RESUMO
BACKGROUND: Rectal mucosal melanoma is a rare and highly aggressive disease. Common symptoms include anal pain, an anal mass, or bleeding. As such, the disease is usually detected on rectal examination of patients with other suspected anorectal diseases. However, due to its rarity and nonspecific symptoms, melanoma of the rectal mucosa is easily misdiagnosed. CASE SUMMARY: This report describes the case of a 58-year-old female patient who presented with a history of blood in her stool for the prior one or two months, without any identifiable cause. During colonoscopy, a bulge of approximately 2.2 cm × 2.0 cm was identified. Subsequently, the patient underwent endoscopic ultrasound (EUS) to characterize the depth of invasion of the lesions. EUS suggested a hypoechoic mucosal mass with involvement of the submucosal layer and heterogeneity of the internal echoes. Following surgical intervention, the excised tissue samples were examined and confirmed to be rectal malignant melanoma. The patient recovered well with no evidence of recurrence during follow-up. CONCLUSION: This case shows that colonoscopy with EUS and pathological examination can accurately diagnose rare cases of rectal mucosal melanoma.
RESUMO
The successful fabrication of the cTnI detection platform is very meaningful for instant diagnosis of the myocardialinjury and related cardiovascular diseases (CVDs). In this research work, the magnetic nanoparticles and aptamer collaboration with the Cas12a/crRNA are used for the electrochemical detection of cTnI. The aptamer is hybridized with its partially complementary DNA (probe 2, P2) and then is modified on the magnetic nanoparticles. In the presence of cTnI, the cTnI combines with the aptamer and P2 is released. The released P2 is hybridized with the crRNA and the trans-cleavage activity of CRISPR/Cas12a is triggered. Therefore, the methylene blue-modified DNA (probe1, P1) on the surface of the electrode is cleaved, resulting in the decrease of the electrochemical signal. Based on the synergy effect of the high specific target recognition of aptamer, target-specifically triggering trans-cleavage activity of CRISPR/Cas12a, as well as good separation ability of magnetic nanoparticles, the developed electrochemical biosensor enables to detect cTnI with high specificity and sensitivity. The detection limit is low down to 10 pg/mL with a linear range from 100 pg/mL to 50000 pg/mL. The developed sensing platform was successfully applied for the detection of cTnI in human serum. This fabricated CRISPR/Cas12a-based electrochemical biosensor can offer a valuable tool for the diagnosis, prognosis, and treatment of patient with CVDs.
Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Técnicas Biossensoriais/métodos , Sistemas CRISPR-Cas/genética , Técnicas Eletroquímicas/métodos , Humanos , Limite de Detecção , Troponina IRESUMO
The critical health risks caused by cadmium (Cd) via dietary exposure are commonly assessed by detecting Cd concentrations in foods. Differently, in this study, the bioaccessibility and bioavailability of Cd in major local harvests were introduced to assess the dietary exposure of local residents from a high-level environmental Cd region. The results indicated that certain Cd was released into the digestive juice after in vitro digestion with a bioaccessibility of 20-63% for rice and 3-32% for leafy vegetables, and the released portion was partially absorbed by Caco-2 cells with a bioavailability of 2-21% for rice and 0.2-13% for leafy vegetables. The results obtained from the toxicokinetic model revealed that the predicted urinary Cd values from the estimated daily intake (EDI) of Cd, which accounted for bioaccessibility and bioavailability, were consistent with the actual measured values, and the EDIs were considerably lower than the acceptable daily intake. This suggests that the bioaccessibility and bioavailability adjusted dietary Cd exposure should be more precise. The key issues addressed in our study implores that a potential health risk cannot be neglected in people with high consumption of rice from high-level zone.
Assuntos
Cádmio , Poluentes do Solo , Disponibilidade Biológica , Células CACO-2 , Cádmio/análise , Cádmio/toxicidade , Exposição Dietética , Contaminação de Alimentos/análise , Humanos , Poluentes do Solo/análise , Poluentes do Solo/toxicidadeRESUMO
Cytochrome P450 (CYP) 2A13 is mainly expressed in the respiratory system and has the ability to metabolize aflatoxin B(1) (AFB(1)). However, the role of CYP2A13-mediated AFB(1) metabolism and its consequences in human lung epithelial cell is not clear. Therefore, the objectives of this study were to investigate the significance of CYP2A13 in AFB(1)-induced cytotoxicity, DNA adducts, and apoptosis. To achieve these objectives, CYP2A13 was stably over-expressed in immortalized human bronchial epithelial BEAS-2B cells (B-2A13) and its significance in AFB(1)-induced cytotoxicity, DNA adducts, and apoptosis was compared to cells with stably expression of CYP1A2 (B-1A2), the predominant AFB(1) metabolizing enzyme in liver, as well as CYP2A6 (B-2A6) as controls. AFB(1) induced B-2A13 cytotoxicity and apoptosis in a dose- and time-dependent manner. The cytotoxic and apoptotic effects of AFB(1) were significantly remarkable in B-2A13 cells than those of B-1A2 and B-2A6 cells. The increased expression of pro-apoptotic proteins, such as C-PARP, C-caspase-3, and Bax, and decreased expression of anti-apoptotic proteins, such as caspase-3, Bcl-2, and p-Bad further confirmed the data of AFB(1)-induced cytotoxicity and apoptosis. Furthermore, increased DNA adduct was observed in B-2A13 after AFB(1) treatment as compared to B-1A2 cells and B-2A6 cells. Finally, treatment with nicotine, a competitor of AFB(1), and 8-methoxypsoralen (8-MOP), an inhibitor of CYP enzyme, further confirm the critical role of CYP2A13 in AFB(1)-induced cytotoxicity and apoptosis. Collectively, these findings suggest adverse effects of AFB(1) in respiratory diseases mediated by CYP2A13.
Assuntos
Aflatoxina B1/toxicidade , Apoptose/efeitos dos fármacos , Hidrocarboneto de Aril Hidroxilases/metabolismo , Brônquios/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Hidrocarboneto de Aril Hidroxilases/genética , Brônquios/enzimologia , Brônquios/patologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Adutos de DNA/metabolismo , Relação Dose-Resposta a Droga , Células Epiteliais/enzimologia , Células Epiteliais/patologia , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Plasmídeos , Fatores de Tempo , TransfecçãoRESUMO
Apoptosis is very common during various stages of mammalian germ cell development and differentiation, and the BCL2 gene is one of the most important apoptotic regulators. Although its genetic variants are reported to be involved in cancers and autoimmune diseases, little information is available regarding BCL2 polymorphisms in male spermatogenesis. In the present study, single nucleotide polymorphisms (SNPs) in coding regions of the BCL2 gene were examined in a hospital-based, case-control study including 198 infertile patients with idiopathic azoospermia and 183 fertile controls. Subsequently, a functional study was conducted for comparison of paclitaxel-induced cytotoxicity and apoptosis between the BCL2 variant and the wild type in vitro. Three SNPs were found in exon 2--A21G (rs1801018), G127A (rs1800477), and C300T (rs61733416)--with the latter first reported in the Han-Chinese population. The frequency of G127A (GA+AA) genotype was significantly lower in azoospermic, infertile men compared to the age-matched controls (P = 0.01). This genotype may confer a lower risk of azoospermia (adjusted odd ratio [OR] = 0.448, 95% confidence interval = 0.226-0.889). In addition, HeLa cells expressing the BCL2 Ala43Thr (G127A), similar to the control cells, were more sensitive to paclitaxel-induced cytotoxicity and apoptosis than those expressing wild-type BCL2. Consistently, the cleaved PARP and p-BCL2 proteins were subsequently increased after paclitaxel treatment, as also predicted by the bioinformatics analysis. Considering the decreased antiapoptotic function of BCL2, these results suggest that the Ala43Thr variant is associated with protection against azoospermia in the Han-Chinese population.
Assuntos
Azoospermia/genética , Genes bcl-2 , Espermatogênese/genética , Adulto , Antineoplásicos Fitogênicos/farmacologia , Apoptose/genética , Apoptose/fisiologia , Azoospermia/fisiopatologia , Estudos de Casos e Controles , Sobrevivência Celular/efeitos dos fármacos , Distribuição de Qui-Quadrado , China , DNA/química , DNA/genética , Variação Genética , Genótipo , Células HeLa , Humanos , Immunoblotting , Masculino , Paclitaxel/farmacologia , Reação em Cadeia da Polimerase , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNA , Espermatogênese/fisiologia , TransfecçãoRESUMO
OBJECTIVE: To establish new criteria of antibody detection for the diagnosis of cerebral cysticercosis in combining with imaging examinations for reducing the missed and neglected diagnosis of the disease. METHODS: 1,160 cases with adequate clinical data were collected for the study, among them all cases received antibody detection and computerized tomography(CT), 538 cases were examined by magnetic resonance imaging(MRI). Following the locations that cysticerci parasitized, the cases were grouped in four types of cerebral cysticercosis: 1,087 cases in brain parenchyma (93.7%), 42 cases in brain ventricles (3.6%), 22 cases in brain meninges (1.9%), and 9 mixed cases (0.8%). According to the number of cysticerci showed by imaging analysis, cases involving parenchyma were further divided as subgroups of slight, moderate, and heavy infection with 1-2, 3-9 and over 10 parasites, with 552 cases(50.8%), 443 cases (39.8%) and 102 cases (9.4%) respectively. IHA and ELISA were used for detecting antibodies in the sera. RESULTS: 635 cases showed an IHA titer of 1:8 and above (54.7%), 700 cases (60.3%) showed positive ELISA and 460 cases (39.7%) showed weak positive. In the group of light infection (552 cases), 94.7% showed an IHA titer of less than 1:8, only 29 cases (5.3%) with a titer of 1:8 and above; 94 cases (17%) showed positive ELISA and 458 cases (83%) were weak positive. In the groups of moderate and heavy infections, all cases showed IHA titer of 1:8 and over, and positive or weak positive ELISA. CONCLUSION: Antibody titers are positively relevant to the intensity of Cysticercus infection. Most cases with light infection showed a low IHA titer (less than 1:8) and a weak positive ELISA, a fact that these cases would have been missed by the immunological tests. Therefore, an integrated analysis of the results with immunological test and clinical imaging technique is important in diagnosing cerebral cysticercosis.