to anxiolytic medication, and 11 trials compared oral XYS plus anxiolytics to anxiolytic treatment alone. The pooled results showed that the efficacy of treatment in the XYS + anxiolytics groups was significantly higher than that of the anxiolytics alone group (RR = 1.19; 95% CI: [1.13, 1.26]; p < 0.00001; I2 = 0) and the adverse event rates in the XYS + anxiolytics groups were significantly lower than those in the anxiolytics alone group (RR = 0.44; 95% CI: [0.28, 0.82]; p = 0.001 < 0.05; I2 = 13). The efficacy of treatment in the XYS alone groups was also significantly higher than that of the anxiolytics alone groups (RR = 5.41; 95% CI: [2.23, 13.11]; p < 0.0001; I2 = 0). However, there was no statistical difference between the adverse events of the XYS alone group and the anxiolytics alone group, although the incidence of adverse events in the XYS alone group was lower than that in the anxiolytics alone group. The results of the TSA confirmed the above findings. Conclusion: The use of XYS combined with anxiolytics for treating anxiety was found to be safe and effective. However, although XYS alone is effective in the treatment of anxiety disorder, more large-scale research is needed to investigate adverse events. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=350358, identifier CRD42022350358.

Unearthing the alleviatory mechanisms of hydrogen sulfide in aluminum toxicity in rice.

Hydrogen sulfide (H2S) improves aluminum (Al) resistance in rice, however, the underlying mechanism remains unclear. In the present study, treatment with 30-µM Al significantly inhibited rice root growth and increased the total Al content, apoplastic and cytoplasm Al concentration in the rice roots. However, pretreatment with NaHS (H2S donor) reversed these negative effects. Pretreatment with NaHS significantly increased energy production under Al toxicity conditions, such as by increasing the content of ATP and nonstructural carbohydrates. In addition, NaHS stimulated the AsA-GSH cycle to decrease the peroxidation damage induced by Al toxicity. Pretreatment with NaHS significantly inhibited ethylene emissions in the rice and then inhibited pectin synthesis and increased the pectin methylation degree to reduce cell wall Al deposition. The phytohormones indole-3-acetic and brassinolide were also involved in the alleviation of Al toxicity by H2S. The transcriptome results further confirmed that H2S alleviates Al toxicity by increasing the pathways relating to material and energy metabolism, redox reactions, cell wall components, and signal transduction. These findings improve our understanding of how H2S affects rice responses to Al toxicity, which will facilitate further studies on crop safety.

Phylogenomics and Comparative Genomics Highlight Specific Genetic Features in Ganoderma Species.

The Ganoderma species in Polyporales are ecologically and economically relevant wood decayers used in traditional medicine, but their genomic traits are still poorly documented. In the present study, we carried out a phylogenomic and comparative genomic analyses to better understand the genetic blueprint of this fungal lineage. We investigated seven Ganoderma genomes, including three new genomes, G. australe, G. leucocontextum, and G. lingzhi. The size of the newly sequenced genomes ranged from 60.34 to 84.27 Mb and they encoded 15,007 to 20,460 genes. A total of 58 species, including 40 white-rot fungi, 11 brown-rot fungi, four ectomycorrhizal fungi, one endophyte fungus, and two pathogens in Basidiomycota, were used for phylogenomic analyses based on 143 single-copy genes. It confirmed that Ganoderma species belong to the core polyporoid clade. Comparing to the other selected species, the genomes of the Ganoderma species encoded a larger set of genes involved in terpene metabolism and coding for secreted proteins (CAZymes, lipases, proteases and SSPs). Of note, G. australe has the largest genome size with no obvious genome wide duplication, but showed transposable elements (TEs) expansion and the largest set of terpene gene clusters, suggesting a high ability to produce terpenoids for medicinal treatment. G. australe also encoded the largest set of proteins containing domains for cytochrome P450s, heterokaryon incompatibility and major facilitator families. Besides, the size of G. australe secretome is the largest, including CAZymes (AA9, GH18, A01A), proteases G01, and lipases GGGX, which may enhance the catabolism of cell wall carbohydrates, proteins, and fats during hosts colonization. The current genomic resource will be used to develop further biotechnology and medicinal applications, together with ecological studies of the Ganoderma species.

Involvement of YTHDF1 in renal fibrosis progression via up-regulating YAP.

Renal fibrosis is a progressive, fatal renal disease characterized by the aberrant accumulation of myofibroblasts that produce excess extracellular matrix (ECM) in the renal interstitium and glomeruli. Yes-associated protein (YAP) has been regarded as a crucial modulator in myofibroblast transformation, but its upstream regulator remains a mystery. In the present study investigating the participation of m6A methylation during renal fibrosis through bioinformatics analysis, we identified YTHDF1, a modulator of m6A methylation, as a key contributor for renal fibrosis because it was highly expressed in human fibrotic kidneys and had a significant correction with YAP. Their co-localization in human fibrotic kidneys was additionally shown by immunofluorescence. We then found that YTHDF1 was also up-regulated in fibrotic mouse kidneys induced by unilateral ureteral obstruction (UUO), high-dose folic acid administration, or the unilateral ischemia-reperfusion injury, further supporting a causal role of YTHDF1 during renal fibrosis. Consistent with this notion, YTHDF1 knockdown alleviated the progression of renal fibrosis both in cultured cells induced by transforming growth factor-beta administration and in the UUO mouse model. Meanwhile, YAP was accordingly down-regulated when YTHDF1 was inhibited. Furthermore, the specific binding of YTHDF1 to YAP mRNA was detected using RNA Binding Protein Immunoprecipitation, and the up-regulation of fibrotic related molecules in cultured cells induced by YTHDF1 over-expression plasmid was attenuated by YAP siRNA. Taken together, our data highlight the potential utility of YTHDF1 as an indicator for renal fibrosis and suggest that YTHDF1 inhibition might be a promising therapeutic strategy to alleviate renal fibrosis via downregulating YAP.

A-Lipoic Acid Alleviates Folic Acid-Induced Renal Damage Through Inhibition of Ferroptosis.

Folic acid (FA)-induced acute kidney injury (AKI) is characterized by the disturbance of redox homeostasis, resulting in massive tubular necrosis and inflammation. Α-lipoic acid (LA), as an antioxidant, has been reported to play an important role in renal protection, but the underlying mechanism remains poorly explored. The aim of this study is to investigate the protective effect of LA on FA-induced renal damage. Our findings showed that LA could ameliorate renal dysfunction and histopathologic damage induced by FA overdose injection. Moreover, FA injection induced severe inflammation, indicated by increased release of pro-inflammatory cytokines tumor necrosis factor (TNF)-α and IL-1ß, as well as infiltration of macrophage, which can be alleviated by LA supplementation. In addition, LA not only reduced the cellular iron overload by upregulating the expressions of Ferritin and ferroportin (FPN), but also mitigated reactive oxygen species (ROS) accumulation and lipid peroxidation by increasing the levels of antioxidant glutathione (GSH) and glutathione peroxidase-4 (GPX4). More importantly, we found that LA supplementation could reduce the number of Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive tubular cells caused by FA, indicating that the tubular cell death mediated by ferroptosis may be inhibited. Further study demonstrated that LA supplementation could reverse the decreased expression of cystine/glutamate antiporter xCT (SLC7A11), which mediated GSH synthesis. What is more, mechanistic study indicated that p53 activation was involved in the inhibitory effect of SLC7A11 induced by FA administration, which could be suppressed by LA supplementation. Taken together, our findings indicated that LA played the protective effect on FA-induced renal damage mainly by inhibiting ferroptosis.

An Efficacy Predictive Method for Diabetic Ulcers Based on Higher-Order Markov Chain-Set Pair Analysis.

BACKGROUND: Clinical comprehensive decision-making of diabetic ulcers includes curative effect evaluation and curative effect prediction. Nevertheless, there are few studies on the prediction of diabetic ulcers. METHODS: Set pair analysis (SPA) was used to assess the curative effect evaluation, and therapeutic effect was evaluated by connection degree (CD). The higher-order Markov chain-SPA curative effect prediction model was established to predict the future curative effect development. The predicted results with higher-order Markov chain-SPA and traditional first-order Markov-SPA model were compared with the actual results of the patients to verify the effectiveness of prediction. RESULTS: The connection degree of index levels I and II of 15 patients with diabetic ulcers after traditional Chinese medicine (TCM) treatment increased with time, while that of index levels IV and V decreased, indicating that the curative effect tends to improve. The higher-order Markov chain-SPA model was used to predict the curative effect. The results showed that the relative errors were fewer than the traditional first-order Markov-SPA model. CONCLUSIONS: The present study suggests that a method of SPA combined with higher-order Markov-SPA is relatively effective and can be applied to the clinical prediction of diabetic ulcers, which has higher accuracy than traditional first-order curative effect prediction model.

Effects of Electroacupuncture Therapy and Cognitive Behavioral Therapy in Chronic Insomnia: A Randomized Controlled Study.

OBJECTIVE: To evaluate the efficacy of spirit-regulating electroacupuncture (EA), cognitive behavioral therapy (CBT), and combined EA/CBT to treat insomnia. METHODS: In this prospective clinical study, patients were randomly assigned to receive EA, CBT, or EA/CBT. Outcomes were assessed using PSQI, ISI, ESS, DBAS-16, HAM-A, and HAM-D at two- and four-week follow-up. RESULTS: Overall, the PSQI and ISI scores decreased after treatment in all three groups. At two-week follow-up, the EA/CBT group obtained lower PSQI and ISI scores than the EA group. The daytime functional factor score in the EA group was lower than that of the CBT group after the second week of treatment, and the EA/CBT PSQI score was lower than that of the CBT group on the second week of follow-up. In comparison with baseline, the EA group had a decreased ESS score after the second and fourth weeks of treatment, while the ESS score increased in the CBT group after the fourth week of treatment. ESS scores were unchanged following treatment in the EA/CBT group. After the second and fourth weeks of treatment, the ESS scores from the CBT group were higher than the EA group. The DBAS-16 decreased in the CBT and EA/CTB groups, while the EA group had a higher DBAS-16 score. In all three groups, HAM-A and HAM-D scores decreased after treatment; the EA/CBT HAM-A and HAM-D scores were lower than the other two groups. CONCLUSION: 1. Spirit-regulating EA therapy is effective. In terms of improving sleep quality and mood, EA has the same effect as CBT and can improve daytime function earlier. 2. The curative effect of the EA/CBT group lasts longer than that of the EA group, and EA/CBT is better at improving daytime function compared to CBT alone and better at improving mood compared to CBT or EA alone.

Application of a Cloud Model-Set Pair Analysis in Efficacy Assessment for Diabetic Ulcers.

Because treatment of diabetic ulcers includes various uncertainties, efficacy assessments are needed and significant. In previous studies, set pair analysis (SPA) has been applied to the efficacy assessments of traditional Chinese medicine (TCM) that pick out uncertainties related to the development and prognosis of disease. Optimized clinical protocols of SPA improve clinical efficacy. In the article, cloud model (CM) is employed to improve SPA, and a novel efficacy assessment method for a treatment of diabetic ulcers is proposed based on the cloud model-set pair analysis (CM-SPA). It is recommended to replace connection degree (CD) with cloud connection degree (CCD) that the efficacy assessment results are shown as normal clouds. Then, three diabetic ulcers patients treated with TCM made importance assessment by both CM-SPA and AHP based SPA. The comparison of assessment results shows that the CM-SPA is efficacious for the efficacy assessment of a treatment for diabetic ulcers and the results will be more scientific and accurate via CM-SPA.

[Investigation and application of Dendrobium resources in Qinba Mountains with a discussion on industrial poverty alleviation model].

The Dendrobium species are rare and endangered medicinal plants, and it is difficult to investigate their wild resources with conventional methods because of typical epiphytic herbaceous. We explored Dendrobium resources(include culture resource) of Qinba Mountains and the boundary Mountain area in Hubei, Chongqing using the methods of literatures and field investigation, and found that the cultural base of Dendrobium were profound in Qinba Mountains region. Furthermore, its germplasm resources of Dendrobium were established for the first time in Wanzhou Luotian town. In case the advantages of local rock resources and poverty alleviation demand, we have actively carried out the cultivating mode of Dendrobium which grow on rock, and the poverty alleviation model of local characteristic Dendrobium industry were established preliminarily. Our application case can provide reference for the mining and transformation of traditional Chinese medicine resources census results.

Investigation and application of Dendrobium resources in Qinba Mountains with a discussion on industrial poverty alleviation model / 中国中药杂志

The Dendrobium species are rare and endangered medicinal plants, and it is difficult to investigate their wild resources with conventional methods because of typical epiphytic herbaceous. We explored Dendrobium resources(include culture resource) of Qinba Mountains and the boundary Mountain area in Hubei, Chongqing using the methods of literatures and field investigation, and found that the cultural base of Dendrobium were profound in Qinba Mountains region. Furthermore, its germplasm resources of Dendrobium were established for the first time in Wanzhou Luotian town. In case the advantages of local rock resources and poverty alleviation demand, we have actively carried out the cultivating mode of Dendrobium which grow on rock, and the poverty alleviation model of local characteristic Dendrobium industry were established preliminarily. Our application case can provide reference for the mining and transformation of traditional Chinese medicine resources census results.

[Original materials of traditional Chinese medicinal names of "Jinchai" and "Jinchai Shihu" based on vegetative morphology].

"Jinchai Shihu" were called Jinchai and recoded in "Taishang Zhouhou Yujingfang" of Tang Dynasty, which first clearly documented the name of Shihu in complex Dendrobium medicines and were condiered as superior medicinal articles. Morphological features are one of the naming principles for Chinese medicines. In this paper, botanical origin plants under the names of "Jinchai" and "Jinchai Shihu" were investigated. Based on documents from the local Chronicles and historical accounts, the Chinese characters of Jinchai have the distinctive features of gold color and two hair clasps. Moreover, the hair clasps are usually cylindrical in shape with uniform thickness in middle and upper part, and tapers off to the foot. And its bottom part style is simple and head part is complex. Thus we speculated the herbal "Jinchai" and "Jinchai Shihu" should have similar morphologic features as Chinese characters of Jinchai, including golden color and hairpin shape of stems without braches, short and solid sterm. After comparing the dried vegetative morphology of 10 common medicinal Dendrobium species, we suggested that of Dendrobium flexicaule matches well with the morphological features from historical herbal records.

Original materials of traditional Chinese medicinal names of "Jinchai" and "Jinchai Shihu" based on vegetative morphology / 中国中药杂志

"Jinchai Shihu" were called Jinchai and recoded in "Taishang Zhouhou Yujingfang" of Tang Dynasty, which first clearly documented the name of Shihu in complex Dendrobium medicines and were condiered as superior medicinal articles. Morphological features are one of the naming principles for Chinese medicines. In this paper, botanical origin plants under the names of "Jinchai" and "Jinchai Shihu" were investigated. Based on documents from the local Chronicles and historical accounts, the Chinese characters of Jinchai have the distinctive features of gold color and two hair clasps. Moreover, the hair clasps are usually cylindrical in shape with uniform thickness in middle and upper part, and tapers off to the foot. And its bottom part style is simple and head part is complex. Thus we speculated the herbal "Jinchai" and "Jinchai Shihu" should have similar morphologic features as Chinese characters of Jinchai, including golden color and hairpin shape of stems without braches, short and solid sterm. After comparing the dried vegetative morphology of 10 common medicinal Dendrobium species, we suggested that of Dendrobium flexicaule matches well with the morphological features from historical herbal records.

[Investigation of original materials under traditonal Chinese medicine names of "Jinchai" and "Jinchai Shihu"].

To clear from botanical view the original materials under the traditional Chinese medicine names of "Jinchai", "Jinchai Shihu" within the genus Dendrobium of the family Orchidaceae. Combined of different methods including study of historical records from the local chronicles and historical accounts of past event in Hubei, Sichuan, Chongqing, Henan and Shaanxi provinces, interviewing face to face with the old traditional Chinese workers and folk doctors in 20 downtowns and countrysides, such as, Laohekou, Lichuan, Fangxian, Xixia, Neixiang, and Ankang, and collecting a few plants of "Jinchai" for taxonomic identification. The traditional Chinese medicine names of "Jinchai", "Jinchai Shihu" were widely used by the local people from the eastern Chongqing, western Hubei, northeasten Sichuan, southeastern Shaanxi, western Henan. Those two names were frequently found in the local Chronicles and historical accounts of past event, even in the local daily life such as folk songs and stories. The botanical identification results showed that a endemic species of D. flexicaule is the original materials of the traditional Chinese medicine names "Jinchai" and "Jinchai Shihu", and this species are also called "Longtoujin", "Renzijin", "Huanzijin" and "Longtoufengweijin" by the local people. The dried artifactitious specimens of D. flexicaule are traditionally named as "Jinerhuan". The botanic resource plants of the traditional Chinese medicine names of "Jinchai", "Jinchai Shihu" are the endemic species of D. flexicaule that is distributed mainly in central areas of China including eastern Chongqing, western Hubei, northeasten Sichuan, southeastern Shaanxi, and western Henan, rather than D. nobile as referring in both Chinese and English version of Flora of China, and in official recorded serious versions of The Chinese Pharmacopoeia since 1977. In order to avoid confusion in the traditional Chinese medicine dendrobiums industry, the Chinese name of D. nobile is suggested as "Biancao Shihu", which characterized one stem feature of this species, and the traditional Chinese medicine names "Jinchai" or "JinchaiShihu" is suggested to refer to the species D. flexicaule.

Investigation of original materials under traditonal Chinese medicine names of "Jinchai" and "Jinchai Shihu" / 中国中药杂志

To clear from botanical view the original materials under the traditional Chinese medicine names of "Jinchai", "Jinchai Shihu" within the genus Dendrobium of the family Orchidaceae. Combined of different methods including study of historical records from the local chronicles and historical accounts of past event in Hubei, Sichuan, Chongqing, Henan and Shaanxi provinces, interviewing face to face with the old traditional Chinese workers and folk doctors in 20 downtowns and countrysides, such as, Laohekou, Lichuan, Fangxian, Xixia, Neixiang, and Ankang, and collecting a few plants of "Jinchai" for taxonomic identification. The traditional Chinese medicine names of "Jinchai", "Jinchai Shihu" were widely used by the local people from the eastern Chongqing, western Hubei, northeasten Sichuan, southeastern Shaanxi, western Henan. Those two names were frequently found in the local Chronicles and historical accounts of past event, even in the local daily life such as folk songs and stories. The botanical identification results showed that a endemic species of D. flexicaule is the original materials of the traditional Chinese medicine names "Jinchai" and "Jinchai Shihu", and this species are also called "Longtoujin", "Renzijin", "Huanzijin" and "Longtoufengweijin" by the local people. The dried artifactitious specimens of D. flexicaule are traditionally named as "Jinerhuan". The botanic resource plants of the traditional Chinese medicine names of "Jinchai", "Jinchai Shihu" are the endemic species of D. flexicaule that is distributed mainly in central areas of China including eastern Chongqing, western Hubei, northeasten Sichuan, southeastern Shaanxi, and western Henan, rather than D. nobile as referring in both Chinese and English version of Flora of China, and in official recorded serious versions of The Chinese Pharmacopoeia since 1977. In order to avoid confusion in the traditional Chinese medicine dendrobiums industry, the Chinese name of D. nobile is suggested as "Biancao Shihu", which characterized one stem feature of this species, and the traditional Chinese medicine names "Jinchai" or "JinchaiShihu" is suggested to refer to the species D. flexicaule.

Sphaerisporangium dianthi sp. nov., an endophytic actinomycete isolated from a root of Dianthus chinensis L.

A novel actinomycete, designated strain NEAU-CY18(T), was isolated from the root of a Chinese medicinal plant Dianthus chinensis L and subjected to a polyphasic taxonomic study. The novel strain was found to develop spherical sporangia with non-motile spores on aerial mycelium. The cell-wall peptidoglycan was found to contain meso-diaminopimelic acid. The whole-cell sugars were identified as madurose, mannose, ribose, galactose and glucose. The phospholipid profile was found to contain diphosphatidylglycerol, phosphatidylmethylethanolamine, phosphatidylethanolamine, hydroxy-phosphatidylmethylethanolamine, phosphatidylglycerol, phosphatidylinositol, phosphatidylinositol mannosides and an unidentified phospholipid. The predominant menaquinones were identified as MK-9(H4), MK-9(H2) and MK-9(H6). The major fatty acids were identified as C17:0 10-methyl, iso-C16:0 and C16:0. EzTaxon-e analysis of the 16S rRNA gene sequence indicated that the strain belongs to the genus Sphaerisporangium and was most closely related to Sphaerisporangium cinnabarinum JCM 3291(T) (98.9 %) and Sphaerisporangium melleum JCM 13064(T) (98.3 %). Phylogenetic analysis based on the 16S rRNA gene sequence indicated that strain NEAU-CY18(T) forms a monophyletic clade with S. cinnabarinum JCM 3291(T), an association that was supported by a bootstrap value of 97 % in the neighbour-joining tree and also recovered with the maximum-likelihood algorithm. Comparisons of some phenotypic properties and low DNA-DNA relatedness values enabled the strain to be differentiated from S. cinnabarinum JCM 3291(T) and S. melleum JCM 13064(T). Therefore, it is concluded that strain NEAU-CY18(T) represents a novel Sphaerisporangium species, for which the name Sphaerisporangium dianthi sp. nov. is proposed. The type strain is NEAU-CY18(T) ( = CGMCC 4.7132(T) = DSM 46736(T)).

Synergistic myoprotection of L-arginine and adenosine in a canine model of global myocardial ischaemic reperfusion injury / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Endogenous nitric oxide and adenosine increase simultaneously to keep the balance of energy demand and supply when the oxygen supply is insufficient, which suggests that nitric oxide and adenosine might exert a synergistic myoprotection during tissue hypoxia. In this study, we tested this hypothesis utilizing a canine model of prolonged global myocardial ischaemic reperfusion injury.</p><p><b>METHODS</b>In this double blind, controlled study, the hearts of 24 anaesthetized mongrel dogs were arrested for 2 hours with aortic cross clamping and blood cardioplegia. The treatment groups were those supplemented with 2 mmol/L L-arginine (ARG), supplemented with 1 mmol/L adenosine (ADO), ARG + ADO supplemented with both, and no supplementation (control) (n = 6 in each group). Haemodynamics, biochemical indices, adenosine triphosphate (ATP) content and myeloperoxidase activities of myocardium were determined to evaluate myocardial injury. Statistical comparison was performed by two way ANOVA.</p><p><b>RESULTS</b>Although the requirements for inotropic supports were higher, the cardiac outputs were lower in control group than in ARG, ADO and the combination groups. Plasma cardiac troponin I levels were higher and the areas of hydropic changes were larger in control group than in ARG and ADO groups. Combination of arginine and adenosine provided further myoprotection with respect to better cardiac performance, lower release of cardiac troponin I, and smaller areas of hydropic changes compared with ARG and ADO groups. ATP content was higher, but myeloperoxidase activities of myocardium were significantly lower in the combination group than in control, ARG and ADO groups (P < 0.05).</p><p><b>CONCLUSIONS</b>Combination of L-arginine and adenosine provides synergistic myoprotection in a canine model of global myocardial ischaemia. Thus, the combination is recommended when the heart is exposed to a prolonged ischaemia during cardiac surgery.</p>

[Enhancement of the production of SAM by overexpression of SAM synthetase in Pichia pastoris].

S-Adenosyl-L-methionine(SAM) is an important metabolic intermediate in the metabolic flux of sulphur. SAM is involved in three key metabolic pathways: transmethylation, transsulfuration and polyamine synthesis. As a potential therapeutic agent, SAM is being used as over the counter drug and nutrient supplement. An expression vector, harboring SAM synthetase 2 gene from S. cerevisiae and regulated by the glyceraldehyde-3-phosphate dehydrogenase gene promoter P(GAP), was transformed into GS115 strain of P. pastoris. Through zeocin resistance and expression screening, a recombinant strain was obtained that had high SAM yield and the fermentation conditions were optimized. The results showed that carbon source, nitrogen source, pH and dissolved oxygen had significant effects on the accumulation of SAM. The SAM production of the recombinant cells reached 2.49 g/L after fermentation for three days under the optimized conditions. The present studies show that fermentation of recombinant P. pastoris strain, expressing heterologous SAM synthetase gene, may be a promising approach for the production of SAM.