ABSTRACT
5-lipoxygenase (5-LOX) and leukotriene A4 hydrolase (LTA4H), as the major targets of 5-LOX branch in the arachidonic acid (AA) metabolic pathway, play an important role in the treatment of inflammation. Rhei Radix et Rhizoma, Notopterygii Rhizoma et Radix and Genitana Macrophyllae Radix have clear anti-inflammation activities. In this paper, the targets of 5-LOX and LTA4H were used as the research carrier, and Hiphop module in DS4.0 (Discovery studio) was used to construct ingredients database for preliminary screening of three traditional Chinese medicines based on target inhibitor pharmacophore, so as to obtain 5-LOX and LTA4H potential active ingredients. The ingredients obtained in initial pharmacophore screening were further screened by using CDOCKER module, and the screening rules were established based on the score of initial compound and the key amino acids to obtain 12 potential 5-LOX inhibitors and 7 potential LTA4H inhibitors. To be more specific, the potential 5-LOX inhibitors included 6 ingredients in Rhei Radix et Rhizoma, such as procyanidins B2-3,3'-O-double gallate and revandchinone 2; four ingredients in notopterygium, such as dodecanoic acid and so on. On the other hand, potential LTA4H inhibitors included revandchinone 1, revandchinone 4 in Rhei Radix et Rhizoma, tridecanoic acid, tetracosanoic acid and methyl eicosanoate in Notopterygii Rhizoma et Radix, montanic acid methyl ester and N-docosanoyl-O-aminobenzoate in Genitana Macrophyllae Radix and so on. The molecular simulation methods were highly efficient and time-saving to obtain the potential inhibitors of 5-LOX and LTA4H, which could provide assistance for discovering the chemical quality indicators of anti-inflammatory efficacy of three Chinese herbs, and may be helpful to promote the whole-process quality control of three Chinese herbs.
ABSTRACT
Synergistic effect is main pharmacological mechanism of traditional Chinese medicine(TCM). The research method based on the key targets combination is an important method to explore the synergistic effect of TCM. Peptide transporter 1 (PepT1) is an essential target for drug uptake into the bloodstream, accounting for about 50% of the total transporter protein content from the small intestine. Peroxisome proliferator-activated receptor α(PPARα) is the lipid-lowering target of fibrates, which have a good hypolipidemic effect by activating PPARα. It has been reported that PPARα could activate the gene expression of PepT1s, and PPARα agonists can promote the uptake of PepT1 substrates, indicating their synergistic effect. In this paper, PepT1 substrates and PPARα agonists from TCM were discovered, and their synergistic mechanism was also been discussed based on the target combination of PepT1 and PPARα. The support vector machine(SVM) model of PepT1 substrates was first constructed and utilized to predict potential TCM components. Meanwhile, merged pharmacophore and docking model of PPARα agonists was used to screen the potential active ingredients from TCM. According to the analysis results of two groups, the TCM combination of Panax notoginseng and Ganoderma lucidum, as well as TCM combination of P. notoginseng and Salvia miltiorrhiza were identified to have the synergistic mechanism based on target combination of PepT1 and PPARα. In this study, synergistic mechanism of TCM was analyzed for absorption and hypolipidemic effect based on target combination, which provides a new way to explore the synergetic mechanism of TCM related to pharmacokinetics.
ABSTRACT
Pinctada fucata oligopeptide is one of key pharmaceutical effective constituents of P. fucata. It is significant to analyze its pharmacological effect and mechanism. This study aims to discover the potential oligopeptides from P. fucata and analyze the mechanism of P. fucata oligopeptide based on in silico technologies and protein interaction network(PIN). First, main protein sequences of P. fucata were collected, and oligopeptides were obtained using in silico gastrointestinal tract proteolysis. Then, key potential targets of P. fucata oligopeptides were obtained through pharmacophore screening. The protein-protein interaction(PPI) of targets was achieved and implemented to construct PIN and analyze the mechanism of P. fucata oligopeptides. P. fucata oligopeptide database was constructed based on in silico technologies, including 458 oligopeptides. Twelve modules were identified from PIN by a graph theoretic clustering algorithm Molecular Complex Detection(MCODE) and analyzed by Gene ontology(GO) enrichment. The results indicated that P. fucata oligopeptides have an effect in treating neurological diseases, such as Alzheimer's disease. In silico proteolysis could be used to analyze the protein sequences of traditional Chinese medicine(TCM). According to the combination of in silico proteolysis and PIN, the biological activity of oligopeptides could be interpreted rapidly based on the known TCM protein sequence. The study provides the methodology basis for rapidly and efficiently implementing the mechanism analysis of TCM oligopeptides.
ABSTRACT
Oligopeptides are one of the the key pharmaceutical effective constituents of traditional Chinese medicine(TCM). Systematic study on composition and efficacy of TCM oligopeptides is essential for the analysis of material basis and mechanism of TCM. In this study, the potential anti-hypertensive oligopeptides from Glycine max and their endothelin receptor A (ETA) antagonistic activity were discovered and predicted based on in silico technologies.Main protein sequences of G. max were collected and oligopeptides were obtained using in silico gastrointestinal tract proteolysis. Then, the pharmacophore of ETA antagonistic peptides was constructed and included one hydrophobic feature, one ionizable negative feature, one ring aromatic feature and five excluded volumes. Meanwhile, three-dimensional structure of ETA was developed by homology modeling methods for further docking studies. According to docking analysis and consensus score, the key amino acid of GLN165 was identified for ETA antagonistic activity. And 27 oligopeptides from G. max were predicted as the potential ETA antagonists by pharmacophore and docking studies.In silico proteolysis could be used to analyze the protein sequences from TCM. According to combination of in silico proteolysis and molecular simulation, the biological activities of oligopeptides could be predicted rapidly based on the known TCM protein sequence. It might provide the methodology basis for rapidly and efficiently implementing the mechanism analysis of TCM oligopeptides.
ABSTRACT
<p><b>OBJECTIVE</b>To report the operative technique and clinical results of the neurocutaneous vascular axial flap with perforating vessels as its pedicle.</p><p><b>METHODS</b>An axial skin flap was designed along the axis of small paraneural vessels that was close to a concomitant cutaneous nerve. The cutaneous perforating branches of major arteries were used as the pedicle, which provided a rotation arc for the flap to cover the defects in the distal site of extremities. 43 neurocutaneous vascular axial flaps were transferred, including 13 sural neurocutaneous axial flaps (30 cm x 12 cm to 16 cm x 8 cm) supplied by perforating branches of the peroneal vessel; 9 saphenous neurocutaneous axial flaps (15 cm x 8 cm to 5 cm x 4 cm) with posterior tibial perforators as the pedicle; 8 posterior antebrachial neurocutaneous axial flaps (16 cm x 6 cm to 10 cm x 4 cm) based on the dorsal branch of the anterior interossea vessel and 13 reversed neurocutaneous axial flaps (6.0 cm x 3.5 cm to 2.5 cm x 1.5 cm) on the dorsal hand pedicled with the perforators at the interdigital web space.</p><p><b>RESULTS</b>42 flaps survived completely. One flap underwent venous congestion with necrosis on the distal one fourth of the flap. The color and texture of the flaps were good. The appearance and functional results were satisfactory as revealed by follow-up for 6 to 24 months.</p><p><b>CONCLUSIONS</b>The modified operation combines the advantages of both the perforator flap and the neurocutaneous axial flap, enlarges the size of the flap and extends the scope of reconstruction. The flap is characterized with delicate designation, easy dissection and reliable blood supply. It is a good method in repairing the skin defects of the extremities.</p>
Subject(s)
Adolescent , Adult , Aged , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Young Adult , Plastic Surgery Procedures , Methods , Skin , Skin Transplantation , Methods , Surgical FlapsABSTRACT
<p><b>OBJECTIVE</b>To sum up the clinical experience in the reparation of burn wounds with different types of skin flaps in patients with severe electrical injury.</p><p><b>METHODS</b>Free skin flap, axile island flap with vascular pedicle and muscular skin flap were employed to repair 64 wounds in 49 cases.</p><p><b>RESULTS</b>Skin flap necrosis happened in 2 cases, congestion and necrosis at the edge of skin flaps in 4 cases, and complete survival of the skin flaps and primary healing of the wounds in the remaining cases.</p><p><b>CONCLUSION</b>Reparation of wounds with proper skin flaps according to the degree of the electrical injury is effective and reliable, which might be beneficial to the prevention of necrobiosis and the infection in deep tissue.</p>
Subject(s)
Adolescent , Adult , Child , Female , Humans , Male , Middle Aged , Burns, Electric , General Surgery , Surgical FlapsABSTRACT
<p><b>OBJECTIVE</b>To present the clinical application of composite graft of acellular allo-dermis matrix (ADM) with thin auto-microskin on burn wound.</p><p><b>METHODS</b>8 inpatients with 18 full thickness skin burn wounds were transplanted with allo-ADM after eschar was excised, then the auto-microskin and allo-human skin were covered on the area of the matrix, the wound where no allo-ADM grafting were covered as control groups only with auto-microskin and allo-human skin. The area of donor to wound is 1:5 - 1:8.</p><p><b>RESULTS</b>Survived rate of 18 pieces composite skin that allo-ADM with auto-microskin were grafted were 94%. After following up for 3 to 13 months, the skins of complex grifting had well elastic and smooth texture compared to auto-microskin grafted, they appeared less cicatrisation and ulceration. 3 months after operation, it was indicated by histological examination that tightknit the epithelial-dermal conjunction and epidermal papilla structure could be identified in the allo-ADM skin and there were orderly collagenous fibres, but scar skin structure was observed in that auto-microskin grifted area.</p><p><b>CONCLUSION</b>The graft effectiveness of allo-ADM and auto-microskin was better than that of auto-microskin, and this method could be used on major deep burn wound healing.</p>