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Purpose: We aimed to investigate the antioxidant activity of nebivolol against possible damage to the ovarian tissue due to the application of deltamethrin as a toxic agent, by evaluating histopathological proliferating cell nuclear antigen (PCNA) and tumor necrosis factor-alpha (TNF-α) signal molecules immunohistochemically. Methods: The animals were divided into three groups as control, deltamethrin and deltamethrin + nebivolol groups. Vaginal smears were taken after the animals were mated and detected on the first day of pregnancy. After the sixth day, deltamethrin (0.5 mL of 30 mg/kg BW undiluted ULV), and 2 mL of sterile nebivolol solution were administered intraperitoneally every day for 6-21 periods. After routine histopathological follow-up, the ovarian tissue was stained with hematoxylin and eosin stain. Results: Control group showed normal histology of ovarium. In deltamethrin group, hyperplasic cells, degenerative follicles, pyknotic nuclei, inflammation and hemorrhagic areas were observed. Nebivolol treatment restored these pathologies. Deltamethrin treatment increased TNF-α and PCNA reaction. However, nebivolol decreased the expression. Conclusions: It was thought that deltamethrin toxicity adversely affected follicle development by inducing degeneration and apoptotic process in preantral and antra follicle cells, and nebivolol administration might reduce inflammation and slow down the apoptotic signal in the nuclear phase and regulate reorganization.
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Animals , Rats , Ovary/drug effects , Toxicity , Nebivolol/administration & dosage , AntioxidantsABSTRACT
Objective:To analyze the expression level of minichromosome maintenance protein 6 (MCM6) in colon cancer tissues, the correlation between the expression level of MCM6 and the clinicopathological characteristics of colon cancer patients, and the correlation between MCM6 and PCNA expression.Methods:The expression levels of MCM6 in different tumor tissues were analyzed based on the Human Protein Atlas (HPA) database. The expression levels and correlations of MCM6 and PCNA in colon cancer tissues were analyzed based on The Cancer Genome Atlas (TCGA) database and immunohistochemical experiments. The correlation between MCM6 expression level and clinical characteristics of colon cancer patients was analyzed. The correlation between MCM6 and PCNA expression in colon cancer was analyzed based on TCGA database and Gene Expression Profile Interaction Analysis (GEPIA) database.Results:Bioinformatics analysis and immunohistochemical results confirmed that MCM6 was highly expressed in colon cancer tissues, and its expression level was correlated with the tumor stage of patients ( P=0.01). In colon cancer, the expression of MCM6 and PCNA was correlated with statistical significance ( P<0.05). Conclusions:MCM6 is highly expressed in colon cancer tissue and is related to the clinical characteristics of patients, suggesting that MCM6 can be used as a potential marker of colon cancer.
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Objective To investigate the effect of upstream transcription factor 2 (USF2) on the proliferation and apoptosis of human gastric cancer BGC-823 cells. Methods Lipofectamine?3000 transfection reagent was used to transfect USF2 siRNA into BGC-823 cells (siRNA-USF2 group). Blank control and negative control (siRNA-NC) groups were also prepared. The mRNA and protein expression levels of USF2 in transfected BGC-823 cells were detected by real-time fluorescence quantitative PCR and Western blot, respectively. The proliferation and clone formation abilities of BGC-823 cells in each group were investigated by CCK-8 and plate cloning assay. The apoptosis of gastric cancer cells was examined by flow cytometry. The expression levels of PCNA and apoptosis-related proteins Bax and Bcl-2 in BGC-823 cells were measured by Western blot. Results Compared with those in the blank control and siRNA-NC groups, the mRNA and protein expression levels of USF2 significantly decreased in the siRNA-USF2 group (P < 0.05). At 72 h after transfection, the absorbance in the siRNA-USF2 group was lower than that in the blank control group (P < 0.05). Compared with that in the blank control and siRNA-NC groups, the number of BGC-823 cell clones significantly decreased in the siRNA-USF2 group (P < 0.05). The apoptosis rate of BGC-823 cells significantly differed among the blank control, siRNA-NC, and siRNA-USF2 groups (P < 0.05). Compared with those in the blank control and siRNA-NC groups, the expression of PCNA and Bcl-2 protein decreased and that of Bax protein increased in the siRNA-USF2 group (P < 0.05). Conclusion Inhibiting USF2 expression can suppress the proliferation of human gastric cancer cells and induce their apoptosis. USF2 inhibitors may have important value in the treatment of gastric cancer.
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ObjectiveTo explore the effects of different treatment methods of "soothing liver， invigorating spleen， soothing liver and invigorating spleen， soothing liver first and then soothing liver and invigorating spleen， as well as invigorating spleen first and then soothing liver and invigorating spleen" on liver depression combined with liver injury in rats and their action mechanisms. MethodA six-week rat model of liver depression combined with liver injury was established by restraint stress and subcutaneous injection of carbon tetrachloride （CCl4， 5.89 g·kg-1， once every three days）. At the same time， the drugs were given by gavage. Forty-eight male SD rats of clean grade were randomly divided into eight groups， namely the normal group， model group， bicyclol （0.2 g·kg-1） group， Sinisan （4.32 g·kg-1） group， Liu Junzitang （9.26 g·kg-1） group， Chaishao Liu Junzitang A （Chai A， soothing liver and invigorating spleen，13.57 g·kg-1） group， Chaishao Liu Junzitang B （Chai B， soothing liver first and then soothing liver and invigorating spleen， 13.57 g·kg-1） group， and Chaishao Liu Junzitang C （Chai C， invigorating spleen first and then soothing liver and invigorating spleen， 13.57 g·kg-1） group， with six rats in each group. The pathological changes in liver and colon tissues of each group were observed under light microscope and electron microscope. The serum biochemical indexes of the liver were detected using an automatic biochemical analyzer. The relative mRNA expression levels of Takeda G protein-coupled receptor 5 （TGR5） and intestinal mucosal zona occluden-1 （ZO-1）， Occludin， and Claudin-1 in the liver and colon were detected by reverse-transcription polymerase chain reaction （RT-PCR）. The positive expression rate of proliferating cell nuclear antigen （PCNA） in the colon was detected by immunohistochemistry. ResultCompared with normal group， the model group exhibited significantly elevated serum alkaline phosphatase （ALP）， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， total bilirubin （TBIL）， and direct bilirubin （DBIL） （P<0.01）， lowered TGR5 mRNA expression in liver tissue， up-regulated TGR5 mRNA expression in the colon tissue （P<0.05，P<0.01）， and down-regulated ZO-1， Occludin， and tight junction protein-1 (Claudin-1) mRNA expression and PCNA in the colon tissue （P<0.01）. Compared with the model group， bicyclol and Chai C remarkably decreased the levels of serum ALP， ALT， AST， TBIL， and DBIL （P<0.05，P<0.01）， while Liu Junzitang， Chai A， Chai B， and Chai C significantly up-regulated the TGR5 mRNA expression in the liver and down-regulated its expression in the colon （P<0.01）. Bicyclol， Chai A， Chai B， and Chai C enhanced the ZO-1 and Claudin-1 mRNA expression in the colon （P<0.05，P<0.01）. Bicyclol， Sinisan， and Chai C increased PCNA expression （P<0.01）. The comparison with the Chai C group showed that the TGR5 mRNA expression in the liver and ZO-1 mRNA expression in the colon of the bicyclol and Sinisan groups were lower， whereas the TGR5 mRNA expression in the colon was higher （P<0.01）. However， the PCNA expression in the colon of the Liu Junzitang and Chai B groups declined significantly （P<0.05）. ConclusionIn the presence of liver injury， invigorating spleen first helps to relieve the liver injury， and the efficacy of "spleen-invigorating" therapy in increasing the intestinal mucosal tight junction proteins and improving the gastrointestinal function is related to its activation of TGR5 to improve the intestinal mucosal barrier function， promote the renewal of intestinal stem cells， and drive the regeneration after injury.
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Objective @#To investigate the effect of silencing histone deacetylase 9 (HDAC9) expression on the proliferation and osteogenic differentiation of periodontal ligament stem cells (PDLSCs).@*Methods@# PDLSCs were isolated, cultured and identified in vitro. An siRNA construct specific for HDAC9 was transfected into PDLSCs (siHDAC9 group), and a nontargeting siRNA was used as a control (siNC group). The interference effect was determined by qRT-PCR. The cell cycle progression of PDLSCs was detected using flow cytometry. The proliferation activity of PDLSCs was detected via CCK-8 assay. Western blotting was used to detect the protein expression of proliferating cell nuclear antigen (PCNA). The mRNA expression of runt-related transcription factor 2 (RUNX2) and alkaline phosphatase (ALP) was investigated by qRT-PCR. The protein expression of RUNX2 was detected by western blotting. In addition, the formation of mineralized nodules was assessed by alizarin red staining. @*Results@#Compared with that in the siNC group, the mRNA expression of HDAC9 in the siHDAC9 group was lower (P < 0.01). Moreover, compared with those in the siNC group, the proliferation index (P<0.01), proliferation activity (P<0.05) and protein expression of PCNA (P<0.01) in the siHDAC9 group were all increased. Compared with the siNC group, the siHDAC9 group exhibited higher mRNA expression of RUNX2 and ALP (P < 0.05), and the protein expression of RUNX2 showed the same results (P < 0.01). The results of alizarin red staining showed that compared to the siNC group, the siHDAC9 group formed more mineralized nodules.@* Conclusion@#Silencing HDAC9 expression can promote the proliferation and osteogenic differentiation of PDLSCs.
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Objective:To investigate the changes of the expression levels of serum proliferating cell nuclear antigen (PCNA), tumor-specific growth factor (TSGF), soluble E-cadherin (SE-CAD) and the relationship with clinical prognosis of advanced non-small cell lung cancer (NSCLC) patients treated with intensity-modulated radiotherapy combined with chemotherapy.Methods:Eighty-four patients (29 cases of Ⅲ A, 30 Ⅲ B and 25 Ⅳ) with advanced NSCLC treated in our hospital from January 2016 to January 2018 were selected, and all patients were given with intensity-modulated radiotherapy combined with chemotherapy. The expression levels of serum PCNA, TSGF, and SE-CAD were compared among different TNM stages and before and after treatment. The serum PCNA, TSGF, SE-CAD levels were compared among patients with different clinical efficacy. The relationship between serum PCNA, TSGF and SE-CAD levels and clinical efficacy was assessed by Logistic regression analysis. The survival analysis was performed with Kaplan- Meier method. Results:The expression levels of serum PCNA, TSGF and SE-CAD before treatment in stage Ⅳ patients were significantly higher than those in stage Ⅲ B and Ⅲ A patients (584.11±60.25 pg/ml vs. 531.06±51.37 pg/ml and 477.54±46.49 pg/ml, 96.13±7.54 U/ml vs. 8.52±5.91 U/ml and 82.41±5.0 U/ml, 3.02±0.26 ng/ml vs. 2.87±0.22 ng/ml and 2.71±0.15 ng/ml, all P<0.05), and the serum levels of three cytokines in Ⅲ B stage patients were significantly higher than those in their Ⅲ A stage counterparts (all P<0.05). After treatment, the serum levels of PCNA, TSGF and SE-CAD were significantly lower than those before treatment (396.11±50.23 pg/ml vs. 528.37±75.09 pg/ml, 74.81±4.72 U/ml vs. 88.68±6.13 U/ml, 1.92±0.24 ng/ml vs.2.86±0.31 ng/ml, all P<0.05). At 18 months after treatment, the serum levels of PCNA, TSGF and SE-CAD in surviving patients were significantly lower than those of dead patients (332.51±54.32 pg/ml vs. 444.92±60.07 pg/ml, 70.59±6.20 U/ml vs. 78.05±8.44 U/ml, 1.71±0.24 ng/ml vs. 2.08±0.27 ng/ml, all P<0.05). The serum levels of PCNA, TSGF and SE-CAD were significantly associated with clinical prognosis (all P<0.05). Among 84 NSCLC patients, the objective response rate after treatment was 29%(24/84). The survival curves in patients with high expression levels of serum PCNA, TSGF and SE-CAD were significantly lower than those in the low-expression group (all P<0.05). Conclusion:Serum PCNA, TSGF and SE-CAD are highly expressed in patients with advanced NSCLC, which are closely correlated with clinical staging and prognosis and contribute to predicting survival status.
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Objective:To observe the ultrasonographic features of cervical lymph node metastasis and analyze their relationship with the expression of cell proliferation-associated nuclear antigen (Ki-67).Methods:The clinical data of 92 patients with cervical lymph node metastasis who received treatment in Zhejiang Quhua Hospital, China between June 2017 and July 2019 were retrospectively analyzed. The correlation between ultrasonographic features of cervical lymph node metastasis and Ki-67 expression was analyzed.Results:Among the 92 patients, 158 metastatic lymph nodes were confirmed by pathological examination. The main ultrasonic imaging features were the length ratio of long diameter to short diameter < 2 in 119 (75.32%) lymph nodes, disappearance of portal hyperechoic signal in 127 (80.38%) lymph nodes, punctate hyperechoic signal in 108 (68.35%) lymph nodes, cystic degeneration in 57 (36.08%) lymph nodes, mixed types of peripheral blood flow signal in 124 (78.48%) lymph nodes, microcalcification in 123 (77.85%) lymph nodes. The length ratio of long diameter to short diameter < 2, punctate hyperechoic signal and mixed types of peripheral blood flow signal were correlated with high expression of Ki-67 ( χ2 = 24.252, 15.732, 17.033, all P < 0.05). Conclusion:High expression of Ki-67 is correlated with the length ratio of long diameter to short diameter < 2, punctate hyperechoic signal and mixed types of peripheral blood flow signal in cervical lymph node metastasis.
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OBJECTIVES@#The effect of Vps4b gene mutation on the expressions of cytokeratin 14 (CK14) and proliferating cell nuclear antigen (PCNA) in the Hertwig's epithelial root sheath (HERS) is investigated.@*METHODS@#The bilateral mandibular tissues of mouse on postnatal days 5, 9, 11, 15, and 19 were removed. The mandibular first molar tissue sections were obtained after paraffin embedding. The CK14 and PCNA expressions in the epithelial root sheath of the normal mouse and Vps4b knockout mouse were compared through immunohistochemistry.@*RESULTS@#On postnatal day 5, the normal mouse began to form HERS and had a strong positive PCNA expression in the HERS cells; on postnatal day 9, the HERS structure was continuous, and PCNA was positive in the HERS cells; on postnatal day 11, a small portion of HERS began to break, and PCNA was weakly positive in the HERS cells; on postnatal day 15, HERS continued to fracture; PCNA was weakly and positively expressed in the HERS cells on the root surface; on postnatal day 19, the tooth root reached normal physiological length, and PCNA was positively expressed in the HERS cells of the terminal part. Similar to the normal mouse, the gene knockout mouse also formed a HERS structure on postnatal day 5. However, HERS began to break on postnatal day 9. On postnatal day 19, only a few fragments of HERS were found on the root surface, and the root development was immature. Moreover, the expression intensity of PCNA in the gene knockout mouse was decreased.@*CONCLUSIONS@#The Vps4b gene mutation may change the CK14 and PCNA expressions, leading to abnormal root development.
Subject(s)
Animals , Mice , ATPases Associated with Diverse Cellular Activities , Endosomal Sorting Complexes Required for Transport , Epithelial Cells , Keratin-14 , Mice, Knockout , Proliferating Cell Nuclear Antigen , Tooth RootABSTRACT
Objective:To analyze the expressions of minichromosome maintenance protein 4(MCM4) and proliferating cell nuclear antigen (PCNA) in gastric cancer tissues, to explore the relationship between MCM4/PCNA and gastric cancer, and to investigate the possibility of MCM4/PCNA as a potential biomarker for gastric cancer.Methods:Bioinformatics methods were used to analyze the mRNA expressions of MCM4 and PCNA in gastric cancer tissues and adjacent normal tissues. The clinicopathological data of 69 patients with gastric cancer who underwent surgery were retrospectively analyzed. The expression levels of MCM4 and PCNA in gastric cancer tissues and adjacent normal tissues were detected by immunohistochemistry, and their relationship with the clinicopathological characteristics of gastric cancer patients was analyzed.Results:The mRNA levels of MCM4 and PCNA in gastric cancer tissues are significantly higher than those in adjacent normal tissues (all P<0.05). The expression of MCM4 is correlated with the tumor size of gastric cancer ( P=0.037), but there is no significant correlation with gender, age and tumor grade (all P>0.05). Both MCM4 and PCNA proteins are highly expressed in gastric cancer patients. Conclusions:The expression levels of MCM4 and PCNA have a clear correlation with the occurrence of gastric cancer. MCM4 and PCNA are expected to be potential biomarkers for the diagnosis and treatment of gastric cancer.
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To assess the effect of nesiritide on the endothelial function of iliac arteries following endothelia trauma. Right iliac artery trauma was created with a balloon catheter. Ten rabbits were treated with a 4-week subcutaneous injection of nesiritide at a fixed daily dose of 0.1mg/kg. Ten rabbits received daily normal saline injection. Plasma endothelin 1 (ET-1), nitric oxide (NO), and Von Willebrand Factor (vWF) were measured before and after the therapies. Tissue proliferating cell nuclear antigen (PCNA) was measured after the treatment. After the treatment, in the therapeutic group, the area under internal elastic membrane and the residual lumen area were higher than in the normal saline group (P <0.05). The plasma levels of ET-1 (91.6±6.8 vs 114.9±6.3 ng/L, P =0.001), vWF (134.6±10.8% vs 188.8±10.4%, P =0.001) and the ratio of PCNA positive expression (11.7±4.2% vs 36.2±11.4%, P =0.005) in the therapeutic group was lower than in the normal saline group, while the plasma levels of NO was higher (89.7±9.3 vs 43.5±5.3 µmol/L, P =0.001). Nesiritide inhibited remodeling of rabbit iliac artery following endothelial trauma. The inhibition of vascular remodeling may be related to the alleviated endothelial dysfunction and reduced expression of tissue proliferating cell nuclear antigen
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Animals , Male , Rabbits , Iliac Aneurysm/classification , Endothelin-1/adverse effects , Natriuretic Peptide, Brain/analysis , Endothelial Cells/drug effects , Wounds and Injuries/classification , von Willebrand Factor/analysis , Catheters/classification , Iliac Artery , Nitric Oxide/analysisABSTRACT
OBJECTIVE@#To study the effect of rapamycin on scar formation in rabbit eyes following filtering operation and explore the possible mechanism.@*METHODS@#Ninety-six healthy adult rabbits were subjected to trabeculectomy of the left eye and subsequently randomly divided into 4 groups (=24) for treatment with castor oil (control) or rapamycin (1%, 3%, or 5%) eye drops of the operated eyes 4 times a day. The morphology and function of the filtering blebs of the rabbits were compared at 7, 14, 21 and 28 days after the operation; at each of the time points, 6 rabbits from each group were euthanized for detection of expressions of proliferating cell nuclear antigen (PCNA) and α-smooth muscle actin (α-SMA) in the tissues in the surgical area using immunohistochemistry. Cultured rabbit subconjunctival fibroblasts (RTFSs) were treated with different concentrations of rapamycin (0.06, 0.25, 1, and 4 mg/L) and the cell apoptosis was detected using flow cytometry.@*RESULTS@#In the first, second and third weeks after the operation, the rate of functional follicle formation was significantly higher in the 3 rapamycin groups than in the control group ( < 0.05), and the number of α- SMA-positive fibroblasts decreased over time in the 3 rapamycin groups. In cultured RTFSs, treatment with rapamycin at different concentrations resulted in increased apoptosis of the cells, and rapamycin above 0.25 mg/L significantly increased the cell apoptosis in a dose-dependent manner.@*CONCLUSIONS@#Rapamycin can inhibit hyperplasia of the filtering passage tissue, helps to preserve the functional filtering blebs and prolong their life span, and induces apoptosis of RTFS.
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Objective@#To evaluate the effect of aminolevulinic acid-based photodynamic therapy (ALA-PDT) on the expression of vascular endothelial growth factor (VEGF) and proliferating cell nuclear antigen (PCNA) in condyloma acuminatum (CA) tissues.@*Methods@#A total of 56 patients with CA were enrolled from Department of Dermatology, The First Affiliated Hospital of Zhengzhou University from October 2016 to September 2017, and skin lesions were obtained before and 1 week after the first ALA-PDT treatment. Immunohistochemical SP method was used to determine the expression of VEGF and PCNA in keratinocytes in the CA tissues. Chi-square test and rank sum test were carried out to analyze differences between pre- and post-treatment expression rate and intensity of VEGF and PCNA, and Spearman correlation analysis was conducted to analyze the correlations between the protein expression of VEGF and PCNA.@*Results@#The expression rates of VEGF and PCNA in keratinocytes in the CA tissues were 71.43% (40/56) and 73.21% (41/56) respectively before ALA-PDT, and 44.64% (25/56) and 41.07% (23/46) respectively after ALA-PDT. There were significant differences between pre- and post-treatment expression rate and intensity of VEGF and PCNA (expression rate: χ2 = 8.25, 11.81 respectively, both P < 0.05; expression intensity: H = 11.29, 12.22 respectively, both P < 0.05) . The expression of VEGF was positively correlated with the expression of PCNA in the CA tissues before and after the ALA-PDT treatment (rs = 0.202, 0.273, respectively, both P < 0.05) .@*Conclusion@#The expression of VEGF and PCNA decreased in CA tissues after ALA-PDT treatment, which may be one of the mechanisms underlying the treatment of CA with ALA-PDT.
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Objective To evaluate the effect of aminolevulinic acid-based photodynamic therapy (ALA-PDT) on the expression of vascular endothelial growth factor (VEGF) and proliferating cell nuclear antigen (PCNA) in condyloma acuminatum (CA) tissues.Methods A total of 56 patients with CA were enrolled from Department of Dermatology,The First Affiliated Hospital of Zhengzhou University from October 2016 to September 2017,and skin lesions were obtained before and 1 week after the first ALA-PDT treatment.Immunohistochemical SP method was used to determine the expression of VEGF and PCNA in keratinocytes in the CA tissues.Chi-square test and rank sum test were carried out to analyze differences between pre-and post-treatment expression rate and intensity of VEGF and PCNA,and Spearman correlation analysis was conducted to analyze the correlations between the protein expression of VEGF and PCNA.Results The expression rates of VEGF and PCNA in keratinocytes in the CA tissues were 71.43％ (40/56) and 73.21％ (41/56) respectively before ALA-PDT,and 44.64％ (25/56) and 41.07％ (23/46)respectively after ALA-PDT.There were significant differences between pre-and post-treatment expression rate and intensity of VEGF and PCNA (expression rate:x2 =8.25,11.81 respectively,both P ＜ 0.05;expression intensity:H =11.29,12.22 respectively,both P ＜ 0.05).The expression of VEGF was positively correlated with the expression of PCNA in the CA tissues before and after the ALA-PDT treatment (rs =0.202,0.273,respectively,both P ＜ 0.05).Conclusion The expression of VEGF and PCNA decreased in CA tissues after ALA-PDT treatment,which may be one of the mechanisms underlying the treatment of CA with ALA-PDT.
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The choroid plexus is composed of highly specialized vascularized epithelial tissues present in 4 ventricles of the brain. The central core of the choroid plexus is occupied by blood vessels. The choroid plexus has many functions like CSF production and synthesis of bioactive peptides. Antigen like Proliferating cell nuclear antigen PCNA, a 36 kd DNA polymerase delta auxiliary protein; is involved in the proliferation of neoplastic and non-neoplastic cells. PCNA has a role in DNA synthesis and repair. Previous studies reported that the PCNA expression in the cytoplasm of cells can be demonstrated by histochemical stains. Total 50 adult male New Zealand rabbits (Oryctolagus cuniculus) were sacrificed, a sample of lateral and 4th ventricles was prepared for H and E and immunohistochemical stains for PCNA. PCNA expression was more in lateral ventricle than 4th one indicates the higher involvement in biological function. The higher PCNA expression in the choroidal cells of the lateral ventricle suggests the clinical importance and pharmacological role in many neurological diseases. Significance Statement: The study is conducted to study the differences in choroid plexus of the ventricles separately, and to see the clinical importance for that, and also to evaluate the PCNA agent expression in lateral and 4th ventricles.
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SUMMARY: Reproductive dysfunction is a complication for many diseases and toxins. Its early diagnosis and treatment are immensely important. Here the morphological histoarchitecture changes in early testicular and cauda toxicity before and after treatment with angiotensin receptor blockers were evaluated. Low-grade testicular damage was induced using thioacetamide (TAA, 50 mg/kg/day) intraperitoneally for two weeks in rats. The rats were randomly divided into four groups (n = 8) treated daily orally for three weeks as follows: Normal control (distilled water), TAA (positive control), TAA+candesartan (0.2 mg/kg) and TAA+losartan (7.5 mg/kg). Serum testosterone and testicular malondialdehyde and glutathione were measured. The changes in histoarchitecture of testis and cauda epididymis were evaluated by hematoxylin and eosin for general structure, Masson's trichrome for collagen, periodic acid Schiff for basement membrane, and caspase-3 and proliferating cell nuclear antigen (PCNA) for immunohistochemical analysis. The TAA-rats showed decreases of serum testosterone and testicular glutathione, increases in testicular malondialdehyde, degenerative changes and apoptosis in germ cells, thickening of tubular basal lamina and increases in expression of caspase 3, and decreases in expression of PCNA. The ARBs (candesartan and losartan) significantly reversed these changes with non-significant differences in-between. Treatment with ARBs (candesartan and losartan) significantly reversed TAA-induced low-grade testicular and cauda toxicity in rats. This could be potentially useful for early treatment of male patients with occupational toxicant-induced reproductive dysfunction especially if they are using ARBs for other comorbidities.
RESUMEN: La disfunción reproductiva es una complicación por muchas enfermedades y toxinas. Su diagnóstico y tratamiento tempranos son inmensamente importantes. Aquí se evaluaron los cambios morfológicos en la histoarquitectura en la toxicidad precoz testicular y cauda antes y después del tratamiento con bloqueadores de receptores de angiotensina. Se indujo daño testicular de bajo grado usando tioacetamida (TAA, 50 mg / kg / día) por vía intraperitoneal durante dos semanas en ratas. Las ratas se dividieron aleatoriamente en cuatro grupos (n = 8) tratados diariamente por vía oral durante tres semanas de la siguiente manera: control normal (agua destilada), TAA (control positivo), TAA + candesartan (0,2 mg / kg) y TAA + losartán (7,5 mg / kg). Se midieron la testosterona sérica, el malondialdehído testicular y el glutatión. Los cambios en la histoarquitectura de los testículos y la epidermis de la cauda se evaluaron mediante Hematoxilina y Eosina para determinar la estructura general, con tricrómicro de Masson para el colágeno, ácido periódico de Schiff para la membrana basal y la caspasa-3 y el antígeno nuclear de células proliferantes (PCNA) para análisis inmunohistoquímico. Las ratas TAA mostraron disminución de la testosterona sérica y glutatión testicular, aumentos en el malondialdehído testicular, cambios degenerativos y apoptosis en células germinales, engrosamiento de la lámina basal tubular y aumentos en la expresión de la caspasa 3, y disminución en la expresión de PCNA. Los ARB (candesartán y losartán) revirtieron significativamente estos cambios con diferencias no significativas en el medio. El tratamiento con BRA (candesartán y losartán) revirtió significativamente la toxicidad testicular y cauda inducida por TAA en ratas. Esto podría ser potencialmente útil para el tratamiento temprano de pacientes con disfunción reproductiva inducida por tóxicos ocupacionales, especialmente si están usando BRA para otras comorbilidades.
Subject(s)
Animals , Male , Rats , Testis/drug effects , Thioacetamide/toxicity , Benzimidazoles/pharmacology , Losartan/pharmacology , Angiotensin II Type 1 Receptor Blockers/pharmacology , Testis/pathology , Testosterone/analysis , Tetrazoles/pharmacology , Immunohistochemistry , Rats, Sprague-Dawley , Proliferating Cell Nuclear Antigen/metabolism , Caspase 3/metabolism , Glutathione/analysis , Malondialdehyde/analysisABSTRACT
Abstract Purpose To investigate the effects of pine needle extract (PNE) on the expression of proliferating cell nuclear antigen (PCNA) and Ki-67 during liver regeneration induced by 70% partial hepatectomy (PH) in rat. Methods Forty-eight male rats (SD, 7 weeks) had surgery (70% PH). They were randomly divided into two groups. PH + PNE group was only provided PNE diluted in water (10%) for drinking and PH group was provided water from 5 days before surgery to the time of sacrifice. PNE was made by pressing and filtering. Animals were sacrificed at 12h, 24h, 36h, 60h, 84h, 168h after PH, respectively. The expressions of PCNA and Ki-67 were determined as proliferation indices. Results Immunohistochemistry turned out to increase the expression of PCNA and Ki-67. PCNA expression of PH+PNE group increased up to twice of that of PH group. Western blot also seemed to increase the PCNA expression. These results indicated the promotion of cell proliferation in liver tissue and hepatic regeneration. Conclusions Pine needle extract stimulates the expression of some mitotic proteins during liver regeneration induced by 70% PH in rats. It suggests that administration of pine needle extract could accelerate the liver regeneration after partial hepatectomy.
Subject(s)
Animals , Male , Rats , Plant Extracts/pharmacology , Proliferating Cell Nuclear Antigen/drug effects , Ki-67 Antigen/adverse effects , Pinus/chemistry , Hepatectomy/methods , Liver Regeneration/drug effects , Time Factors , Rats, Sprague-Dawley , Proliferating Cell Nuclear Antigen/metabolism , Ki-67 Antigen/metabolism , Cell Proliferation , Mitotic IndexABSTRACT
Albizzia julibrissin (AJ) is an herbal medicine that shows low toxicity, promotes promoting blood circulation and mitigates the inflammation and has mild side effects. Benign prostate hyperplasia (BPH) is one of the most common diseases that occurs in older males and often results in lower urinary tract symptoms. This study was conducted to evaluate the protective effect of AJ against BPH using LNCaP cells and Sprague Dawley rats treated with testosterone. Treatment with AJ extract reduced the expression of androgen receptor (AR) and prostate-specific antigen (PSA) in vitro. In vivo, rats were divided into 6 groups: 1 (Normal Control); 2 (Testosterone propionate (TP) alone); 3 (TP + finasteride); 4 (TP + AJ 10 mg/kg); 5 (TP + AJ 50 mg/kg); 6 (TP + AJ 300 mg/kg). The groups treated with AJ showed reduced the relative prostate weights and BPH-related proteins were altered, with decreased AR, PSA and proliferating cell nuclear antigen (PCNA) observed by western blot. Histopathological analysis revealed the therapeutic effect of AJ, with a decreased thickness of epithelial cells and reduced level of PCNA and 5α-reductase type 2. These results suggest that AJ extract could ameliorate testosterone-induced benign prostatic hyperplasia.
Subject(s)
Animals , Humans , Male , Rats , Albizzia , Blood Circulation , Blotting, Western , Diethylpropion , Epithelial Cells , Herbal Medicine , Hyperplasia , In Vitro Techniques , Inflammation , Lower Urinary Tract Symptoms , Proliferating Cell Nuclear Antigen , Prostate , Prostate-Specific Antigen , Prostatic Hyperplasia , Rats, Sprague-Dawley , Receptors, Androgen , Testosterone , Weights and MeasuresABSTRACT
Objective To evaluate the efficacy of self-made Jianpi-Yiqi decoction in the treatment of chronic atrophic gastritis (CAG). Methods A total of 100 patients with CAG who met the inclusion criteria were randomly divided into two groups, 50 in each group. The control group received oral omeprazole enteric-coated capsules and the observation group oral Jianpi-Yiqi decoction. Both groups were treated for 8 weeks. The clinical efficacy, proliferating cell nuclear antigen (PCNA), B cell lymphoma-2 (Bcl-2), TNF-α and PCNA, Bcl-2 mRNA expression were evaluated and compared. Results The total effective rate was 92.0％(46/50) in the observation group and 80.0％ (40/50) in the control group. The difference between the two groups was statistically significant (χ2=9.623, P=0.031). The total effective rate of endoscopy was 94.0％ (47/50) in the observation group and 74.0％ (37/50) in the control group. The difference between the two groups was statistically significant (χ2=11.254, P=0.026). After treatment, the PCNA (4.36 ± 1.95 μg/mg vs. 8.62 ± 2.43 μg/mg, t=8.465), Bcl-2 (3.06 ± 1.63 μg/mg vs. 7.54 ± 1.73 μg/mg, t=9.316), TNF-α (4.13 ± 1.86 μg/mg vs. 7.29 ± 2.14 μg/mg, t=9.473) in the observation group were significantly lower than those in the control group (P<0.05). After treatment, the PCNA (0.053 ± 0.033 vs. 0.074 ± 0.023, t=2.316), Bcl-2 (0.004 ± 0.003 vs. 0.006 ± 0.002, t=5.842) mRNA expression in the observation group were significantly lower than those in the control group (P<0.05). Conclusions The self-made Jianpi-Yiqi decoction can down-regulate the expression of PCNA, Bcl-2 and TNF-α protein and PCNA and Bcl-2 mRNA in gastric mucosa, improve the symptoms of CAG patients and improve clinical efficacy.
ABSTRACT
Benign prostate hyperplasia (BPH) is a male reproductive disease that has gained increasing importance in recent years. The present study investigated whether Pycnogenol® (PYC), a standardized French maritime pine bark extract, could prevent BPH induced by testosterone propionate (TP) in rats. Male Sprague-Dawley rats were randomly divided into five groups of six rats. One group was used as a normal control rats and the other groups received subcutaneous injections of TP for 4 weeks to induce BPH. In the two treatment groups, PYC (20 or 40 mg/kg) was administered daily for 4 weeks by oral gavage concurrently with the induction of TP. All rats were sacrificed at the scheduled termination time, the prostates were weighed, and histopathologic examinations were conducted. Dihydrotestosterone (DHT) levels in serum and the prostate were measured, and the expression of proliferating cell nuclear antigen (PCNA) and Ki-67 proteins was investigated. BPH-treated animals showed increases in the relative weight of the prostate, higher concentrations of DHT in serum and the prostate, and higher expression of PCNA and Ki-67 in the prostate; in contrast, PYC-treated animals had significant reductions in these factors compared with the BPH animals. These findings indicated that PYC inhibited the development of BPH and that this was closely associated with a reduction in DHT concentration.
Subject(s)
Animals , Humans , Male , Rats , Dihydrotestosterone , Hyperplasia , Injections, Subcutaneous , Models, Animal , Proliferating Cell Nuclear Antigen , Prostate , Prostatic Hyperplasia , Rats, Sprague-Dawley , Testosterone Propionate , TestosteroneABSTRACT
Objective@#To study the expression of TNF-α and PCNA in human breast tissue with polyacrylamide hydrogel(PAHG) injection, and to provide the initial theory basis for its prognosis and clinical treatment.@*Methods@#Immunohistochemistry was used to measure the expression of tumor necrosis factor α(TNF-α)and proliferating cell nuclear antigen (PCNA) in 20 normal breast tissues and 40 cases with PAHG injection, analysis was also done by HE staining.@*Results@#①HE staining showed that there were a large number of homogeneous amorphous gel-like injections under optical microscope. Around PAHG there were different degrees of fibrous tissue hyperplasia with or without fibrous degeneration and lots of inflammatory cells. Local foreign body giant cell reaction and ductal dilatation also can be seen around PAHG. ②The IA levels of TNF-α and PCNA in the experimental group were 3.9± 0.3 and 3.2 ± 0.2, the IA levels of TNF-α and PCNA in the control group were 1.0 ± 0.1 and 1.3 ± 0.3, the IA level in the experimental group was significantly higher than that in the control group (P=0.000). The difference was statistically significant. The positive rates of TNF-α and PCNA in the experimental group were 90% (36/40)and 85% (34/40)respectively; the positive rates of TNF-α and PCNA in the control group were 30% (6/20), 40% (8/20). The positive expression rate in the experimental group was significantly higher than that in the control group (P=0.000). The difference was statistically significant. TNF-α and PCNA has Pearson positive relevance in the changes(r=0.3, P=0.040), the difference was statistically significant.@*Conclusions@#TNF-α and PCNA are involved in the immunoreaction of mammalian breast tissue injected with polyacrylamide hydrogel, which may induce the aseptic inflammation, fibrous tissue hyperplasia and related issues through mutual influence.