RESUMO
Arginine rich, mutated in early stage of tumours (Armet), is a well-characterized bifunctional protein as an unfolded protein response component intracellularly and a neurotrophic factor extracellularly in mammals. Recently, a new role of Armet as an effector protein mediating insect-plant interactions has been reported; however, its molecular mechanisms underlying the regulation of plant defences remain unclear. We investigated the molecular mechanisms underlying whitefly-secreted Armet-mediated regulation of insect-plant interaction by agrobacterium-mediated transient expression, RNA interference, electrical penetration graph, protein-protein interaction studies, virus-induced gene silencing assay, phytohormone analysis and whitefly bioassays. Armet, secreted by Bemisia tabaci whitefly, is highly expressed in the primary salivary gland and is delivered into tobacco plants during feeding. Overexpression of the BtArmet gene in tobacco enhanced whitefly performance, while silencing the BtArmet gene in whitefly interrupted whitefly feeding and suppressed whitefly performance on tobacco plants. BtArmet was shown to interact with NtCYS6, a cystatin protein essential for tobacco anti-whitefly resistance, and counteract the negative effects of NtCYS6 on whitefly. These results indicate that BtArmet is a salivary effector and acts to promote whitefly performance on tobacco plants through binding to the tobacco cystatin NtCYS6. Our findings provide novel insight into whitefly-plant interactions.
Assuntos
Cistatinas , Hemípteros , Neoplasias , Animais , Arginina/metabolismo , Cistatinas/análise , Cistatinas/metabolismo , Hemípteros/fisiologia , Mamíferos , Neoplasias/metabolismo , Plantas , Saliva/metabolismo , Nicotiana/genética , Nicotiana/metabolismoRESUMO
Phloem-feeding insects feed on plant phloem using their stylets. While ingesting phloem sap, these insects secrete saliva to circumvent plant defenses. Previous studies have shown that, to facilitate their feeding, many phloem-feeding insects can elicit the salicylic acid- (SA-) signaling pathway and thus suppress effective jasmonic acid defenses. However, the molecular basis for the regulation of the plant's defense by phloem-feeding insects remains largely unknown. Here, we show that Bt56, a whitefly-secreted low molecular weight salivary protein, is highly expressed in the whitefly primary salivary gland and is delivered into host plants during feeding. Overexpression of the Bt56 gene in planta promotes susceptibility of tobacco to the whitefly and elicits the SA-signaling pathway. In contrast, silencing the whitefly Bt56 gene significantly decreases whitefly performance on host plants and interrupts whitefly phloem feeding with whiteflies losing the ability to activate the SA pathway. Protein-protein interaction assays show that the Bt56 protein directly interacts with a tobacco KNOTTED 1-like homeobox transcription factor that decreases whitefly performance and suppresses whitefly-induced SA accumulation. The Bt56 orthologous genes are highly conserved but differentially expressed in different species of whiteflies. In conclusion, Bt56 is a key salivary effector that promotes whitefly performance by eliciting salicylic acid-signaling pathway.
Assuntos
Hemípteros/metabolismo , Herbivoria/fisiologia , Ácido Salicílico/metabolismo , Saliva/metabolismo , Transdução de Sinais/fisiologia , Animais , Proteínas de Homeodomínio/metabolismo , Proteínas de Plantas/metabolismoRESUMO
BACKGROUND: Plant viruses in agricultural crops are of great concern worldwide, and over 75% of them are transmitted from infected to healthy plants by insect vectors. Tomato yellow leaf curl virus (TYLCV) is a begomovirus, which is the largest and most economically important group of plant viruses, transmitted by the whitefly Bemisia tabaci. The circulation of TYLCV in the insect involves complex insect-virus interactions, whereas the molecular mechanisms of these interactions remain ambiguous. The insect gut as a barrier for viral entry and dissemination is thought to regulate the vector specificity. However, due to its tiny size, information for the responses of whitefly gut to virus infection is limited. METHODS: We investigated the transcriptional response of the gut of B. tabaci Middle East-Asia Minor 1 species to TYLCV infection using Illumina sequencing. RESULTS: A total of 5207 differentially expressed genes (DEGs) between viruliferous and non-viruliferous whitefly guts were identified. Enrichment analyses showed that cargo receptor and ATP-binding cassette (ABC) transporters were enriched in DEGs, and might help the virus to cross gut barrier. TYLCV could perturb cell cycle and DNA repair as a possible result of its replication in the whitefly. Our data also demonstrated that TYLCV can activate whitefly defense responses, such as antimicrobial peptides. Meanwhile, a number of genes involved in intracellular signaling were activated by TYLCV infection. CONCLUSIONS: Our results reveal the complex insect-virus relationship in whitefly gut and provide substantial molecular information for the role of insect midguts in virus transmission.
Assuntos
Begomovirus , Trato Gastrointestinal/metabolismo , Trato Gastrointestinal/virologia , Hemípteros/genética , Hemípteros/virologia , Interações Hospedeiro-Patógeno/genética , Transcriptoma , Animais , Biologia Computacional/métodos , Perfilação da Expressão Gênica , Ontologia Genética , Sequenciamento de Nucleotídeos em Larga Escala , Anotação de Sequência Molecular , Vírus de Plantas , Reprodutibilidade dos TestesRESUMO
Cycloaddition reactions play a pivotal role in synthetic chemistry for the direct assembly of cyclic architectures. However, hurdles remain for extending the C4 synthon to construct diverse heterocycles via programmable [4+n]-cycloaddition. Here we report an atom-economic and modular intermolecular cycloaddition using furan-fused cyclobutanones (FCBs) as a versatile C4 synthon. In contrast to the well-documented cycloaddition of benzocyclobutenones, this is a complementary version using FCB as a C4 reagent. It involves a C-C bond activation and cycloaddition sequence, including a Rh-catalyzed enantioselective [4 + 2]-cycloaddition with imines and an Au-catalyzed diastereoselective [4 + 4]-cycloaddition with anthranils. The obtained furan-fused lactams, which are pivotal motifs that present in many natural products, bioactive molecules, and materials, are inaccessible or difficult to prepare by other methods. Preliminary antitumor activity study indicates that 6e and 6 f exhibit high anticancer potency against colon cancer cells (HCT-116, IC50 = 0.50 ± 0.05 µM) and esophageal squamous cell carcinoma cells (KYSE-520, IC50 = 0.89 ± 0.13 µM), respectively.
Assuntos
Reação de Cicloadição , Ciclobutanos , Furanos , Catálise , Ciclobutanos/química , Humanos , Furanos/química , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Linhagem Celular Tumoral , Estereoisomerismo , Células HCT116RESUMO
Realization of low temperature and high efficiency oxidation of CaSO3 is the key to solve the issue of ecological hazards caused by semi-dry sintering flue gas desulfurization ash. The subcritical hydrothermal technology was employed for the oxidation of CaSO3, achieving 89.83% of CaSO3 at 180 °C, 2 MPa for 120 min with a solid-to-liquid ratio of 1:20. The macroscopic oxidation kinetics of CaSO3 in the subcritical hydrothermal reaction system was investigated. A mathematical model was established, incorporating the intrinsic reaction, CaSO3 dissolution, oxygen diffusion and CaSO4 precipitation. It was concluded that the macroscopic oxidation of CaSO3 was co-controlled by the oxygen diffusion and CaSO4 precipitation. Subcritical hydrothermal technology promises not only higher efficiency, but more importantly, potentially "one-step" preparation of CaSO4 whiskers, enabling cost-effective and high value-added resource utilization of the semi-dry FGD ash.
Assuntos
Temperatura Baixa , Ferro , Cinética , Oxirredução , OxigênioRESUMO
Carbonyl sulfide (COS), a poisonous and harmful gas, is found in industrial gas products from various coal-firing processes. The emission of COS into the atmosphere contributes to aerosol particles that affect the global climate, posing a risk to climate change and population health. In recent years, the total amount of anthropogenic COS emissions has increased significantly, resulting in the prominent COS pollution problem and becoming a vital environmental issue. This review summarizes the research progress of removing COS from industrial gases. According to the characteristics of different industrial gas products, the COS removal mechanism and influence factors, as well as the advantages and disadvantages for various methods, are discussed, including oxidation, absorption/adsorption, hydrogenation, and hydrolysis. Although COS emission control technologies have attracted widespread attention, the progress of application in blast furnace gas purification has been extremely slow, insufficient and sporadic. To fill the gap, this work provides a timely review on blast furnace gas characteristics and application process of various methods for removing COS from blast furnace gas with varying compositions, and their challenges and future development. This work aims to provide guidance on how effective processes and techniques for removal of COS from blast furnace gas can be developed. This review emphasizes the desirability of direct COS removal from blast furnace gas compared to expensive terminal desulfurization technologies. Furthermore, the development of a new process for low-temperature COS removal from blast furnace gas based on a dual-functional catalyst of hydrolysis/adsorption is advocated.
Assuntos
Carvão Mineral , Óxidos de Enxofre , Gases , EnxofreRESUMO
Alkaline phosphatases (ALPs: EC 3.1.3.1) are ubiquitous enzymes and play crucial roles in the fundamental phosphate uptake and secretory processes. Although insects are regarded as the most diverse group of organisms, the current understanding of ALP roles in insects is limited. As one type of destructive agricultural pest, whitefly Bemisia tabaci, a phloem feeder and invasive species, can cause extensive crop damage through feeding and transmitting plant diseases. In this study, we retrieved five ALP genes in MEAM1 whitefly, nine ALP genes in MED whitefly via comparative genomics approaches. Compared with nine other insects, whiteflies' ALP gene family members did not undergo significant expansion during insect evolution, and whiteflies' ALP genes were dispersed. Moreover, whiteflies' ALP gene family was conserved among insects and emerged before speciation via phylogenetic analysis. Whiteflies' ALP gene expression profiles presented that most ALP genes have different expression patterns after feeding on cotton or tobacco plants. Female/male MED whiteflies possessed higher ALP activities on both cotton and tobacco plants irrespective of sex, relative to MEAM1 whiteflies. Meanwhile, adult MED whiteflies possessed higher ALP activity in both whole insect and salivary samples, relative to MEAM1 whiteflies. We also found that both MED and MEAM1 whiteflies could upregulate ALP activities after feeding on cotton compared with feeding on tobacco plants. These findings demonstrated the functions of whiteflies ALPs and will assist the further study of the genomic evolution of insect ALPs.
Assuntos
Fosfatase Alcalina/metabolismo , Gossypium/parasitologia , Hemípteros/fisiologia , Proteínas de Insetos/metabolismo , Nicotiana/parasitologia , Doenças das Plantas/parasitologia , Fosfatase Alcalina/genética , Animais , Feminino , Perfilação da Expressão Gênica , Hemípteros/enzimologia , Proteínas de Insetos/genética , MasculinoRESUMO
Apoptosis is generally considered the first line of defense against viral infection. However, the role of apoptosis in the interactions between plant viruses and their insect vectors has rarely been investigated. By studying plant DNA viruses of the genus Begomovirus within the family Geminiviridae, which are transmitted by whiteflies of the Bemisia tabaci species complex in a persistent manner, we revealed that virus-induced apoptosis in insect vectors can facilitate viral accumulation and transmission. We found that infection with tomato yellow leaf curl virus activated the apoptosis pathway in B. tabaci Suppressing apoptosis by inhibitors or silencing caspase-3 significantly reduced viral accumulation, while the activation of apoptosis increased viral accumulation in vivo Moreover, the positive effect of whitefly apoptosis on virus accumulation and transmission was not due to its cross talk with the autophagy pathway that suppresses begomovirus infection in whiteflies. We further showed that viral replication, rather than the viral coat protein, is likely the critical factor in the activation of apoptosis by the virus. These novel findings indicate that similarly to many animal and a few plant RNA viruses, plant DNA viruses may activate apoptosis in their insect vectors leading to enhanced viral accumulation and transmission.IMPORTANCE Of the approximately 1,100 known plant viruses, about one-third are DNA viruses that are vectored by insects. Plant virus infections often induce cellular and molecular responses in their insect vectors, which can, in many cases, affect the spread of viruses. However, the mechanisms underlying vector responses that affect virus accumulation and transmission are poorly understood. Here, we examined the role of virus-induced apoptosis in the transmission of begomoviruses, a group of single-stranded plant DNA viruses that are transmitted by whiteflies and cause extensive damage to many crops worldwide. We demonstrated that virus infection can induce apoptosis in the insect vector conferring protection to the virions from degradation, leading to enhanced viral accumulation and transmission to host plants. Our findings provide valuable clues for designing new strategies to block the transmission of insect-vectored plant viruses, particularly plant DNA viruses.
RESUMO
Acetamiprid and imidacloprid are two important neonicotinoid insecticides that are widely utilized under field conditions for the management of sucking insect pests, including the solenopsis mealybug Phenacoccus solenopsis Tinsley (Hemiptera: Pseudococcidae). Although some information is available regarding their lethal effects, nothing is currently known about the sublethal effects of these insecticides. We, therefore, performed a series of experiments to test the lethal and sublethal effects of these chemicals on oviposition duration and fecundity. We also assessed sublethal effects on feeding behavior using the electrical penetration graph (EPG) technique. The results of this study reveal that acetamiprid toxicity is higher than imidacloprid and that both insecticides have negative effects on the oviposition, fecundity, and feeding behavior of P. solenopsis when applied at sublethal dosages. These chemicals also significantly reduce oviposition duration and fecundity and significantly prolong nonprobing duration, increase penetration problems, and reduce phloem and xylem feeding activities when compared with adults exposed to just water. No significant differences were detected in all waveform durations and events when adults previously exposed to foliage treated with each of these two insecticides were compared. The results of this study, therefore, suggest that both insecticides are capable of protecting crops from mealybug damage by not only killing these pests directly but also reducing their fecundity and inhibiting feeding behaviors when applied at sublethal dosages.
Assuntos
Hemípteros , Inseticidas , Solanum lycopersicum , Animais , Feminino , Neonicotinoides , OviposiçãoRESUMO
OBJECTIVE: To evaluate the association between genetic polymorphisms of CYP2E1 RsaI and GSTM1 and development of bladder cancer in a south-eastern Han Chinese population. METHODS: We hypothesized that the CYP2E1-1019T>A and GSTM1 polymorphisms were associated with risk of bladder cancer. In a hospital-based case-control study of 202 case patients with newly diagnosed bladder transitional cell carcinoma and 272 cancer-free controls frequency-matched by the age and sex, we genotyped these two polymorphisms using a polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: We found that the GSTM1 null genotype was associated with an increased risk of bladder cancer (adjusted odds ratio [OR] = 1.73, 95% confidence interval [CI] = 1.17-2.56) compared with those with the non-null genotype, but the CYP2E1-1019T>A polymorphisms did not show any association. In the stratification analysis of the GSTM1 polymorphism, we found that the increased risk was more pronounced among subgroups aged < or =60 years (OR = 2.02, 95% CI = 1.08-3.77), smokers (OR = 1.94, 95% CI = 1.11-3.38) and non-drinkers (OR = 3.86, 95% CI = 1.28-11.60). CONCLUSION: GSTM1 polymorphism (but not CYP2E1 RsaI polymorphism) appears to contribute to the etiology of bladder cancer in a south-eastern Chinese population.
Assuntos
Carcinoma de Células de Transição/genética , Citocromo P-450 CYP2E1/genética , Glutationa Transferase/genética , Polimorfismo Genético , Neoplasias da Bexiga Urinária/genética , Estudos de Casos e Controles , China , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
OBJECTIVE: To study the etiopathogenesis, clinical manifestations, diagnosis and management of persistent Müllerian duct syndrome (PMDS). METHODS: Two cases of PMDS were reported, one accompanied by transverse testicular ectopia and the other associated with cryptorchidism. Corporeal hysterectomy and orchidopexy were given to both the patients and cryptorchidectory the latter. RESULTS: Vascular supply and texture of the testis were normal in both the 2 patients after 1.5-2 years' follow-up. CONCLUSION: PMDS is male pseudohermaphroditism, for which means should be taken to preserve the blood supply and fertility function of the testis in surgical management, and attention should be paid to possible development of testis tumor in follow-up.
Assuntos
Transtornos do Desenvolvimento Sexual/patologia , Ductos Paramesonéfricos/anormalidades , Adulto , Seguimentos , Humanos , Masculino , SíndromeRESUMO
CONTEXT: In rodents and monkeys, a combination of hormonal and physical agents accelerates germ cell death. OBJECTIVE: A "proof of concept" study was performed to investigate whether addition of heat exposure or a progestin to an androgen induces germ cell death and more complete and rapid spermatogenesis suppression. DESIGN AND SETTINGS: A randomized clinical trial was performed at academic medical centers. PARTICIPANTS: We treated four groups of healthy male volunteers (18 per group) for 18 wk: 1) testosterone undecanoate (TU) 1000 mg im (first dose), followed by 500 mg im every 6 wk; 2) submersion of scrota at 43 C in water for 30 min/d for 6 consecutive days; 3) TU plus heat; and 4) TU plus oral levonorgestrel (LNG) 250 microg/d. MAIN OUTCOME MEASURES: Semen parameters, testicular histology, and germ cell apoptosis were the main outcome measures. RESULTS: Heat alone and TU plus heat suppressed sperm counts more than TU alone by wk 6. By wk 9, recovery began in the heat only group, whereas spermatogenesis remained suppressed in the TU plus heat group. Oral LNG plus TU suppressed spermatogenesis earlier and more severely than TU alone. At wk 2, significantly greater germ cell apoptosis occurred in heat and heat plus TU subjects, but not in subjects without heat treatment, compared with pretreatment subjects. By 9 wk, markedly smaller seminiferous tubule diameters and fewer spermatocytes and spermatids were noted in all 12 biopsies from men receiving TU, TU plus LNG, with most dramatic differences for the TU plus heat group, whereas no differences from pretreatment biopsies were observed in men who received heat treatment only. CONCLUSIONS: Heat causes a rapid and transient suppression of spermatogenesis. TU plus heat resulted in low-sperm output that was maintained by continuous treatment with TU. Addition of an oral progestin accelerated spermatogenesis suppression by TU alone. Increased germ cell apoptosis contributed to suppression of spermatogenesis.
Assuntos
Antiespermatogênicos/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Febre/fisiopatologia , Células Germinativas/efeitos dos fármacos , Células Germinativas/fisiologia , Levanogestrel/farmacologia , Escroto/fisiologia , Espermatogênese/efeitos dos fármacos , Espermatogênese/fisiologia , Testosterona/farmacologia , Adulto , Antiespermatogênicos/sangue , Azoospermia/patologia , Contagem de Células , Regulação da Expressão Gênica/fisiologia , Temperatura Alta , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Oligospermia/patologia , Contagem de Espermatozoides , Espermatogênese/genética , Testículo/citologia , Testículo/patologia , Testosterona/sangue , Fixação de TecidosRESUMO
The incidence rate for bladder cancer has been increasing in many countries, and bladder cancer is the most common urinary cancer in China. We explored the association of single-nucleotide polymorphisms in DNA repair genes with bladder cancer. The hypothesis is that the xeroderma pigmentosum complementary group D (XPD) 156-22541C-->A and 751-35931A-->C polymorphisms are associated with the risk of bladder cancer. In a population-based case-control study, 215 patients with newly diagnosed bladder transitional cell carcinoma and 245 cancer-free controls/healthy subjects (frequency-matched by the age and sex) were genotyped. These two polymorphisms were studied using the polymerase chain reaction restriction fragment length polymorphism method. We found that the A allele of XPD Arg156Arg (C22541A) and the C allele of XPD Lys751Gln (A35931C) is associated with increased risk of bladder cancer (adjusted odds ratio = 1.54 and 95% confidence interval = 1.19-2.01, 1.65, and 1.12-2.73, respectively). Smoking is also a risk factor in the etiology of bladder cancer, but alcohol intake is a protective factor during the development of bladder cancer. These two XPD polymorphisms may play an important role in the etiology of bladder cancer in the southeastern Chinese population.
Assuntos
DNA de Neoplasias/genética , Predisposição Genética para Doença , Polimorfismo Genético , Neoplasias da Bexiga Urinária/genética , Proteína Grupo D do Xeroderma Pigmentoso/genética , Povo Asiático , Estudos de Casos e Controles , China/epidemiologia , Reparo do DNA , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Polimorfismo de Fragmento de Restrição , Fatores de Risco , Fumar , Neoplasias da Bexiga Urinária/epidemiologiaRESUMO
AIM: To investigate the association among XRCC1 polymorphisms, smoking, drinking and the risk of prostate cancer (PCa) in men from Han, Southern China. METHODS: In a case-control study of 207 patients with PCa and 235 cancer-free controls, frequency-matched by age, we genotyped three XRCC1 polymorphisms (codons 194, 280 and 399) using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RELP) method. RESULTS: Among the three polymorphisms, we found that the XRCC1 Arg399Gln variant allele was associated with increased PCa risk (adjusted odd ratio [OR]: 1.67, 95% confident interval [CI]: 1.11-2.51), but the XRCC1 Arg194Trp variant allele had a 38% reduction in risk of PCa (adjusted OR: 0.62, 95% CI: 0.41-0.93). However, there was no significant risk of PCa associated with Arg280His polymorphism. When we evaluated the three polymorphisms together, we found that the individuals with 194Arg/Arg wild-type genotype, Arg280His and Arg399Gln variant genotypes had a significantly higher risk of PCa (adjusted OR: 4.31; 95% CI: 1.24-14.99) than those with three wild-type genotypes. In addition, we found that Arg399Gln variant genotypes had a significant risk of PCa among heavy smokers (adjusted OR: 2.04; 95% CI: 1.03-4.05). CONCLUSION: These results suggest that polymorphisms of XRCC1 appear to influence the risk of PCa and may modify risks attributable to environmental exposure.
Assuntos
Adenocarcinoma/genética , Proteínas de Ligação a DNA/genética , Predisposição Genética para Doença , Polimorfismo de Fragmento de Restrição , Neoplasias da Próstata/genética , Adenocarcinoma/sangue , Adenocarcinoma/epidemiologia , Idoso , China/epidemiologia , Proteínas de Ligação a DNA/sangue , Genótipo , Humanos , Masculino , Razão de Chances , Neoplasias da Próstata/sangue , Neoplasias da Próstata/epidemiologia , Fatores de Risco , Estudos Soroepidemiológicos , Proteína 1 Complementadora Cruzada de Reparo de Raio-XRESUMO
OBJECTIVE: To investigate the association of XRCC1 Arg399Gln polymorphism, smoking and drinking with the risk of prostate cancer (PCa) in the population of Han nationality in Jiangsu and Anhui. METHODS: A case-control study including 207 PCa patients and 235 age-matched controls was conducted. The polymorphisms of XRCC1 Arg399Gln sites were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique using genomic DNA isolated from peripheral blood lymphocytes. We compared the correlations between the susceptibility to PCa and different genotypes, and investigated the effect of smoking and drinking. RESULTS: The heterozygous Arg/Gln genotype was associated with statistically significantly increased risk of PCa (OR = 1.55, 95% CI: 1.01-2.39) compared with those with Arg/Arg wild-type homozygote. An increased susceptibility to PCa was shown to be associated with the 399Gln allele (either the heterozygous Arg/Gln or the homozygous Gin/Gln genotypes, OR = 1.61, 95% CI: 1.07-2.44) , and heavy smokers (smoking index; > or =20) (OR = 1.94, 95% CI: 1.02-3.71) and superficial smokers (taking smoke into the mouth only) (OR = 2.44, 95% CI: 1.02-5.80) with 399Gln allele demonstrated a significantly increased risk in comparison with those carrying wild genotype. CONCLUSION: XRCC1 Arg399Gln polymorphism might contribute to the susceptibility to PCa. The Arg/Gln and Gln/Gln genotypes might increase the risk of PCa and have synergistic effect with smoking.
Assuntos
Proteínas de Ligação a DNA/genética , Predisposição Genética para Doença/genética , Polimorfismo Genético , Neoplasias da Próstata/genética , Idoso , Idoso de 80 Anos ou mais , Alelos , Estudos de Casos e Controles , China/epidemiologia , Reparo do DNA , Etnicidade , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Neoplasias da Próstata/epidemiologia , Proteína 1 Complementadora Cruzada de Reparo de Raio-XRESUMO
The objective of this study was to evaluate the intravesical application of N-(4-hydroxyphenyl) retinamide (4-HPR) and adriamycin (ADM), as a treatment modality in a an animal model of chemically-induced bladder cancer. Bladder cancer developed in 50.0% of female Wistar rats, 4-6 weeks after intravesical application of the chemical carcinogen, N-methyl-N-nitrosourea (MNU). There was no significant difference in side effects induced by local versus systemic 4-HPR. Although tumor growth was inhibited by 4-HPR and ADM alone, tumor size was lower when both agents were used together. Apoptosis occurred at a higher rate in the combination group than when 4-HPR or ADM was used alone. The results suggest that intravesical use of 4-HPR and ADM may increase their efficacy in treatment of bladder cancer.
Assuntos
Antibióticos Antineoplásicos/farmacologia , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Doxorrubicina/farmacologia , Fenretinida/farmacologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Administração Intravesical , Alquilantes , Animais , Antibióticos Antineoplásicos/administração & dosagem , Antineoplásicos/administração & dosagem , Ciclo Celular/efeitos dos fármacos , Modelos Animais de Doenças , Doxorrubicina/administração & dosagem , Feminino , Fenretinida/administração & dosagem , Citometria de Fluxo , Marcação In Situ das Extremidades Cortadas , Metilnitrosoureia , Ratos , Ratos Wistar , Neoplasias da Bexiga Urinária/induzido quimicamenteRESUMO
In this report, genetic polymorphism of phase I and II metabolic enzyme (CYP2E1, CYP17, GSTM1 and GSTT1) genes, living habits, and risk of prostate cancer (PCa) was studied in 163 patients with prostate carcinoma of Han nationality in Southern China and 202 age-matched controls. The genotypic polymorphism of CYP2E1, CYP17, GSTM1 and GSTT1 genes was analyzed by PCR-RFLP assay using genomic DNA isolated from peripheral blood lymphocytes. The significant risk factors for PCa included long-term exposure to toxicant (OR=2.27, 95%CI: 1.26-4.09), the tumor history of lineal consanguinity (OR=2.19, 95%CI: 1.30-3.67), sexual history before age 30 of no more than 8 times per month (OR=1.85, 95%CI: 1.22-2.81), deep inhalation of cigarette smoke (OR=2.01, 95%CI: 1.20-3.37) or heavy smoking (OR=1.67,95%CI: 1.01-2.76). Among individuals with long-term heavy smoking without tea-drinking habit, the risk increased significantly (OR=4.27, 95%CI: 1.62-11.24 and OR), 2.76, 95%CI: 1.20-6.32). CYP2E1 C1/C1 genotype significantly increased the risk for PCa (OR=1.61, 95%CI: 1.04-2.49) with an apparent interaction with alcohol (OR=2.07, 95%CI: 1.07-4.00). However, stratification by the amount of accumulative smoking revealed that among people with a heavy smoking history, the individuals with the CYP2E1 C1/C1 genotype (OR=2.55, 95%CI: 1.20-5.43) and the individuals with GSTT1 null genotype (OR=2.23, 95%CI: 1.09-4.57) showed a significantly increased risk. Any other significant results with GSTM1 or CYP17 genes were not observed in this research. Individuals with more sensitive genotypes (from one to four) were at an increased risk. The data show that, in the development of PCa, there are many interactions among predisposing genotypes and genetic polymorphisms and unhealthy living habits. Individuals with more susceptible genotypes and unhealthy habits such as prolonged exposure to smoking are at an increased risk.
Assuntos
Predisposição Genética para Doença , Estilo de Vida , Polimorfismo Genético , Neoplasias da Próstata/enzimologia , Neoplasias da Próstata/genética , Idoso , Estudos de Casos e Controles , China/etnologia , Citocromo P-450 CYP2E1/genética , Meio Ambiente , Marcadores Genéticos , Genótipo , Glutationa Transferase/genética , Humanos , Masculino , Neoplasias da Próstata/etnologia , Fatores de Risco , Esteroide 17-alfa-Hidroxilase/genéticaRESUMO
AIM: To investigate the differences in microvessel densities (MVD) and the expressions of vascular endothelial growth factor (VEGF), VEGF-C and VEGF receptor-3 (VEGFR-3) between prostate cancer (PCa) tissues and adjacent benign tissues, and to explore the correlations among MVD, Jewett-Whitmore staging, Gleason scores and expressions of VEGF, VEGF-C and VEGFR-3 in the progression of PCa. METHODS: An immunohistochemical approach was adopted to detect the expressions of CD34, VEGF, VEGF-C and VEGFR-3 in both cancer areas and peripheral benign areas of 71 primary prostatic adenocarcinoma specimens. A statistic analysis was then performed according to the experimental and clinic data. RESULTS: Significantly upregulated expressions of VEGF, VEGF-C and VEGFR-3 were all found in malignant epithelium/cancer cells compared with adjacent benign epithelium (P<0.01). Patients in stage D had a significantly higher score than patients in stage A, B or C when comparing the expression of VEGF-C or VEGFR-3 in the tumor area (P<0.01). In addition, significant correlations were observed between Jewett-Whitmore staging and VEGF-C (r(s)=0.738, P<0.01), clinical staging and VEGFR-3 (r(s)=0.410, P<0.01), VEGF-C and Gleason scores (r(s)=0.401, P<0.01), VEGFR-3 and Gleason scores (r(s)=0.581, P<0.001) and MVD and VEGF (r(s)=0.492, P<0.001). CONCLUSION: Increased expressions of VEGF and VEGF-C were closely associated with progression of PCa. The main contribution of increased VEGF expression for PCa progression was to upregulate MVD, which maintained the growth advantage of tumor tissue. However, the chief role of increased expressions of VEGF-C and VEGFR-3 was to enhance lymphangiogenesis and provide a main pathway for cancer cells to disseminate.
Assuntos
Neoplasias da Próstata/fisiopatologia , Fator A de Crescimento do Endotélio Vascular/biossíntese , Fator C de Crescimento do Endotélio Vascular/biossíntese , Receptor 3 de Fatores de Crescimento do Endotélio Vascular/biossíntese , Idoso , Idoso de 80 Anos ou mais , Antígenos CD34/análise , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica/patologia , Neoplasias da Próstata/irrigação sanguíneaRESUMO
OBJECTIVE: To investigate the changes of antisperm antibodies (AsAb), sexual hormones, and inhibin B (INH B) in patients before and after testicular torsion, as well as the effects of these factors on testicular function and reproduction. METHODS: Ten patients with single acute testicular torsion (left side 9 and right side 1), aged 16-45 years (19.6 on average), disease course of 3-6 days (averaging 4.7 days), underwent surgical removal of the damaged testis. Before and after the operation, serum AsAb (IgG, IgM, IgA) and INH B were measured by ELISA, and serum follicle-stimulating hormone (FSH), luteotropic hormone (LH), and testosterone (T) determined by chemoluminescence autoanalyzer. RESULTS: After the operation, the AsAb levels rose significantly and remained high for at least 26 weeks. The level of INH B was the lowest in the 3rd week and restored to normal in the 12th week, with significant difference between preoperation and the 3rd or the 6th week after the operation. The levels of LH and INH B in the 26th week were elevated significantly compared with the 6th. CONCLUSION: Testicular injury induced the elevation of AsAb, which would last a very long time. The change of INH B was closely related with the injury of the testis, which reflected the degree of testicular injury and functional restoration of the patients after the operation. Our study showed that AsAb and INH B can be used as useful tools for monitoring testicular function and reproduction.
Assuntos
Autoanticorpos/sangue , Inibinas/sangue , Torção do Cordão Espermático/imunologia , Torção do Cordão Espermático/fisiopatologia , Espermatozoides/imunologia , Testículo/fisiopatologia , Adolescente , Adulto , Hormônio Foliculoestimulante/sangue , Humanos , Hormônio Luteinizante/sangue , Masculino , Pessoa de Meia-Idade , Orquiectomia , Torção do Cordão Espermático/cirurgia , Testosterona/sangueRESUMO
OBJECTIVE: To evaluate the correlation of epididymal protease inhibitor(Eppin) and Semenogelin(Sg) on human ejaculated spermatozoa. METHODS: The experimental approaches include: (1) Immunoprecipitation of Eppin with anti-Eppin from semen; (2) Colocalization of Eppin and Sg by immunofluorescence; (3) Immunoprecipitation of rEppin and rSg;(4) Far-Western blotting of rEppin and rSg;(5) Competition of saturated 125I-rSg binding to rEppin with unlabeled Sg, and direct binding of 125I-rSg to rEppin on a blot; (6) Autoradiography of 125I-rSg with rEppin. RESULTS: Eppin-Sg complex present on the surface of human ejaculated spermatozoa, Cys-239 is the only cystein for rEppin binding rSg. Reduction and carboxymethylation of Cys-239 blocks binding of 125I-rEppin to rSg. CONCLUSION: Our study demonstrates that Eppin and Sg bind to each other on human ejaculated spermatozoa. A disulfide linkage occurs between Sg and Eppin, indicating the specificity of binding.