RESUMO
The prevalence of chronic hyperglycemia and its complications, imposing a critical burden on the worldwide economy and the global healthcare system, is a pressing issue. Mounting evidence indicates that oxidative stress and hypoxia, two noticeable features of hyperglycemia, play a joint crucial role in mediating cellular apoptosis. However, the underlying detailed molecular mechanism remains elusive. Triggered by the observation that insulin-like growth factor (IGF1)-binding protein 3 (IGFBP3) can mediate, in renal cells, high-glucose-induced apoptosis by elevating oxidative stress, we wish to, in this study, know whether or not the similar scenario holds in cardiac cells and, if so, to find its relevant molecular key players, thereby dissecting the underlying molecular pathway. Specifically, we used a combination of three different cellular sources (H9c2 cells, diabetic rats, and neonatal rat ventricular cardiomyocytes) as our model systems of study. We made use of Co-IP assay and western blot analysis in conjunction with loss-of-function reasoning, gain-of-function logic, and inhibitor treatment as our main analytical tools. As a result, briefly, our main findings are that hyperglycemia can induce cardiac IGFBP3 overexpression and secretion, that high levels of IGFBP3 can sequester IGF1 from IGF1 survival pathway, leading to apoptosis, and that IGFBP3 gene upregulation is hypoxia-inducible factor (HIF)1α-dependent and reactive oxygen species dependent. Piecing these findings together allows us to propose the improved molecular regulatory mechanism. In conclusion, we have established the molecular roles of IGFBP3, HIF1, and prolyl hydroxylase domain in connecting oxidative stress with hypoxia and in cellular apoptosis under hyperglycemia.
Assuntos
Hiperglicemia/metabolismo , Hiperglicemia/patologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Animais , Apoptose/fisiologia , Linhagem Celular , Sobrevivência Celular/fisiologia , Hiperglicemia/genética , Prolina Dioxigenases do Fator Induzível por Hipóxia/metabolismo , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Regulação para CimaRESUMO
Species in the Simulium (Simulium) striatum species-group (Diptera: Simuliidae) in Taiwan and Japan are morphologically reevaluated. Simulium (S.) yanpingense sp. nov. is described as the third member in this species-group from Taiwan and a revised description of S. (S.) quinquestriatum (Shiraki) is provided. The species previously regarded as S. (S.) quinquestriatum in Japan is described as a new species, S. (S.) tanegashimaense. Simulium (S.) yanpingense sp. nov. is similar to S. (S.) pingtungense Huang & Takaoka from Taiwan, in many characteristics including the haired basal portion of the female radius, dark leg color, and male scutum with brassy hairs, but it is distinguished from the latter species by the number of male upper-eye (large) facets, which are in 17 (rarely 18) vertical columns and 17 or 18 horizontal rows in this new species but in 19 vertical columns and 20 horizontal rows in S. (S.) pingtungense. Simulium (S.) tanegashimaense sp. nov. is similar to S. (S.) quinquestriatum originally described from Taiwan by having the male scutum with yellow fine hairs, but is distinguished from the latter species by the number of male upper-eye (large) facets, which are in 17 (rarely 16) vertical columns and 17 horizontal rows in this new species but in 19 or 20 vertical columns and 19 or 20 horizontal rows in S. (S.) quinquestriatum. The morphological differences between these two new species and their related species from India, Malaysia, Thailand and Vietnam are noted.
Assuntos
Simuliidae , Animais , Feminino , Japão , Larva/anatomia & histologia , Masculino , Pupa/anatomia & histologia , Simuliidae/anatomia & histologia , TaiwanRESUMO
Two new black fly species, Simulium (Gomphostilbia) kaohsiungense and S. (G.) shoufengense, are described from females, males and pupae in Taiwan. These new species are placed in the S. asakoae species-group. Simulium (G.) kaohsiungense sp. nov. is characterized by a combination of the elongate female sensory vesicle, male upper-eye (large) facets in 15 vertical columns and 15 or 16 horizontal rows, male hind basitarsus 1.02-1.15 times the width of the hind femur, and widened pupal terminal hooks. These characteristics distinguish this new species from most species of the S. asakoae species-group. Simulium (G.) shoufengense sp. nov. is similar in the female and male to S. (G.) asakoae Takaoka & Davies originally described from Peninsular Malaysia but is distinguished from the latter species in the pupa by the combined length of the primary and secondary stalks of the dorsal triplet of gill filaments as long as or longer than the common basal stalk of the gill, and dorsum of abdominal segments 1 and 2 not darkened. The species previously regarded in Taiwan as S. (G.) metatarsale Brunetti, originally described from India, is morphologically and molecularly identified as S. (G.) asakoae.
Assuntos
Simuliidae , Animais , Feminino , Larva , Masculino , Pupa , Simuliidae/anatomia & histologia , Simuliidae/classificação , TaiwanRESUMO
The species status of two cytoforms of two species complexes in the Simulium (Simulium) tuberosum species-group, which are almost indistinguishable in the pupal stage, was morphologically and genetically evaluated. Cytoform 'L' of the S. (S.) tani Takaoka & Davies complex, previously recognized as S. (S.) suzukii Rubtsov in Taiwan, is described as a new species, S. (S.) jianshiense. It is morphologically distinguishable as adults from two members of the S. (S.) suzukii complex: cytoform 'C' from Hokkaido, selected to represent the type of S. (S.) suzukii sensu stricto, and cytoform 'D' from Okinawa Island and, based on our chromosomal analysis, also from Amami Island. This new species is genetically separated from both cytoforms of the S. (S.) suzukii complex with a genetic distance of 5.31-6.67%. Cytoform 'D' is distinguished from cytoform 'C' by the color of the male forecoxa and relative length of the female sensory vesicle to the third maxillary palpomere. Accordingly, the name S. (S.) ryukyuense Ogata, once regarded as a synonym of S. (S.) suzukii, is revalidated and applied to cytoform 'D'. The genetic distance between S. (S.) ryukyuense and S. (S.) suzukii sensu stricto is 1.24-1.60%.
Assuntos
Simuliidae , Animais , Feminino , Ilhas , Japão , Masculino , Pupa , Simuliidae/genética , TaiwanRESUMO
A new black fly species, Simulium taichungense, is described on the basis of one female, one male and two pupal exuviae from Taiwan. This new species is placed in the S. crocinum species-group of Simulium (Simulium) (Diptera: Simuliidae). It is characterized by the pupal gill with six unpigmented short filaments and pupal abdomen with distinct spine-combs on the dorsal surface of segments 7-9, by which it is easily distinguished from most species in the S. crocinum species-group including two species from Taiwan: Simulium serenum Huang Takaoka and S. ufengense Takaoka. It is the third species of the S. crocinum species-group from Taiwan. In addition, the male of S. serenum is described for the first time, and intraspecific variations in a few features of the male of S. chungi Takaoka Huang of the S. chungi species-group are noted.
Assuntos
Simuliidae , Animais , Feminino , Brânquias , Larva , Masculino , Pupa , TaiwanRESUMO
Perspicuous assessments of taxonomic boundaries and discovery of cryptic taxa are of paramount importance in interpreting ecological and evolutionary phenomena among black flies (Simuliidae) and combating associated vector-borne diseases. Simulium tani Takaoka & Davies is the largest and perhaps the most taxonomically challenging species complex of black flies in the Oriental Region. We use a DNA sequence-based method to delineate currently recognized chromosomal and morphological taxa in the S. tani complex on the Southeast Asian mainland and Taiwan, while elucidating their phylogenetic relationships. A molecular approach using multiple genes, coupled with morphological and chromosomal data, supported recognition of cytoform K and morphoform 'b' as valid species; indicated that S. xuandei, cytoform L, and morphoform 'a' contain possible cryptic species; and suggested that cytoform B is in the early stages of reproductive isolation whereas lineage sorting is incomplete in cytoforms A, C, and G.
Assuntos
Genes de Insetos , Análise de Sequência de DNA/métodos , Simuliidae/classificação , Simuliidae/isolamento & purificação , Animais , Variação Genética , Malásia , Filogenia , Filogeografia , Simuliidae/genética , Taiwan , Tailândia , VietnãRESUMO
BACKGROUND: Allopatric populations present challenges for biologists working with vectors. We suggest that conspecificity can be concluded in these cases when data from four character sets-chromosomal, ecological, molecular, and morphological-express variation no greater between the allopatric populations than between corresponding sympatric populations. We use this approach to test the conspecificity of Simulium nodosum Puri on the mainland of Southeast Asia and Simulium shirakii Kono & Takahasi in Taiwan. The validity of these two putative species has long been disputed given that they are morphologically indistinguishable. FINDINGS: The mitochondria-encoded cytochrome c oxidase subunit I (COI), 12S rRNA, and 16S rRNA genes and the nuclear-encoded 28S rRNA gene support the conspecific status of S. nodosum from Myanmar, Thailand, and Vietnam and S. shirakii from Taiwan; 0 to 0.19 % genetic differences between the two taxa suggest intraspecific polymorphism. The banding patterns of the polytene chromosomes of the insular Taiwanese population of S. shirakii and mainland populations of S. nodosum are congruent. The overlapping ranges of habitat characteristics and hosts of S. nodosum and S. shirakii corroborate the chromosomal, molecular, and morphological data. CONCLUSIONS: Four independent sources of evidence (chromosomes, DNA, ecology, and morphology) support the conspecificity of S. nodosum and S. shirakii. We, therefore, synonymize S. shirakii with S. nodosum. This study provides a guide for applying the procedure of testing conspecificity to other sets of allopatric vectors.
Assuntos
Variação Genética , Cromossomos Politênicos/genética , Simuliidae/classificação , Animais , Ásia , Sequência de Bases , Ecologia , Dados de Sequência Molecular , Mianmar , Análise de Sequência de DNA , Simuliidae/genética , Especificidade da Espécie , Taiwan , Tailândia , VietnãRESUMO
To determine the geographic origin of the black fly Simulium suzukii on Okinawa Island, Japan, macrogenomic profiles derived from its polytene chromosomes were compared with those of mainland and other insular populations of S. suzukii and of the isomorphic Simulium tani species complex. The Okinawan population is a chromosomally unique cytoform, designated 'D,' which is essentially monomorphic and differs by about 27 fixed rearrangements from the chromosomal standard sequence for the subgenus Simulium and by two fixed differences from its nearest known relative, representing the type of S. suzukii, on the main islands of Japan. Chromosomal band sequences revealed two additional, sympatric cytoforms of S. suzukii, designated 'A' and 'B,' each with species status, in Korea, and a third cytoform, designated 'C,' on Hokkaido, Japan. A new cytoform, 'K,' of S. tani from Malaysia, representing the type of S. tani, is more closely related to cytoforms in Thailand, as are populations from Taiwan previously treated as S. suzukii but more closely aligned with S. tani and newly recognized as cytoform 'L' of the latter nominal species. Rooting of chromosomal band sequences by outgroup comparisons allowed directionality of chromosomal rearrangements to be established, enabling phylogenetic inference of cytoforms. Of 41 macrogenomic rearrangements discovered in the five new cytoforms, four provide evidence for a stepwise origin of the Okinawan population from populations characteristic of the main islands of Japan. The macrogenomic approach applied to black flies on Okinawa Island illustrates its potential utility in defining source areas for other species of flies including those that might pose medical and veterinary risks.
Assuntos
Genoma de Inseto , Larva/classificação , Filogenia , Cromossomos Politênicos/química , Simuliidae/classificação , Animais , Bandeamento Cromossômico , Inversão Cromossômica , Mapeamento Cromossômico , Feminino , Especiação Genética , Variação Genética , Ilhas , Japão , Larva/genética , Masculino , Filogeografia , Simuliidae/genética , SimpatriaRESUMO
BACKGROUND: This case-control study investigates the role of xenobiotic-metabolizing genes, including glutathione S-transferases (GSTs) and cytochrome P450 1A1 (CYP1A1) and 2E1 (CYP2E1), in the susceptibility to oral potentially malignant disorders (OPMDs). METHODS: The genotypes of GSTM1, GSTT1, GSTP1, CYP1A1*2C, and CYP2E1 PstI/RsaI polymorphisms were determined for 217 OPMD cases and 492 age- and sex-matched controls from a Taiwanese penitentiary. RESULTS: Compared to the GSTM1-present genotype, the GSTM1-null genotype was significantly associated with increased risk of leukoplakia (odds ratio [OR]=1.46, 95% confidence interval [CI]=1.01-2.10). Similarly, compared to the CYP1A1*2C A/G+G/G genotype, the CYP1A1*2C A/A genotype was significantly associated with increased risk of leukoplakia (OR=1.64, 95% CI=1.12-2.40), particularly for smokers consuming > 13 pack-years of cigarettes (OR=2.40, 95% CI=1.40-4.11) (Interaction P=0.039). In addition, participants with 4-5 risk genotypes (OR > 1) experienced higher risks for leukoplakia than those with 0-1 risk genotypes (OR=3.19, 95% CI=1.65-6.15) (Trend test P=0.001). CONCLUSIONS: Our findings suggest that the CYP1A1*2C A/A genotype may increase the risk of leukoplakia, especially for heavy smokers. Xenobiotic-metabolizing genes may simultaneously modulate this disease risk. These observations require further confirmation with larger samples.
Assuntos
Predisposição Genética para Doença , Leucoplasia Oral/etiologia , Nicotiana , Polimorfismo Genético , Fumar , Xenobióticos/metabolismo , Adulto , Sequência de Bases , Primers do DNA , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Fatores de Risco , TaiwanRESUMO
Cardiovascular disease is one of the major causes of mortality in diabetic patients. Mounting studies have shown that garlic exhibits, possibly through its antioxidant potential, diverse biological activities. In this study, we investigated the alleviating effects of garlic oil (GO) and its two major components, diallyl disulfide (DADS) and diallyl trisulfide (DATS), on diabetic cardiomyopathy in rats. Physiological cardiac parameters were obtained using echocardiography. Apoptotic cells were evaluated using TUNEL and DAPI staining. Protein expression levels were determined using Western blotting analysis. Our findings indicated that in diabetic rat hearts significantly decreased fractional shortening percentage, increased levels of nitrotyrosine, an elevated number of TUNEL-positive cells, enhanced levels of caspase 3 expression, and decreased PI3K-Akt signaling pathway activities were observed. Furthermore, all of these alterations were reversed following both GO and DATS (or DADS) administrations through increasing PI3K-Akt signaling pathway activities and inhibiting both the death receptor-dependent and the mitochondria-dependent apoptotic pathways. In conclusion, this study shows that DATS and DADS, with the efficacy order DATS > DADS, have the therapeutic potential for ameliorating diabetic cardiomyopathy. Furthermore, the therapeutic effects of GO on diabetic cardiomyopathy should be mainly from DATS and DADS.
Assuntos
Compostos Alílicos/farmacologia , Apoptose/efeitos dos fármacos , Cardiomiopatias/tratamento farmacológico , Diabetes Mellitus Experimental/tratamento farmacológico , Dissulfetos/farmacologia , Sulfetos/farmacologia , Animais , Cardiomiopatias/metabolismo , Caspase 3/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Alho , Coração/efeitos dos fármacos , Masculino , Mitocôndrias/metabolismo , Proteína Oncogênica v-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Ratos , Ratos Wistar , Receptores de Morte Celular/metabolismo , Transdução de Sinais , Superóxido Dismutase/metabolismo , Superóxido Dismutase-1 , Tirosina/análogos & derivados , Tirosina/metabolismoRESUMO
Simulium (Gomphostilbia) taitungense sp. nov. is described on the basis of reared adult, pupal and mature larval specimens collected from Taitung, Taiwan. This new species is placed in the ceylonicum species-group within the subgenus Gomphostilbia and is distinguished from related known species by the characteristic colour markings on the ventral surface of the head capsule and on the dorsal surface of the abdomen in the larva. The male of Simulium (Gomphostilbia) tuenense Takaoka, which was originally described from a pharate pupa and a larva, is described for the first time; the association of the adult stage with the larval stage was confirmed by the comparison of the sequences of the mitochondrial 16S rRNA gene; this species is also placed in the ceylonicum species-group.