Zingiber officinale preserves testicular structure and the expression of androgen receptors and proliferating cell nuclear antigen in diabetic rats.

The aim of this study was to assess the efficacy of Zingiber officinale, commonly referred to as ginger, in preserving the structural integrity of testis in streptozotocin (STZ)-induced diabetic rats compared to the efficacy of metformin, the traditional effective antidiabetic drug. STZ was utilised for the induction of diabetes mellitus in male Sprague Dawley rats. The study included five groups (n = 6 each), namely the normal control, ginger-treated normal, nontreated diabetic, metformin-treated diabetic and ginger-treated diabetic groups. Biochemical assessment of fasting blood glucose level (BGL) and total antioxidant capacity (TAC) was performed. Histopathological assessment of the testes was performed using routine and immunohistochemical techniques. Fasting BGL significantly (p = .01) reduced, whereas TAC significantly increased (p < .001) in metformin- and ginger-treated diabetic rats compared to those in untreated diabetic rats. Metformin and ginger reduced the degenerative changes observed in the testes of diabetic rats, significantly reduced (p < .001) caspase-3 immunoexpression, and significantly increased (p < .001) the immune-expression of androgen receptors and proliferating cell nuclear antigen. Ginger has antidiabetic effects and preserves testicular structural integrity and, thus, is recommended as an adjuvant therapy for male diabetic patients in the reproductive period.

Mechanism of Yanghe Pingchuan granules treatment for airway remodeling in asthma.

PURPOSE: Yanghe Pingchuan granules (YPG), a hospital preparation developed by The First Affiliated Hospital, Anhui University of Chinese Medicine, has been used for the clinical treatment of bronchial asthma (BA) for several decades. This study aimed to explore the mechanism of action of YPG in the treatment of BA. MATERIALS AND METHODS: Male Sprague Dawley rats (n=60) were randomly divided into six groups (n=10 per group): control, a BA model, positive drug control (Guilong Kechuanning capsules; a proven effective treatment for BA), and model rats treated with a high, medium, or low dose of YPG. H&E staining was used to detect pathological changes in the bronchial tubes. The mRNA expression levels of PI3K, PKB, PCNA, and AR were determined by real-time PCR, and the protein levels of phospho- (p-)PI3K, p-PKB, p-PCNA, and p-AR were detected by Western blotting. ELISAs were used to detect the expression of PIP2, PIP3 IL-6, IL-8, IL-1ß, and epinephrine (EPI). RESULTS: H&E staining demonstrated that BA can be ameliorated using YPG. Real-time PCR, Western blotting, and ELISA indicated that use of YPG decreased expression of the phosphoinositide 3-kinase (PI3K) signaling pathway and PCNA, and can also ameliorate the condition kidney Yang deficiency, which is associated with BA in Chinese traditional medicine. CONCLUSION: YPG can attenuate BA therapeutically in a dose-dependent manner. The mechanism underlying its therapeutic effect comprises influences on three features that contribute to BA: the PI3K signaling pathway, cell proliferation, and "kidney-Yang deficiency".

Effect of aqueous extract of the leaves of Baccharis trimera on the proliferation of hepatocytes after partial hepatectomy in rats.

PURPOSE:: To evaluate the effect of aqueous extract of Baccharis trimera leaves on the proliferative capacity of the liver after partial hepatectomy (PH) in rats. METHODS:: Twenty Wistar rats weighing between 300 and 450g were divided into two groups: control (HP) and test (HP100-rats that received the aqueous extract of Baccharis trimera for four days at a dose of 100 mg / kg / day). On the fifth day, animals from both groups underwent resection of 70% of the liver. Twenty-four hours later, they were sacrificed and the remnant liver was removed and prepared for studied through PCNA immunohistochemistry. Data analysis for comparison between the two groups was made through the non-parametric statistical test Mann-Whitney test. RESULTS:: In all the animals studied was found most abundant nuclear immunostaining positive hepatocytes interlobular located in regions of the liver. Quantitative analysis of PCNA-positive cells revealed positivity rate significantly higher mean (p = 0.02) in HP100 group (77.1 ± 13.6) compared to the HP group (45.8 ± 12.9). CONCLUSION:: DAdministration of aqueous extract of the leaves of Baccharis trimera 100 mg/kg of animal has a significant positive effect on liver regeneration in rats, 24 hours after hepatectomy (70%).

Effect of aqueous extract of the leaves of Baccharis trimera on the proliferation of hepatocytes after partial hepatectomy in rats

Abstract Purpose: To evaluate the effect of aqueous extract of Baccharis trimera leaves on the proliferative capacity of the liver after partial hepatectomy (PH) in rats. Methods: Twenty Wistar rats weighing between 300 and 450g were divided into two groups: control (HP) and test (HP100-rats that received the aqueous extract of Baccharis trimera for four days at a dose of 100 mg / kg / day). On the fifth day, animals from both groups underwent resection of 70% of the liver. Twenty-four hours later, they were sacrificed and the remnant liver was removed and prepared for studied through PCNA immunohistochemistry. Data analysis for comparison between the two groups was made through the non-parametric statistical test Mann-Whitney test. Results: In all the animals studied was found most abundant nuclear immunostaining positive hepatocytes interlobular located in regions of the liver. Quantitative analysis of PCNA-positive cells revealed positivity rate significantly higher mean (p = 0.02) in HP100 group (77.1 ± 13.6) compared to the HP group (45.8 ± 12.9). Conclusion: DAdministration of aqueous extract of the leaves of Baccharis trimera 100 mg/kg of animal has a significant positive effect on liver regeneration in rats, 24 hours after hepatectomy (70%).

Protective and curative role of Citrus sinensis peel on cadmium-induced testicular and spermatic damage: a morphometric and immunohistochemical evaluation using monoclonal antibodies against Ki-67 and proliferating cell nuclear antigen

This study examined the protective and curative effects of aqueous zest extract of Citrus sinensis on Cadmium-induced testicular tumor in animal models. Twenty four male Wistar rats (10 to 12 weeks old) weighing 165-275 g were divided into group A (treated orally with 2.5 ml/kg body weight/daily of normal saline), Group B (treated intraperitoneally with a single dose of 5mg/kg of cadmium), group C (Treated intraperitoneally with 5 mg/kg of cadmium before 10 mg/kg aqueous zest extract of Citrus sinensis orally), group D (treated with 5mg/kg of cadmium before 40 mg/kg extract), group E (treated with 10 mg/kg extract before 5 mg/kg of cadmium) and group F (treated with 40 mg/kg extract before 5mg/kg of cadmium). The procedure lasted for 8 weeks. Group B rats showed a significant (p< 0.05) decrease in testis weight, testis volume, sperm count (p > 0.001), sperm motility (p > 0.001), abnormal sperm morphology (p<0.001) and a significant decrease in tubular diameter, length (p <0.05), cross sectional area, width, germinal epithelia height, numerical density (p <0.01), perimeter, number (p < 0.001) and a significant increase in tubular lumen of the seminiferous tubules. Rats that were treated with cadmium without pre-treatment or post-treatment with extract showed marked degeneration and atrophied seminiferous tubules with absence of late stage germ cells. There was also a reduction in proliferative cell nuclear antigen (PCNA) materials and Ki67 positive cells in these rats. Interestingly, all these parameters were however attenuated in the groups that were pre-treated and post-treated with the extract. Taken together therefore, it was concluded that aqueous zest extract of Citrus sinensis have protective and curative roles in the abatement of cadmium-induced testicular tumor and that these effects might be as a result of the antioxidant and free radical scavenging potentials of these neutraceuticals

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Protective effects of Urtica dioica L. on experimental testicular ischaemia reperfusion injury in rats.

In this study, it was aimed to examine the effects of Urtica dioica L. (UD) that has antioxidant feature in the experimental testicular I/R model in rats in terms of anti-apoptotic and antioxidative effects. In our study, 24 male rats were divided into three groups: control group, I/R group and I/R + UD (2 mg kg-1 ) group. Seminiferous tubule calibre measurement, Johnson score, haematoxylin-eosin staining, proliferative cell nucleus antigen (PCNA) immunohistochemical staining and TUNEL as histopathological have been conducted. The structural deterioration in the testicular on I/R group has reduced after the treatment of UD. Our data indicate a significant reduction in the activity of in situ identification of apoptosis using terminal dUTP nick end labelling (TUNEL), and there was a rise in the expression of proliferating cell nuclear antigen (PCNA) in testis tissues of UD-treated rats in the I/R group. The I/R + UD group showed a decrease in malondialdehyde levels and an increase in the activities of superoxide dismutase, catalase and glutathione peroxidase in comparison with the I/R group. It could be concluded that protective effects of UD on the I/R testicles are via reduction of histological damage, apoptosis, oxidative stress and lipid peroxidation.

Effects of herbal Epimedium on the improvement of bone metabolic disorder through the induction of osteogenic differentiation from bone marrow-derived mesenchymal stem cells.

Herbal Epimedium (HE) has been commonly used as a tonic, antirheumatic agent and in the treatment of bone­associated diseases including osteoporosis. Treatment for osteoporosis is important to increase bone mass density and maintain to balance of bone remodeling. The present study was performed to investigate the effects of HE on mouse bone marrow mesenchymal stem cell (mBMMSC) proliferation and osteogenic differentiation, using MTT assays, proliferating cell nuclear antigen (PCNA) detection and apoptosis and differentiation assays. HE was demonstrated to inhibit the proliferation of mBMMSCs up to 45.43±3.33% and to decrease the level of PCNA expression compared with untreated cells. HE also induced late apoptosis at 24 and 48 h after treatment up to 71.93 and 67.03%, respectively, while only 14.93% of untreated cells exhibited apoptosis. By contrast, HE induced differentiation of mBMMSCs into an osteogenic lineage at the beginning of three weeks after commencement of treatment. This suggested that HE is a candidate as an inducer of osteogenesis from bone marrow mesenchymal stem cells, and additionally has potential for use in the treatment of bone metabolic disorders such as osteoporosis.

Fraction of Auxemma oncocalyx and Oncocalyxone A Affects the In Vitro Survival and Development of Caprine Preantral Follicles Enclosed in Ovarian Cortical Tissue.

BACKGROUND: Auxemma oncocalyx and its main component oncocalyxone A (onco A) have a high level of antioxidant and antitumor activity, but there are no studies on the action of both of these drugs regarding folliculogenesis. MATERIAL AND METHODS: Caprine ovarian tissue fragments were fixed (non-cultured control) or cultured for 1 or 7 days in α-MEM+ alone (cultured control) or supplemented with dimethyl sulfoxide (DMSO; 20% v/v), bone morphogenetic protein 15 (BMP-15; 100 ng/ml), doxorubicin (DXR; 0.3 g/ml), or different concentrations of A. oncocalyx (1.2, 12, or 34 g/ml) or onco A (1, 10, or 30 g/ml). We analyzed for follicular morphology and growth, apoptosis (terminal deoxynucleotidyl transferase dUTP-biotin nick end labeling (TUNEL) assay), and cell proliferation (silver staining of argyrophilic nucleolus organizer regions (AgNOR) and test for proliferating cell nuclear antigen (PCNA)). RESULTS: A. oncocalyx and onco A (in a concentration-dependent manner) and DXR decreased (P < 0.05) the number of morphologically normal follicles, with no effect (P > 0.05) on follicular growth. A. oncocalyx reduced (P < 0.05) the percentage of normal follicles compared to onco A, whereas DXR, A. oncocalyx 1.2 g/ml, and onco A 1 g/ml increased (P < 0.05) the percentage of TUNEL-positive follicles. DXR decreased (P < 0.05) the number of nucleolus organizer regions. CONCLUSION: A. oncocalyx and onco A affected the in vitro caprine folliculogenesis in a concentration-dependent manner. Onco A (1 g/ml) has a less harmful effect than DXR on goat preantral follicle survival.

Chemopreventive Effects of Eryngium foetidum L. Leaves on COX-2 Reduction in Mice Induced Colorectal Carcinogenesis.

To investigate the potential effects of Eryngium foetidum Linn. leaves (EF) in colitis-induced colorectal carcinogenesis in mice by azoxymethane (AOM) and dextran sulfate sodium (DSS), 39 ICR male mice were studied and divided into 6 groups. The mice were received a modified AIN-76 diet in Group 1, whereas Group 2 was given an AOM, DSS, and AIN-76 diet. Groups 3 and 4 were fed with 0.8% and 3.2% freeze-dried EF with AIN-76 diets, for 5 wk. Groups 5 and 6 were fed with 0.8% and 3.2% EF diets for 5 wk during AOM/DSS administration. The mice were necropsied at Week 20 and their colons were collected. The results indicated that the incidences of tumors in Groups 2, 5, and 6 was 100%, 75%, and 88%, with multiplicities (mean ±SE) of 3.75 ±0.92, 2.38 ± 0.96 and 4.25 ± 0.79, respectively. Interestingly, there was a significant difference in COX-2 expression in mice received 3.2% EF in their diet, but the proliferative cell nuclear antigen index and iNOS protein expression were not significantly different. We concluded that EF at a dose level of 3.2% in their diet had a preventive effect on colorectal carcinogenesis via the proinflammatory cytokine, COX-2.

Coumestrol suppresses proliferation of ES2 human epithelial ovarian cancer cells.

Coumestrol, which is predominantly found in soybean products as a phytoestrogen, has cancer preventive activities in estrogen-responsive carcinomas. However, effects and molecular targets of coumestrol have not been reported for epithelial ovarian cancer (EOC). In the present study, we demonstrated that coumestrol inhibited viability and invasion and induced apoptosis of ES2 (clear cell-/serous carcinoma origin) cells. In addition, immunoreactive PCNA and ERBB2, markers of proliferation of ovarian carcinoma, were attenuated in their expression in coumestrol-induced death of ES2 cells. Phosphorylation of AKT, p70S6K, ERK1/2, JNK1/2, and p90RSK was inactivated by coumestrol treatment in a dose- and time-dependent manner as determined in western blot analyses. Moreover, PI3K inhibitors enhanced effects of coumestrol to decrease phosphorylation of AKT, p70S6K, S6, and ERK1/2. Furthermore, coumestrol has strong cancer preventive effects as compared to other conventional chemotherapeutics on proliferation of ES2 cells. In conclusion, coumestrol exerts chemotherapeutic effects via PI3K and ERK1/2 MAPK pathways and is a potentially novel treatment regimen with enhanced chemoprevention activities against progression of EOC.

[Effect of puerarin on hypoxia induced proliferation of PASMCs by regulating reactive oxygen].

To discuss the effect of puerarin (Pue) on the proliferation of hypoxia-induced pulmonary artery smooth muscle cells (PASMCs) and discuss whether its mechanism is achieved by regulating reactive oxygen. PASMCs of primarily cultured rats (2-5 generations) were selected in the experiment. MTT, Western blot, FCM and DCFH-DA were used to observe Pue's effect the proliferation of PASMCs. The Western blot was adopted to detect whether ROS participated in Pue's effect in inhibiting PASMC proliferation. The PASMCs were divided into five groups: the normoxia group, the hypoxia group, the hypoxia + Pue group, the hypoxia + Pue + Rotenone group and the hypoxia + Rotenone group, with Rotenone as the ROS blocker. According to the results, under the conditions of normoxia, Pue had no effect on the PASMC proliferation; But, under the conditions of hypoxia, it could inhibit the PASMC proliferation; Under the conditions of normoxia and hypoxia, Pue had no effect on the expression of the tumor necrosis factor-α (TNF-α) among PASMCs, could down-regulate the expression of hypoxia-induced cell cycle protein Cyclin A and proliferative nuclear antigen (PCNA). DCFH-DA proved Pue could reverse ROS rise caused by hypoxia. Both Rotenone and Pue could inhibit the up-regulated expressions of HIF-1α, Cyclin A, PCNA caused by anoxia, with a synergistic effect. The results suggested that Pue could inhibit the hypoxia-induced PASMC proliferation. Its mechanism may be achieved by regulating ROS.

In vivo inhibition followed by exogenous supplementation demonstrates galactopoietic effects of prolactin on mammary tissue and milk production in dairy cows.

It has been previously shown that the long-term inhibition of milking-induced prolactin (PRL) release by quinagolide (QN), a dopamine agonist, reduces milk yield in dairy cows. To further demonstrate that PRL is galactopoietic in cows, we performed a short-term experiment that used PRL injections to restore the release of PRL at milking in QN-treated cows. Nine Holstein cows were assigned to treatments during three 5-d periods in a 3×3 Latin square design: 1) QN: twice-daily i.m. injections of 1mg of QN; 2) QN-PRL: twice-daily i.m. injections of 1mg of QN and twice-daily (at milking time) i.v. injections of PRL (2µg/kg body weight); and 3) control: twice-daily injections of the vehicles. Mammary epithelial cells (MEC) were purified from milk so that their viability could be assessed, and mammary biopsies were harvested for immunohistological analyses of cell proliferation using PCNA and STAT5 staining. In both milk-purified MEC and mammary tissue, the mRNA levels of milk proteins and BAX were determined using real-time reverse-transcription PCR. Daily QN injections reduced milking-induced PRL release. The area under the PRL curve was similar in the control and PRL injection treatments, but the shape was different. The QN treatment decreased milk, lactose, protein, and casein production. Injections of PRL did not restore milk yield but tended to increase milk protein yield. In mammary tissue, the percentage of STAT5-positive cells was reduced during QN but not during QN-PRL in comparison with the control treatment. The percentage of PCNA-positive cells was greater during QN-PRL injections than during the control or QN treatment and tended to be lower during QN than during the control treatment. In milk-purified MEC, κ-casein and α-lactalbumin mRNA levels were lower during QN than during the control treatment, but during QN-PRL, they were not different from the control treatment. In mammary tissue, the BAX mRNA level was lower during QN-PRL than during QN. The number of MEC exfoliated into milk was increased by QN injections but tended to be decreased by PRL injections. Injections of PRL also increased the viability of MEC harvested from milk. Although PRL injections at milking could not reverse the effect of QN treatment on milk production, their effects on cell survival and exfoliation and on gene expression suggest that the effect of QN treatment on the mammary gland is due to QN's inhibition of PRL secretion.

Ricinus communis L. stem bark extracts regulate ovarian cell functions and secretory activity and their response to Luteinising hormone.

Ricinus communis L. has ethnopharmacological contraceptive reputation but its stem bark has unexplored mechanisms of action in female reproductive system. In the present study, the effect of methanolic and aqueous extracts from the stem bark of the plant was examined on basic porcine ovarian granulosa cell functions and its response to Luteinising hormone (LH)-the upstream hormonal regulator. Systemic treatment of methanolic and aqueous extracts stimulated cell proliferation (proliferating cell nuclear antigen, PCNA) and also promoted cell apoptosis (caspase-3). Aqueous extract has inverted the stimulatory effect of LH on PCNA but not on caspase-3. Methanolic extract stimulated as well as inhibited progesterone release and stimulated testosterone secretion. Whereas aqueous extract inhibited both steroid releases and suppressed the stimulatory effect of LH on progesterone release and promoted the inhibitory effect of LH on testosterone release. In conclusion, the present study unveils the mechanism of action of R. communis stem bark in in vitro condition. These suggest its possible contraceptive efficacy by exerting its regulatory role over LH and on basic ovarian cell functions and secretion activity.

Favourable effects of grape seed extract on intestinal epithelial differentiation and barrier function in IL10-deficient mice.

The impairment in the rate of cell proliferation and differentiation leads to a negative consequence on the renewal of the intestinal epithelium, which is the aetiological factor of a number of digestive diseases. Grape seed extract (GSE), a rich source of proanthocyanidins, is known for its beneficial health effects. The present study evaluated the beneficial effects of GSE on colonic cell differentiation and barrier function in IL10-deficient mice. Female mice aged 6 weeks were randomised into two groups and given drinking-water containing 0 or 0.1 % GSE (w/v) for 12 weeks. GSE supplementation decreased serum TNF-α level and intestinal permeability, and increased the colonic goblet cell density that was associated with increased mRNA expression of mucin (Muc)-2. Immunohistochemical analyses showed lower accumulation of ß-catenin in the crypts of colon tissues of the GSE-supplemented mice, which was associated with a decreased mRNA expression of two downstream effectors of Wingless and Int (Wnt)/catenin signalling, myelocytomatosis oncogene protein (Myc) and cyclin D1 (Ccnd1). Consistently, GSE supplementation decreased the number of colonic proliferating cell nuclear antigen-positive cells, a well-known cell proliferation marker, and a weakened extracellular signal-regulated kinases 1 and 2 (ERK1/2) signalling. In summary, these data indicate that supplementation of 0.1 % GSE for 12 weeks improved gut barrier function and colonic cell differentiation in the IL10-deficient mice probably via inhibiting Wnt/ß-catenin pathway.

[Effects of serum enatninine Gumibao (Chinese character: see text) on the aroliferation and differentiation of osteoblast induced by dexamethasone].

OBJECTIVE: To investigate the effects of serum containing Gumibao (Chinese character: see text) on the proliferation and differentiation of osteoblast induced by dexamethasone. METHODS: Osteoblasts were extracted from skulls in newly born (within 24 hours) SD rats, and digested with collagenase. The first passage of cells were used for experiments. Cells were cultured in the medium containing different concentrations of dexamethasone (0, 10(-8), 10(-7), 10(-6), 10(-5) ,10(-4) mol/L). Alkaline phosphatase staining were carried out after 1 week and numbers of mineralized nodes with alizarin red staining were observed after 3 weeks. Accordingly, following the treatment of 10(-5) mol/L dexamethasone for 1 week, cells were cultured in the medium with serum containing Gumibao (Chinese character: see text). One week after Cumibao (Chinese character: see text) treatment, cells were stained with Alkaline phosphatase and collagen I and PCNA were examined by Western-blot. However, the observation of numbers of mineralized nodes with alizarin red stain required one more week. RESULTS: High concentration of dexamethasone could inhibit the expression of PCNA, collagen I, alkaline phosphatase and reduce the number of mineralized nodes of osteoblast, while serum containing Gumibao (Chinese character: see text) could reverse the inhibition. CONCLUSION: High concentration of dexamethasone could inhibit the proliferation and differentiation of osteoblastic cells, while serum containing Gumibao (Chinese character: see text) could reverse the inhibition.

Lard and/or canola oil-rich diets induce penile morphological alterations in a rat model.

PURPOSE: To investigate the effect of dietary lipid quantity and/or quality on penis morphology in adult rats. METHODS: Thirty-eight male Wistar rats were divided into 4 groups: normal lipid diet (NL), high-fat diet rich in saturated fatty acids (HF-S), high-fat diet rich in polyunsaturated fatty acids (HF-P), and high-fat diet rich in saturated and polyunsaturated fatty acids (HF-SP). Blood samples were collected and the penises were removed for histomorphometrical and immunohistochemical analysis. RESULTS: All high-fat diets promoted an increase in the body mass (p<0.0001). The HF-S and HF-SP groups presented hyperglycemia (p=0.0060), hyperinsulinemia (p=0.0030), and hypercholesterolemia (p=0.0020). Concerning the penis, the high-fat diets led to an increase in the collagen fibers (p<0.0001) and smooth muscle cell density area (p=0.0027), and a decline in the sinusoidal space density area (p<0.0001) and corpus cavernosum cell proliferation (p=0.0003). CONCLUSION: Diets rich in saturated and/or polyunsaturated fatty acids promoted overweight and induced penile changes in rodent models, which may lead to the development of erectile dysfunction.

Green tea extract inhibition of human leiomyoma cell proliferation is mediated via catechol-O-methyltransferase.

BACKGROUND/AIMS: To investigate the inhibitory effect of green tea extract, epigallocatechin gallate (EGCG), on wild-type human leiomyoma (WT-HuLM) cells and its potential action via catechol-o-methyltransferase (COMT) activity. METHODS: Cell proliferation of WT-HuLM and COMT gene-silenced HuLM (COMT-shRNA-HuLM) cells treated with 0 or 100 µM EGCG for 7 days was measured using the MTT method. Total RNA and protein were extracted from cells treated with 0 or 100 µM of EGCG for 48 h. Gene expression profiling was performed using Human Signal Transduction PathwayFinder. Proliferation cell nuclear antigen (PCNA), cyclin-dependent kinase 4 (Cdk4) and COMT protein levels were detected by Western blot analyses. COMT enzyme activity was evaluated by HPLC. RESULTS: EGCG-treated WT-HuLM cells showed significantly decreased COMT expression (p < 0.001) and enzyme activity (p < 0.05) compared to untreated WT-HuLM cells, while COMT-shRNA-HuLM cells showed no significant change. At 100 µM of EGCG, survival of WT-HuLM cells was significantly lower (p < 0.05) compared to COMT-shRNA-HuLM cells. EGCG treatment modulated multiple signaling pathways in WT-HuLM compared to untreated control, while changes were minimal or reversed in COMT-shRNA-HuLM cells. EGCG significantly decreased PCNA, Cdk4 and soluble COMT protein levels (p < 0.001) in WT-HuLM, but not in COMT-shRNA-HuLM cells. CONCLUSIONS: The antiproliferative and gene-modulating effects of EGCG on HuLM cells are mediated, at least partially, via its effect on COMT expression and enzyme activity.

Effect of frequent application of low-level laser therapy on corticotomized tooth movement in dogs: a pilot study.

PURPOSE: The purposes of the present study were to evaluate the effects of frequent applications of low-level laser therapy (LLLT) on corticotomy-assisted tooth movement in a beagle dog model and to compare the effects in the mandible and maxilla. MATERIALS AND METHODS: In 4 male beagles, the maxillary and mandibular second premolars were extracted. The third premolars were corticotomized and then protracted from the canines with a continuous force of 200 g. Daily LLLT (using an aluminum gallium indium phosphide [AlGaInP] diode) was applied at the buccal mucosa of the corticotomized premolars on 1 side only. The tooth movement was measured for 8 weeks. Fluorochromes were injected intravenously at the start of the experiment (T0) and after 2 (T2), 4 (T4), and 8 (T8) weeks to evaluate new bone formation on the tension sides. Histomorphometric and immunohistologic evaluations were performed. RESULTS: In the mandible, the movement of the corticotomized premolars in the LLLT plus corticotomy group was less than that in the corticotomy-only group, although the difference was not statistically significant. In the maxilla, no significant differences between the 2 groups were found. Osteoclastic and proliferating cell activities and the amount of new bone formation were greater in the mandibular LLLT plus corticotomy group than in the corticotomy-only group. CONCLUSIONS: The frequent application of LLLT showed no significant effect on the corticotomized tooth movement.

Assessment of Augmented Immune Surveillance and Tumor Cell Death by Cytoplasmic Stabilization of p53 as a Chemopreventive Strategy of 3 Promising Medicinal Herbs in Murine 2-Stage Skin Carcinogenesis.

Cancer is the final outcome of a plethora of events. Targeting the proliferation or inducing programmed cell death in a proliferating population is a major standpoint in the cancer therapy. However, proliferation is regulated by several cellular and immunologic processes. This study reports the inhibition of proliferation by augmenting immune surveillance, silencing acute inflammation, and inducing p53-mediated apoptosis of skin cancer by 3 promising medicinal extracts. We used the well-characterized model for experimental skin carcinogenesis in mice for 32 weeks to study the chemopreventive effect of the methanolic extracts of Trigonella foenumgraecum, Eclipta alba, and Calendula officinalis. All 3 extracts reduced the number, incidence, and multiplicity of tumors, which was confirmed by the pathologic studies that showed regressed tumors. There was a significant reduction in the PCNA+ nuclei in all treatment groups 32 weeks after the initiation. Mechanistic studies revealed that proliferative population in tumors is diminished by the restoration of the endogenous antioxidant defense, inhibition of the stress-related signal-transducing element NFκB, reduction of inflammation, enhancement of immunosurveillance of the genetically mutated cells, along with silencing of the cell cycle progression signals. Finally, all 3 medicinal extracts induced stable expression of p53 within the tumors, confirmed by the CFDA-Cy3 apoptosis assay. Results of our study confirm that these extracts not only limit the rate of proliferation by inhibition of the processes integral to cancer development but also induce stable cytoplasmic expression of p53-mediated apoptosis, leading to fewer and regressed tumors in mice.