OBJECTIVETo discuss the mechanism of traditional Chinese medicines reducing phlegm and resolving masses in treatment of iodine deficiency-induced goiter by observing the expression of growth factors and the balance-regulating mechanism of proliferation and apoptosis.

METHOD180 four-week-old Wistar rats were selected to establish the iodine deficiency model. After the modeling, the rats were randomly divided into six groups: the normal control group, the model control group, the iodine group, the phlegm compound group, the L-T4 group and the phlegm compound and L-T4 group. At the 21st day and 77th day after administration, 15 rats in each group were killed to collect specimens. Doses were calculated and adjusted according to body surface area and body weight. TT3, TT4 radioimmunoassay, TSH, immunoradiometric method were adopted. Fas, FasL and PCNA protein expressions are detected using immunohistochemical methods.

RESULTCompared with the normal group and the model group, the expressions of fas and FasL in the phlegm Group significantly increased, the expressions of fas and FasL in the phlegm and L-T4 group were also increased significantly. The expression of fas in the L-T4 Group was significantly lower than that of the L-T4 group and the phlegm compound and L-T4 group. Compared with the normal group, the expression of PCNA of the phlegm group and the phlegm and L-T4 group was significantly lower. Compared with the model group, the expression of PCNA of the iodine group, the phlegm groups and the phlegm and L-T4 group were significantly lower. Compared with the normal group, the expression of VEGF in the iodine group significantly decreased after treatment. Compared with the iodine group, the expression of VEGF in the phlegm group and the L-T4 group significantly reduced. Compared with the normal group, the expression of TGF-beta1 in the model group and the phlegm group significantly increased. Compared with model group, the expression of TGF-beta1 in the iodine group significantly reduced. Compared with the phlegm group, the expression of TGF-beta1 in the phlegm compound and L-T4 group was significantly reduced.

CONCLUSIONTraditional Chinese medicines reducing phlegm and resolving masses can completely recover goiter by promoting apoptosis of thyroid cells, inhibiting their proliferation and the expression of growth factors and enhancing the expression of TGF-beta, without causing injury on thyroid cells.

Animals ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Gene Expression ; drug effects ; Goiter ; drug therapy ; genetics ; metabolism ; Humans ; Male ; Proliferating Cell Nuclear Antigen ; genetics ; metabolism ; Rats ; Rats, Wistar ; Thyroid Hormones ; secretion ; Vascular Endothelial Growth Factor A ; genetics ; metabolism

OBJECTIVETo investigate the distribution of estrogen receptor beta (ERbeta) gene polymorphisms between the Uygurs and the Hans in Urumqi and the association of the polymorphisms with intrahepatic cholestasis of pregnancy (ICP).

METHODSICP cases and controls from a hospital were recruited from April 2008 to April 2011,and a total of 105 ICP patients in Uygurs case group and 105 ICP patients in Hans case group were randomly selected, meanwhile, 105 Uygurs and 105 Hans healthy pregnant women were recruited as control group. The distribution of Rsa I and Alu I of ERbeta gene polymorphism were analyzed by PCR amplification and restriction and other molecular biology approaches. Data were analyzed by chi2 and Fisher exact probability.

RESULTSIn Uygurs case group, the genotype frequencies of rr, Rr,RR,aa, Aa and AA were 39.0% (41 cases), 50.5% (53 cases), 10.5% (11 cases), 62.7% (66 cases), 30.5% (32 cases), 6.8% (7 cases). In Uygurs control group, the frequencies were 21.0% (22 cases), 56.2% (59 cases), 22.8% (24 cases), 80.0% (84 cases), 18.1% (19 cases), 1.9% (2 cases). In Hans case group, the genotype frequencies of rr, Rr, RR, aa, Aa and AA were 40. 0% (42 cases), 45.7% (48 cases), 14.3% (15 cases), 66.7% (70 cases), 29.5% (31 cases), 3.8% (4 cases). In Hans control group,the frequencies were 29.5% (31 cases), 57.2% (60 cases), 13.3% (14 cases), 74.2% (78 cases), 23.8% (25 cases), 2.0% (2 cases). The genotype frequencies were not statistically significant between the two case groups and between the two control groups (all P values > 0.05), and between two Hans groups (P > 0.05). The frequencies of RRaa in the Uygur case group was lower(4. 76% ,5 cases)than control group (13.33%, 14 cases) (P <0.05), while the frequencies of rrAa in the Uygur case group was significantly higher (14. 29% ,15 cases)than control group (2.86%, 3 cases) (all P values < 0.05).

CONCLUSIONThe distribution of ERbeta gene polymorphism is of no significant difference between the Uygurs and Hans, ERbeta gene polymorphism may correlate with pathogenesis of ICP in the Uygurs other than in the Hans, and rrAa might be risk factor for ICP in the Uygurs.

Alleles ; Asian Continental Ancestry Group ; genetics ; Case-Control Studies ; China ; epidemiology ; Cholestasis, Intrahepatic ; ethnology ; genetics ; Estrogen Receptor beta ; genetics ; Female ; Gene Frequency ; Genotype ; Humans ; Minority Groups ; Polymorphism, Genetic ; Pregnancy ; Pregnancy Complications ; ethnology ; genetics ; Risk Factors

BACKGROUNDIntratracheal instillation of blood induces self-repaired acute lung injury. However, the mechanism of repair has been unclear. Heme-oxygenase (HO)-1, which catalyzes heme breakdown, acts as an inducible defense against oxidative stress and plays an important role in inflammation. The objective of this study was to test the role of HO-1 in lung injury caused by intratracheal instillation of red cells.

METHODSForty healthy, male Sprague-Dawley rats were randomly divided into five groups: normal group, saline group, erythrocyte group, erythrocyte+zinc-protoporphyrin (ZnPP, HO-1 inhibitor) group and saline+ZnPP group. At 2 days after intratracheal instillation of red cells, lung tissues and lavage samples were isolated for biochemical determinations and histological measurements.

RESULTSHistological analysis revealed that administration of ZnPP worsened the acute lung injury induced by instilled erythrocytes. HO-1 was over-expressed in the erythrocyte group and in the erythrocyte + ZnPP group. Compared with the erythrocyte + ZnPP group, the levels of total protein, lactate dehydrogenase and tumor necrosis factor-alpha in the lavage were lower (P < 0.01), while the level of interleukin-10 was higher in the erythrocyte group (P < 0.01).

CONCLUSIONHO-1 protects against erythrocyte-induced inflammatory injury in lung.

Animals ; Erythrocytes ; physiology ; Heme Oxygenase (Decyclizing) ; analysis ; physiology ; Interleukin-10 ; analysis ; Lung ; pathology ; Lung Injury ; prevention & control ; Male ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; analysis

Diabetic retinopathy(DR)is a prevalent microvascular complication of diabetes and the leading cause of blindness and severe visual impairment in adults.The high levels of glucose trigger multiple intracellular oxidative stress pathways,such as POLDIP2,resulting in excessive reactive oxygen species(ROS)pro-duction and increased expression of vascular cell adhesion molecule-1(VCAM-1),hypoxia-inducible factor 1α(HIF-1α),and vascular endothelial growth factor(VEGF),causing microvascular dysfunction.Dihydromyricetin(DMY)is a natural flavonoid small molecule antioxidant.However,it exhibits poor solubility in physiological environments,has a short half-life in vivo,and has low oral bioavailability.In this study,we present,for the first time,the synthesis of ultra-small Fe-DMY nano-coordinated polymer particles(Fe-DMY NCPs),formed by combining DMY with low-toxicity iron ions.In vitro and in vivo experiments confirm that Fe-DMY NCPs alleviate oxidative stress-induced damage to vascular endo-thelial cells by high glucose,scavenge excess ROS,and improve pathological features of DR,such as retinal vascular leakage and neovascularization.Mechanistic validation indicates that Fe-DMY NCPs can inhibit the activation of the Poldip2-Nox4-H2O2 signaling pathway and downregulate vital vascular function indicators such as VCAM-1,HIF-1α,and VEGF.These findings suggest that Fe-DMY NCPs could serve as a safe and effective antioxidant and microangio-protective agent,with the potential as a novel multimeric drug for DR therapy.

OBJECTIVETo evaluate the effects of Tanguticum Maxim polysaccharide (TMP-1) on TNBS-induced colitis in rats.

METHODRats with TNBS/ethanol-induced colitis were used and treated with TMP-1 and dexamethasone (DX). Seventy-two rats, including animals with TNBS-induced colitis, were treated with saline, TMP-1 (100, 200, 400 mg.kg-1) and DX. White blood cells were counted on the fifth day and the rats were killed by ether on the sixth day. SOD activity in serum, MPO and SOD activity of colonic tissue were measured.

RESULTThe remarkable effects of TMP-1 at dosage of 200, 400 mg.kg-1 on TNBS-induced colitis were observed. The ulcerative area was diminished and weight of colon was reduced. White blood cell population was reduced, SOD activity in serum and SOD activity of colon tissue were remarkably increased, and, MPO activity of colonic tissue was reduced.

CONCLUSIONTMP-1 has significant effects on TNBS-induced colitis in rats with lower side effects, which suggests the effective component of rhubarb on colitis perhaps is TMP. The mechanism of the actions of TMP may relate to its antiflammation, antioxidation and immunoloregulation.

Animals ; Anti-Inflammatory Agents, Non-Steroidal ; therapeutic use ; Colitis, Ulcerative ; chemically induced ; drug therapy ; Colon ; enzymology ; pathology ; Male ; Phytotherapy ; Plants, Medicinal ; chemistry ; Polysaccharides ; isolation & purification ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Rheum ; chemistry ; Trinitrobenzenesulfonic Acid

OBJECTIVETo investigate the mechanism of the acupoint sticking therapy with Chuanfuling for preventing and treating asthma.

METHODSThirty male SD rats were randomly divided into a control group (normal saline, p.i. +no acupoint sticking+ normal saline, spray inhalation), model group (normal saline with ovalbumin, p.i. +no acupoint sticking+ normal saline with ovalbumin, spray inhalation), and acupoint sticking group (normal saline with ovalbumin, p.i. +acupoint sticking with Chuan fuling+normal saline with ovalbumin, spray inhalation), 10 rats in each group. The incubation period of nodding breath, symptom of asthmatic attack, expression level of interleukin-4 mRNA (IL-4 mRNA) and interferon-gamma mRNA (IF-gamma mRNA), as well as pathological changes on the middle leaf of right lung, were observed in each group.

RESULTS(1) Comparing with the control group, the model group was showed that the expression level of IL-4 mRNA in the peripheral blood cells (PBMC) was increased, while hyperemia, edema and eosinocyte (EOS) invasion of lung tissue was more serious (P < 0.01). (2) Comparing with the model group, the acupoint sticking group was showed that the expression level of IL-4 mRNA in PBMC was decreased, the incubation period of nodding breath was prolonged for induced asthma on the fifth and seventh time with lower frequency, while in the lung tissue EOS invasion was reduced (P < 0.05), but there were no significant changes on the hyperemia and edema (P > 0.05).

CONCLUSIONAcupoint sticking for treating asthma of model rats with Chuanfuling can inhibit the expression level of IL-4 mRNA in PBMC, and the release of the inflammatory mediator and cytokine from the EOS to the air passage, in order to reduce the injury of epithelial layer and high reaction on the air passage.

Acupuncture Points ; Animals ; Asthma ; drug therapy ; genetics ; immunology ; Disease Models, Animal ; Drugs, Chinese Herbal ; therapeutic use ; Gene Expression ; drug effects ; Humans ; Interleukin-4 ; genetics ; immunology ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley

This study was aimed to clarify whether valproic acid (VPA) induces apoptosis of leukemia HL-60 cell line and its possible mechanism. The effect of different concentrations and treatment time of VPA on HL-60 cell proliferation was assayed by cytotoxicity test (CCK-8 method) and fluorescence microscopy, and flow cytometry was used to detect cell apoptosis. The expressions of telomerase subunit h-tert mRNA and apoptosis-related protein as well as caspase-3 activity were detected by real time-quantitative PCR, Western blot and ELISA respectively. The results indicated that VPA inhibited proliferation of HL-60 cells and induced cell apoptosis in a dose dependent manner (r = -0.87). The expressions of anti-apoptotic protein BCL-2 and h-tert mRNA were significantly decreased while the pro-apoptotic protein BAX and caspase-3 activity increased after treatment with VPA. The apoptosis rate of HL-60 cell was negatively correlated with expression of h-tert mRNA. It is concluded that VPA can inhibit leukemia HL-60 cell proliferation and induce apoptosis. The VPA displays anti-leukemia activity possibly through reducing h-tert mRNA and BCL-2 protein expression, increasing BAX expression and activity of caspase-3.
Apoptosis ; drug effects ; Caspase 3 ; metabolism ; HL-60 Cells ; Humans ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Telomerase ; metabolism ; Valproic Acid ; pharmacology ; bcl-2-Associated X Protein ; metabolism

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a major side effect of anti-cancer drugs. Neurotensin receptors (NTSRs) are widely distributed within the pain circuits in the central nervous system. The purpose of this study was to determine the role of NTSR1 by examining the effects of an NTSR1 agonist in rats with CIPN and investigate the contribution of spinal serotonin receptors to the antinociceptive effect. Methods: Sprague–Dawley rats (weight 150–180 g) were used in this study. CIPN was induced by injecting cisplatin (2 mg/kg) once a day for 4 days. Intrathecal catheters were placed into the subarachnoid space of the CIPN rats. The antiallodynic effects of intrathecally or intraperitoneally administered PD 149163, an NTSR1 agonist, were evaluated. Furthermore, the levels of serotonin in the spinal cord were measured by high-performance liquid chromatography. Results: Intrathecal or intraperitoneal PD 149163 increased the paw withdrawal threshold in CIPN rats. Intrathecal administration of the NTSR1 antagonist SR 48692 suppressed the antinociceptive effect of PD 149163 given via the intrathecal route, but not the antinociceptive effect of intraperitoneally administered PD 149163. Intrathecal administration of dihydroergocristine, a serotonin receptor antagonist, suppressed the antinociceptive effect of intrathecally administered, but not intraperitoneally administered, PD 149163. Injecting cisplatin diminished the serotonin level in the spinal cord, but intrathecal or intraperitoneal administration of PD 149163 did not affect this reduction. Conclusions NTSR1 played a critical role in modulating CIPN-related pain. Therefore, NTSR1 agonists may be useful therapeutic agents to treat CIPN. In addition, spinal serotonin receptors may be indirectly involved in the effect of NTSR1 agonist.

BACKGROUNDWe previously showed that nano-hydroxyapatite/carboxymethyl chitosan (n-Ha/CMCS) displayed excellent mechanical properties, good degradation rates and exceptional biocompatibility, with negligible toxicity. The aim of this study was to determine the effect of the same composite with vascular endothelial growth factor (VEGF)- transfected bone marrow stromal cells (BMSCs) in a rabbit radial defect model.

METHODSThe nano-hydroxyapatite was produced through co-precipitation. The n-HA/CMCS scaffold was produced by particle filtration and lyophilization followed by genipin crosslinking. Total RNA from rabbit bone was reverse-transcribed to synthesize VEGF165-pcDNA3.1 that was transfected into the BMSCs. The composite was implanted into a rabbit radial defect model, and the osteogenic activity examined by gross morphology, X-ray examination and hematoxylin and eosin (HE) staining.

RESULTSThe microstructure and mechanical property of the n-HA/CMCS scaffold resembled natural cancellous bone. Compared with glutaric dialdehyde crosslinked scaffolds, the genipin crosslinked scaffold was less toxic, and displayed a higher capacity to promote cell adhesion and proliferation. Spontaneous fluorescence of the composite permitted visualization of the composite-bone interface and the adhesion behavior of cells on the scaffold under laser scanning confocal microscopy. The scaffold with VEGF-transfected BMSCs bridged the bony defect and promoted healing, with most of the implanted material being replaced by natural bone over time with little residual implant. Using X-ray, we noted obvious callus formation and recanalization of the bone marrow cavity. Furthermore, HE stained sections showed new cortical bone formation.

CONCLUSIONSThe n-HA/CMCS scaffold composite with VEGF-trasnfected BMSCs is biocompatible, nontoxic, promotes the infiltration and formation of the microcirculation, and stimulates bone defect repair. Furthermore, the degradation rate of the composite matched that of growing bone. Overall, this composite material is potentially useful for bone defect repair.

Animals ; Bone Diseases ; surgery ; Bone Marrow Cells ; cytology ; Rabbits ; Stromal Cells ; cytology ; Tissue Engineering ; methods ; Tissue Scaffolds ; chemistry ; Vascular Endothelial Growth Factor A ; chemistry

Acupuncture Points ; Gastritis, Atrophic ; diagnosis ; therapy ; Health Planning Guidelines ; Humans ; Medicine, Chinese Traditional