RESUMEN
A malária é um problema mundial de saúde, com 249 milhões de casos de infecção, ocasionando 608 mil mortes no ano de 2022. Causada pelo gênero Plasmodium, são cinco principais espécies causadoras da malária no ser humano, o Plasmodium malariae, Plasmodium ovale, Plasmodium knowlesi, Plasmodium vivax e Plasmodium falciparum sendo os dois últimos responsáveis pelo maior número de casos clínicos e mortes ao redor do mundo, transmitida pelo mosquito fêmea do gênero Anopheles durante o repasto sanguíneo. Sabe-se ainda que eritrócitos infectados por Plasmodium berghei ANKA causam alteração no citoesqueleto de actina, consequentemente levando a hiperpermeabiliade da barreira endotelial. Em experimentos in vitro, a imunofluorescência, foi observada alteração do citoesqueleto de actina em células estimuladas com eritrócitos parasitados por PbA (EP), em contrapartida, aquelas não estimuladas (NE) e estimuladas com eritrócitos não parasitados por PbA (EnP), não mostraram alterações no mesmo. Nos experimentos in vivo, ao observar dados coletados, sendo estes respiratórios (penh e frequência respiratória) e parasitemia coletados no 7º DPI, foi observado um mesmo padrão entre o experimento 1 e o experimento 2. Os animais infectados com 106 de eritrócitos infectados, foram alocados em dois grupos, sendo eles hiperparasitemia (HP) ou síndrome do desconforto respiratório agudo-associado a malária (SDRA/SDRA-MA) e comparados àqueles não infectados (NI). Os animais NI, não apresentam parasitemia, em contrapartida, os animais SDRA, tem maior parasitemia que os HP, visto que estes têm aumento em sua parasitemia após o 12º DPI, e assim seguem aumentando gradativamente até levar os animais a óbito.O penh tem o mesmo padrão que a parasitemia, os NI com penh mais baixa que os HPs e os SDRA, sendo dentre estes, o grupo SDRA o mais elevado. A frequência respiratória, por sua vez se apresenta mais elevada no grupo NI, sendo o grupo SDRAmenor que o HP, um achado tido como normal, visto que os pulmões de animais com SDRA sofrem maior dano que os HPs. Apesar de não apresentar um valor significativo, as imagens de gel SDS-PAGE (WB) mostram maior concentração da Septina 9 nos animais com SDRA em comparação com os HPs e com os NIs. O mesmo é observado na qRT-PCR, mesmo sem significância estatística, o valor mostrado nos gráficos temmaior concentração nos SDRA. Assim, a Septina 9 está presente nas CEPP, e, mesmo sem significância estatística, da mesma forma que está presente nas amostras de tecido pulmonar utilizadas no WB e qT-PCR. É hipotetizado ainda que esta proteína pode ser ativada e assim sofrer alteração em sua localização intracelular
Malaria is a global health problem, with 249 million cases of infection, causing 608 thousand deaths in the year 2022. Caused by the genus Plasmodium, there are five main species that cause malaria in humans, Plasmodium malariae, Plasmodium ovale, Plasmodium knowlesi, Plasmodium vivax and Plasmodium falciparum, the last two being responsible for the largest number of clinical cases and deaths around the world, transmitted by the female mosquito of the genus Anopheles during blood meal. It is also known that erythrocytes infected by Plasmodium berghei ANKA (PbA) cause changes in the actin cytoskeleton, consequently leading to hyperpermeability of the endothelial barrier. In in vitro experiments, immunofluorescence, changes in the actin cytoskeleton were observed in cells stimulated with erythrocytes parasitized by PbA (EP), in contrast, those not stimulated (NE) and stimulated with erythrocytes not parasitized by PbA (EnP), did not show changes the same. In the in vivo experiments, when observing collected data, these being respiratory (penh and respiratory frequency) and parasitemia collected on the 7th DPI, the same pattern was observed between experiment 1 and experiment 2. Animals infected with 106 infected erythrocytes were allocated into two groups, namely hyperparasitemia (HP) or malaria-associated acute respiratory distress syndrome (ARDS/ARDS-MA) and compared to those not infected (NI). NI animals do not present parasitemia, on the other hand, ARDS animals have greater parasitemia than HP animals, as the latter have an increase in their parasitemia after the 12th DPI, and thus continue to gradually increase until the animals die. the same pattern as parasitemia, NI with lower penh than HPs and ARDS, among these, the ARDS group being the highest. The respiratory rate, in turn, is higher in the NI group, with the ARDS group being lower than the HP, a finding considered normal, given that the lungs of animals with ARDS suffer greater damage than the HPs. Despite not showing a significant value, SDS-PAGE (WB) gel images show a higher concentration of Septin 9 in animals with ARDS compared to HPs and NIs. The same is observed in qRT-PCR, even without statistical significance, the value shown in the graphs has a higher concentration in ARDS. Thus, Septin 9 is present in CEPP, and, even without statistical significance, in the same way that it is present in lung tissue samples used in WB and qT-PCR. It is also hypothesized that this protein can be activated and thus undergo changes in its intracellular location
Asunto(s)
Animales , Masculino , Ratones , Síndrome de Dificultad Respiratoria del Recién Nacido/patología , Malaria/patología , Control Social Formal/clasificación , Técnicas In Vitro/métodos , Endotelio , Anopheles/clasificaciónRESUMEN
Objective:To investigate the clinical application value of plasma SEPT9 gene methylation combined with serum carcinoembryonic antigen (CEA) and carbohydrate antigen 724 (CA724) in the diagnosis of colorectal cancer.Methods:A total of 219 patients with colorectal diseases in Baoji Central Hospital and Yunnan Province New Kun Hua Hospital from May 2018 to October 2021 were selected, including 149 cases of colorectal cancer and 70 cases of colorectal polyp diagnosed by pathology. A total of 100 healthy people in the same period were selected as the healthy control group. The methylation of SEPT9 gene in plasma was measured by using real-time fluorescent polymerase chain reaction (PCR), and the levels of serum CEA and CA724 were measured by using electrochemiluminescence. The expressions of three indicators in each group were compared, and the effect of every single indicator and the combination of the three indicators on the diagnosis of colorectal cancer was analyzed by using receiver operating characteristic (ROC) curve.Results:The positive rate of SEPT9 gene methylation in colorectal cancer group (74.50%, 111/149) was higher than that in colorectal polyp group (22.86%, 16/70) and healthy control group (1.00%, 1/100), and the difference was statistically significant ( P < 0.001). The positive rate of CEA in colorectal cancer group (46.98%, 70/149) was higher than that in colorectal polyp group (40.00%, 28/70) and the healthy control group (3.00%, 3/100) and the difference was statistically significant ( P < 0.001). The positive rate of CA724 in colorectal cancer group (38.93%, 58/149) was higher than that in colorectal polyp group (32.86%, 23/70) and the healthy control group (2.00%, 2/100), and the difference was statistically significant ( P < 0.001). The area under the curve (AUC) of ROC of SEPT9 gene methylation, CEA and CA724 in the single diagnosis of colorectal cancer was 0.823 (95% CI 0.753-0.891), 0.788 (95% CI 0.725-0.852) and 0.689 (95% CI 0.624-0.754), respectively. The optimal cut-off Ct value of SEPT9 gene methylation in the diagnosis of colorectal cancer was 36.5, the sensitivity was 90.30%, and the positive predictive value was 84.68%, which were higher than those of CEA and CA724. The optimal cut-off value of CEA in the diagnosis of colorectal cancer was 8.80 ng/ml, and the specificity (77.50%) and negative predictive value (78.48%) were higher than those of SEPT9 gene methylation and CA724. The sensitivity (97.66%), positive predictive value (93.98%), negative predictive value (81.25%) and AUC (0.846, 95% CI 0.749-0.944) of the combined detection of the three indexes taking the optimal cut-off value of every single indicator were higher than those of the single indicator. Conclusions:The combined detection of plasma SEPT9 gene methylation, CEA and CA724 in the diagnosis of colorectal cancer has high sensitivity and accuracy. The three combined detection can complement each other and improve the diagnostic efficiency, which is of high clinical value for the diagnosis of colorectal cancer.
RESUMEN
Objective@#To explore the expression and clinical significance of plasma methylated Septin9 gene (mSEPT9) in patients with gastric cancer.@*Methods@#From March to October in 2018, 380 patients visited Xijing Hospital of Digestive Diseases were selected. The patients were divided into gastric cancer (GC) group, atrophic gastritis (AG) group and non-atrophic gastritis (NAG) group. The positive expression rate of plasma circulating mSEPT9 of the three groups were detected by polymerase chain reaction (PCR) fluorescence probe method, its correlation with clinicopathological characteristics of gastric cancer were analyzed and also compared with the positive rate of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9). Chi-square test and continuity correction chi-square test were performed for statistical analysis.@*Results@#The actual number of valid samples was 357 including 147 of GC group, 83 of AG group and 127 of NAG group. The positive rate of plasma mSEPT9 of GC group was higher than those of AG group and NAG group (46.9%, 69/147 vs. 4.8%, 4/83 and 3.9%, 5/127), and the differences were statistically significant (χ2=43.438 and 63.912, both P<0.016). The sensitivity and specificity of plasma mSEPT9 in patients with gastric cancers were 46.9%(69/147) and 95.7%(201/210), respectively. The positive rate of mSEPT9 was higher in gastric cancer patients with tumor maximum diameter over 5.0 cm, intestinal-type gastric cancer in Lauren classification, lymphatic metastasis, vascular and neurological invasion, middle-late stage (stage Ⅲ and Ⅳ) in clinical classification, which were 57.6% (38/66) vs. 35.6% (26/73), 52.6%(51/97) vs. 31.0% (13/42), 53.0% (61/115) vs. 25.0% (8/32), 55.6% (65/117) vs. 13.3% (4/30), 50.8% (65/128) vs. 4/19 and 53.5% (61/114) vs. 24.2% (8/33), respectively; and the differences were statistically significant (χ2=6.728, 5.517, 7.905, 17.091, 5.871 and 8.998, all P<0.05). The positive rate of plasma mSEPT9 in gastric cancer patients was higher than those of CEA and CA19-9 (46.9%, 69/147 vs. 32.0%, 47/147 and 17.7%, 26/147, respectively), and the differences were statistically significant (χ2=6.892 and 17.437, both P<0.016).@*Conclusions@#The positive expression of plasma mSEPT9 in gastric cancer patients has not only high sensitivity but good specificity as well, and it is also related to the clinical stage. The detection of this gene may have important clinical significance in non-invasive diagnosis and prognosis evaluation in patients with advanced gastric cancer.
RESUMEN
Background: SEPT9 gene methylation is a specific biomarker of colorectal cancer, and its peripheral blood expression level can assess the risk of colorectal cancer. Aims: To investigate the clinical significance of detection of peripheral blood SEPT9 gene methylation and glycoprotein tumor markers in the diagnosis of colorectal cancer. Methods: A total of 57 normal controls, 61 colorectal adenoma and 71 colorectal cancer patients from Dec. 2016 to Apr. 2017 at the First Affiliated Hospital of Soochow University were enrolled. The peripheral blood SEPT9 gene methylation was detected by PCR fluorescence probe method, and levels of tumor markers CEA, CA125, CA19-9, CA72-4 and CA211 were determined. ROC curve was used to analyze the diagnostic value of above-mentioned indices for colorectal cancer. Logistic regression equation was established and used to evaluate the diagnostic value of SEPT9 gene combined with CEA. Results: The positivity rates of SEPT9 gene methylation in normal control group, adenoma group and colorectal cancer group were 0, 6.6% and 52.1%, respectively. CEA level in colorectal cancer group was significantly higher than that in normal control group and adenoma group (P<0.05). ROC curve analysis showed that AUC of SEPT9, CEA, combination of the two indicators for the diagnosis of colorectal cancer were 0.817, 0.707 and 0.793, respectively. Logistic regression analysis showed that the OR of SEPT9 and CEA for the diagnosis of colorectal cancer were 1.394 (1.198-1.762) and 1.325 (0.997-1.622), respectively. Conclusions: The positivity rate of peripheral blood SEPT9 gene methylation is significantly increased with the progress of disease, and the diagnostic value for colorectal cancer is high. The combination of peripheral blood SEPT9 gene methylation and CEA is helpful for improving the early screening rate of colorectal cancer.
RESUMEN
Objective To explore the expression and clinical significance of plasma methylated Septin 9 gene ( mSEPT9) in patients with gastric cancer .Methods From March to October in 2018, 380 patients visited Xijing Hospital of Digestive Diseases were selected .The patients were divided into gastric cancer (GC) group, atrophic gastritis (AG) group and non-atrophic gastritis (NAG) group.The positive expression rate of plasma circulating mSEPT9 of the three groups were detected by polymerase chain reaction (PCR) fluorescence probe method, its correlation with clinicopathological characteristics of gastric cancer were analyzed and also compared with the positive rate of carcinoembryonic antigen ( CEA), carbohydrate antigen 19-9 ( CA19-9). Chi-square test and continuity correction chi-square test were performed for statistical analysis .Results The actual number of valid samples was 357 including 147 of GC group, 83 of AG group and 127 of NAG group.The positive rate of plasma mSEPT9 of GC group was higher than those of AG group and NAG group (46.9%, 69/ 147 vs.4.8%, 4/83 and 3.9%, 5/127), and the differences were statistically significant ( χ2 ＝43.438 and 63.912, both P?0.016).The sensitivity and specificity of plasma m SEPT9 in patients with gastric cancers were 46.9%(69/147) and 95.7%(201/210), respectively.The positive rate of mSEPT9 was higher in gastric cancer patients with tumor maximum diameter over 5.0 cm, intestinal-type gastric cancer in Lauren classification, lymphatic metastasis, vascular and neurological invasion , middle-late stage (stageⅢandⅣ) in clinical classification, which were 57.6%(38/66) vs.35.6%(26/73), 52.6%(51/97) vs.31.0%(13/42), 53.0%(61/115) vs.25.0%(8/32), 55.6%(65/117) vs.13.3%(4/30), 50.8%(65/128) vs. 4/19 and 53.5%(61/114) vs.24.2%(8/33), respectively; and the differences were statistically significant (χ2 ＝6.728, 5.517, 7.905, 17.091, 5.871 and 8.998, all P?0.05).The positive rate of plasma mSEPT9 in gastric cancer patients was higher than those of CEA and CA 19-9 (46.9%, 69/147 vs.32.0%, 47/147 and 17.7%, 26/147, respectively), and the differences were statistically significant (χ2 ＝6.892 and 17.437, both P?0.016).Conclusions The positive expression of plasma m SEPT9 in gastric cancer patients has not only high sensitivity but good specificity as well , and it is also related to the clinical stage .The detection of this gene may have important clinical significance in non-invasive diagnosis and prognosis evaluation in patients with advanced gastric cancer .
RESUMEN
SEPT9 gene belongs to a member of SEPT gene family.In recent years,it has been found that SEPT9 gene is highly methylated in colorectal cancer cells.Detecting SEPT9 gene methylation in the development of colorectal cancer,the application of different specimen types for the detection of SEPT9 gene methylation and the development of SEPT9 gene methylation detection methods can provide evidence for early diagnosis of colorectal cancer.
RESUMEN
The early detection and diagnosis of colorectal cancer (CRC)is of great clinical importance. Peripheral blood methylated SEPT9 gene was found to be a sensitive and specific biomarker for CRC and was superior to other commonly used screening methods such as fecal occult blood test,serum tumor markers and colonoscopy in a variety of studies. But it is of limited value in screening of adenomas,polyps and other precursors of CRC,and its capacities for assessment of cancer recurrence and therapeutic effects of radiotherapy and chemotherapy need further clinical validation. This article reviewed the progress in application of peripheral blood methylated SEPT9 gene assay for CRC screening.
RESUMEN
The early detection and diagnosis of colorectal cancer (CRC)is of great clinical importance. Peripheral blood methylated SEPT9 gene was found to be a sensitive and specific biomarker for CRC and was superior to other commonly used screening methods such as fecal occult blood test,serum tumor markers and colonoscopy in a variety of studies. But it is of limited value in screening of adenomas,polyps and other precursors of CRC,and its capacities for assessment of cancer recurrence and therapeutic effects of radiotherapy and chemotherapy need further clinical validation. This article reviewed the progress in application of peripheral blood methylated SEPT9 gene assay for CRC screening.
RESUMEN
Colorectal cancer (CRC) is one of the most common gastrointestinal malignancies with poor prognosis and high mortality.SEPT9 gene is a tumor suppressor gene and plays an important role in the end of cell division.Studies have shown that methylation of SEPT9 gene could be used in the early diagnosis of CRC.This article reviewed the advances in study on SEPT9 gene methylation in the screening and diagnosis of CRC.
RESUMEN
Objective To evaluate the significance of detecting plasma methylated Septin9 (SEPT9) alone and combined with fecal immunochemical test (FIT) in screening colorectal cancer (CRC) and adenoma.Methods From October 2014 to April 2015,outpatients received CRC and adenoma screening were enrolled.Colonscopy examination and pathological diagnosis were taken as gold standard.The sensitivity and specificity of plasma methylated SEPT9 and FIT in CRC and adenoma were calculated.The diagnostic value of combined examination was evaluated.Receiver operating characteristic (ROC) curve of SEPT9 in CRC diagnosis was drawn.Results A total of 300 outpatients were enrolled.Among them,CRC was detected in 45 patients (15.0％) and adenoma was detected in 68(22.7％) patients,including 37(12.3％) cases of advanced adenomas.The sensitivity of SEPT9 and FIT for CRC diagnosis was 80.0％ and 88.9％,and the specificity was 95.3 ％ and 54.1％,respectively.The area under concentration curve (AUC) of methylated SEPT9 in CRC diagnosis was 0.923.The sensitivity of SEPT9 and FIT in advanced adenoma diagnosis were 10.8％ and 62.2％,and the specificity were 83.3％ and 49.0％,respectively.The sensitivity of combined examination in CRC diagnosis was 97.8％ and the specificity was 52.9％;the sensitivity in advanced adenoma diagnosis was 67.6％ and the specificity was 47.4％.Conclusions Plasma methylated SEPT9 is helpful in CRC screening,moreover,when combined with FIT,it can increase detection rate of colorectal adenoma.
RESUMEN
Objective To investigate the value of detecting methylated SEPT9 gene (mSEPT9) in serum and stool in screening colorectal cancer in elderly people.Methods Subjects were divided into three groups, the colorectal cancer group (n=82), the colorectal polyps group (n=80) and the healthy control group (n=100).Real-time quantitative polymerase chain reaction (PCR) was used to detect mSEPT9 in peripheral blood and feces.The relationship between mSEPT9 and clinical and pathological characteristics of colorectal cancer was analyzed.The agreement between serum and stool results was analyzed.Results The positive rate of serum mSEPT9 was 73.2％ in the colorectal cancer group, 6.3％ in the colorectal polyps group and 4.0％ in the healthy control group, with statistical significance between the colorectal cancer group and the other two groups (P＜0.01).The sensitivity and specificity for plasma mSEPT9 detection in screening colorectal cancer were 73.2 ％ and 95.6％, respectively.The positive rate was higher in patients with tumor maximum diameter over 3.0 cm, invasion of the entire serosa layer, lower differentiation or advanced clinical staging (P＜0.05).The detection results of plasma mSEPT9 were in complete agreement with those of stool mSEPT9 from the same patients.Conclusions The expression of mSEPT9 is high in elderly patients with colorectal cancer and has a high sensitivity and specificity for PCR detection.Complete agreement can be seen in results from plasma and feces.Detecting mSEPT9 can be a valuable approach to screening colorectal cancer in the elderly.
RESUMEN
Colorectal cancer is a malignancy with poor prognosis and high mortality and is caused by multiple factors. Colonoscopy,flexible sigmoidoscopy,guaiac-based fecal occult blood test,immunochemical fecal occult blood test,fecal DNA test,CT colonoscopy and serum carcinoembryonic antigen test are the methods frequently used for screening of colorectal cancer,but they all have certain limitations. Elevation of methylation of SEPT9 is associated with the pathogenesis of colorectal cancer,and detection of the level of methylation of SEPT9 in peripheral blood can be used for screening of colorectal cancer in susceptible population. This article reviewed the application of peripheral blood SEPT9 DNA methylation assay for screening of colorectal cancer.