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Objective To investigate the role of hydrogen therapy in reducing radiation-induced lung injury and the specific mechanism. Methods Forty C57BL/6 mice were randomly divided into four groups: normal control group, model group, hydrogen therapy group I, and hydrogen therapy group II. A mouse model of radiation-induced lung injury was established. The pathological changes in the lung tissue of the mice were examined with HE staining. Immunofluorescence staining was used to detect the expression of surface markers of M1 and M2 macrophages to observe macrophage polarization. The expression of interleukin (IL)-6, tumor necrosis factor-α (TNF-α), and IL-10 in the lung tissue was measured by immunohistochemistry. The expression of nuclear factor-kappa B (NF-κB) p65 and phosphorylated NF-κB (P-NF-κB) p65 was measured by Western blot. Results HE staining showed that compared with the control group, the model group exhibited alveolar septal swelling and thickening, vascular dilatation and congestion, and inflammatory cell infiltration in the lung tissue; the hydrogen groups had significantly reduced pathological damage and inflammatory response than the model group, with more improvements in hydrogen group II than in hydrogen group I. Immunohistochemical results showed that compared with those in the control group, the levels of the inflammatory cytokines IL-6 and TNF-α were significantly increased in the model group; the hydrogen groups showed significantly decreased IL-6 and TNF-α levels and a significantly increased level of the anti-inflammatory factor IL-10 than the model group, which were more marked in hydrogen group II than in hydrogen group I. Immunofluorescence results showed that compared with the control group, the expression of the surface marker of M1 macrophages in the model group was significantly upregulated; the hydrogen groups showed significantly downregulated M1 marker and significantly upregulated M2 marker, and hydrogen group II showed significantly increased M2 marker compared with hydrogen group I. Western blot results showed that compared with that in the control group, the ratio of P-NF-κB p65/NF-κB p65 in the model group was significantly increased; the P-NF-κB p65/NF-κB p65 ratio was significantly reduced in the hydrogen groups than in the model group, and was significantly lower in hydrogen group II than in hydrogen group I. Conclusion Hydrogen inhalation therapy may reduce the inflammatory response of radiation-induced lung injury by inhibiting the NF-κB signaling pathway to promote the polarization of the macrophage M1 subtype to the M2 subtype.
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Objective To investigate the changes in the expression of cold-inducible RNA-binding protein (CIRBP) in a radiation-induced lung injury model. Methods Thirty male C57BL/6 mice were randomly divided by body weight into control group (no intervention) and model group (single chest X-ray irradiation with a dose of 20 Gy to build a radiation-induced lung injury model). The mice were dissected five weeks after irradiation. Hematoxylin-eosin staining and Masson staining were used to observe the pathological changes of the lung tissue and the deposition of collagen fibers. Immunohistochemistry was used to measure the expression of the inflammatory factors interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the lung tissue. qRT-PCR was used to measure the expression of CIRBP mRNA in the lung tissue. The expression of CIRBP protein in the lung tissue was determined by the immunofluorescence assay and Western blot. Results Compared with the control group, the model group showed significant pulmonary vascular congestion, significant inflammatory cell infiltration, significant thickening of some alveolar septa, significantly increased IL-6 expression [(129.41 ± 5.58) vs (187.22 ± 34.77), t = 3.179, P < 0.05], significantly increased TNF-α expression [(137.52 ± 23.53) vs (187.02 ± 19.16), t = 5.069, P < 0.05], significantly increased CIRBP mRNA expression [(1 ± 0.08) vs (1.97 ± 0.39), t = 3.45, P < 0.05], and significantly increased CIRBP protein expression [(9.32 ± 1.26) vs (14.76 ± 1.61), t = 3.751, P < 0.05], by the immunofluorescence assay; [(1.13 ± 0.17) vs (1.49 ± 0.14), t = 2.819, P < 0.05], by Western blot). Conclusion The expression of CIRBP is significantly increased in the radiation-induced lung injury model, which may be an important pro-inflammatory factor in radiation-induced lung injury.
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Spectrophotometry and single factor test were used in the investigation of effects on extraction results of total flavonoids from the fruit ofVernonia esculenta Hemsl. from aspects of ethanol concentration, frequency of extraction, length of extraction time, and the solid-liquid ratio. The extraction conditions were optimized by orthogonal test. The results showed that the optimum extraction conditions were ethanol concentration of 70%, extracted for 4 times, 1 h for each time, and the solid-liquid ratio of 1:20. Under these extraction conditions, the content of total flavonoids in the fruit ofVernonia esculenta Hemsl. was 103.55 mg·g-1.
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Objective To study on the difference of plasma renin activity ( PRA),angiotensin Ⅱ (Ang Ⅱ ),and aldosterone levels in patients with essential hypertension (EH) or primary aldosteronism (PA) or pheochromocytoma (PHEO),and to analyze the sensitivity and specificity on the diagnosis of PA among patients with hypertension with aldosterone/PRA ratio (ARR).Methods The plasma aldosterone,Ang Ⅱ and PRA concentrations in supine and upright positions were measured by radioimmunoassay from 413 patients including idiopathic hyperaldosteronism (IHA,n =111 ),aldosterone-producing adenoma (APA,n=l18),PHEO (n=98) and EH (n=86).ARR was calculated.Results Plasma aldosterone concentrations in both of supine and upright positions in PHEO group [ 374 (294,465 ) pmol/L and 629 (449,997) pmol/L] and PA group [471 (346,632) pmol/L and 673(499,825) pmol/L] were higher than those in EH group [ 277 (224,332) pmol/L and 427 (341,501 ) pmol/L ] (P ＜ 0.01 ).They were also higher in APA group [576 (416,731 ) pmol/L and 726 (554,906 )pmol/L ] than those in IHA group [399(313,504) pmol/L and 609(485,776)pmol/L ] (P ＜0.01).Ang Ⅱ levels in both positions were lower in PA group [43.2(26.4,74.4) ng/L and 60.1(38.5,103.6) ng/L] than in EH group [56.7 (43.3,78.9) ng/L and 84.3(61.3,108.4) ng/L] or PHEO group [54.3(29.9,101.5) ng/L and 102.8 (49.9,167.0) ng/L] (all P values ＜ 0.01 ),and there was no difference between IHA and APA group (P ＞ 0.05 ).The PRA level in both positions of each group were PHEO group [ 0.3 (0.2,1.0) μg ·L-1 · h-1 and 1.4(0.6,3.4) μg · L-1 · h-1] ＞EH group [0.2(0.1,0.4)μg · L-1 · h-1 and 0.6(0.4,1.0)μg· L-1 ·h-1] (P＜0.01) ＞PAgroup [0.1(0.1,0.1)μg· L-1 · h-1 and 0.2(0.1,0.3)μg·L-1 · h-1] (P＜0.01),and APA group [0.1(0.1,0.1)μg · L-1 · h-1 and0.1(0.1,0.3)μg · L-1 ·h - 1 ] ＜ IHA group [ 0.1 ( 0.1,0.2 ) μg · L - 1 · h - 1 and 0.2 (0.1,0.3 ) μg · L-1 · h - 1 ] ( supine P ＜0.01 ; upright P ＜ 0.05 ).APA was divided into 2 types with renin-Ang Ⅱ -responsive APA ( n =26) and unresponsive APA (n =92).The plasma aldosterone concentration was lower in supine position but higher in upright position in renin-Ang Ⅱ-responsive APA than in unresponsive APA patients.ARR in upright was higher in PA group ( P ＜ 0.01 ) but lower in PHEO group ( P ＜ 0.05 ) compared with EH.ARR was higher in APA than in IHA (P ＜0.01 ).The sensitivity and specificity of ARR as 40 (aldosterone unit:ng/dl;PRA unit:μg · L-1 · h-1; its value should multiply 27.7 when transferred to pmol/L,simili) were 93％ and 76％,respectively.Conclusion The levels of PRA,Ang Ⅱ and aldosterone from patients with EH,PA and PHEO are significant different.ARR as 40 in upright position could be used for PA screening cutoff point.
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The rennin angiotensin system has been recognized for many years as a key regulator in systemic blood pressure and the metabolism of water and salt. Angiotensin converting enzyme 2(ACE2) is the first human homolog of angiotensin converting enzyme which efficiently hydrolyze the angiotensin Ⅱ to vasodilator angiotensin 1-7.ACE2 is now implicated in cardiovascular,renal, lung disease and serves as a receptor for Severe Acute Respiratory Syndrome coronavirus.
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Objective To investigate the effects of long-term,low-dose hormone replacement therapy(HRT) on serum level of creactive protein(CRP) and homocysteine(Hcy) in postmenopausal women.Methods A total of 141 postmenopausal women were selected from medical staff of the Peking Union Medical College Hospital.Of these,63 subjects have been treated with low-dose sex hormone for over 5 years(HRT group),78 subjects have never received hormone replacement therapy as control group.The serum levels of CRP and Hcy in two groups were evaluated.Results The serum level of estradiol(E_2) in HRT group was significant higher than that in control group(median,inter-quartile range;33.8 ng/L,30.9 vs 21.3 ng/L,33.2)(P0.05).There was no correlation between the serum level of CRP,Hcy and the plasma levels of E_2 and FSH respectively.Conclusion Long-term and low-dose HRT does not increase the serum level of CRP and Hcy in postmenopausal women.
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<p><b>OBJECTIVE</b>To gain a primary understanding of the prevalence of 21-hydroxylase deficiency(21-OHD) heterozygote (carrier) among androgen excess women of Chinese Han nationality, compare the molecular genetic changes therein revealed with the results of adrenocorticotropic hormone (ACTH) stimulating test, and assess the carriers' phenotype-genotype correlation.</p><p><b>METHODS</b>Eighty-two androgen excess cases and 14 healthy women underwent ACTH stimulating test during the follicular phase. Molecular genetic analysis of CYP21 for 9 common mutations was performed with the method of amplification-created restriction sites.</p><p><b>RESULTS</b>In androgen excess group, the basal level of F0 (P<0.01), as well as basal 17-OHP0 and the ACTH stimulated concentrations of 17-OHP60 were much higher than controls (P<0.01), and there was no obvious discrepancy in F60 (P>0.05). The net increase of 17-OHP and the ratio of net increase of 17-OHP to net increase of F were also higher than controls (P<0.01). No CYP21 gene mutations were found in control group. Four patients of the androgen excess group were identified as heterozygous carriers of CYP21 mutations. The ACTH stimulating test results from gene normal patients and from carriers overlapped to a certain extent.</p><p><b>CONCLUSION</b>Among 82 patients of Chinese Han nationality androgen excess women, 4.9% were 21-OHD heterozygous. The response of serum 17-OHP is not useful for predicting CYP21 gene mutation carrier status. Genotyping is the most reliable method to detect carrier.</p>
Subject(s)
Adolescent , Adult , Child , Female , Humans , Adrenal Hyperplasia, Congenital , Diagnosis , Ethnology , Genetics , Adrenocorticotropic Hormone , Asian People , Genetics , China , Genetic Carrier Screening , Methods , Genotype , Mutation , Polymerase Chain Reaction , Steroid 21-Hydroxylase , Genetics , MetabolismABSTRACT
Objective: To evaluate the cytotoxicity and targeting ability of self-developed paclitaxel-octreotide (PTX-OCT) conjugates on A549 non-small cell lung cancer (NSCLC) cells and Calu-6 NSCLC cells. Methods: Conjugates PTX-OCT and 2PTX-OCT were synthesized by our school. Reverse transcription-polymerase chain reaction was used to detect mRNA of human somatostatin receptor subtypes (SSTRs) using specific primers. The cells were treated with different concentrations (1, 100 nmol/L and 1 ?mol/L) of paclitaxel and the conjugates for different time periods (24-72 h); we also set up a control group. MTT assay was used to evaluate the cell viability after treatment; cell cycle perturbations were determined by FAC Scan flow cytometer 24 h after treatment with 1 ?mol/L paclitaxel, PTX-OCT, and 2PTX-OCT. Results: Both A549 cell and Calu-6 cell expressed the mRNA of SSTR2 and SSTR5; no SSTR mRNA was detected in the fibroblasts. The conjugates had a similar cytotoxicity to paclitaxel; they both effectively inhibited the growth of A549 cells and Calu-6 cells in a concentration-and time-dependent manner. After 72 h treatment with 1 ?mol/L paclitaxel, PTX-OCT and 2PTX-OCT, the survival rates of A549 cells were (26.9?7.3)%, (26.6?9.2)% and (35.7?4.3)%, respectively; the survival rates of Calu-6 cells were (29.5?5.0)%, (28.2?9.7)% and (26.5?4.9)%, respectively. The survival rate A549 cells at 72 h after treatment was lower than that at 24 h after treatment(P