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OBJECTIVES: To compare the effects of cell lysis method and magnetic beads method in forensic DNA identification and to explore these two methods in forensic DNA identification. METHODS: The genome DNA of THP-1 cells in different quantities was extracted by the cell lysis method and magnetic beads method, and the DNA content was quantified by real-time quantitative PCR. The cell lysis method and magnetic beads method were used to type the STR of human blood with different dilution ratios. RESULTS: When the numbers of THP-1 cell were 100, 400 and 800, the DNA content extracted by cell lysis method were (1.219±0.334), (5.081±0.335), (9.332±0.318) ng, respectively; and the DNA content extracted by magnetic beads method were (1.020±0.281), (3.634±0.482), (7.896±0.759) ng, respectively. When the numbers of THP-1 cells were 400 and 800, the DNA content extracted by the cell lysis method was higher than that by the magnetic beads method. The sensitivity of cell lysis method and magnetic beads method was similar in STR typing of human blood at different dilution ratios. Complete STR typing could be obtained at 100, 300 and 500-fold dilutions of blood samples, but could not be detected at 700-fold dilution. STR typing of undiluted human blood could not be detected by cell lysis method. CONCLUSIONS: The cell lysis method is easy to operate and can retain template DNA to the maximum extend. It is expected to be suitable for trace blood evidence tests.
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DNA , Medicina Legal , Humanos , DNA/genética , Reação em Cadeia da Polimerase em Tempo Real , Fenômenos Magnéticos , Impressões Digitais de DNA/métodos , Repetições de MicrossatélitesRESUMO
Objective To explore the performance and mechanism of(+)-corynoline in treating triple negative breast cancer MDA-MB-436 cells and thus provide an option for the development of drugs against this cancer. Methods The viability,proliferation,apoptosis and migration/invasion of MDA-MB-436 cells treated with(+)-corynoline were detected by CCK-8 assay,colony formation assay,flow cytometry and Transwell assay,respectively.Furthermore,Western blotting was employed to determine the expression of related proteins,and RNA-Seq was performed for the MDA-MB-436 cells treated with(+)-corynoline. Results (+)-corynoline inhibited the proliferation and stemness and promoted the apoptosis of MDA-MB-436 cells.Further,(+)-corynoline may activate the oxidative phosphorylation pathway to play a role in inhibiting triple negative breast cancer. Conclusion (+)-corynoline can inhibit triple negative breast cancer cells,which helps to address the poor efficacy of existing chemotherapeutics and facilitate the development of drugs against this cancer.
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Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Apoptose , Alcaloides de Berberina , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Humanos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/metabolismoRESUMO
RATIONALE: Short-chain fatty acids (SCFAs) are associated with intestinal microbiota and diseases in humans. SCFAs have a low response in mass spectrometry, and in order to increase sensitivity, reduce sample consumption, shorten analysis time, and simplify sample preparation steps, a derivatization method was developed. METHODS: We converted seven SCFAs into amide derivatives with 4-aminomethylquinoline. The reaction occurred for 20 min at room temperature. The analytes were separated on a reversed-phase C18 column and quantitated in the positive ion electrospray ionization mode using multiple reaction monitoring. Acetic acid-d4 was used as the stable-isotope-labeled surrogate analyte for acetic acid in the working solutions, while the other stable-isotope-labeled standards were used as internal standards (ISs). RESULTS: Method validation showed that the intra-day and inter-day precision of quantitation for the seven SCFAs over the whole concentration range was ≤3.8% (n = 6). The quantitation accuracy ranged from 85.5% to 104.3% (n = 6). Most important, the collected feces were vortexed immediately with ethanol. CONCLUSIONS: This study provides a new derivatization method for a precise, accurate, and rapid quantitation of SCFAs in human feces using ultra-performance liquid chromatography/tandem mass spectrometry. This method successfully determined the concentration of SCFAs in human feces and could assist in the exploration of intestinal microbiota and diseases.
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Ácidos Graxos Voláteis/análise , Fezes/química , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida de Alta Pressão/economia , Cromatografia Líquida de Alta Pressão/métodos , Fezes/microbiologia , Microbioma Gastrointestinal , Humanos , Espectrometria de Massas em Tandem/economia , Fatores de TempoRESUMO
In this study, 17 Y-chromosomal short tandem repeats (Y-STRs) were analyzed in 1026 male individuals of Han populations in Changchun City, Jilin Province, Northeast China. The haplotype diversity is 0.99892. The Changchun Han population is close to most Han populations and different from most other minority populations of China. Additionally, the Changchun Han show more affiliations with Han populations in North and Northeast China. These data provide a reference for the Y-STR database in Jilin Province, and they may be valuable for population genetic analysis.
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Cromossomos Humanos Y , Genética Populacional , Repetições de Microssatélites , China , Etnicidade , Frequência do Gene , Haplótipos , Humanos , Masculino , Polimorfismo GenéticoRESUMO
The House of Aisin Gioro, the imperial clan of Qing dynasty (1644-1911), affected the history of China and the formation of Manchu ethnicity greatly. However, owing to the lack of historical records and archeological evidences, the origin of the House of Aisin Gioro remains ambiguous. To clarify the origin of Aisin Gioro clan, we conducted whole Y-chromosome sequencing on three samples and Y-single-nucleotide polymorphism (Y-SNP) genotyping on other four samples beside those reported in previous work. We confirmed that the paternal lineage of the Aisin Gioro clan belongs to haplogroup C3b1a3a2-F8951, a brother branch of C3*-Star Cluster (currently named as C3b1a3a1-F3796, once linked to Genghis Khan), which is quite different from the predominant lineage C3c-M48 in other Tungusic-speaking populations. We also determined a series of unique Y-SNP markers for the Aisin Gioro clan. Diversity analyses of haplogroup C3b1a3a2-F8951 revealed the early migration of the ancestors of the Aisin Gioro clan from the middle reaches of Amur River to their later settlement in southeastern Manchuria. Hence, our results suggest that the Aisin Gioro clan may be descendants of ancient populations in Transbaikal region and closely related to origin of current Daur populations. Our research indicated that detailed research of stemma and deep sequencing of Y chromosomes are helpful to explore the prehistoric activities of populations lacking historical records and archeological evidences.
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Etnicidade/genética , Genealogia e Heráldica , Genética Populacional , Herança Paterna , Filogenia , China , Cromossomos Humanos Y/química , Haplótipos , Sequenciamento de Nucleotídeos em Larga Escala , História do Século XVII , História do Século XVIII , História do Século XIX , História do Século XX , Migração Humana , Humanos , Repetições de Microssatélites , Polimorfismo de Nucleotídeo ÚnicoRESUMO
In previous studies, a specific paternal lineage with a null value for the Y-chromosome short tandem repeat (Y-STR) marker DYS448 was identified as common among Mongolic- and Turkic-speaking populations. This paternal lineage (temporarily named C3*-DYS448del) was determined to be M217+, M93-, P39-, M48-, M407-, and P53.1-, and its origin and phylogeny remain ambiguous. Here, we analyzed Y-chromosome sequences of 10 male that are related this paternal lineage and redefined it as C3b1a1a1a-F1756 (C3b-F1756). We generated a highly revised phylogenetic tree of haplogroup C3b-F1756, including 21 sub-clades and 360 non-private Y-chromosome polymorphisms. Additionally, we performed a comprehensive analysis of the C3*-DYS448del lineage in eastern Eurasia, including 18 270 samples from 297 populations. Whole Y-chromosome sequences, Y-STR haplotypes, and frequency data were used to generate a distribution map, a network, and age estimations for lineage C3*-DYS448del and its sub-lineages. Considering the historical records of the studied populations, we propose that two major sub-branches of C3b-F1756 may correspond to early expansions of ancestors of modern Mongolic- and Turkic-speaking populations. The large number of newly defined Y-chromosome polymorphisms and the revised phylogenetic tree for C3b-F1756 will assist in investigation of the early history of Altaic-speaking populations in the future.
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Cromossomos Humanos Y , Etnicidade/genética , Haplótipos , Repetições de Microssatélites , Herança Paterna , Filogenia , Locos de Características Quantitativas , Evolução Molecular , Marcadores Genéticos , Humanos , Masculino , Mongólia , Polimorfismo de Nucleotídeo Único , TurquiaRESUMO
OBJECTIVE: This study compares endoscopic thyroidectomy by gasless unilateral axillary approach (ETGUA) and sternocleidomastoid leading-edge approach (SLEA) with conventional open thyroidectomy (COT) in hemithyroidectomy. The main focus is on the protection of neck muscles (sternocleidomastoid, omohyoid, sternothyroid) and the postoperative function of voice and swallowing yielded through these common approaches. METHODS: A total of 302 patients who underwent hemithyroidectomy were enrolled and divided into three groups: ETGUA (n = 101), SLEA (n = 100), and COT (n = 101). Ultrasound was used to measure the thickness of bilateral neck muscles, including the sternocleidomastoid, omohyoid, and sternothyroid. The changes in thickness on the surgical side compared to the non-surgical side. Analyzed factors included muscle thickness changes, Swallowing Impairment Score (SIS), Voice Handicap Index (VHI), Scar Cosmesis Assessment and Rating (SCAR), Neck Injury Index (NII), surgery duration, drainage volume, hospitalization, and number of lymph nodes. RESULTS: The clinical characteristics among the three groups were consistent except for differences in sex, age, and BMI. Metrics such as sternocleidomastoid muscle, NII, hypocalcemia, postoperative PTH, transient hoarseness, and number of lymph nodes showed no significant differences among the three groups. However, significant differences were found in the duration of surgery, drainage volume, hospitalization period omohyoid muscle, Sternohyoid muscle, VHI, SIS, and SCAR (all p < 0.001). CONCLUSION: In comparison to COT, ETGUA and SLEA demonstrate superiority in protecting neck muscles and preserving voice and swallowing function without compromising surgical safety or radicality.
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Neoplasias da Glândula Tireoide , Tireoidectomia , Humanos , Deglutição , Músculos do Pescoço/patologia , Endoscopia , Esvaziamento Cervical , Neoplasias da Glândula Tireoide/cirurgiaRESUMO
OBJECTIVE: To investigate the genetic polymorphisms of 15 X-STR loci in Shandong Han population in order to establish the forensic application database. METHODS: The multi-PCR primers of these loci were designed by Primer Premier 5.0 software and labeled by 4 fluoresceins (FAM, VIC, NED and TET). The developed multi-PCR was used to investigate 15 X-STR loci (DXS10011, DXS101, GATA 165B12, DXS6795, DXS6800, DXS6801, DXS6803, DXS7132, DXS7133, DXS7423, DXS7424, DXS8377, DXS8378, DXS9898 and HPRTB) selected from the X chromosome of 481 unrelated individuals (295 females and 186 males) in Shandong Han population. RESULTS: Among the 15 X-STR loci, GATA 165B12, DXS6800, DXS6803, DXS7133 and DXS7423 showed moderate polymorphisms, while the rest 10 X-STR loci showed high polymorphisms (PIC > 0.5 and H > 0.5). No shared haplotype was detected among the males in Shandong Han population. CONCLUSION: The developed multi-PCR system with fluorescence detection provides an effective way to establish X-STR loci database of population genetics in Shandong Han population and shows its forensic application.
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Povo Asiático/genética , Cromossomos Humanos X/genética , Genética Populacional , Repetições de Microssatélites , Polimorfismo Genético , Povo Asiático/etnologia , China , Impressões Digitais de DNA , Primers do DNA , Feminino , Genética Forense , Frequência do Gene , Ligação Genética , Genótipo , Humanos , Masculino , Reação em Cadeia da Polimerase MultiplexRESUMO
Angiosarcoma is a rare subtype of soft tissue sarcoma with identifiable vascular differentiation. It can occur at any age and develop throughout the body, but it is most commonly found in skin, soft, and breast tissues. Primary retroperitoneal angiosarcoma is rarely reported in the relevant literature. This article reports a case of primary retroperitoneal angiosarcoma in a middle-aged man, with the relevant literature reviewed in detail. A 46-year-old male had experienced left waist pain for 2 months. An ultrasonic examination revealed a mass in the left retroperitoneum, and left retroperitoneal lesions were confirmed via computed tomography (CT) and magnetic resonance imaging (MRI). The tumor was removed surgically, and the CT scan revealed local tumor recurrence after 1 month when the first adjuvant therapy was performed. The patient died of a massive hemorrhage from a ruptured tumor. Angiosarcoma has high malignancy and a poor prognosis. Its early diagnosis and treatment significantly impact the long-term survival rate of patients.
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OBJECTIVE: To investigate whether risk factors related to pain vary at different stages of knee osteoarthritis (OA). METHODS: Individuals from the Osteoarthritis Initiative with available Kellgren/Lawrence (K/L) grade and numerical rating scale (NRS) data at baseline were included in this study. Pain severity was classified into 3 categories based on NRS scores: no pain, mild pain, and moderate/severe pain. Knee OA severity was stratified into 4 categories according to the K/L system. Pain risk factors were evaluated using generalized ordinal logistic regression analysis, and a heatmap was created to compare differences in standardized regression coefficients between subgroups of patients with different knee OA severities. RESULTS: A total of 4,446 subjects were included in this study: 1,574 individuals without pain (35.4%), 1,138 individuals with mild pain (25.6%), and 1,734 individuals with moderate/severe pain (39.0%). For the entire population and subjects in the premorbid-stage subgroup, knee injury history, diabetes mellitus, depression, use of nonsteroidal anti-inflammatory drugs (NSAIDs), and valgus malaligned knees were associated with more severe pain. Older age and stronger quadriceps muscles were associated with milder pain. As the disease progressed, the number of significant risk factors decreased. Only age and quadriceps muscle force remained significant in end-stage disease. CONCLUSION: Multiple factors are associated with pain in patients with knee OA. As the disease progresses, the number of significant risk factors gradually reduces. These findings suggest that strategies for managing pain related to knee OA should vary depending on radiographic grades.
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Osteoartrite do Joelho , Humanos , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/epidemiologia , Osteoartrite do Joelho/etiologia , Fatores de Risco , Dor/complicações , Articulação do Joelho/diagnóstico por imagemRESUMO
The applications of sulphate-reducing microorganisms (SRMs) in acid mine drainage (AMD) treatment systems have received extensive attention due to their ability to reduce sulphate and stabilize metal(loid)s. Despite great phylogenetic diversity of SRMs, only a few have been used in AMD treatment bioreactors. In situ enrichment could be an efficient approach to select new effective SRMs for AMD treatment. Here, we performed in situ enrichment of SRMs in highly stratified AMD sediment cores using different kinds of carbon source mixture. The dsrAB (dissimilatory sulfite reductase) genes affiliated with nine phyla (two archaeal and seven bacterial phyla) and 26 genera were enriched. Remarkably, those genes affiliated with Aciduliprofundum and Vulcanisaeta were enriched in situ in AMD-related environments for the first time, and their relative abundances were negatively correlated with pH. Furthermore, 107 dsrAB-containing metagenome-assembled genomes (MAGs) were recovered from metagenomic datasets, with 14 phyla (two archaeal and 12 bacterial phyla) and 15 genera. The relative abundances of MAGs were positively correlated with total carbon and sulphate contents. Our findings expanded the diversity of SRMs that can be enriched in AMD sediment, and revealed the physiochemical properties that might affect the growth of SRMs, which provided guidance for AMD treatment bioreators.
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Microbiota , Sulfatos , Filogenia , Bactérias/genética , Archaea , ÁcidosRESUMO
Microbial lipids, which are also known as single cell oils (SCO), are produced by oleaginous microorganisms including oleaginous bacteria, yeast, fungus and algae through converting carbohydrates into lipids under certain conditions. Due to its unique environment having extremely low temperature and anoxia, the Tibetan Plateau is amongst the regions with numerous rare ecotypes such as arid desert, salt marsh, alpine permafrost, hot spring, and lawn. By using a rapid, convenient screening method, we identified 31 strains of oleaginous microorganisms from different habitats in the Tibetan Plateau, which include wetlands, lawn, hot spring, alpine permafrost, and saline-alkali soil. Molecular identity analysis showed that they belong to 15 different species, 7 of which are reported for the first time as lipid-producing microorganisms, that is, Cladosporium sp., Gibberella fujikuro, Ochrobactrum sp., Plectosphaerella sp., Tilletiopsis albescens, Backusella ctenidia, and Davidiella tassiana. The distribution of the oleaginous microorganisms varies with habitats. 11 strains were found in hot spring (35.5%), 10 in farmland (32.3%), 6 in lawn (19.4%), 2 in sand (6.4%), 1 in wetland (3.2%), and 1 in permafrost (3.2%). Carbon utilization analysis indicated that most of these filamentous fungi can use xylose and carboxymethyl cellulose (CMC) as carbon source, where Backusella ctenidia, Fusarium sp. and Gibberella fujikuroi have the strongest capability.
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OBJECTIVE: To investigate the mutation frequency in 7 mutation hot-spots of deafness gene in southern Jiangsu province and verify the performance of the SNaPshot technology platform, designed for genetic screening of non-syndromic hearing loss (NSHL) in Chinese. METHODS: One hundred and twenty-five NSHL patients were enrolled. Amplification of 235delC, 299-300delAT in GJB2 gene, IVS7-2A>G, 2168 A>G in SLC26A4 gene, and 1555A>G, 7445 A>G and 3243 A>G in mitochondrial DNA (mtDNA) was performed using multiplex polymerase chain reaction (PCR) technology. Afterwards, the sequence-specific probe interrogated each locus and labeled it at the 3' end using fluorescent dideoxynucleotide chemistry by the SNaPshot Multiplex Kit, the resulting products were then separated electrophoretically in ABI PRISM R 3130 Genetic Analyzer and analyzed in the presence of a fifth-dye-labeled size standard. Finally, the genotyping results were verified by direct sequencing or PCR-restriction fragment length polymorphism (PCR-RFLP). RESULTS: (1) The total mutation frequency for the 7 mutation hot-spots was 53.6%. The mutation frequency of 235delC was 24.0%, 299-300delAT was 5.6% in the GJB2 gene, IVS7-2A>G was 15.2%, 2168A>G was 3.2% in the SLC26A4 gene. The mutation frequency of 1555A>G and 7445 A>G in mtDNA was 4.8% and 0.8% respectively. The mutation 3243 A>G was not detected. (2) The SNaPshot results were consistent with that from direct sequencing or PCR-RFLP, and the specificity and sensitivity of detection were 100%. CONCLUSION: (1) More than half of the patients with deafness in southern Jiangsu province carry the mutations of the seven hot-spots. (2) The genetic screening technology platform based on SNaPshot can detect 7 mutations in one reaction, and is efficient and suitable for clinical practice.
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Povo Asiático/genética , Análise Mutacional de DNA/métodos , Testes Genéticos/métodos , Perda Auditiva Neurossensorial/genética , Polimorfismo de Nucleotídeo Único/genética , China , Conexina 26 , Conexinas , Perda Auditiva Neurossensorial/diagnóstico , Humanos , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de RestriçãoRESUMO
OBJECTIVE: To evaluate the potential usefulness of DNA methylation in individual discrimination of monozygotic twins by investigating the differences of DNA methylation profiles in monozygotic twins' blood samples. METHODS: Blood samples from 22 pairs of monozygotic twins were obtained with informed consent. Genomic DNA extracts were bisulfite treated followed by detection with Infinium HumanMethylation27 BeadChip Assays(Illumina, USA). Epigenetic distances between each pair of monozygotic twins and each pair of unrelated individuals of same gender were calculated with Euclidean distance algorithms. Distribution of epigenetic distance in monozygotic twin group was statistically compared with that in unrelated individuals. RESULTS: Difference of epigenetic distance between male and female pairs was not statistically significant in unrelated individual group or in monozygotic twin group (P = 0.0695 and 0.4825, respectively). Epigenetic distance of monozygotic twins was significantly lower than that of unrelated individual pair of same gender (Median: 6.02 vs 7.20, P = 0.0002). However, all the epigenetic distance in monozygotic twin group or in unrelated individuals were significantly higher than 4.00 (P < 0.000 1). CONCLUSION: DNA methylation profiles of monozygotic twin's blood samples were significantly different with each other, which was similar to that in unrelated individuals of same gender. These results indicated that DNA methylation was a useful biomarker in individual discrimination of monozygotic twins.
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Metilação de DNA , Epigenômica , Genoma Humano/genética , Gêmeos Monozigóticos/genética , Adolescente , Adulto , Idoso , Cromossomos Humanos X/genética , Ilhas de CpG , Feminino , Marcadores Genéticos , Variação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Fatores Sexuais , Adulto JovemRESUMO
BACKGROUND: Liver kinase B1 (LKB1) is involved in various human diseases. Aberrant expression of LKB1 expression is involved in glioma progression and associated with prognosis, however, the specific mechanism involving NF-κB/Snail signaling pathways remain unknown. MATERIALS AND METHODS: In the present study, quantitative real-time PCR analysis was used to investigate the expression of LKB1 tumor tissue samples and cell lines. In glioma cell lines, CCK-8 assay, transwell invasion and migration assays were used to investigate the effects of LKB1on proliferation and invasion. RESULTS: We observed that LKB1 knockdown promoted glioma cell proliferation, migration and invasion. This effect was induced through NF-κB/Snail signaling activation. Also, LKB1 overexpression suppressed proliferation, migration, and invasion, which could be rescued by Snail overexpression. CONCLUSION: Taken together, our results show that LKB1 knockdown promotes remarkably glioma cell proliferation, migration and invasion by regulating Snail protein expression through activating the NF-κB signaling. This may serve as a potential prognostic marker and therapeutic target for glioma.
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INTRODUCTION: Insulin-like growth factor-1 (IGF-1) is one of the growth factors that have a wide range of biologic effects. We have confirmed that gene transfer of IGF-1 to the penis could improve erectile capacity. However, there are some limitations in gene therapies, such as toxicity or a risk of insertional mutagenesis. Protein treatment may be another choice for decreasing these risks. AIM: To investigate whether intracavernosal injection of IGF-1 protein can restore erectile function in the aging rat. MAIN OUTCOME MEASURES: Erectile responses, morphological changes, and nitric oxide-cyclic guanosine monophosphate (NO-cGMP) signaling pathways-related marker were determined. METHODS: Ten young (4 months) and 30 old (24 months) Sprague-Dawley male rats were enrolled in this study. The old rats were divided into three groups: vehicle-only (N = 10), IGF-1 1 microg/kg (N = 10) and IGF-1 10 microg/kg treatment group (N = 10). After 4 and 8 weeks of single IGF-1 injection treatment, intracavernous pressure (ICP) responses with electrical stimulation to the cavernous nerve were evaluated. The percent of smooth muscle in corpus cavernosum tissue, the expression of mRNA and protein of endothelial nitric oxide synthase (eNOS) were also evaluated. The activity of nitric oxide synthase (NOS) and concentration of guanosine 3',5'-cyclic-monophosphate (cGMP) that act upon the major NO-cGMP signaling pathways in penile tissue were also analyzed. RESULTS: After IGF-1 treatment, the ICP responses was significantly increased as the young control group in both the IGF-1 1 microg/kg and the IGF-1 10 microg/kg group compared with the vehicle-only group at 4 and 8 weeks (P < 0.05). Masson's trichrom staining showed the percentage of cavernosal smooth muscle was increased in IGF-1 treatment group. IGF-1 increased e-NOS expression. NOS activities and cGMP concentrations were also significantly increased in IGF-1 treatment rats. CONCLUSIONS: IGF-1 improved erectile function in aged rats via restoration the integrity of smooth muscle of corpus cavernosum and modulation of NO-cGMP pathways.
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Envelhecimento/fisiologia , GMP Cíclico/metabolismo , Disfunção Erétil/tratamento farmacológico , Fator de Crescimento Insulin-Like I/farmacologia , Óxido Nítrico/metabolismo , Animais , Pressão Sanguínea , Estimulação Elétrica , Disfunção Erétil/fisiopatologia , Imuno-Histoquímica , Injeções , Masculino , Músculo Liso Vascular/metabolismo , Pênis/inervação , Pênis/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de SinaisRESUMO
OBJECTIVE: To investigate the best dose and the long-term effect of the human insulin-like growth factor-1 (hIGF-1) gene injection into the penis of aged rats. METHODS: Included in this study were 10 young (4 months old) and 40 aged (24 months old) Sprague-Dawley male rats, the latter equally divided into a PBS control and a 10 microg, a 100 microg and a 1 000 microg hIGF-1 injection group. Electrical stimulation was conducted 4 and 8 weeks after hIGF-1 injection into the penile corpus cavernous of the rats to detect the intracavernous pressure (ICP) and mean arterial pressure (MAP). Dose - and time -associated therapeutic results were analyzed and the mRNA expression of hIGF-1 determined by RT - PCR. RESULTS: ICP, MAP and total ICP were significant decreased by electrical stimulation in the aged rats as compared with the young ones (P < 0.05), statistically increased in the three hIGF-1 dose groups in comparison with the PBS controls (P < 0.05), and showed no obvious difference between the young rats and the latter two dose groups at 4 and 8 weeks. Although less obvious effect was achieved in the 10 microg group than in the young rats, the therapeutic result was still of significance. The mRNA expression of the hIGF-1 gene was confirmed in all the hIGF-1 treated rats. CONCLUSION: The hIGF-1 therapy can improve erectile function in aged rats, 100 microg suffices for effective erection and the effect may last at least 8 weeks for a single dose.
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Envelhecimento/fisiologia , Disfunção Erétil/terapia , Fator de Crescimento Insulin-Like I/fisiologia , Animais , Relação Dose-Resposta a Droga , Disfunção Erétil/fisiopatologia , Terapia Genética/métodos , Fator de Crescimento Insulin-Like I/genética , Masculino , Pênis/metabolismo , Pênis/fisiopatologia , Plasmídeos/administração & dosagem , Plasmídeos/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de TempoRESUMO
The Y-chromosome haplogroup C3*-Star Cluster (revised to C2*-ST in this study) was proposed to be the Y-profile of Genghis Khan. Here, we re-examined the origin of C2*-ST and its associations with Genghis Khan and Mongol populations. We analyzed 34 Y-chromosome sequences of haplogroup C2*-ST and its most closely related lineage. We redefined this paternal lineage as C2b1a3a1-F3796 and generated a highly revised phylogenetic tree of the haplogroup, including 36 sub-lineages and 265 non-private Y-chromosome variants. We performed a comprehensive analysis and age estimation of this lineage in eastern Eurasia, including 18,210 individuals from 292 populations. We discovered that the origin of populations with high frequencies of C2*-ST can be traced to either an ancient Niru'un Mongol clan or ordinary Mongol tribes. Importantly, the age of the most recent common ancestor of C2*-ST (2576 years, 95% CI = 1975-3178) and its sub-lineages, and their expansion patterns, are consistent with the diffusion of all Mongolic-speaking populations, rather than Genghis Khan himself or his close male relatives. We concluded that haplogroup C2*-ST is one of the founder paternal lineages of all Mongolic-speaking populations, and direct evidence of an association between C2*-ST and Genghis Khan has yet to be discovered.
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Povo Asiático/genética , Cromossomos Humanos Y/genética , Evolução Molecular , Efeito Fundador , Haplótipos , Humanos , MasculinoRESUMO
Demographic change of human populations is one of the central questions for delving into the past of human beings. To identify major population expansions related to male lineages, we sequenced 78 East Asian Y chromosomes at 3.9 Mbp of the non-recombining region, discovered >4,000 new SNPs, and identified many new clades. The relative divergence dates can be estimated much more precisely using a molecular clock. We found that all the Paleolithic divergences were binary; however, three strong star-like Neolithic expansions at â¼6 kya (thousand years ago) (assuming a constant substitution rate of 1×10(-9)/bp/year) indicates that â¼40% of modern Chinese are patrilineal descendants of only three super-grandfathers at that time. This observation suggests that the main patrilineal expansion in China occurred in the Neolithic Era and might be related to the development of agriculture.
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Povo Asiático/genética , Cromossomos Humanos Y/genética , Genética Populacional/métodos , Polimorfismo de Nucleotídeo Único , Algoritmos , Povo Asiático/estatística & dados numéricos , China , Cromossomos Humanos Y/classificação , Variação Genética , Genética Populacional/estatística & dados numéricos , Genótipo , Geografia , Haplótipos , Humanos , Masculino , Modelos Genéticos , Taxa de Mutação , Filogenia , Dinâmica Populacional , Análise de Sequência de DNA , Fatores de TempoRESUMO
Hepatitis C virus (HCV) infection is a major global health problem. There is no effective vaccine and the current treatment regimen with pegylated interferon α and ribavirin is associated with significant adverse events. Therefore, there is an urgent need to identify new antiviral targets for HCV therapy. In recent years, a growing number of microRNAs (miRNAs) have been reported to be able to regulate HCV replication and infection by interacting with the HCV genome directly or by regulating host innate immunity to build a nonspecific antiviral state within cells. In this review, we discuss HCV virology and standard of care followed by miRNA in general, and then give a brief overview of miRNAs involved in HCV infection and discuss their potential application as a therapeutic option for the treatment of HCV infection.