MicroRNAs bind to Toll-like receptors to induce prometastatic inflammatory response

MicroRNAs (miRNAs) are small noncoding RNAs, 19-24 nucleotides in length, that regulate gene expression and are expressed aberrantly in most types of cancer. MiRNAs also have been detected in the blood of cancer patients and can serve as circulating biomarkers. It has been shown that secreted miRNAs within exosomes can be transferred from cell to cell and can regulate gene expression in the receiving cells by canonical binding to their target messenger RNAs. Here we show that tumor-secreted miR-21 and miR-29a also can function by another mechanism, by binding as ligands to receptors of the Toll-like receptor (TLR) family, murine TLR7 and human TLR8, in immune cells, triggering a TLR-mediated prometastatic inflammatory response that ultimately may lead to tumor growth and metastasis. Thus, by acting as paracrine agonists of TLRs, secreted miRNAs are key regulators of the tumor microenvironment. This mechanism of action of miRNAs is implicated in tumor-immune system communication and is important in tumor growth and spread, thus representing a possible target for cancer treatment.     

nNOS expression in the brain of rats after burn and the effect of the ACE inhibitor captopril

Objective

To investigate the role of endogenous neuronal nitric oxide synthase (nNOS) on brain injury after burn and the effects of the captopril.

Methods

Wistar albino rats (200–250 g) were exposed on the dorsal surface to 90 °C (burn) or 25 °C (sham) water for 10 s. The ACE group was treated with intraperitoneal 10 mg/kg captopril immediately after burn and this treatment was repeated twice daily. At the end of the 24 h brain samples were taken. nNOS was studied in brain areas by immunohistochemistry.

Results

There was no difference between the cerebellar and hypothalamic areas the nNOS expression of all groups. nNOS expression increased in the frontal cortex, striatum and midbrain in the burn group compared to the control group. In the frontal cortex, nNOS expression significantly decreased after ACE inhibitor treatment (p < 0.05). The striatal nNOS of the ACE group significantly increased when compared to the control group (p = 0.001). In the midbrain of the animals, nNOS decreased in the ACE group. Hippocampal nNOS expression did not change after burn and significantly increased after ACE inhibitor therapy (p < 0.05).

Conclusions

Our data showed that the pathophysiological events following burn appear to be related to an acute inflammatory reaction which is associated with nNOS in the frontal cortex, striatum and midbrain, and captopril treatment abrogates the nNOS response in the frontal cortex and midbrain.     

Comparison of microscopic (pT3a) and gross extravesical extension (pT3b) in pathological staging of bladder cancer: analysis of patient outcomes

Objective

To determine the prognostic value of pT3 bladder urothelial carcinoma substaging in patients without lymphatic involvement.

Patients and methods

Pathologic and clinical data were reviewed on patients who underwent radical cystectomy for urothelial carcinoma between 1991 and 2010. Of the 460 reviewed patients, 74 patients were diagnosed with pathologic T3No urothelial carcinoma of the bladder. The impact of pathologic substaging (pT3a vs. pT3b) was examined to determine the effect on overall and disease-specific survival.

Results

Five years disease-specific and overall survival rates were 46.9 % and 39.6 % for patients with pT3aNo tumor, whereas these ratios were 34.4 and 30.3 %, respectively, for patients with pT3bNo tumor (p > 0.05). Mean disease-specific survival time was 43.94 ± 6.50 months for pT3aNo, while it was 39.01 ± 7.19 months for pT3bNo (p = 0.539). In multivariate cox regression analysis, age (p = 0.459), gender (p = 0.710), urinary diversion type (p = 0.088), and pT3 substaging (p = 0.554) were not noticed as an independent predictive factor for survival.

Conclusion

Macroscopic extravesical extension (pT3b) is not associated with a worse outcome than pT3a disease in lymph node-negative cases of bladder urothelial carcinoma.     

Dehiscence and fenestration in patients with different vertical growth patterns assessed with cone-beam computed tomography

Abstract Objective: To test the null hypothesis that the presence of alveolar defects (dehiscence and fenestration) was not different among patients with different vertical growth patterns. Materials and Methods: A total of 1872 teeth in 26 hyper-divergent (mean age: 24.4 ± 4.8?years), 27 hypo-divergent (mean age: 25.1 ± 4.5?years), and 25 normo-divergent (mean age: 23.6 ± 4.1?years) patients with no previous orthodontic treatment were evaluated using cone-beam computed tomography. Axial and cross-sectional views were evaluated with regard to whether dehiscence and/or fenestration on buccal and lingual surfaces existed or not. For statistical analysis, the Pearson chi-square test was used at a P < .05 significance level. Results: According to the statistical analysis, the hypo-divergent group (6.56%) had lower dehiscence prevalence than the hyper-divergent (8.35%) and normo-divergent (8.18%) groups (P = .004). Higher prevalences of dehiscence and fenestration were found on buccal sides in all vertical growth patterns. While fenestration was a common finding for the maxillary alveolar region, dehiscence was a common finding in the mandible in all groups. Conclusion: The null hypothesis was rejected. Although the prevalence of fenestrations was not different, significant differences for dehiscences were found in patients with different vertical growth patterns.     

Preventive effects of thymoquinone in a rat periodontitis model: a morphometric and histopathological study

Ozdemir H, Kara MI, Erciyas K, Ozer H, Ay S. Preventive effects of thymoquinone in a rat periodontitis model: a morphometric and histopathological study. J Periodont Res 2012; 47: 74–80. © 2011 John Wiley & Sons A/S Background and Objective: Thymoquinone has a variety of pharmacologic properties, including antihistaminic, antibacterial, antihypertensive, hypoglycemic, anti‐inflammatory and anti‐oxidative activities. Through its anti‐inflammatory and antioxidant properties, thymoquinone may play an important role in preventing periodontal diseases. The aim of this study was to evaluate the effectiveness of thymoquinone in preventing the initiation and progression of periodontitis in a rat periodontitis model. Material and Methods: Twenty‐four rats were randomly divided into three experimental groups: a nonligated (NL) treatment group (n = 8), a ligature‐only (LO) treatment group (n = 8) and a ligature plus thymoquinone (10 mg/kg, daily for 11 d) (TQ) treatment group. In order to induce experimental periodontitis, a 4/0 silk suture was placed at the gingival margin of the right‐mandibular first molars of the rats. Thymoquinone was administered by gastric feeding until the animals were killed on day 11. Changes in the alveolar bone levels of rats in each group were measured clinically, and tissues of rats in each group were examined histopathologically to determine inflammatory cell infiltration (ICI), osteoblast and osteoclast activities, and osteoclast morphology. Results: Alveolar bone loss around the mandibular molar tooth was significantly higher in the LO group compared with NL and TQ groups (p < 0.05). The ratio of the presence of ICI and osteoclast numbers was significantly higher in the LO group than in the NL and TQ groups (p < 0.05). Osteoblastic activity was significantly lower in the LO group than in the NL and TQ groups (p < 0.05). Conclusion: The present study showed that the oral administration of thymoquinone diminishes alveolar bone resorption in a rat periodontitis model.     

Relationship of olfactory function with olfactory bulbus volume,disease duration and Unified Parkinson’s disease rating scale scores in patients with early stage of idiopathic Parkinson’s disease

We aimed to investigate the relationship between olfactory function and olfactory bulbus (OB) volume, disease duration and Unified Parkinson’s disease rating scale (UPDRS) scores in early stage idiopathic Parkinson’s disease patients. The University of Pennsylvania Smell Identification Test (UPSIT) was used for the evaluation of olfactory function. UPSIT scores for patients with Parkinson’s disease were significantly lower than controls. There was no significant difference between stage 1 and stage 2 patients. OB volumes were higher in stage 1 and 2 patients than controls, but there was no statistical difference between the three groups. No significant correlation was found between UPSIT and UPDRS total scores, nor between UPSIT scores and disease duration in stage 1 and 2 patients. According to our results, we propose UPSIT be used as a screening test to diagnose presymptomatic patients, but not OB volumes.     

Computer-assisted analysis contour lines of aesthetic unit for the assessment of lip augmentation

Background

Lip augmentation and changing contour lines have become more popular ways of improving the appearance. However, validated measures of lip fullness for quantification of outcomes are needed; ethnic background and personal goals can optimise outcomes while tailoring lip enhancement treatment to each individual’s anatomy. The aim of this study is to analyse the morphological features of the lip in detail and to clarify the objective parameters in related with the subjective ones regarding the lip augmentation and lip reconstruction.

Methods

Standard photographs of the lips of 200 young Anatolian adults were calculated with linear and angular components. The features of the lower third of the face were analysed with the software program. Linear analyses (heights of the upper lip, the upper vermilion, the lower lip height, the lower vermillion and the chin height) and angular analyses (the upper lip, the lower lip, the apex and Cupid’s bow angles) were measured as reference points. The lip shape was classified into five groups: thin, very thin, medium, full and very full.

Results

The lower third of the face was divided into three segments (Sn–Sto, Sm–Me and Sto–Sm), and the largest portion of the lower face was occupied by the chin and the smallest by the lower lip height in both genders. The upper vermilion height was 8.07?±?1.8 mm in males and 7.08?±?1.5 mm in females. The lower vermilion height was 10.1?±?2.4 mm in males and 9.7?±?1.9 mm in females. The upper lip angle was calculated as 30.3?±?9.6° in males and 24.2?±?6.2°mm in females. The lower lip angle was calculated as 38.3?±?9.7° in males and 36.5?±?6.4° in females. Meanwhile, the angular measurements of Cupid’s bow (i.e., the apex and the central angle of Cupid’s bow) were smaller in men than in women. When the lip was analyzed, the medium and full types in upper and lower lips accounted for substantial fractions in men, whereas medium and thin types were predominant also in women.

Conclusions

With the help of certain software, this research has made possible to define the best cosmetical redesign solution of lip construction and augmentation with a natural appearance for the patient.Level of Evidence: Level III, diagnostic study.

     

Sympathetic skin responses in patients with hyperthyroidism

BACKGROUND: The aim of this study was to investigate the disorders of sympathetic nervous system in patients with hyperthyroidism using sympathetic skin response (SSR). MATERIAL AND METHODS: Twenty-two newly diagnosed cases with hyperthyroidism were included in the study. The results were compared with those of 20 healthy controls. SSR was recorded with the contralateral electrical stimulation of the median nerve (of the upper extremities) and tibial nerve (of the lower extremities) with active electrodes placed on palms and soles and reference electrodes attached on the dorsal aspects of hands and feet. RESULTS: Ages of the cases with hyperthyroidism and controls ranged between 15-65 years (mean: 46.7 +/- 15.0 years) and 24-62 years (mean: 39.6 +/- 9.8 years) respectively (p > 0.05). In all the control subjects SSR could be obtained, while from the lower extremities of 4 cases with hyperthyroidism (18.0%) SSR could not be elicited. Mean SSR latencies of lower extremities were found significantly longer than control group (p < 0. 05). No difference was detected between mean amplitudes of SSR in upper and lower extremities. CONCLUSION: These findings suggest that SSR is useful for investigation of sympathetic nervous system involvement in cases with hyperthyroidism.     

The effects of calcium channel blockers are not related to their chemical structure in the collar model of the rabbit

Placing a silicone collar around the rabbit carotid artery induces intimal thickening, an early stage in atherosclerosis and restenosis. We investigatedwhethertreatment with oral pranidipine, a new potent, long-lasting dihydropyridine calcium channel blocker (CCB), inhibited collar-induced intimal thickening in addition to the changes in vascular reactivity usually observed in this model. Pranidipine treatment did not inhibit collar-induced intimal thickening. Placing the collar around the carotid artery resulted in the characteristic changes in vascular reactivity, such as increased sensitivity to 5-hydroxytryptamine. Treatment with Nomega-nitro-L-arginine (100 microM) and pranidipine, however, did not affect collar-induced changes in vascular reactivity. From results of this and previous studies, we conclude that pranidipine does not prevent collar-induced intimal thickening or collar-induced changes in vascular reactivity. Not all CCBs prevent collar-induced intimal thickening, suggesting that the effects of these agents are not related to their chemical structure and/or their calcium channel-blocking actions.