This study aimed to explore the molecular mechanism of Juanbi Qianggu Formula(JBQGF), an empirical formula formulated by the prestigious doctor in traditional Chinese medicine, in the treatment of rheumatoid arthritis based on network pharmacology and cell function experiments. The main active components and targets of JBQGF were obtained through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and Encyclopedia of Traditional Chinese Medicine(ETCM), and the core targets underwent functional enrichment analysis and signaling pathway analysis. Cytoscape 3.6.0 was used to construct a visualized "active component-target-signaling pathway" network of JBQGF. After screening, nine potential pathways of JBQGF were obtained, mainly including G protein-coupled receptor signaling pathway and tyrosine kinase receptor signaling pathway. As previously indicated, the fibroblast growth factor receptor 1(FGFR1) signaling pathway was highly activated in active fibroblast-like synoviocytes(FLS) in rheumatoid arthritis, and cell and animal experiments demonstrated that inhibition of the FGFR1 signaling pathway could significantly reduce joint inflammation and joint destruction in collagen-induced arthritis(CIA) rats. In terms of the tyrosine kinase receptor signal transduction pathway, the analysis of its target genes revealed that FGFR1 might be a potential target of JBQGF for rheumatoid arthritis treatment. The biological effect of JBQGF by inhibiting FGFR1 phosphorylation was preliminarily verified by Western blot, Transwell invasion assay, and pannus erosion assay, thereby inhibiting matrix metalloproteinase 2(MMP2) and receptor activator of nuclear factor-κB ligand(RANKL) and suppressing the invasion of fibroblasts in rheumatoid arthritis and erosive effect of pannus bone. This study provides ideas for searching potential targets of rheumatoid arthritis treatment and TCM drugs through network pharmacology.
Rats ; Animals ; Synoviocytes ; Matrix Metalloproteinase 2/metabolism* ; Network Pharmacology ; Receptor, Fibroblast Growth Factor, Type 1/therapeutic use* ; Arthritis, Rheumatoid/genetics* ; Signal Transduction ; Fibroblasts ; Drugs, Chinese Herbal/therapeutic use*

Objective To study the influence of recombinant bovine basic fibroblast growth factor as an adjuvant therapy on scar alleviation and inflammatory cytokines in patients with atrophic acne scar. Methods The random number table was employed to randomly assign 120 patients with atrophic acne scar into a test group and a control group.Both groups of patients were treated with CO₂ lattice laser.After the operation,the control group was routinely smeared with erythromycin ointment and the test group was coated with recombinant bovine basic fibroblast growth factor gel.The clinical efficacy,clinical indicators,scar alleviation,and inflammatory cytokine levels before and after treatment were compared,and adverse reactions were counted. Results The test group had higher total effective rate(P=0.040) and lower total incidence of adverse reactions(P=0.028) than the control group.Compared with the control group,the test group showcased short erythema duration after treatment(P=0.025),early scab forming(P=0.002),and early edema regression(P<0.001).After treatment,the proportion of grade 1 scars graded by Goodman and Baron's acne scar grading system in the test group and control group increased(P=0.001,P=0.027),and the proportion of grade 4 scars decreased(P<0.001,P=0.034).Moreover,the proportion of grade 1 scars in the test group was higher than that in the control group(P=0.031) after treatment,and the proportion of grade 4 scars presented an opposite trend(P=0.031).After treatment,the levels of tumor necrosis factor-α(TNF-α) and interleukin-1β(IL-1β) in both groups declined(all P<0.001),and the test group had lower TNF-α and IL-1β levels than the control group(all P<0.001). Conclusion The recombinant bovine basic fibroblast growth factor gel as an adjuvant therapy of CO₂ lattice laser can effectively alleviate the atrophic acne scar,relieve local inflammatory reaction,and has good curative effect and less adverse reactions.
Acne Vulgaris/drug therapy* ; Animals ; Atrophy/complications* ; Carbon Dioxide ; Cattle ; Cicatrix/pathology* ; Fibroblast Growth Factor 2/therapeutic use* ; Humans ; Treatment Outcome ; Tumor Necrosis Factor-alpha

This study aims to investigate the therapeutic effects of alkaloids in Tibetan medicine Bangna(Aconiti Penduli et Aconiti Flavi Radix) on osteoarthritis(OA) rats in vitro and in vivo and the underlying mechanisms. Chondrocytes were isolated from 2-3 week-old male SD rats and lipopolysaccharide(LPS) was used to induce OA in chondrocytes in vitro. Methyl thiazolyl tetrazolium(MTT) assay was used to investigate the toxicity of seven alkaloids(12-epi-napelline, songorine, benzoylaconine, aconitine, 3-acetylaconitine, mesaconitine, and benzoylmesaconine) to chondrocytes. Chondrocytes were classified into the control group, model group(induced by LPS 5 μg·mL~(-1) for 12 h), and administration groups(induced by LPS 5 μg·mL~(-1) for 12 h and incubated for 24 h). The protein expression of inflammatory factors cyclooxygenase-2(COX-2), inducible nitric oxide synthetase(iNOS), tumor necrosis factor-α(TNF-α), and interleukin-1β(IL-1β) in each group were detected by Western blot, and the protein expression of matrix metalloprotease-13(MMP-13), aggrecan, collagen Ⅱ, fibroblast growth factor 2(FGF2) by immunofluorescence staining. For the in vivo experiment, sodium iodoacetate was used to induce OA in rats, and the expression of MMP-13, TNF-α, and FGF2 in cartilage tissues of rats in each group was detected by immunohistochemistry. The results showed that the viability of chondrocytes could reach more than 90% under the treatment of the seven alkaloids in a certain dose range. Aconitine, 12-epi-napelline, songorine, 3-acetylaconitine, and mesaconitine could decrease the protein expression of inflammatory factors COX-2, iNOS, TNF-α and IL-1β compared with the model group. Moreover, 12-epi-napelline, aconitine, and mesaconitine could down-regulate the expression of MMP-13 and up-regulate the expression of aggrecan and collagen Ⅱ. In addition, compared with the model group and other Bangna alkaloids, 12-epi-napelline significantly up-regulated the expression of FGF2. Therefore, 12-epi-napelline was selected for the animal experiment in vivo. Immunohistochemistry results showed that 12-epi-napelline could significantly reduce the expression of MMP-13 and TNF-α in cartilage tissues, and up-regulate the expression of FGF2 compared with the model group. In conclusion, among the seven Bangna alkaloids, 12-epi-napelline can promote the repair of OA in rats by down-regulating the expression of MMP-13 and TNF-α and up-regulating the expression of FGF2.
Aconitine/therapeutic use* ; Aconitum/chemistry* ; Aggrecans/metabolism* ; Alkaloids/therapeutic use* ; Animals ; Cells, Cultured ; Cyclooxygenase 2/metabolism* ; Fibroblast Growth Factor 2/therapeutic use* ; Interleukin-1beta/metabolism* ; Iodoacetic Acid/therapeutic use* ; Lipopolysaccharides ; Male ; Matrix Metalloproteinase 13/metabolism* ; Medicine, Tibetan Traditional ; NF-kappa B/metabolism* ; Osteoarthritis/drug therapy* ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha/metabolism*

Objective: To explore the effects of Kudzu Root plus Cinnamon Granules (KR+C) on prostatic hyperplasia (PH) in mice. METHODS: Sixty 4-week-old Kunming male mice were randomly divided into six groups: blank control, PH model, high-, medium- and low-dose KR+C, and finasteride control. All the mice except those in the blank control group were subcutaneously injected with testosterone propionate (5 mg / ［kg·d］) at 7 days after surgical castration. The animals of different groups were treated intragastrically with different doses of KR+C, finasteride, and normal saline respectively for 3 weeks and then sacrificed for weighing of the prostate, calculation of the prostatic index, observation of the morphological changes in the prostate after HE staining, determination of the expressions of FGF2, Ki67 and TGF-β1 by immunohistochemistry, detection of 5α-reductase activity by ELISA, and measurement of the apoptosis index of the prostatic cells by TUNEL. RESULTS: Compared with the model controls, the mice of the other groups showed significantly reduced prostatic volume (P <0.05), prostatic index (P <0.05), expressions of FGF2, Ki67 and TGF-β1, and activity of 5 α-reductase (P <0.05), but remarkably increased apoptosis index of the prostatic cells (P <0.05). However, no statistically significant differences were observed in the above parameters between the finasteride control and the three KR+C groups (P>0.05). CONCLUSIONS KR+C can reduce the prostatic volume of PH mice by decreasing the activity of 5α- reductase, inhibiting the expressions of FGF2, Ki67 and TGF-β1, and promoting the apoptosis of prostatic cells.
Animals ; Apoptosis ; Cholestenone 5 alpha-Reductase ; metabolism ; Cinnamomum zeylanicum ; chemistry ; Fibroblast Growth Factor 2 ; metabolism ; Finasteride ; therapeutic use ; In Situ Nick-End Labeling ; Ki-67 Antigen ; metabolism ; Male ; Mice ; Organ Size ; Phytotherapy ; methods ; Plant Roots ; chemistry ; Prostate ; pathology ; Prostatic Hyperplasia ; drug therapy ; metabolism ; pathology ; Pueraria ; chemistry ; Random Allocation ; Testosterone Propionate ; administration & dosage ; Transforming Growth Factor beta1 ; metabolism ; Urological Agents ; therapeutic use

OBJECTIVETo investigate the clinical efficacy of regimen consisting of lenalidomide combined with chemotherapy for acute leukemia and its impact on vascular endothilial growth factor (vEGF) and basic fibroblast growth factor (bFGF), and to analyze the relationship lenalidomide with therapeutic efficacy of leukemia.

METHODSThe patients with newly diagnosed acute myeloid leukemia (except M3) from October 2013 to October 2014 in our hospital were randomly divided into 2 groups: chemotherapy+placebo (CP) group and lenalidomide+chemotherapy (LC) group. In addition, healthy persons were used as healthy controls (HC). The expression of VEGF and bFGF was detected by ELISA, and the therapeutic efficacy for AML patients was analyzed.

RESULTSThe therapeutic efficacy in LC group and CP group was 87.9% and 77.2% respectively. Before treatment, the VEGF level in LC and CP groups was obviously higher than that in HC group; after treatment, the VEGF level significanthy decreased, and the decreased degree in LC group was larger than that in CP group. Before treatment, the bFGF level in LC and CP groups was higher than that in HC group; after treatment, the bFGF level decreased, and decreased degree in LC group was larger than that in CP group.

CONCLUSIONThe lenalidomide combined with chemotherapy can significantly decrease the expression level of VEGF and bFGF, and enhance the remission rate of patients with AML.

Acute Disease ; Antineoplastic Agents ; administration & dosage ; therapeutic use ; Drug Therapy, Combination ; Fibroblast Growth Factor 2 ; metabolism ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; Thalidomide ; administration & dosage ; analogs & derivatives ; therapeutic use ; Vascular Endothelial Growth Factor A ; metabolism

OBJECTIVETo investigate the effects of Heijiangdan Ointment ( HJD) on oxidative stress in (60)Co γ-ray radiation-induced dermatitis in mice.

METHODSFemale Wistar mice with grade 4 radiation dermatitis induced by (60)Co γ-rays were randomly divided into four groups (n=12 per group); the HJD-treated, recombinant human epidermal growth factor (rhEGF)-treated, Trolox-treated, and untreated groups, along with a negative control group. On the 11th and 21st days after treatment, 6 mice in each group were chosen for evaluation. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), and lactate dehydrogenase (LDH) were detected using spectrophotometric methods. The fibroblast mitochondria were observed by transmission electron microscopy (TEM). The expressions of fibroblast growth factor 2 (FGF-2) and transforming growth factor β1 (TGF-β1) were analyzed by western blot.

RESULTSCompared with the untreated group, the levels of SOD, MDA and LDH, on the 11th and 21st days after treatment showed significant difference (P<0.05). TEM analysis indicated that fibroblast mitochondria in the untreated group exhibited swelling and the cristae appeared fractured, while in the HJD group, the swelling of mitochondria was limited and the rough endoplasmic reticulum appeared more relaxed. The expressions of FGF-2 and TGF-β1 increased in the untreated group compared with the negative control group (P<0.05). After treatment, the expression of FGF-2, rhEGF and Trolox in the HJD group were significantly increased compared with the untreated group (P<0.05), or compared with the negative control group (P<0.05). The expression of TGF-β1 showed significant difference between untreated and negative control groups (P<0.05). HJD and Trolox increased the level of TGF-β1 and the difference was marked as compared with the untreated and negative control groups (P<0.05).

CONCLUSIONHJD relieves oxidative stress-induced injury, increases the antioxidant activity, mitigates the fibroblast mitochondrial damage, up-regulates the expression of growth factor, and promotes mitochondrial repair in mice.

Animals ; Biological Products ; pharmacology ; therapeutic use ; Cell Proliferation ; drug effects ; radiation effects ; Cobalt Radioisotopes ; Dermatitis ; complications ; drug therapy ; pathology ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Fibroblast Growth Factor 2 ; genetics ; metabolism ; Fibroblasts ; drug effects ; pathology ; radiation effects ; Gamma Rays ; Humans ; L-Lactate Dehydrogenase ; metabolism ; Malondialdehyde ; metabolism ; Mice ; Mitochondria ; drug effects ; metabolism ; radiation effects ; Ointments ; Oxidative Stress ; drug effects ; radiation effects ; Pharmaceutical Preparations ; Radiation Injuries ; complications ; drug therapy ; pathology ; Superoxide Dismutase ; metabolism ; Transforming Growth Factor beta1 ; genetics ; metabolism ; Up-Regulation ; drug effects ; radiation effects

OBJECTIVETo observe the effects of artificial dermis combined with basic fibroblast growth factor (bFGF) on the treatment of cicatrix and deep skin wounds.

METHODSThe clinical data of 72 patients with wounds repaired with artificial dermis, hospitalized in our unit from October 2010 to April 2015, conforming to the study criteria, were retrospectively analyzed. The types of wounds were wounds after resection of cicatrices, deep burn wounds without exposure of tendon or bone, and wounds with exposure of small area of tendon or bone, in a total number of 102. Wounds were divided into artificial dermis group (A, n=60) and artificial dermis+ bFGF group (B, n=42) according to whether or not artificial dermis combined with bFGF. In group A, after release and resection of cicatrices or thorough debridement of deep skin wounds, artificial dermis was directly grafted to wounds in the first stage operation. After complete vascularization of artificial dermis, wounds were repaired with autologous split-thickness skin grafts in the second stage operation. In group B, all the procedures were exactly the same as those in group A except that artificial dermis had been soaked in bFGF for 30 min before grafting. Operation area, complete vascularization time of artificial dermis, survival of skin grafts, and the follow-up condition of wounds in the two groups were recorded. Data were processed with t test and Fisher's exact test.

RESULTS(1) Operation areas of wounds after resection of cicatrices, deep burn wounds without exposure of tendon or bone, and wounds with exposure of small area of tendon or bone in the two groups were about the same (with t values from -1.853 to -0.200, P values above 0.05). Complete vascularization time of artificial dermis in wounds after resection of cicatrices, deep burn wounds without exposure of tendon or bone, and wounds with exposure of small area of tendon or bone in group B were respectively (15.6 ± 2.9), (14.7 ± 2.7), and (20.3 ± 4.4) d, and they were shorter by an average time of 2.7, 4.0, 7.4 d, respectively, as compared with those in corresponding types of wounds in group A [respectively (18.3 ± 4.7), (18.7 ± 4.2), and (27.7 ± 8.8) d, with t values from -2.779 to -2.383, P values below 0.05]. (2) The ratio of skin grafts with excellent survival in the three types of wounds in group B were higher than those in corresponding types of wounds in group A, but there were no statistically significant differences (with P values above 0.05). (3) Patients were followed up for 1 to 48 months, and there were no obvious cicatrices in skin graft sites and the donor sites during the following time.

CONCLUSIONSArtificial dermis combined with bFGF can effectively shorten the vascularization time of artificial dermis in wounds after resection of cicatrices and deep skin wounds.

Burns ; therapy ; Cicatrix ; therapy ; Debridement ; Dermis ; injuries ; Fibroblast Growth Factor 2 ; therapeutic use ; Humans ; Retrospective Studies ; Skin Transplantation ; Skin, Artificial ; Soft Tissue Injuries ; therapy ; Transplantation, Autologous ; Wound Healing

OBJECTIVE: This study investigated the effects and Numerical Rating Pain Scale (NRS) of using absorbable shanching satin rb-bFGF prepreg sheet and expansion hemostatic sponge together nasal packing in the control of epistaxis with blood disease, and compared it with traditional vaseline gauze. METHOD: Ninety-six blood disease patient with epistaxis were enrolled between January 2009 and February 2011, they were divided into two groups at random, and differently treated with absorbable shanching satin rb-bFGF prepreg sheet and the vaseline gauze nasal packing for haemostasis. Then haemostasis efficacy,the hemorrhage rate after nasal packing removed and host response, such as nasal pain and headache, which evaluated pain degrees against NRS, were all observed. RESULT: There was no significant difference between the two groups of the haemostatic effect. But the hemorrhage rate of treatment group was obviously lower than that of the control group after paching,in addition, host responses, such as nasal pain and headache, remarkably better than the control group, the difference had statistical significance. CONCLUSION It is indicate that absorbable shanching satin rb-bFGF prepreg sheet presents reliable hemostasis effect, good biocompatibility and compliance; the pain and headache caused by packing are superior to vaseline gauze. Moreover, this method avoids the direct touch of vaseline gauze with nasal mucosal wound, and reduce hemorrhage after packing. Absorbable shanching satin rb-bFGF prepreg sheet and expansion hemostatic sponge together is better to select the nasal packing material for blood disease patient with epistaxis.
Adolescent ; Adult ; Aged ; Bandages ; Child ; Epistaxis ; etiology ; therapy ; Female ; Fibroblast Growth Factor 2 ; therapeutic use ; Hematologic Diseases ; complications ; Hemostatic Techniques ; Humans ; Male ; Middle Aged ; Nasal Cavity ; Treatment Outcome ; Young Adult

OBJECTIVETo observe the effect of Yifei Qinghua Granule (YQG) on vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), angiostatin, and endostatin in tumor tissue of Lewis Lung cancer mice, and to explore its anti-tumor mechanisms.

METHODSTotally 70 C57BL/6 mice were randomly divided into the model group, the low, medium, and high dose YQG groups, the gefitinib group, the gefitinib plus medium dose YQG group, and the cyclophosphamide (CTX) group, 10 in each group. The models were established by subcutaneously injecting Lewis lung cancer cells from the right axilla of C57BL/6 mice. Mice in the model group were given with 0.4 mL pure water by gastrogavage, once daily. Mice in the low and medium dose YHG groups were given with YHG at the daily dose of 5 and 10 g/kg by gastrogavage, once daily. Those in the high dose YHG group were given with YHG at 10 g/kg by gastrogavage, twice daily. Those in the gefitinib group were given with gefitinib 100 mg/ kg by gastrogavage, once daily. Those in the gefitinib plus medium dose YHG group were given with gefitinib at 100 mg/kg by gastrogavage in the morning and YHG at 10 g/kg by gastrogavage in the afternoon. All medication was started from the 2nd day of inoculation, lasting 14 successive days. Those in the CTX group were given CTX at 60 mg/kg by peritoneal injection on the 3rd and the 7th day of the experiment. Mice were sacrificed at the fifteenth day of the experiment. Tumors were taken out. Expressions of VEGF, bFGF, angiostatin, and endostatin in the tumor tissue were detected using immunohistochemical assay.

RESULTSCompared with the model group, the expression of VEGF significantly decreased, expressions of angiostatin and endostatin significantly increased in each group (P < 0.01). The expression of bFGF significantly decreased in the gefitinib group (P < 0.05). There was no statistical difference in VEGF among all groups (P > 0.05). The angiostatin expression was significantly higher in the CTX group than in the low dose YQG group (P < 0.01). The expression of endostatin was significantly higher in the high dose YQG group and the gefitinib plus medium dose YQG group than in the low and the medium dose YQG groups (P < 0.01). The expression of endostatin was significantly higher in the gefitinib plus medium dose YQG group than in the gefitinib group (P < 0.05).

CONCLUSIONThe action mechanism of YQG in treating lung cancer might be achieved through reducing the expression of angiogenesis promoting factor VEGF and increasing expressions of angiogenesis inhibitors angiostatin and endostatin.

Angiostatins ; metabolism ; Animals ; Carcinoma, Lewis Lung ; drug therapy ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Endostatins ; metabolism ; Fibroblast Growth Factor 2 ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Phytotherapy ; Vascular Endothelial Growth Factor A ; metabolism

OBJECTIVETo observe the effect of San-huang-sheng-fu oil on wounds of full-thickness scald in rabbits.

METHODSFull-thickness scald wounds with area of 6 cm(2) were reproduced on both sides of the back in 9 experimental rabbits by water vapor. These rabbits were divided into sesame oil (S1), San-huang-sheng-fu oil (S2), and mupirocin ointment (M) groups according to the random number table, with 3 rabbits (6 wounds) in each group. Two wounds of each rabbit in the three groups were respectively treated with sesame oil, San-huang-sheng-fu oil, and mupirocin ointment, in a dose of 0.15 mL/cm(2), 2-3 times per day. The general condition of wounds was observed on post scald day (PSD) 1, 11, 22, and 45. The wound healing time was recorded. The wound healing rate was calculated on PSD 5, 11, 15, and 22. All the rabbits were sacrificed on PSD 45, and wound tissues were subjected to histomorphological study with HE staining. The protein expressions of transforming growth factor β1 (TGF-β1), basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF) were observed with immunofluorescence staining for the other part of wound tissues. Data were processed with one-way analysis of variance or LSD-t test.

RESULTS(1) The wound healing quality of rabbits in S2 group was better than that in the other two groups. (2) The wound healing time of rabbits in S2 group [(11.2 ± 2.3) d] was significantly shorter than that in S1 group [(21.2 ± 3.1) d, t = 2.591, P < 0.05]. (3) The wound healing rate of rabbit in each group was increased gradually on PSD 5-22. The wound healing rates of rabbits in S2 group on PSD 5-22 were significantly higher than those in S1 group (with t values from 3.920 to 8.605, P values all below 0.05). (4) Histomorphological observation showed that the structure of wound tissues in S2 group was in much better integrity than that in the other two groups, including regenerated hair follicles in the corium layer and regularly arranged collagen fibers. The protein expressions of TGF-β1, bFGF, and VEGF in S2 group were all higher than those in the other two groups.

CONCLUSIONSSan-huang-sheng-fu oil can up-regulate the protein expressions of TGF-β1, bFGF, and VEGF, induce vascular regeneration, promote wound healing, and shorten wound healing time.

Animals ; Burns ; drug therapy ; Disease Models, Animal ; Drugs, Chinese Herbal ; therapeutic use ; Fibroblast Growth Factor 2 ; metabolism ; Mupirocin ; therapeutic use ; Rabbits ; Transforming Growth Factor beta1 ; metabolism ; Vascular Endothelial Growth Factor A ; metabolism ; Wound Healing ; drug effects