Identification of HAGHL as a novel metabolic oncogene regulating human colorectal cancer progression.

PURPOSE: Cancer development remains the most challenging obstacle in colorectal cancer (CRC) treatment. The current study aims to identify and demonstrate novel oncogenes for CRC. METHODS: The CRC data of the Cancer Genome Atlas database and the Gene Expression Omnibus database were subjected to bioinformatics analysis to identify the novel potential diagnostic and prognostic biomarkers for CRC. Immunohistochemical assay, western blot, and quantitative PCR (qPCR) were used to analyze hydroxyacylglutathione hydrolase-like (HAGHL) gene expression in CRC tissues and cultured CRC cells. D-Lactate colorimetric assay was applied to determine concentration of D-lactate in supernatants from CRC tissues and cell culture medium. Cell counting kit-8 (CCK-8) assay, flow cytometry, tumor xenografts experiment, and TUNEL staining analysis were performed to evaluate the function of HAGHL in CRC. RESULTS: We comprehensively analyzed the CRC data of the Cancer Genome Atlas database and the Gene Expression Omnibus database, and identified several novel potential diagnostic and prognostic biomarkers for CRC, including HAGHL, DNTTIP1, DHX34, and AP1S3. The expression of HAGHL, the strongest oncogenic activity gene, is positively related to D-lactate levels in CRC tissues and negatively associated with patient prognosis. HAGHL downregulation suppressed the production of D-lactate and induced apoptosis, resulting in inhibition of cell proliferation in vitro. In vivo experiment showed that knockdown of HAGHL induced cell apoptosis and inhibited tumor growth. CONCLUSION: These findings suggest that HAGHL acts as a novel metabolic oncogene and demonstrate the underlying mechanism by which HAGHL regulates CRC progression, highlighting its utility as a diagnostic and prognostic factor and as a potential therapeutic target for the treatment of CRC.

Modeling of lactose enzymatic hydrolysis using Monte Carlo method

Background: Mathematical modeling is useful in the analysis, prediction, and optimization of an enzymatic process. Unlike the conventional modeling methods, Monte Carlo method has special advantages in providing representations of the molecule's spatial distribution. However, thus far, Monte Carlo modeling of enzymatic system is namely based on unimolecular basis, not suitable for practical applications. In this research, Monte Carlo modeling is performed for enzymatic hydrolysis of lactose for the purpose of real-time applications. Results: The enzyme hydrolysis of lactose, which is conformed to Michaelis­Menten kinetics, is modeled using the Monte Carlo modeling method, and the simulation results prove that the model predicts the reaction kinetics very well. Conclusions: Monte Carlo modeling method can be used to model enzymatic reactions in a simple way for real-time applications.

Impact of 1,25(OH) 2 D 3 on TG content in liver of rats with type 2 diabetes.

PURPOSE: To evaluate the effects of 1,25 dihydroxy vitamin D3 (1,25(OH)2D3) on the content of triglyceride (TG), as well as on the gene and protein expressions of adiponectin receptor 2 (AdipoR2), p38 mitogen-activated protein kinase (P38MAPK), and lipoprotein lipase (LPL) in the liver of rats with type 2 diabetes mellitus (T2DM) so as to provide theoretical basis for exploring the mechanism by which 1,25(OH)2D3 regulates TG. METHODS: Wistar rats were divided into four groups (n=25), with different treatments and detected the gene and protein expressions of AdipoR2, p38MAPK, and LPL in the liver tissue by reverse transcription polymerase chain reaction (RT-PCR) and Western blotting. Meanwhile, the content of TG in the liver tissue was detected by the Enzyme-linked immunosorbent assay. RESULTS: The expression of AdipoR2, p38MAPK, LPL gene and protein in the liver of VitD intervention group was significantly higher than that in T2DM group (P <0.05), while the TG content was significantly lower than that in T2DM group (P <0.05). CONCLUSION: 1,25(OH)2D3 can decrease the content of TG in the liver, and its mechanism may be achieved by upregulating the expressions of AdipoR2, p38MAPK, and LPL in the liver.

Impact of 1 25(OH) 2 D 3 on TG content in liver of rats with type 2 diabetes

Abstract Purpose: To evaluate the effects of 1,25 dihydroxy vitamin D3 (1,25(OH)2D3) on the content of triglyceride (TG), as well as on the gene and protein expressions of adiponectin receptor 2 (AdipoR2), p38 mitogen-activated protein kinase (P38MAPK), and lipoprotein lipase (LPL) in the liver of rats with type 2 diabetes mellitus (T2DM) so as to provide theoretical basis for exploring the mechanism by which 1,25(OH)2D3 regulates TG. Methods: Wistar rats were divided into four groups (n=25), with different treatments and detected the gene and protein expressions of AdipoR2, p38MAPK, and LPL in the liver tissue by reverse transcription polymerase chain reaction (RT-PCR) and Western blotting. Meanwhile, the content of TG in the liver tissue was detected by the Enzyme-linked immunosorbent assay. Results: The expression of AdipoR2, p38MAPK, LPL gene and protein in the liver of VitD intervention group was significantly higher than that in T2DM group (P <0.05), while the TG content was significantly lower than that in T2DM group (P <0.05). Conclusion: 1,25(OH)2D3 can decrease the content of TG in the liver, and its mechanism may be achieved by upregulating the expressions of AdipoR2, p38MAPK, and LPL in the liver.

Impact of 1, 25(OH) 2 D 3 on TG content in liver of rats with type 2 diabetes

Purpose: To evaluate the effects of 1,25 dihydroxy vitamin D3 (1,25(OH)2D3) on the content of triglyceride (TG), as well as on the gene and protein expressions of adiponectin receptor 2 (AdipoR2), p38 mitogen-activated protein kinase (P38MAPK), and lipoprotein lipase (LPL) in the liver of rats with type 2 diabetes mellitus (T2DM) so as to provide theoretical basis for exploring the mechanism by which 1,25(OH)2D3 regulates TG. Methods: Wistar rats were divided into four groups (n=25), with different treatments and detected the gene and protein expressions of AdipoR2, p38MAPK, and LPL in the liver tissue by reverse transcription polymerase chain reaction (RT-PCR) and Western blotting. Meanwhile, the content of TG in the liver tissue was detected by the Enzyme-linked immunosorbent assay. Results: The expression of AdipoR2, p38MAPK, LPL gene and protein in the liver of VitD intervention group was significantly higher than that in T2DM group (P<0.05), while the TG content was significantly lower than that in T2DM group (P<0.05). Conclusion: 1,25(OH)2D3 can decrease the content of TG in the liver, and its mechanism may be achieved by upregulating the expressions of AdipoR2, p38MAPK, and LPL in the liver.(AU)

Function of obturator prosthesis after maxillectomy and prosthetic obturator rehabilitation / Função da prótese obturadora após maxilectomia e reabilitação protética obturadora

ABSTRACT INTRODUCTION: Maxillary defects are usually rehabilitated by a prosthetic obturator. OBJECTIVE: This study aimed to evaluate the functioning of obturators prosthesis in patients with unilateral defects after maxillectomy. METHODS: Of 49 patients, 28 underwent to maxillectomy as a result of tumor ablative surgery, and acquired unilateral maxillary defects. Evaluation of the function was performed by applying the Obturator Functional Scale (OFS). RESULTS: From a total of 49 patients, 28 were treated as follows: 9 with a conventional retained obturator prosthesis (COP), 11 (39%) with an enhanced retentive obturator prosthesis with stud attachment (POP) and 8 (28%) with an enhanced retentive obturator prosthesis with magnetic attachment (POM). The mean OFS score was 80. Scores on functions of speech, swallowing and chewing reached statistical significances (p < 0.05) among these three subgroups. Comparing COP and MOP groups, the scores of OFS in the domains of "Speech-ability to speak in public" and "Swallowing-leakage with liquids" were significantly higher in AOP group. Comparing COP group, the scores of OFS in "Swallowing-leakage with solid" and "Chewing/eating" domains were increased significantly (p < 0.05) both in MOP and AOP groups. CONCLUSION: Obturator prosthesis improves oral function of patients after maxillary defects; the retention of the obturator prosthesis enhanced by the addition of attachments showed more benefits in oral function.

RESUMO INTRODUÇÃO: Em geral, os defeitos da maxila são reabilitados por uma prótese obturadora. OBJETIVO: O estudo avaliou o funcionamento da prótese obturadora em pacientes com defeitos unilaterais após maxilectomia. MÉTODO: De 49 pacientes, 28 foram submetidos a maxilectomia como cirurgia de ablação tumoral e tiveram como sequela defeitos maxilares unilaterais. A avaliação do funcionamento foi efetuada pela aplicação da Escala Funcional do Obturador (EFO). RESULTADOS: De um total de 49 pacientes, 28 foram tratados da seguinte forma: nove com prótese obturadora retentiva convencional (POC), 11 (39%) com prótese obturadora retentiva com fixação por pino (POP) e oito (28%) com prótese obturadora retentiva com fixação magnética (POM). O escore médio na EFO foi de 80. Os escores para funções da fala, deglutição e mastigação alcançaram significância estatística (p < 0,05) entre os três subgrupos. Na comparação entre os grupos POC e POM, os escores da EFO nos domínios da "Fala-capacidade de discursar em público" e "Deglutição-vazamento de líquidos" foram significativamente mais altos no grupo POP. Na comparação com o grupo POC, os escores da EFO nos domínios de "Deglutição-vazamento com sólido" e "Mastigação/ingestão" estavam significativamente aumentados (p < 0,05) nos grupos POM e POP. CONCLUSÃO: A prótese obturadora melhorou o funcionamento oral de pacientes com defeitos maxilares; a retenção da prótese obturadora reforçada pela adição de dispositivos de fixação demonstrou maiores benefícios na função oral.

Function of obturator prosthesis after maxillectomy and prosthetic obturator rehabilitation.

INTRODUCTION: Maxillary defects are usually rehabilitated by a prosthetic obturator. OBJECTIVE: This study aimed to evaluate the functioning of obturators prosthesis in patients with unilateral defects after maxillectomy. METHODS: Of 49 patients, 28 underwent to maxillectomy as a result of tumor ablative surgery, and acquired unilateral maxillary defects. Evaluation of the function was performed by applying the Obturator Functional Scale (OFS). RESULTS: From a total of 49 patients, 28 were treated as follows: 9 with a conventional retained obturator prosthesis (COP), 11 (39%) with an enhanced retentive obturator prosthesis with stud attachment (POP) and 8 (28%) with an enhanced retentive obturator prosthesis with magnetic attachment (POM). The mean OFS score was 80. Scores on functions of speech, swallowing and chewing reached statistical significances (p<0.05) among these three subgroups. Comparing COP and MOP groups, the scores of OFS in the domains of "Speech-ability to speak in public" and "Swallowing-leakage with liquids" were significantly higher in AOP group. Comparing COP group, the scores of OFS in "Swallowing-leakage with solid" and "Chewing/eating" domains were increased significantly (p<0.05) both in MOP and AOP groups. CONCLUSION: Obturator prosthesis improves oral function of patients after maxillary defects; the retention of the obturator prosthesis enhanced by the addition of attachments showed more benefits in oral function.

Loss of cytokeratin 20 and acquisition of thyroid transcription factor-1 expression in a merkel cell carcinoma metastasis to the brain.

Merkel cell carcinoma (MCC) is recognized by its morphologic features and by its classic immunophenotypic properties. Although MCCs demonstrating nonclassic immunoreactivities have been described, a case documenting a change in immunophenotype during the course of disease progression has not been previously reported. We report a case of MCC that initially demonstrated cytokeratin 20 positivity but lost expression in subsequent metastases. Likewise, thyroid transcription factor-1 was initially negative in the tumor but expression was present in metastatic lesions.

Analysis of batch and repeated fedbatch productions of Candida utilis cell mass using mathematical modeling method

Background: Candida utilis is widely used in bioindustry, and its cell mass needs to be produced in a cost effective way. Process optimization based on the experimental results is the major way to reduce the production cost. However, this process is expensive, time consuming and labor intensive. Mathematical modeling is a useful tool for process analysis and optimization. Furthermore, sufficient information can be obtained with fewer experiments by using the mathematical modeling, and some results can be predicted even without doing experiments. Results: In the present study, we performed the mathematical modeling and simulation for the cell mass production of Candida utilis based on limited batch and repeated fedbatch experiments. The model parameters were optimized using genetic algorithm (GA), and the processes were analyzed. Conclusions: Taken together, this newly developed method is efficient, labor saving and cost effective.