This study was to investigate the role of macrophage migration inhibitory factor (MIF) in mouse acute otitis media (AOM), we hypothesize that blocking MIF activity will relieve mouse AOM. A mouse AOM model was constructed by injecting lipopolysaccharide (LPS) into the middle ear of C57BL/6 mice through the tympanic membrane (TM). MIF levels were measured by real-time PCR (RT-PCR) and ELISA after LPS application. Normal or AOM mice were given PBS or ISO-1 (MIF antagonist) every day for 10 days and the hearing levels were determined by measuring auditory brainstem response (ABR) threshold. After the ABR test finished, H&E staining was conducted and the inflammation was also measured by detecting interleukin (IL)-1?, tumor necrosis factor (TNF)-? and vascular endothelial growth factor (VEGF) levels with RT-PCR and ELISA. TLR-4 expression was determined by western blotting and NF-?B activation was determined by electrophoretic mobility shift assays. Compared with the normal control, MIF levels in the middle ear of LPS-induced AOM mice were significant increased. The ABR results showed that mean ABR thresholds in ISO-1 treated AOM mice were significantly reduced compared with PBS treated AOM mice since day 7, indicating that ISO-1 treatment potentially improved the hearing levels of AOM mice. H&E staining showed that ISO-1 treatment could reduce the mucosal thickness of AOM mice. In ISO-1 treated mice, TLR-4 expression and levels of IL-1?, TNF-? and VEGF were significantly lower compared with PBS treated AOM mice. ISO-1 treatment also significantly inhibited NF-?B activation in AOM mice compared with PBS treated AOM mice. These results suggested that blocking the activity of MIF by ISO-1 could reduce the inflammation in AOM mice in which process TLR-4 and NF-?B were involved. The reduction in MIF activity is conducive to alleviate mouse AOM, which may serve as a potential therapeutic target for the treatment of AOM.
iASPP is an inhibitory member of the apoptosis-stimulating proteins of P53 (ASPP) family. iASPP is over expressed in several malignant tumors and potentially affects cancer progression. However, the expression and potential role of iASPP in oral tongue squamous cell carcinoma (OTSCC) have not been addressed. In our study, we detected iASPP expression in OTSCC by immunohistochemistry. iASPP expression is up-regulated in OTSCC tissues. Moreover, in clinical pathology specimens, we found that increased iASPP expression correlates with poor differentiation and lymph node metastasis. Using multicellular tumor spheroids (MTS) and flow cytometry, we demonstrated that iASPP down-regulation arrests OTSCC cells at the G0/G1 phase, induces OTSCC cell apoptosis and inhibits OTSCC cell proliferation. These results indicate that iASPP plays a significant role in the progression of OTSCC and may serve as a biomarker or therapeutic target for OTSCC patients.
Radiation is an important modality in cancer treatment, and eighty percent of cancer patients need radiotherapy at some point during their clinical management. However, radiation-induced damage to normal tissues restricts the therapeutic doses of radiation that can be delivered to tumours and thereby limits the effectiveness of the treatment. The use of radioprotectors represents an obvious strategy to obtain better tumour control using a higher dose in radiotherapy. However, most of the synthetic radioprotective compounds studied have shown inadequate clinical efficacy owing to their inherent toxicity and high cost. Hence, the development of radioprotective agents with lower toxicity and an extended window of protection has attracted a great deal of attention, and the identification of alternative agents that are less toxic and highly effective is an absolute necessity. Recent studies have shown that alpha-2-macroglobulin (?2M) possesses radioprotective effects. ?2M is a tetrameric, disulfide-rich plasma glycoprotein that functions as a non-selective inhibitor of different types of non-specific proteases and as a carrier of cytokines, growth factors, and hormones. ?2M induces protein factors whose interplay underlies radioprotection, which supports the idea that ?2M is the central effector of natural radioprotection in the rat. Pretreatment with ?2M has also induced a significant reduction of irradiation-induced DNA damage and the complete restoration of liver and body weight. Mihailovi? et al. concluded that the radioprotection provided by ?2M was in part mediated through cytoprotection of new blood cells produced in the bone marrow; these authors also indicated that an important aspect of the radioprotective effect of amifostine was the result of the induction of the endogenous cytoprotective capability of ?2M. The radioprotective effects of ?2M are possibly due to antioxidant, anti-fibrosis, and anti-inflammatory functions, as well as the maintenance of homeostasis, and enhancement of the DNA repair and cell recovery processes. This review is the first to summarise the observations and elucidate the possible mechanisms responsible for the beneficial effects of ?2M. The lacunae in the existing knowledge and directions for future research are also addressed.
A series of retrospectively recorded patients with cleft lip and palate was uniquely investigated to demonstrate and analyze the complications after cleft repairing operations in a selected Chinese population.
Growing evidence indicates that bone marrow-derived mesenchymal stem cells (BM-MSCs) enhance wound repair via paracrine. Because the extent of environmental oxygenation affects the innate characteristics of BM-MSCs, including their stemness and migration capacity, the current study set out to elucidate and compare the impact of normoxic and hypoxic cell-culture conditions on the expression and secretion of BM-MSC-derived paracrine molecules (e.g., cytokines, growth factors and chemokines) that hypothetically contribute to cutaneous wound healing in vivo. Semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) analyses of normoxic and hypoxic BM-MSCs and their conditioned medium fractions showed that the stem cells expressed and secreted significantly higher amounts of basic fibroblast growth factor (bFGF),vascular endothelial growth factor A (VEGF-A) interleukin 6 (IL-6) and interleukin 8 (IL-8) under hypoxic conditions. Moreover, hypoxic BM-MSC-derived conditioned medium (hypoCM) vs. normoxic BM-MSC-derived conditioned medium (norCM) or vehicle control medium significantly enhanced the proliferation of keratinocytes, fibroblasts and endothelial cells, the migration of keratinocytes, fibroblasts, endothelial cells and monocytes, and the formation of tubular structures by endothelial cells cultured on Matrigel matrix. Consistent with these in vitro results, skin wound contraction was significantly accelerated in Balb/c nude mice treated with topical hypoCM relative to norCM or the vehicle control. Notably increased in vivo cell proliferation, neovascularization as well as recruitment of inflammatory macrophages and evidently decreased collagen I, and collagen III were also found in the hypoCM-treated group. These findings suggest that BM-MSCs promote murine skin wound healing via hypoxia-enhanced paracrine.
Atoh1 is a transcription factor that regulates neural development in multiple tissues and is conserved among species. Prior mouse models of Atoh1, though effective and important in the evolution of our understanding of the gene, have been limited by perinatal lethality. Here we describe a novel point mutation of Atoh1 (designated Atoh1(trhl) ) underlying a phenotype of trembling gait and hearing loss. Histology revealed inner ear hair cell loss and cerebellar atrophy. Auditory Brainstem Response (ABR) and Distortion Product Otoacoustic Emission (DPOAE) showed functional abnormalities in the ear. Normal lifespan and fecundity of Atoh1(trhl) mice provide a complementary model to facilitate elucidation of ATOH1 function in hearing,central nervous system and cancer biology.
Fixed vestibular appliances decrease the "self-cleansing" action of saliva and promote aggregation of dental plaque by disturbing the salivary flow field on tooth surfaces, leading to a higher prevalence of enamel demineralization and periodontal diseases. In the current study, we investigated the salivary dynamic characteristics of plaque retention and periodontal status around appliances during orthodontic treatment. By reconstructing lower central incisors and orthodontic appliances, we simulated saliva flow on the tooth surface and then characterized and quantified the salivary flow pattern surrounding the bracket and archwire. In parallel, we tested the total peri-bracket bacterial counts and periodontal status to assess interrelations. Our results demonstrate that orthodontic appliances disturb the salivary flow field on tooth surfaces and can lead to a decrease in salivary velocity and an increase in bacterial numbers. Local vortexes forming in the areas gingival to the bracket, together with the narrow space limitation, contributed to the periodontal inflammatory response. This study confirms that changes in salivary flow are an obvious predisposing factor for bacterial accumulation, and advances the ability to replicate, in vitro, the salivary characteristics of plaque retention and periodontal status around appliances during orthodontic treatment.
Combretastatin A4 phosphate (CA4P) is currently undergoing clinical trials as a tumor vascular-targeting agent. Here, we defined the antivascular effect and programmed cell death (PCD) induced by CA4P in vascular endothelial cells. CA4P induced time- and dose-dependent antiproliferative activities against human umbilical vein endothelial cells (HUVECs), and caused G2/M arrest accompanied with DNA fragmentation. The in vitro wound assay and tube formation assay indicated that CA4P potently inhibited migration of endothelial cells and tube formation. The apoptosis and autophagy marker microtubule-associated protein light chain 3 (LC3)-II was induced in CA4P-treated HUVECs. The current study demonstrates that CA4P is a promising antivascular agent with potent PCD-inducing activities. CA4P may be useful in the treatment of cancer and hemangioma.
We previously reported that sodium depletion increased renin secretion from the normal kidney in mice. We postulated that the combined procedures of sodium depletion and ?-adrenoceptor blockade would affect the activity of the renin-angiotensin system. To test this hypothesis, we investigated the interaction of low sodium intake (LSI) and propranolol (PRO) on renin synthesis and secretion. To prevent the influence of tubule flow on renin secretion, mice with a left hydronephrotic kidney were used. LSI increased plasma renin concentration (PRC) 5.6-fold in the right renal vein (P<0.01). There was no net increase of PRC in the left renal vein. Tissue renin concentration (TRC) was elevated 3.6-fold and 1.3-fold in the right and left kidneys (P<0.01), respectively. After administration of PRO, PRC decreased by 34% in the right renal vein and 47% in the aorta (P<0.05); TRC was reduced by 37.5% in the right and 29.3% in the hydronephrotic kidneys (P<0.05). The combination of LSI and PRO increased PRC 3.4-fold and 1.8-fold in the right (P<0.01) and left renal veins (P<0.05), respectively. TRC increased 3.4-fold in the right (P<0.01) but only 61% in the left kidneys (P<0.05). The pattern in change of renin mRNA levels was similar to TRC but the absolute amount was smaller. There were correlations between PRC and renin mRNA, and between TRC and renin mRNA in both kidneys (P<0.001). Thus, LSI increased renin synthesis in both kidneys. However, there was no apparent renin secretion in the hydronephrotic kidney. PRO treatment suppressed renin synthesis and renin secretion, irrespective of hydronephrosis and LSI. The macula densa is critical for renin secretion under all of the circumstances studied.
Cervical ectopic thymus (CET), an embryological anomaly detected incidentally at autopsy, is rarely described in clinical patients. Furthermore, aberrant cervical thymic tissue is an infrequently reported cause of neck masses, and especially for pediatric patients. However, according to clinical work, it should be included in the differential diagnosis of neck masses, particularly for children patients. Thymic tissue rests can be found all along the route of thymic descent from the neck into the anterior mediastinum. In routine practice, the preoperative diagnosis of ectopic cervical thymus is seldom considered and it is often misdiagnosed as a possible tumor or as a lymph node, which leads to biopsy or surgical removal. Here, a case of ectopic thymic tissue was presented in the neck misdiagnosed as cystic hydroma (one type of lymphatic malformation). Our misdiagnosis was introduced, the literature about diagnosis and management controversy were reviewed in recent years.
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