Chinese materia medica resource (CMM resource) is the foundation of the development of traditional Chinese medicine. In the study of sustainable utilization of CMM resource, adopting innovative theory and method to find new CMM resource is one of hotspots and always highlighted. Pharmacophylogeny interrogates the phylogenetic relationship of medicinal organisms (especially medicinal plants), as well as the intrinsic correlation of morphological taxonomy, molecular phylogeny, chemical constituents, and therapeutic efficacy (ethnopharmacology and pharmacological activity). This new discipline may have the power to change the way we utilize medicinal plant resources and develop plant-based drugs. Phylogenomics is the crossing of evolutionary biology and genomics, in which genome data are utilized for evolutionary reconstructions. Phylogenomics can be integrated into the flow chart of drug discovery and development, and extends the field of pharmacophylogeny at the omic level, thus the concept of pharmacophylogenomics could be redefined in the context of plant pharmaceutical resources. This contribution gives a brief discourse of knowledge pedigree of pharmacophylogeny, epistemology and paradigm shift, highlighting the theoretical and practical values of pharmacophylogenomics. Many medicinally important tribes and genera, such as Clematis, Pulsatilla, Anemone, Cimicifugeae, Nigella, Delphinieae, Adonideae, Aquilegia, Thalictrum, and Coptis, belong to Ranunculaceae family. Compared to other plant families, Ranunculaceae has the most species that are recorded in China Pharmacopoeia (CP) 2010. However, many Ranunculaceae species, e. g., those that are closely related to CP species, as well as those endemic to China, have not been investigated in depth, and their phylogenetic relationship and potential in medicinal use remain elusive. As such, it is proposed to select Ranunculaceae to exemplify the utility of pharmacophylogenomics and to elaborate the new concept empirically. It is argued that phylogenetic and evolutionary relationship of medicinally important tribes and genera within Ranunculaceae could be elucidated at the genomic, transcriptomic, and metabolomic levels, from which the intrinsic correlation between medicinal plant genotype and metabolic phenotype, and between genetic diversity and chemodivesity of closely related taxa, could be revealed. This proof-of-concept study regards pharmacophylogenomics as the updated version of pharmacophylogeny and would enrich the intension and spread the extension of pharmacophylogeny. The interdisciplinary knowledge and techniques will be integrated in the proposed study to promote development of CMM resource discipline and to boost sustainable development of Chinese medicinal plant resources.
China ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Knowledge ; Medicine, Chinese Traditional ; Phylogeny ; Plants, Medicinal ; chemistry ; classification ; genetics

Objective To explore the effect of different processing and drying methods of corn and hot pepper on fluorine content in coal-burning type of the endemic fluorosis areas, and to screen food processing and drying methods which meet the quality requirements of grain drying and able to effectively reduce the total fluoride intake of local population. Methods Farmers of endemic fluorosis area in Bijie, Guizhou province were divided into 3 groups: sun-baked drying group, stove drying group with air-tight cover and stove drying group with no cover, 10 households in each group. Corn and fresh hot pepper and samples dried for 2 weeks, or 1, 3, 6-month were collected, and water and fluoride content were detected, and the total daily fluoride intake were calculated in accordance with the "Determination of Water in Food" (GB/T 5009.3-2003) and "Determination of Fluorine in Foods"(GB/T 5009.18-2003). Results Fluoride content in fresh corn and dried for 2 weeks, or 1, 3, 6-month [of sunbaked drying group: (1.40 ± 0.16), (1.56 ± 0.14), (2.15 ± 0.47), (2.70 ± 0.64), (4.06 ± 1.75)mg/kg, stove drying group with air-tight cover: (1.41 ± 0.16), (2.39 ± 0.56), (4.60 ± 0.97), (8.46 ± 5.55), (11.36 ± 3.60)mg/kg,stove drying group with no cover: (1.40 ± 0.13), (4.69 ± 3.97), (4.47 ± 2.77), (9.65 ± 6.47), (26.12 ± 14.52)mg/kg] and pepper[sun-baked drying group: (5.41 ± 1.61), (16.60 ± 7.62), (32.60 ± 7.88), (50.26 ± 17.60),(240.20 ± 272.49)mg/kg, stove drying group with air-tight cover: (754 ± 2.95), (3238 ± 11.50), (119.18 ± 156.45),(224.00 ± 196.58), (495.70 ± 417.29)mg/kg, stove drying group with no cover: (4.82 ± 1.25), (44.30 ± 13.48),(122.89 ± 66.43), (334.23 ± 166.05), (531.01 ± 397.40)mg/kg] increased with elongation of drying time, and the group difference was significant(F = 44.77, 128.71, 126.87, 41.61, 53.63, 170.63, all P ＜ 0.05), with the largest rate of increase in stove drying group with no cover, and the lowest in sun-baked drying group;fluoride was significantly lower (t = 7.93,63.07,5.36,11.98,55.76,7.45, all P ＜ 0.05) after sample washing;total fluoride intake per person per day was 2.57 mg in local adult when ate washed and sun-baked corn, peppers, the total fluoride intake were 5.92, 8.14 mg when ate the food processed by other two drying methods and washed corn, peppers,respectively. Conclusions In the coal-burning type of fluorosis endemic area, should take appropriate health education measures, and instruct local residents to use sun bake their edible corn and pepper for human consumption, and cultivate a habit of washing corn and pepper before cooking, which can reduce the population total fluoride intake, and control endemic fluorosis.

Objective To clarify the clinical features,therapeutic strategy and prognosis of lipid storage myopathy (LSM).Methods The clinical data and therapeutic effects of 42 LSM patients were summarized retrospectively.All patients were followed up to evaluate their prognosis.Results Data of short-term therapeutic results of all the 42 patients were available.Thirty-three cases were placed in low- doses prednisone and 9 cases in riboflavin.All patients showed marked and quick improvement of symptoms within one month.Among thirty-two patients followed up for more than one year,26 cases had a full recovery and 6 remained to have intolerance to heavy exercise.Thirteen patients had relapses of muscle weakness in various degrees and most of which were induced by exertion,exposure to coldness and upper respiratory tract infection.In 5 patients the symptoms were recurred for more than one time.Among 13 cases with relapses, 7 had family history.Conclusions Our data suggest that LSM is a treatable disease and well responsive to low-doses prednisone.The disease tends to recur,especially in patients with family history.Glutaric aciduria type Ⅱ should be considered in LSM patients who are responsive well to riboflavin,indicating drug therapeutic strategy for LSM should be based on the etiology of the disease.

Objective To investigate the clinical,neuroimaging and myopathological features of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes(MELAS).Methods The clinical manifestations,neuroimaging and myopathological features of 31 patients with MELAS diagnosed in our Neuromuscular Center in the recent 7 years were retrospectively analyzed.A3243G point mutations were analyzed by RFLP method in 10 patients.Results ①Clinical features:There were 18 male patients and 13 female patients.The age of onset ranged from 3 to 43 years,averaging 21.9 years.The averaged duration was 4.9 years.Thirteen patients in this group had family history of maternal inheritance pattern.The main clinical manifestations included short stature(26 patients),recurrent headache and vomiting(24 patients), muscle weakness(22 patients),epileptic seizure(21 patients),cognitive decline(19 patients),visual disturbance(17 patients),sensorineural deafness(16 patients),ataxia(6 patients),psychiatric symptom (8 patients),external ophathalmoplegia(2 patients)and diabetes mellitus(9 patients).The serum CK level was slightly elevated in 6 patients,and the fasting blood lactic acid was increased in 15 of the 18 detected patients.②Neuroimaging features:The stroke-like lesions were mostly confined to cerebral cortex, including temporal lobe(24 patients),occipital lobe(21 patients),parietal lobe(12 patients)and frontal lobe(4 patients).Three patients had deep white matter involvement.Migrating stroke-like lesions were confirmed in 4 patients by repeated cranial CT/MRI examination.In addition,cerebral atrophy(17 patients)and bilateral basilar ganglion calcification(11 patients)were found.③Myopathological features: Scattered ragged red fibers(RRF)in various number were found in all the patients by MGT staining.Other founding included strongly SDH-reactive blood vessel(27 patients),COX enzyme deficiency(19 patients), and mild to moderate lipid storage in RRF(20 patients).④MtDNA analysis showed 9 patients with A3243G point mutation in all the detected 13 patients.Conclusion The clinical and neuroimaging features may offer important clue to the diagnosis of MELAS,but a definite diagnosis of MELAS relies on the myopathology and mtDNA mutation analysis.

Objective To explore the mechanism of skeletal fluorosis via observation on the expression of bone γ-carboxyglutamic acid-containing protein (BGP) and osteoprotegerin (OPG) in the residents of coal-burning fluorosis regions, and to provide a basical data for further monitoring and evaluating the effects of fluoride-reducing projects. Methods Stratified sampling was applied, the 6 villages of fluorosis were chosen as focusing areas for investigation. The residents of villages underwent clinical examination of the skeletal fluorosis. And according to the degree of skeletal fluorosis, villages were divided into three groups, namely light, moderate and severe villages. Radio-Immunoassay and Enzyme-linked immunosorbent assay were used to check the expression of BGP and OPG in the serum. Results The levels of serum BGP in the severe skeletal fluorosis cases[(6.78±4.43)μg/L] were significantly higher(P<0.05) than those in the normal, moderate and the severe groups [ (3.58±1.53), (3.44±2.66), (3.41±2.20)μg/L], respectively. The expression of OPG in the light, moderate and the severe groups [(1251.55±998.31), (1265.94±931.77), (1560.55±858.07)ng/L] were significantly higher (P<0.05) than those in the normal[(520.81±385.05)ng/L], respectively. The levels of BGP in mixed type[(6.09±2.62)μg/L] were much higher(P<0.05) than no mixed type[(3.97±1.53), (3.20±2.12)μg/L]. The levels of OPG in the osteosclerosis, osteoporesis and mixed type[(1321.63±1017.00), (1205.42±852.22), (1529.01±402.83)ng/L] were significantly higher(P<0.05) than those of the normal, respectively. The levels of OPG in the light villages [(452.06±338.10)ng/L] were significantly lower(P<0.05) than moderate and severe villages[(1266.30±899.14), (1851.80±956.08 )ng/L], respectively. The levels of OPG in the severe villages were significantly higher(P<0.05) than moderate villages. Conclusions It indicates that OPG can be used as an early indicator in coal-burning pollution endemic fluorosis results in biochemical changes in the composition of bone.

In this study, reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the changes in mRNAs levels of preproadrenomedullin (ppADM) gene encoding adrenomedullin (ADM) and the essential receptor components of ADM, calcitonin receptor-like receptor (CRLR), and the receptor activity modifying protein 2 and 3 (RAMP2 and RAMP3) in the medulla oblongata, hypothalamus, midbrain, pituitary gland and adrenal gland of the stress-induced hypertensive rats. It was shown that chronic foot-shock and noise stress for 15 consecutive days induced a significant increase in systolic blood pressure (SBP) and unique changes in ppADM and its receptor components mRNAs in all areas studied. As compared with the control group, the level of ppADM mRNA, normalized against a glyceraldehydes-3-phosphate dehydrogenase (GAPDH) control, was up-regulated in the hypothalamus-pituitary-adrenal (HPA) axis, but down-regulated in the medulla oblongata and midbrain (P<0.01 and P<0.05, respectively). The relative amount of CRLR mRNA was higher in the hypothalamus than that in other areas. The level of CRLR mRNA expression was significantly increased in the medulla oblongata of the stress group (P<0.01), but decreased in the midbrain (P<0.01) as well as hypothalamus(P<0.05), as compared with that of the control group. Chronic stress for 15 consecutive days produced an increase in the level of RAMP2 mRNA expression in the medulla oblongata (P<0.01) and a decrease in the adrenal gland (P<0.01), as compared with the control. No significant stress-related changes in RAMP2 mRNA were observed in the midbrain, hypothalamus and pituitary gland. The amount of RAMP3 mRNA was relatively higher in the midbrain and hypothalamus than that in the medulla oblongata, adrenal gland and adrenal gland. Stress-induced hypertensive rats exhibited an increased RAMP3 mRNA expression in the hypothalamus and pituitary gland (P<0.01 and P<0.05, respectively) and a decrease in the adrenal gland and midbrain (P<0.05). No significant stress-related change in RAMP3 mRAN was observed in the medulla oblongata. Taken together, our results indicate that the significant changes in ppADM and its receptor components mRNAs expression in the HPA axis and autonomic centers may be related to the development of the stress-induced hypertension. Nevertheless, the pathophysiological significance of brain-derived ADM and its receptors in stress and blood pressure regulation and their roles in stress-induced hypertension still await further investigation.
Adrenomedullin ; Animals ; Brain Stem ; metabolism ; Hypertension ; etiology ; metabolism ; Hypothalamo-Hypophyseal System ; metabolism ; Male ; Peptides ; genetics ; metabolism ; Pituitary-Adrenal System ; metabolism ; RNA, Messenger ; biosynthesis ; genetics ; Rats ; Rats, Sprague-Dawley ; Receptors, Adrenomedullin ; Receptors, Peptide ; biosynthesis ; genetics ; Stress, Physiological

OBJECTIVETo investigate the co-culture of keratinocytes with Malassezia isolates which cause the pityriasis versicolor with different color and to analyze the changes of cytokines associated with melanogenesis.

METHODSThe effects of Malassezia species with different proportions on the growth rate of keratinocytes was assessed with 5 g/L methyl thiazolyl tetrazolium (MTT). Co-culture of keratinocytes and Malassezia species were performed with isolates from hyer- and hypo-pigmentation areas of pityriasis versicolor. The supernatants were collected at different time points, and the changes of basic fibroblast growth factor (b-FGF), endothelin-1 (ET-1), nerve growth factor-beta (NGF-beta), interleukin-1alpha (IL-1alpha), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), stem cell factor (SCF) were recorded. Three control groups were established accordingly.

RESULTSWhen the ratio between keratinocytes and Malassezia species was lower than 1: 10, the growth rate of keratinocytes was not affected by Malassezia (P > 0.05). When the ratio was increased above 1:20, the growth rate of keratinocytes was significantly inhibited by Malassezia (P < 0.01). The secretions of IL-1alpha, IL-6, TNF-alpha, and ET-1 was significantly increased after the co-culture of keratinocytes and Malassezia (P < 0.01), while those of b-FGF, NGF-beta, and SCF had no significant changes (P > 0.05). Compared with the isolates from the hypo-pigmentation area, ET-1 induced by isolate from hyperpigmentation area significantly increased (P < 0.01).

CONCLUSIONWhen Malassezia isolates are co-cultured with keratinocytes, the secretions of cytokines associated with melanogenesis may differ from each other. ET-1 may play certain role in the hyper-pigmentation of pityriasis versicolor.

Cell Proliferation ; Cells, Cultured ; Cytokines ; biosynthesis ; Humans ; Keratinocytes ; cytology ; metabolism ; microbiology ; Malassezia ; isolation & purification ; physiology ; Melanins ; biosynthesis ; Tinea Versicolor ; microbiology

OBJECTIVETo study a new method of venous flap that is improved on its persistence and quality.

METHODSNew Zealand white rabbits were subdivided randomly into 4 groups. All rabbits were operated by harvesting a flap from the latero-abdominal wall and then sutured it in the original position. Group A: the superficial epigastric vein in the pedicle was left open (only one inflow vein remained). Group B: the pedicle vein of the proximal and distant end were left open (keeping an inflow vein and a principal out). Group C: the pedicle vein and a tributary vein were left open (keeping an inflow vein and a tributary outflow vein). Group D: the pedicle vein and two tributary veins were left open (keeping an inflow vein and two tributary outflow veins). Survival rate, MDA of the tissue, histology and ultra-microstructure were examined.

RESULTSSurvival rate of A, B, C, D were improved in order. Statistic difference is significant (P < 0.05) between group and group other than C and D. The content of MDA was heightened with statistically significant differences (A > B > C > D) among the four groups 8 hours postoperatively, but fell back to the normal level in group D and C and kept a high level in group A and B at 72 hour postoperatively. Histology and ultra-microstructure exam showed that degeneration of collagen fiber and karyopyknosis of cell is more obvious in Group A and Group B than Group C and Group D.

CONCLUSIONSThe higher survival rate of venous flap is possible by designing the more reasonable venous flap outputs pedicles which can alleviate the high tension dropsy and maintain the valid equilibrium of pour with flow in the venous flap.

Animals ; Graft Survival ; Rabbits ; Surgical Flaps ; blood supply ; Veins ; transplantation

OBJECTIVETo evaluate the effect of compound branch chain amino acids injection (Aminic) on protein metabolism in patients with radical resection of cardiac carcinoma.

METHODSEighty patients with radical resection of cardiac carcinoma were randomly divided into two groups:study group (40 cases) with compound branch chain amino acids injection (Aminic), and control group(40 cases) with amino acids(MPR- F). The patients received total parenteral nutrition with equal calorie and nitrogen from 1st-7th days after operation by central or peripheral vein with infusing time over 12 hours per day. The change of body weight was observed. The serum levels of total protein, albumin,pre-albumin,transferring, and fibronectin were measured.

RESULTSThe body weight was decreased in the two groups after operation, while compared with the study group,the body weight was significantly decreased in the control group (P=0.0250). The positive nitrogen balance recovered two days earlier in study group than that in the control group. Decrease of total protein,albumin were more severe in the control group than those in study group (P=0.0446,P=0.0314 respectively). Compared with the control group,the level of Valine was increased (P=0.0073),and the level of Arginine was decreased more obviously in the study group (P= 0.0212).

CONCLUSIONThe compound branch chain amino acids injection (Aminic) is more beneficial for patients with radical resection of cardiac carcinoma to correct negative nitrogen balance,it can also inhibit decomposition of muscles protein,and improve nutritional conditions.

Adult ; Aged ; Aged, 80 and over ; Amino Acids, Branched-Chain ; therapeutic use ; Female ; Heart Neoplasms ; metabolism ; therapy ; Humans ; Male ; Middle Aged ; Parenteral Nutrition ; Postoperative Period ; Prospective Studies ; Proteins ; metabolism

To investigate the eletrophysiological effect of rat adrenomedullin (rADM) on barosensitive neurons in the rostral ventrolateral medulla (rVLM) and its potential mechanisms, the extracellular recording and multi-barrel iontophoresis methods were used. Of the 29 barosensitive neurons in the rVLM, 20 neurons demonstrated excitatory response to iontophoretically applied rADM and increased the firing rate from (10.8 +/- 2.7) spikes/s to (14.6 +/- 3.6), (19.8 +/- 4.7) and (31.9 +/- 6.4) spikes/s (P<0.05, n=20) at the current of 30, 60 and 90 nA, respectively. Application of human adrenomedullin (22-52) [hADM (22-52)], a specific antagonist of rADM receptor, distinctly attenuated the augmentation of firing rate induced by rADMjthe firing rate was increased by 15.4% [(11.4 +/- 2.5) spikes/s, P<0.05, n=10]. Another antagonist, human calcitonin gene-related peptide (8-37) [hCGRP (8-37)] had no significant effect on rADM-induced excitation. Other 23 barosensitive neurons were recorded to test the influence of nitric oxide synthase (NOS) inhibitors on the excitatory effect of rADM. In 10 neurons, 7-NiNa (neuronal NOS inhibitor) decreased the firing rate from (10.1 +/- 3.5) spikes/s to (7.5 +/- 2.5), (5.3 +/- 2.1) and (3.1 +/- 1.4) spikes/s (P<0.05, n=10) at the current of 10, 20 and 40 nA, respectively. The excitatory effect of rADM (60 nA, 30 s) during 7-NiNa application was nearly eliminated and the magnitude of firing rate was increased only by 17% of the basal level (6.2 +/- 1.9) spikes/s (P<0.05, n=7). While aminoguanidine (AG, iNOS inhibitor) increased the firing rate at the resting level from (11.5 +/- 5.1) spikes/s to (17.8 +/- 5.6), (22.5 +/- 6.3) and (29.1 +/- 6.4) spikes/s (P<0.05, n=8) at the current of 10, 20 and 40 nA in 8 barosensitive neurons, respectively. When rADM (60 nA, 30 s) was delivered during AG iontophoresis period, the firing rate significantly increased by 60% of the basal level [(22.5 +/- 6.3) spikes/s, n=5]. These results indicate that rADM activates the barosensitive neurons in the rVLM directly and acts as a cardiovascular regulator, and that this function might be mediated by its specific receptor. NO, mainly neuronal NOS-originated might be involved in the excitatory effect of rADM in the rVLM.
Adrenomedullin ; physiology ; Animals ; Electrophysiological Phenomena ; Male ; Medulla Oblongata ; physiology ; Neurons ; physiology ; Nitric Oxide ; physiology ; Nitric Oxide Synthase Type I ; physiology ; Pressoreceptors ; physiology ; Rats ; Rats, Sprague-Dawley