Late-stage cascade of oxidation reactions during the biosynthesis of oxalicine B in Penicillium oxalicum

Oxalicine B ( 1) is an α-pyrone meroterpenoid with a unique bispirocyclic ring system derived from Penicillium oxalicum. The biosynthetic pathway of 15-deoxyoxalicine B ( 4) was preliminarily reported in Penicillium canescens, however, the genetic base and biochemical characterization of tailoring reactions for oxalicine B ( 1) has remained enigmatic. In this study, we characterized three oxygenases from the metabolic pathway of oxalicine B ( 1), including a cytochrome P450 hydroxylase OxaL, a hydroxylating Fe(II)/α-KG-dependent dioxygenase OxaK, and a multifunctional cytochrome P450 OxaB. Intriguingly, OxaK can catalyze various multicyclic intermediates or shunt products of oxalicines with impressive substrate promiscuity. OxaB was further proven via biochemical assays to have the ability to convert 15-hydroxdecaturin A ( 3) to 1 with a spiro-lactone core skeleton through oxidative rearrangement. We also solved the mystery of OxaL that controls C-15 hydroxylation. Chemical investigation of the wild-type strain and deletants enabled us to identify 10 metabolites including three new compounds, and the isolated compounds displayed potent anti-influenza A virus bioactivities exhibiting IC50 values in the range of 4.0-19.9 μmol/L. Our studies have allowed us to propose a late-stage biosynthetic pathway for oxalicine B ( 1) and create downstream derivatizations of oxalicines by employing enzymatic strategies.

Clinical Observations on Heat-sensitive Point Dazhui (GV14) Moxibustion for the Treatment of Cervical Spondylotic Radiculopathy / 上海针灸杂志

Objective To investigate the clinical efficacy of heat-sensitive point Dazhui(GV14) moxibustion in treating cervical spondylotic radiculopathy. Method Ninety-six patients with cervical spondylotic radiculopathy were randomly allocated to a heat-sensitive point Dazhui moxibustion (observation) group of 30 cases, a non-heat-sensitive point Dazhui suspended moxibustion (control) group of 33 cases and a medication group of 33 cases. The observation group received heat-sensitive point Dazhui moxibustion; the control group, non-heat-sensitive point Dazhui suspended moxibustion; the medication group, oral administration of Jingtong granules. The clinical symptoms were assessed and serum hypersensitive C-reactive protein (HsCRP) and interleukin-8 (IL-8) were measured in the three groups before and after 15 days of treatment. Result All the three treatments had a certain effect on cervical spondylotic radiculopathy. The therapeutic effect was best in the observation group (P0.05). Conclusion The therapeutic effect of heat-sensitive point Dazhui moxibustion is better than those of non-heat-sensitive point Dazhui suspended moxibustion and oral Jingtong granules. It is a more ideal way to treat cervical spondylotic radiculopathy. The mechanism of its action may be related to post-treatment decrease in inflammatory factors in the lesion.

Warm needling combined with element calcium for postmenopausal osteoporosis / 中国针灸

<p><b>OBJECTIVE</b>To observe the clinical effectiveness of warm needling combined with element calcium on postmenopausal osteoporosis, and to explore its action mechanism.</p><p><b>METHODS</b>Eighty-five postmenopausal patients were randomly divided into an observation group (43 cases) and a control group (42 cases). Both the two groups were treated with oral administration of caltrate-D tablet, 600 mg per day, once a day before sleep for one year. Patients in the observation group were treated with warm needling at Dazhu (BL 11), Shenshu (BL 23), Xuan-zhong (GB 39), once a day; 30 days of treatment were taken as a course, and totally 4 courses were given with an interval of 60 days between courses. The bone mineral density (BMD) of the lumbar vertebra and hip joint, and the level of serum bone gla protein (S-BGP) and hydroxyproline/creatinine (Hyp/Cr) were observed before and after treatment in the two groups.</p><p><b>RESULTS</b>(1)After treatment, the BMD in the observation group was significantly increased [lumbar vertebra (0. 811±0. 024) g/cm2 vs (0. 892±0.019) g/cm2, femoral neck (0. 512±0.014) g/cm2 vs (0. 554±0. 015) g/cm2, femoral trochanter (0. 716±0. 028) g/cm2 vs (0.769±0.026) g/cm2, Ward's trigonum (0. 590±0. 013) g/cm2 vs (0. 660±0. 017) g/cm2, all P<0. 05)]; the improvement in the observation group was more significant than that in the control group (all P<0. 05). (2)After treatment, the index of bone metabolism in the control group was increased, and the serum S-BGP, the Hyp/Cr in the control group were higher than those in the observation group (both P<0. 05).</p><p><b>CONCLUSION</b>The treatment of warm needling combined with element calcium on postmenopausal osteoporosis is significant, which is likely to be achieved by reducing the bone metabolism of postmenopausal patients.</p>

Clinical Observations on Heat-sensitivePoint Yaoyangguan Moxibustion for Treatment of Sciatica / 上海针灸杂志

ObjectiveTo investigate the clinical efficacy of heat-sensitivepoint Yaoyangguan(GV3)moxibustion for sciatica and preliminarily explore the mechanism of its action.MethodOne hundred and twelve sciatica patients were randomly allocated to heat-sensitive point Yaoyangguan moxibustion (observation), non-heat-sensitive point Yaoyangguan suspended moxibustion (control) and medication groups. The observation group received heat-sensitive point Yaoyangguan moxibustion; the control group, non-heat-sensitive point Yaoyangguan suspended moxibustion; the medication group, oral administration of Yaobitong capsules. The clinical symptoms were scored, the Pain Rating Index (PRI), the Visual Analogue Scale (VAS) and the Present Pain Intensity (PPI) scores were counted and serum IL-8 content was measured in the three groups beforeand after 15 days of treatment.ResultAfter 15 days of treatment, all the three treatments had a certain therapeutic effect on sciatica. The therapeutic effect was bestin the observation group (P0.05).ConclusionHeat-sensitive point Yaoyangguan moxibustion has a better therapeutic effect than non-heat-sensitive point Yaoyangguan suspended moxibustion and oral administration of Yaobitong capsules. This method is an ideal treatment for sciatica. The mechanism may be related to a posttreatment decrease in inflammatory factors in the diseased region.

Effect of acupuncture at Geshu on activating blood circulation and resolving stasis / 中国组织工程研究

BACKGROUND: Geshu (BL 17) is one of eight influential points of blood, acting on tonifying blood, nourishing blood, activating blood circulation and resolving stasis.OBJECTIVE: To explore the effect of Geshu (BL 17) on activating blood circulation and resolving stasis in blood stagnation syndrome with acupuncture.DESIGN: Randomized controlled and normal controlled observations were designed.SETTING: Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology.PARTICIPANTS: Totally 65 cases of blood stagnation syndrome were selected from inpatients in Department of Acupuncture and Moxibustion in Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology.METHODS: Totally 65 cases were randomized into experiment group (33cases) and the control (32 cases). In the control, the patent Chinese drug,longxuejie was administrated orally for activating blood circulation and resolving stasis, 4 tablets/time, 3 times/day, 15 days made 1 course of treatment. In experiment group, Geshu (BL 17) was localized bilaterally; after routine sterilization on the points, a filiform needle, 25 mm in length was inserted and manipulated with even technique after arrival of qi for 5 minutes. In 15 minutes of needle retaining, the needle was manipulated for another 5 minutes and retained for 10 minutes, and then, the needle was withdrawn. The treatment was given once a day. Radioimmunoassay (RIA)was applied to determine the levels of 6-K-P and thromboxane B2 (TXB2)in plasma. Criteria on clinical therapeutic effects: Being cured is determined by slight red tongue, retarded and forceful pulse, disappearance of limb pain, skin and mucosal ecchymosis and dysmenorrhea, basic recovery of motor function in hemiplegia and disappearance of numbness. Being effective is by dark red tongue, slightly hesitant pulse, alleviation of limb pain, reducing of skin and mucosal ecchymosis, alleviation of dysmenorrhea, partial recovery of motor function in hemiplegia and alleviation of numbness. No effect is by none of any change of clinical symptoms in comparison before and after treatment.MAIN OUTCOME MEASURES: ① Observation of therapeutic effects between two groups. ② Observation of plasma 6-K-P and TXB2 levels and 6-K-P/TXB2RESULTS: Totally 65 cases were all in the result analysis. ① Observation of therapeutic effects between two groups: The therapeutic effect in experiment group was higher remarkably than that in the control [be cured:(15,10); be effective: (13,11)]. ② Comparison of plasma 6-K-P levels: In experiment group, it was higher remarkably after treatment compared with that before treatment [(159.28±16.48), (117.25±16.47) μg/L, P ＜ 0.05]. In the control, it was higher remarkably after treatment compared with that before treatment [(133.51±13.97), (114.64±16.39) μg/L, P ＜ 0.05]. ③Comparison of plasma TXB2 level: In experiment group, it was lower remarkably after treatment compared with that before treatment [(98.21±11.38), (110.45±1067) μg/L, P ＜ 0.05]. In the control, it was lower remarkably after treatment compared with that before treatment [(101.15 ±12.14), (109.21±11.58) μg/L, P ＜ 0.05]. ④ Plasma 6-K-P/TXB2: In experiment group, it was higher remarkably after treatment compared with that before treatment (1.621±0.203, 1.101±0.316, P ＜ 0.05). In the control,it was higher remarkably after treatment compared with that before treatment (1.322±0.216, 1.234±0.305, P ＜ 0.05).CONCLUSION: Acupuncture on Geshu (BL 17) increases 6-K-P level and 6-K-P/TXB2 and reduces TXB2 level. It is explained that acupuncture on Geshu (BL 17) regulates imbalance of PGI2-TXA2 system in blood stagnation syndrome so that the blood circulation is activated and stasis is resolved.