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A 3-year-6-month-old boy presented with multiple asymptomatic banded white macules at birth, which expanded in proportion to his body, and deformity of his right thumb with slight dyskinesia. The patient showed difficulty in communication and concentration compared with children of the same age. The family history was unremarkable. The child had clear consciousness, passable spirits, and poor language ability. Physical examination revealed a special face and slight macrodactyly of the right thumb joints, and the heart, lung, and abdominal examination was otherwise normal. Skin examination showed multiple banded or confluent irregular white macules of varying sizes and slightly elevated plaques distributed along the Blaschko′s lines on the right chest, the flexor aspect of the right upper limb, the median line of the lower abdomen, and the right lower limbs, and banded brown macules on the palmar side of the right hand and radial aspect of the right thumb. Histopathological findings of the while macule on the lower limb were consistent with basaloid follicular hamartoma. Cranial magnetic resonance imaging revealed agenesis of the corpus callosum. Whole-exome sequencing of the lesional tissue showed a mutation c.1234C>T (p.L412F) in the SMO gene, which was not found in his parents. A diagnosis of Curry-Jones syndrome was made based on the skin lesions, and pathological and genetic findings. The mutation c.1234C>T (p.L412F) in the SMO gene may contribute to the disease. The patient continued functional exercises to improve the mobility of his right thumb, and underwent a close follow-up.
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The unique characteristics of 2-dimensional hetero structure offers efficient gas sensing with high selectivity to identify gases from the interference gases which is quite difficult. In the present work, ZnO: SnO2Nano composite clusters (NCC) is prepared. A resistive metal oxide volatile organic compound (VOC) gas sensor is fabricated with nullifying the effect of humidity by increasing temperature optimally. A single-step SOL-GEL (SG) synthesis is used to prepare ZnO: SnO2 NCC with maximum Zn/Sn molar concentration ratio of 3. The morphological studies through Scanning Electron Microscopy (SEM), electrical properties due to oxygen vacancies and energy band variations of Nanocomposite are measured. The enhancement of gas sensor sensitivity due to highly mesoporous nature of the composite is observed. From the findings, the abundant mesopores in the range of 2 nm-14 nm and specific surface area of 54.2 m2 g?1 with the average crystal size of 14.236 nm, and polar surface area of the composite 25.9651Åis achieved. When compared to bare ZnO and SnO2 gas sensors, the present gas sensor offers the higher selectivity with enhanced performance due to the mesoporous structure. Fast repeatability rate of 2200 sec at 350?C to ethanol is attained and the overall selectivity of the sensor increased twice as 2.085. The NCC compound is tested firstly with micro organisms such as B. subtilis (B. S), Bacillus cereus (B. C), B. coagulans (B. C), Pseudonymous auriginosa (P. A) are considered for antimicrobial activity. From the findings, zinc stannate compound showed good efficacy towards B. cereus Gram positive and P.A gram-negative. A bacterial growth is arrested highly with B. cereus.
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@#Introduction: Hedgehog (HH) pathway is an important signalling cascade for growth and patterning during embryonic development. Constitutive activation of Hedgehog pathway can be found in various types of malignancies including medulloblastoma, basal cell carcinoma, gastrointestinal, breast, pancreatic, prostate cancer and leukaemia. Little is known about the expression and role of Hedgehog signalling in bladder cancer. Materials and Methods: The purpose of this study was to investigate the immunohistochemical expression of SMO in 112 bladder cancer cases and determine their association with demographic and clinicopathological parameters. Bladder cancer tissues were obtained from the Hospital Kuala Lumpur. Results: SMO was expressed in the cytoplasm of all cases of bladder cancer. 6 cases (5.4%) showed low expression, while 106 cases (94.6%) showed high expression. Positive expression of SMO protein was correlated with a few variables which include grade and stage of tumour, lymph node metastasis and distant metastasis. SMO expression showed statistically significant association with higher grade (p=0.001) and higher stage (p=0.042) of bladder cancer. SMO expression also showed borderline association with lymph node metastasis (p=0.056). Conclusion: These findings indicate that SMO expression may be a poor prognostic marker in bladder cancer.
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Aim To investigate the effects of a novel spermine oxidase (SMO) inhibitor SI-4650 on proliferation, apoptosis and autophagy of human glioma U87MG cells as well as its possible mechanism. Methods MIT assay was used to detect cell proliferation. The chemiluminescence assay was used to determine enzyme activities of SMO and N'-acetylpolyamine oxidase (APAO). High performance liquid chromatography (HPI.C) was performed to detect cellular polyamine content. Transwell assay was used to evaluate the migration ability of U87MG cells. PI single-staining/flow cytometry( FCM ) were used to analyze cell cycle. PI/ FITC-Annexin V double-staining/ FCM and Western blot were used to analyze apoptosis. Confocal laser scanning microscopy ( LSCM) and Western blot were used to analyze autophagy. Results SI-4650 could significantly inhibit the activities of SMO and APAO, interfere with polyamine metabolism and reduce the content of total polyamine in U87MG cells. Treatment of U87MG cells with SI-4650 inhibited the proliferation and migration, caused G0/G, cell cycle arrest and induced apoptotic and autophagic cell death. Conclusions SI-4650 has the pharmacological activity of killing glioma U87MG cells, and its mechanism may be related to the interference of polyamine metabolism and induction of cell apoptosis and autophagy.
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Objective To study the mechanism of the Hedgehog signaling transduction intervened by polypeptide extract from scorpion venom (PESV) on K562/BALB/c-nu leukemia mice. Trying to analyze the molecular mechanisms and targets of the inhibited effect of PESV on chronic myeloid leukemia (CML) in vivo. Methods After establishing the K562/BALB/c-nu leukemia mice successfully, the model mice were divided into six groups which were the blank group, the PESV high, medium, and low doses (0.3, 0.6, 1.2 mg/kg) group, the Imatinib (50 mg/kg) group, and the model group. After 14 d drug intervention, the levels of gene and protein expression of Hedgehog signaling pathway upstream factors Shh, Ptch, and Smo were detected by qRT-PCR and Western blotting, and the protein expression of downstream factor Gli1 was determined by ELISA test. Results Compared to the model group, the genetic and protein expression of Shh which was an upstream factor were increased in the PESV groups. The mRNA and protein expression of Ptch and Smo in PESV low-dose and medium-dose groups were decreased. There were no significant differences of upstream factors between Imatinib group and model group. The concentration of downstream Gli1 protein significantly decreased within low-dose and medium-dose PESV groups, while there was no significant difference between high-dose PESV group and Imatinib group. Conclusion PESV can inhibit the expression of Hedgehog signaling pathway upstream factor Ptch, Smo and downstream factor Gli1 on the mRNA and protein level, while Imatinib has no obvious inhibitory effect on the Hedgehog signaling pathway.
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<p><b>OBJECTIVE</b>To evaluate whether mono (2-ethylhexyl) phthalate (MEHP) affects genomic DNA methylation and the methylation status of some specific genes such as patched gene (PTCH) and smoothened gene (SMO) in LNCaP cells.</p><p><b>METHODS</b>LNCaP cells were treated with MEHP (0, 1, 5, 10, and 25 μmol/L) for 3 days. An ELISA assay was preformed to detect genomic methylation, including 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) content. A pyrosequencing assay was applied to assess DNA methylation in PTCH and SMO gene promoters. The correlation between DNA methylation and gene expression was assessed.</p><p><b>RESULTS</b>The proportion of cytosines with 5-mC methylation in LNCaP cells was significantly decreased by MEHP (1, 5, 10, and 25 μmol/L) in a dose-dependent manner (P < 0.01). For genes in the Hedgehog pathway, there was no significant MEHP concentration-dependent difference in the DNA methylation of PTCH and SMO.</p><p><b>CONCLUSION</b>MEHP might affect the progression of prostate cancer through its effect on global DNA methylation.</p>
Subject(s)
Humans , Male , Antineoplastic Agents , Chemistry , Pharmacology , Cell Line, Tumor , DNA Methylation , Phthalic Acids , Chemistry , Prostatic Neoplasms , MetabolismABSTRACT
Introduction: The Hedgehog (Hh) signalling pathway is a developmental signalling pathway involved in normal mammalian developmental and homeostasis of adult renewable tissues. In most adult tissues, this pathway remains silent and previous studies have shown that constitutive activation of Hedgehog signalling pathway leads to various types of malignancies including medulloblastomas, basal cell carcinoma, gastrointestinal, breast and prostate cancer. The purpose of this study was to investigate the immunohistochemical expression of Hedgehog pathway proteins in Diffuse Large B-cell Lymphoma and determine their association with overall survival (OS). Methods: Positive control using normal tonsils were included in each batch of immunohistochemical staining procedure. Results: PTCH1 proteins were highly expressed in DLBCL and showed strong staining intensity in 107 (100%) cases and SMO proteins were expressed in 105 (98.1%) cases. PTCH1 proteins were localised in the nucleus of tumour cells, whereas SMO proteins were mainly localised in the cytoplasm of tumour cells. Positive expression of PTCH1 and SMO proteins and overall survival of DLBCL patients were correlated with age, gender, race and tumour location. There was no significant correlation between the expression of these two proteins with any of the parameters. PTCH1 expression showed significant association with SMO expression (P=0.03). Conclusions: Our findings suggest that high expression of both PTCH1 and SMO may be important in the pathogenesis of DLBCL. However, additional mechanisms that may contribute to the activation of HH signalling in DLBCL needs to be further explored.
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AIM:To investigate the effect of Hedgehog(Hh) signaling pathway on the viability and apoptosis of cervical carcinoma cells by shRNA technique to knock down Smoothened (Smo) gene. METHODS:Smo shRNA was used to transfect the cervical carcinoma HeLa cells. The expression of Smo and Gli1 at mRNA and protein levels in the He-La cells was determined by RT-PCR and Western blot,respectively. The effect of Smo gene silencing on the growth of the cells was measured by MTT assay. The apoptosis and cell cycle were determined by flow cytometry. RESULTS:Compared with control group,the mRNA and protein expression of Smo and Gli1 were evenly reduced obviously after transfected with Smo shRNA for 72 h(P<0.05). The viability of HeLa cells transfected with Smo shRNA was significantly inhibited. The percentages of the cells in G0/G1phase and early apoptosis rate were obviously higher in Smo shRNA transfection group than those in control group. CONCLUSION:Smo gene silencing effectively inhibits the cell growth and induces the apop-tosis of human cervical carcinoma cells.
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AIM To investigate the effect of ke tamine on ATP-sensitive K + currents (I K ATP ) in single airway smooth muscle (ASM) cells of asthmatic rat. METHODS Single ASM cells of asthmatic rat were isolated with enzymatic dissociation technique. Effect of ketamine on I K ATP in single ASM cells was studied using the whole-cell configu ration of patch clamp technique. RESULTS Ketamine opened the ATP -sensitive K + channel (K ATP channel) in a dose-dependent manner. When the concentrations of ketamine were 1?10 -7 ,1?10 -6 ,1?10 -5 and 1?10 -4 mol?L -1 , the amplitude values of I K ATP were increased to 63 86?19 33 pA/pF(n=8,P