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1.
Mol Biol Evol ; 39(12)2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36413509

RESUMO

African wild suids consist of several endemic species that represent ancient members of the family Suidae and have colonized diverse habitats on the African continent. However, limited genomic resources for African wild suids hinder our understanding of their evolution and genetic diversity. In this study, we assembled high-quality genomes of a common warthog (Phacochoerus africanus), a red river hog (Potamochoerus porcus), as well as an East Asian Diannan small-ear pig (Sus scrofa). Phylogenetic analysis showed that common warthog and red river hog diverged from their common ancestor around the Miocene/Pliocene boundary, putatively predating their entry into Africa. We detected species-specific selective signals associated with sensory perception and interferon signaling pathways in common warthog and red river hog, respectively, which contributed to their local adaptation to savannah and tropical rainforest environments, respectively. The structural variation and evolving signals in genes involved in T-cell immunity, viral infection, and lymphoid development were identified in their ancestral lineage. Our results provide new insights into the evolutionary histories and divergent genetic adaptations of African suids.


Assuntos
Adaptação Fisiológica , Animais , Suínos , Filogenia , Especificidade da Espécie , Adaptação Fisiológica/genética , África
2.
Genomics ; 112(6): 5180-5187, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32818634

RESUMO

Mitochondrial genomes (mitogenomes) help advance our learning of molecular evolution and phylogenetic relationships. The mitogenome of H. latimera is 16,246 bp in length, which typically contains 37 animal mitogenome genes consisting of 13 protein-coding genes (PCGs), two rRNA genes, and 22 tRNA genes, as well as a control region. The AT content of H. latimera is 69.1%. The A + T skew of the mitogenome of H. latimera was slightly negative (-0.017). The size of Thirteen PCGs is from 162 bp to 1731 bp. Twenty-two tRNA genes ranged from 62 to 73 bp and were highly A + T biased. All tRNA genes owed a typical cloverleaf structure, not including the trnS1 gene lacking a dihydroxyuridine arm. One PCG, two rRNAs, and 12 of the tRNAs were rearranged compared to the pancrustacean gene order. Phylogenetic analysis revealed the locationt of H. latimera among the Varunidae family.


Assuntos
Braquiúros/genética , Genoma Mitocondrial , Animais , Braquiúros/classificação , Proteínas Mitocondriais/genética , Filogenia , RNA de Transferência/genética
3.
Mediators Inflamm ; 2020: 3278081, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32454789

RESUMO

This case-control study aimed to investigate potential associations between interleukin (IL) gene polymorphisms and the risks of developing extremity posttraumatic osteomyelitis (PTOM) in Chinese Han population. Altogether, 189 PTOM patients and 200 healthy controls were genotyped of IL-1α (rs17561, rs1800587), IL-1ß (rs16944, rs1143627, rs1143634, rs2853550), IL-1RN (rs4251961, rs419598, rs315951), IL-4 (rs2243248, rs2243250), IL-6 (rs1800795, rs1800796, rs1800797), IL-8 (rs4073, rs2227306, rs2227307), IL-10 (rs3024491, rs3024496, rs1800871, rs1800872, rs1800896), IL-17A (rs2275913), and IL-17F (rs763780) using the SNaPshot genotyping method. Statistical differences were observed regarding the genotype distributions of rs16944 (P = 0.049) and rs4251961 (P = 0.007) between the patients and healthy controls. In addition, significant associations were found between rs16944 and the risk of PTOM development by dominant (OR = 1.854, P = 0.017), homozygous (OR = 1.831, P = 0.041), and heterozygous (OR = 1.869, P = 0.022) models, and of rs1143627 by dominant (OR = 1.735, P = 0.032) and homozygous (OR = 1.839, P = 0.040) models. Moreover, significant links were also identified between rs4251961 and the susceptibility to PTOM by dominant (OR = 0.446, P = 0.005) and heterozygous (OR = 0.409, P = 0.003) models, and of rs1800796 by dominant (OR = 4.184, P = 0.029), homozygous (OR = 4.378, P = 0.026), and heterozygous (OR = 3.834, P = 0.046) models. The present outcomes demonstrated that rs16944, rs1143627, and rs1800796 associate with increased risks, while rs4251961 links to a decreased risk of PTOM development in Chinese Han population.


Assuntos
Predisposição Genética para Doença , Interleucina-1beta/genética , Interleucinas/genética , Osteomielite/genética , Polimorfismo Genético , Acidentes de Trânsito , Adulto , Calcâneo , China , Feminino , Fêmur , Genótipo , Homozigoto , Humanos , Proteína Antagonista do Receptor de Interleucina 1/genética , Interleucina-6/genética , Masculino , Pessoa de Meia-Idade , Razão de Chances , Osteomielite/etnologia , Staphylococcus aureus , Resultado do Tratamento , Fator de Necrose Tumoral alfa/genética
4.
J Orthop Sci ; 24(5): 817-821, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30777362

RESUMO

BACKGROUND: The most commonly reported complication after acromioclavicular (AC) joint dislocation treated with the Suture-button is loss of reduction. Loss of reduction is a major factor influencing the patient's joint function and subjective satisfaction. The objective of this study is to analyze the risk factors causing loss of reduction after AC joint dislocation treated with the Suture-button. METHODS: One hundred and thirty patients with AC joint dislocation who were surgically treated the Suture-button in our hospital from February 2009 to February 2015, were recorded their age, sex, BMI, time from injury to surgery, Rockwood's classification, with or without osteoporosis, double or triple button technique, position of the clavicle tunnel, tunnel diameter, coracoid button position, alignment of the button, acromioclavicular ligament repair or not, different methods of postoperative limb immobilization, and so on. Mean comparisons or chi-square test was used for univariate analysis of the above factors, and then multivariate logistic regression analysis was performed to predict risk factors. RESULTS: Reduction was lost in 23.1% of the patients. Univariate analysis showed that button alignment, double or triple button technique, coracoid button position, position of the clavicle tunnel, acromioclavicular ligament repair or not and osteoporosis had statistically significant association with loss of reduction for AC joint (P = 0.031, 0.034, 0.000, 0.042, 0.047 and 0.000 respectively). Multivariate logistic regression analysis demonstrated that osteoporosis (P = 0.003), position of the clavicle tunnel (P = 0.032) and coracoid button position (P < 0.001) were the risk factors that significantly associated with the loss of reduction after AC joint dislocation treated with the Suture-button. CONCLUSIONS: Clavicle tunnel location using relative ratio method, accurate placement of button plate under coracoid process (inside or outside deviation <20°), various reinforcement operations for patients with osteoporosis are important factors in preventing loss of reduction.


Assuntos
Articulação Acromioclavicular/lesões , Articulação Acromioclavicular/cirurgia , Luxações Articulares/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Técnicas de Sutura/efeitos adversos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos de Cirurgia Plástica/efeitos adversos , Fatores de Risco
5.
Acta Orthop Belg ; 85(1): 54-62, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31023200

RESUMO

The purpose of this study was to assess the clinical results of patients treated with either one suture-button device or two suture-button devices for acute acromioclavicular (AC) joint dislocations. Eighty patients were randomized to operative stabilization either by one suture-button device (OSB, 40) or by two suture-button devices (TSB, 40). Postoperative complications, the Constant, VAS and SST scores, patient subjective satisfaction result were reviewed. The total incidence of complications was similar in both groups (16/40 vs. 17/40, P =0 .820). There were no significant differences in the length of hospitalization, the Constant, VAS and SST scores, and the ability to return to previous work between the two groups. However, the patients of TSB group had longer incision length, more blood loss, more operative and radiation time and more hospitalization costs (P < 0.01). The radiological evaluation showed no significant difference in the CC distance between the two groups (P = 0.557). Our results indicated that one suture-button device could achieve the same good radiological and clinical results as two suture-button devices did.


Assuntos
Articulação Acromioclavicular/lesões , Articulação Acromioclavicular/cirurgia , Luxações Articulares/cirurgia , Procedimentos Ortopédicos/métodos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Ortopédicos/efeitos adversos , Complicações Pós-Operatórias/etiologia , Técnicas de Sutura/instrumentação , Suturas , Adulto Jovem
6.
Pediatr Emerg Care ; 32(11): 773-778, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26555307

RESUMO

OBJECTIVES: Pediatric forearm torus fracture, a frequent reason for emergency department visits, can be immobilized by both rigid cast and nonrigid methods. However, controversy still exists regarding the optimal treatment of the disease. The aim of this study was to compare, in a systematic review, clinical efficacy of rigid cast with nonrigid methods for immobilization of the pediatric forearm torus fractures. METHODS: Literature search was performed of PubMed and Cochrane Library by 2 independent reviewers to identify randomized controlled trials comparing rigid cast with nonrigid methods for pediatric forearm torus fractures from inception to December 31, 2013, without limitation of publication language. Trial quality was assessed using the modified Jadad scale. RESULTS: Eight randomized controlled trials with a total of 781 participants met all inclusion criteria. The nonrigid methods for immobilization included soft cast, splint, bandage, and slab. Results showed that nonrigid immobilizations had better clinical efficacy than rigid cast regarding functional recovery, treatment cost, and complication rate (relative risk, 3.02; 95% confidence interval, 1.70-5.37; P = 0.0002). Compared with rigid cast, more patients would like to choose the nonrigid methods of immobilization for future use. However, discrepant results sill surrounds the pain levels of the patients. CONCLUSIONS: The current study suggests that the nonrigid immobilization methods have more advantages than rigid cast for immobilization of pediatric forearm torus fracture. The former strategies are also safe enough for clinical therapy.


Assuntos
Dispositivos de Fixação Ortopédica/estatística & dados numéricos , Fraturas do Rádio/terapia , Adolescente , Bandagens/efeitos adversos , Bandagens/estatística & dados numéricos , Moldes Cirúrgicos/efeitos adversos , Moldes Cirúrgicos/estatística & dados numéricos , Criança , Pré-Escolar , Gerenciamento Clínico , Feminino , Humanos , Masculino , Dispositivos de Fixação Ortopédica/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Contenções/efeitos adversos , Contenções/estatística & dados numéricos , Resultado do Tratamento
7.
BMC Med Genomics ; 17(1): 38, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38287380

RESUMO

BACKGROUND: Single nucleotide polymorphisms (SNPs) in the nucleotide-binding domain leucine-rich repeat protein-3 (NLRP3) gene are reported to be linked to many inflammatory disorders. However, uncertainty persists over the associations between these SNPs and susceptibilities to chronic osteomyelitis (COM). This study aimed to investigate potential relationships between NLRP3 gene SNPs and the risks of developing COM in a Chinese Han cohort. METHODS: The four tag SNPs of the NLRP3 gene were genotyped in a total of 428 COM patients and 368 healthy controlsusing the SNapShot technique. The genotype distribution, mutant allele frequency, and the four genetic models (dominant, recessive, homozygous, and heterozygous) of the four SNPs were compared between the two groups. RESULTS: A significant association was found between rs10754558 polymorphism and the probability of COM occurence by the heterozygous model (P = 0.037, odds ratio [OR] = 1.541, 95% confidence interval [CI] = 1.025-2.319), indicating that rs10754558 may be associated with a higher risk of developing COM.In addition, possible relationship was found between rs7525979 polymorphism and the risk of COM development by the outcomes of homozygous (P = 0.073, OR = 0.453, 95% CI = 0.187-1.097) and recessive (P = 0.093, OR = 0.478, 95% CI = 0.198-1.151) models, though no statistical differences were obtained. CONCLUSIONS: Outcomes of the present study showed, for the first time, that rs10754558 polymorphism of the NLRP3 gene may increase the risk of COM development in this Chinese Han population, with genotype CG as a risk factor. Nonetheless, this conclusion requires verification from further studies with a larger sample size.


Assuntos
Proteína 3 que Contém Domínio de Pirina da Família NLR , Osteomielite , Humanos , Estudos de Casos e Controles , China , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Osteomielite/genética , Polimorfismo de Nucleotídeo Único
8.
Biochem Biophys Res Commun ; 434(3): 498-502, 2013 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-23583396

RESUMO

The level of reactive oxygen species (ROS) and the activity of spontaneous, transient, localized Ca(2+) increases (known as Ca(2+) sparks) in tracheal smooth muscle cells (TSMCs) in an experimental allergic asthma mouse model has not yet been investigated. We used laser confocal microscopy and fluorescent dyes to measure ROS levels and Ca(2+) sparks, and we found that both events were significantly increased in TSMCs obtained from ovalbumin (OVA)-sensitized/-challenged mice compared with control mice. ROS levels began to increase in TSMCs after the first OVA challenge, and this increase was sustained. However, this elevation and Ca(2+)-spark increase was abolished after the administration of the ROS scavenger N-acetylcysteine amide (NACA) for 5days. Furthermore, a similar inhibition was also observed following the direct perfusion of NACA into cells isolated from the (OVA)-sensitized mice that were not treated with NACA. Moreover, we used 0.1-mM caffeine treatment to increase the Ca(2+) sparks in single TSMCs and observed cell shortening. In addition, we did not find increases in the mRNA levels of ryanodine (RyRs) and inositol 1,4,5-trisphosphate (IP3Rs) receptors in the tracheal smooth muscle cells of (OVA)-sensitized mice compared with controls. We concluded that ROS and Ca(2+) sparks increased in (OVA)-sensitized TSMCs. We found that ROS induces Ca(2+) sparks, and increased Ca(2+) sparks resulted in the contraction of (OVA)-sensitized TSMCs, resulting in the generation of airway hyperresponsiveness (AHR). This effect may represent a novel mechanism for AHR pathogenesis and might provide insight into new methods for the clinical prevention and treatment of asthma and asthmatic AHR.


Assuntos
Cálcio/metabolismo , Músculo Liso/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Traqueia/metabolismo , Animais , Camundongos , Músculo Liso/citologia , Ovalbumina/administração & dosagem , Traqueia/citologia
9.
Pflugers Arch ; 464(6): 671-80, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23053477

RESUMO

Airway ciliary beat activity (CBA) plays a pivotal role in protecting the body by removing mucus and pathogens from the respiratory tract. Since CBA is complicated and cannot be characterized by merely frequency, we recorded CBA using laser confocal line scanning and defined six parameters for describing CBA. The values of these parameters were all above 0 when measured in beating ciliated cells from mouse tracheae. We subsequently used 10 µM adenosine-5'-triphosphate (ATP) to stimulate ciliated cells and simultaneously recorded intracellular Ca(2+) levels and CBA. We found that intracellular Ca(2+) levels first increased, followed by an increase in CBA. Among the six parameters, frequency, amplitude, and integrated area significantly increased, whereas rise time, decay time, and full duration at half maximum markedly decreased. The results suggest that these six parameters are appropriate for assessing CBA and that increased intracellular Ca(2+) levels might enhance CBA. We next used our established methods to observe changes in mechanically stimulated cilia tips. We found that mechanical stimulation-induced changes in both intracellular Ca(2+) levels and CBA were not only similar to those induced by ATP, but were also blocked by treatment with a Ca(2+) chelator, BAPTA-AM, (10 µM) for 10 min. Moreover, while the same blockage was observed under Ca(2+)-free conditions, addition of 2 mM Ca(2+) into the chamber restored increases in both intracellular Ca(2+) levels and CBA. Taken together, we have provided a novel method for real-time measurement and complete analysis of CBA as well as demonstrated that mechanical stimulation of cilia tips resulted in Ca(2+) influx that led to increased intracellular Ca(2+) levels, which in turn triggered CBA enhancement.


Assuntos
Cálcio/fisiologia , Cílios/fisiologia , Microscopia Confocal/métodos , Traqueia/fisiologia , Trifosfato de Adenosina/metabolismo , Animais , Cálcio/metabolismo , Cílios/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Traqueia/metabolismo
10.
J Inflamm Res ; 15: 2745-2759, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35509324

RESUMO

Introduction: Osteomyelitis is characterized by intensive inflammatory bone disease and remains a clinical challenge in orthopedic surgery, despite the advances made in medical and surgical therapies. Staphylococcus aureusis a major causative agent of osteomyelitis, causing the progressive inflammatory destruction of bone. Prophylaxis of osteomyelitis during orthopedic surgery is necessary. NFκB essential modulator-binding domain (NBD) peptides are cell-permeable peptide inhibitors of the IκB-kinase complex. The prophylactic effect of NBD peptides in relieving inflammation and inhibiting bone defects in osteomyelitis is still under investigation. Our purpose was to determine the preventive effect of NBD peptides in S. aureus infection-induced bone defects in osteomyelitis. Methods: An S. aureus osteomyelitis rabbit model was used in this study. The rabbits were divided into four groups: NBD, cefazolin, control, and PBS. Clinical and laboratory indicators of erythrocyte-sedimentation rate, CRP, and TNFα levels were assessed to monitor systemic reactions. The efficacy of NBD peptides in S. aureus-induced osteomyelitis was evaluated by radiological, histological, and microbiological examinations, immunohistochemistry, immunofluorescence, and micro-CT scans. Results: In general, NBD peptides effectively reduced clinical signs in rabbits when compared with the control group. Radiography indicated that there was more severe osteomyelitis in the bacterium-infection control group. There was no significance between cefazolin- and NBD-group average scores. The histological results of the lesion slices further confirmed different severity among the groups. Additionally, significant pathological differences were found between the cefazolin and NBD groups, and the PBS group showed no obvious pathological changes. Conclusion: Prophylactic administration of NBD peptides to bone-defect areas inhibited bacterial spread and promoted bone regeneration, making NBD peptides a possible treatment option for prophylaxis in bone infections.

11.
Am J Transl Res ; 13(9): 10163-10177, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34650688

RESUMO

FAM107A may have a dual role in regulating the biological functions of tumors; however, its role in prostate adenocarcinoma (PRAD) remains unknown. We analyzed FAM107A expression by employing databases to clarify its potential prognostic value for PRAD, as well as its role in the pathogenesis of PRAD. We observed that the FAM107A expression level is decreased in PRAD, and the reduced expression is considerably associated with poor overall survival and progression-free survival (PFS). To explore the mechanism of FAN107A in PRAD, we performed an immune cell infiltration analysis and a gene set enrichment analysis. The results showed that FAM107A expression is positively related to mast cells and natural killer cells. The Wnt signaling pathway, the MAPK signaling pathway, and the immune responses are differentially enriched in the FAM107A high-expression phenotype. The FAM107A low-expression phenotype is linked to apoptosis-induced DNA fragmentation and DNA methylation in PRAD. To assess the relationship between the clinical features and the FAM107A expression, we performed a logistic regression analysis and observed that a decreased FAM107A expression is associated with poor prognostic features, including the T stage, the N stage, the Gleason score, residual tumors, and the TP53 status. Our multivariate Cox regression results showed that the Gleason score, the primary therapy outcome, and the FAM107A expression are independent prognostic factors in PFS. In summary, we consider FAM107A an independent risk factor for PFS in PRAD. Moreover, several pathways may reveal the role of FAM107A in triggering carcinogenesis. These discoveries provide novel perspectives for future research to elucidate the pathogenic mechanism underlying PRAD.

12.
Biomed Res Int ; 2021: 3664564, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34853789

RESUMO

Tumor necrosis factor-α is a common cytokine that increases in inflammatory processes, slows the differentiation of bone formation, and induces osteodystrophy in the long-term inflammatory microenvironment. Our previous study confirmed that the Elongation protein 2 (ELP2) plays a significant role in osteogenesis and osteogenic differentiation, which is considered a drug discovery target in diseases related to bone formation and differentiation. In this study, we applied an in silico virtual screening method to select molecules that bind to the ELP2 protein from a chemical drug molecule library and obtained 95 candidates. Then, we included 11 candidates by observing the docking patterns and the noncovalent bonds. The binding affinity of the ELP2 protein with the candidate compounds was examined by SPR analysis, and 5 out of 11 compounds performed good binding affinity to the mouse ELP2 protein. After in vitro cell differentiation assay, candidates 2# and 5# were shown to reduce differentiation inhibition after tumor necrosis factor-α stimulation, allowing further optimization and development for potential clinical treatment of inflammation-mediated orthopedic diseases.


Assuntos
Peptídeos e Proteínas de Sinalização Intracelular/antagonistas & inibidores , Osteogênese/efeitos dos fármacos , Fator de Necrose Tumoral alfa/farmacologia , Células 3T3 , Animais , Calcificação Fisiológica/efeitos dos fármacos , Calcificação Fisiológica/fisiologia , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Diferenciação Celular/fisiologia , Linhagem Celular , Bases de Dados de Produtos Farmacêuticos , Avaliação Pré-Clínica de Medicamentos , Marcadores Genéticos , Técnicas In Vitro , Peptídeos e Proteínas de Sinalização Intracelular/química , Ligantes , Camundongos , Modelos Moleculares , Simulação de Acoplamento Molecular , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Osteogênese/genética , Osteogênese/fisiologia , Ligação Proteica , Relação Estrutura-Atividade , Ressonância de Plasmônio de Superfície , Interface Usuário-Computador
13.
J Ethnopharmacol ; 266: 113430, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33011366

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Astragalus mongholicus, Solanum nigrum Linn, Lotus plumule, Ligusticum are widely used traditional herbal medicines for cancer treatment in China. They were typical drugs selected from Gubenyiliu II and series of formula (GYII), which were developed on the foundation of YIQIHUOXUEJIEDU theory. In the present study, four active ingredients (Astragaloside IV, α-solanine, neferine, and 2,3,5,6-tetramethylpyrazine) derived from medicines above were applied in combination as SANT. AIM OF THE STUDY: Triple-negative breast cancer (TNBC) is a serious threat to women's health worldwide. Heparanase (HPSE) is often up-regulated in breast cancer with the properties of facilitating tumorigenesis and influencing the autophagy process in cancer cells. This study aimed at evaluating the anti-tumor potential of SANT in treating HPSE related TNBC both in-vitro and in-vivo. MATERIALS AND METHODS: In this study, we explored the correlation between HPSE expression and survival of breast cancer patients in databases. We performed MTS, trans-well and wound scratch assays to assess the impact of SANT on cell proliferation and migration. Confocal microscopy observation and western blots were applied to verify the autophagy flux induced by SANT. Mice models were employed to evaluate the efficacy and safety of SANT in-vivo by tumor weights and volumes or serum index, respectively. To analyze the underlying mechanisms of SANT, we conducted human autophagy PCR array and angiogenesis proteome profiler on tumor tissues. RESULTS: Patients with elevated HPSE expression were associated with a poor outcome in both RFS (P = 1.7e-12) and OS (P = 0.00016). SANT administration significantly inhibited cancer cells' proliferation and migration, enhanced autophagy flux, and slightly reduced the active form of HPSE in-vitro. SANT also suppressed tumor growth and angiogenesis in-vivo. Human autophagy PCR array results indicated that SANT increased the ATG16L1, ATG9B, ATG4D gene expressions while decreased TMEM74 and TNF gene expressions.Angiogenesis proteome profiler results showed SANT reduced protein level of HB-EGF, thrombospondin-2, amphiregulin, leptin, IGFBP-9, EGF, coagulation factor III, and MMP-9 (pro and active form) in tumor, raised the protein expression of serpin E1 and platelet factor 4. CONCLUSIONS: These findings indicated that herbal compounds SANT may be a promising candidate in anti-cancer drug discovery. It also provides novel strategies for using natural compounds to achieve optimized effect.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Autofagia/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/farmacologia , Animais , Antineoplásicos Fitogênicos/administração & dosagem , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Medicamentos de Ervas Chinesas/administração & dosagem , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glucuronidase/genética , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/patologia , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Zool Res ; 41(1): 94-96, 2020 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-31840950

RESUMO

Many functional elements associated with traits and diseases are located in non-coding regions and act on distant target genes via chromatin looping and folding, making it difficult for scientists to reveal the genetic regulatory mechanisms. Capture Hi-C is a newly developed chromosome conformation capture technology based on hybridization capture between probes and target genomic regions. It can identify interactions among target loci and all other loci in a genome with low cost and high resolution. Here, we developed CaptureProbe, a user-friendly, graphical Java tool for the design of capture probes across a range of target sites or regions. Numerous parameters helped to achieve and optimize the designed probes. Design testing of CaptureProbe showed high efficiency in the design success ratio of target loci and probe specificity. Hence, this program will help scientists conduct genome spatial interaction research. CaptureProbe and source code are available at https://sourceforge.net/projects/captureprobe/.


Assuntos
Cromossomos/genética , Sondas de DNA/genética , Genômica/métodos , Software , Animais , Humanos
15.
Zool Res ; 41(4): 471-475, 2020 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-32543792

RESUMO

Cis-regulatory elements play an important role in the development of traits and disease in organisms (Ma et al., 2020; Woolfe et al., 2005) and their annotation could facilitate genetic studies. The Encyclopedia of DNA Elements (ENCODE) (Davis et al., 2018) and Functional Annotation of Animal Genomes (FAANG) (FAANG Consortium et al., 2015) offer pioneering data on regulatory elements in several species. Currently, however, regulatory element annotation data remain limited for most organisms. In this study, we developed a tool (OrthReg) for annotating conserved orthologous cis-regulatory elements in targeted genomes using an annotated reference genome. Cross-species validation of this annotation tool using human and mouse ENCODE data confirmed the robustness of this strategy. To explore the efficiency of the tool, we annotated the pig genome and identified more than 28 million regulatory annotation records using the reference human ENCODE data. With this regulatory annotation, some putative regulatory non-coding variants were identified within domestication sweeps in European and East Asian pigs. Thus, this tool can utilize data produced by ENCODE, FAANG, and similar projects, and can be easily extended to customized experimental data. The extensive application of this tool will help to identify informative single nucleotide polymorphisms (SNPs) in post-genome-wide association studies and resequencing analysis of organisms with limited regulatory annotation data.


Assuntos
Sequência de Bases , Sequência Conservada , Estudo de Associação Genômica Ampla/métodos , Genoma , Camundongos/genética , Sus scrofa/genética , Animais , Estudo de Associação Genômica Ampla/veterinária , Humanos
16.
Natl Sci Rev ; 7(6): 952-963, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34692117

RESUMO

Abundant and diverse domestic mammals living on the Tibetan Plateau provide useful materials for investigating adaptive evolution and genetic convergence. Here, we used 327 genomes from horses, sheep, goats, cattle, pigs and dogs living at both high and low altitudes, including 73 genomes generated for this study, to disentangle the genetic mechanisms underlying local adaptation of domestic mammals. Although molecular convergence is comparatively rare at the DNA sequence level, we found convergent signature of positive selection at the gene level, particularly the EPAS1 gene in these Tibetan domestic mammals. We also reported a potential function in response to hypoxia for the gene C10orf67, which underwent positive selection in three of the domestic mammals. Our data provide an insight into adaptive evolution of high-altitude domestic mammals, and should facilitate the search for additional novel genes involved in the hypoxia response pathway.

17.
Biomed Res Int ; 2019: 7483537, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30949508

RESUMO

BACKGROUND: Previous studies had indicated that interleukin-1 beta (IL-1ß) gene single nucleotide polymorphisms (SNPs) associate with different inflammatory diseases. However, potential links between these polymorphisms and susceptibility to extremity chronic osteomyelitis (COM) remain unclear. This study aimed to investigate relationships between IL-1ß gene polymorphisms (rs16944, rs1143627, rs1143634, and rs2853550) and risks of developing extremity COM in Chinese Han population. METHODS: Altogether 233 extremity COM patients and 200 healthy controls were genotyped for the four tag SNPs of the IL-1ß gene using the SNapShot genotyping method. Comparisons were performed regarding genotype distribution, mutant allele frequency, and four genetic models (dominant, recessive, homozygous, and heterozygous models) of the four SNPs between the two groups. RESULTS: Significant associations were identified between rs16944 polymorphism and the risk of developing COM by dominant model (P = 0.026, OR = 1.698, 95% CI 1.065-2.707) and heterozygous model (P = 0.030, OR = 1.733, 95% CI 1.055-2.847). Although no statistical differences were found of rs1143627 polymorphism between the two groups, there existed a trend that rs1143627 may be linked to an elevated risk of developing COM by outcomes of dominant (P = 0.061), homozygous (P = 0.080) and heterozygous (P = 0.095) models. However, no statistical correlations were found between rs1143634 and rs2853550 polymorphisms and susceptibility to COM in Chinese Han population. CONCLUSIONS: To our knowledge, we reported for the first time that IL-1ß gene rs16944 polymorphism may contribute to the increased susceptibility to extremity COM in Chinese Han population, with genotype of AG as a risk factor.


Assuntos
Povo Asiático , Frequência do Gene , Predisposição Genética para Doença , Interleucina-1beta/genética , Osteomielite , Polimorfismo de Nucleotídeo Único , Adulto , Povo Asiático/etnologia , Povo Asiático/genética , China/etnologia , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteomielite/etnologia , Osteomielite/genética
18.
Int J Biol Macromol ; 137: 317-326, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31265851

RESUMO

The mitochondrial genome (mitogenome) can provide information for phylogenetic analysis and evolutionary biology. Here, we determined the complete mitogenome sequence of Sinna extrema (Noctuoidea: Nolidae). The newly determined mitogenome was 15,345 bp in length and included 13 protein-coding genes (PCGs), 2 ribosomal RNA genes, 22 transfer RNA genes and a control region (CR) similar to the known mitogenome of other lepidopterans. The entire mitogenome was biased towards using A and T, with an A + T content of 90.6%. Both the AT and GC skews in the mitogenome of S. extrema were negative. All PCGs were initiated with the standard start codon ATN, while cox1 began with CGA. All tRNA genes had the typical cloverleaf structure, except for the trnS1, which lacked a dihydroxyuridine arm. A gene rearrangement (trnM) was also found in the S. extrema mitogenome. To understand evolutionary relationships, we performed phylogenetic analysis using Bayesian inference (BI) and Maximum likelihood (ML) methods. Our phylogenetic analysis indicated that S. extrema and Gabala argentata cluster together with high nodal support values, and G. argentata is a member of the family Nolidae, which suggests that S. extrema belongs to Nolidae. Our results provide reference for further phylogenetic research of Noctuoidea species.


Assuntos
Genoma Mitocondrial , Genômica , Lepidópteros/classificação , Lepidópteros/genética , Filogenia , Animais , Composição de Bases , Sequência de Bases , Genômica/métodos , Fases de Leitura Aberta , Sequências Reguladoras de Ácido Nucleico
19.
Sci Rep ; 9(1): 11463, 2019 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-31391504

RESUMO

Tibetan pig is native to the Qinghai-Tibet Plateau and has adapted to the high-altitude environmental condition such as hypoxia. However, its origin and genetic mechanisms underlying high-altitude adaptation still remain controversial and enigmatic. Herein, we analyze 229 genomes of wild and domestic pigs from Eurasia, including 63 Tibetan pigs, and detect 49.6 million high-quality variants. Phylogenomic and structure analyses show that Tibetan pigs have a close relationship with low-land domestic pigs in China, implying a common domestication origin. Positively selected genes in Tibetan pigs involved in high-altitude physiology, such as hypoxia, cardiovascular systems, UV damage, DNA repair. Three of loci with strong signals of selection are associated with EPAS1, CYP4F2, and THSD7A genes, related to hypoxia and circulation. We validated four non-coding mutations nearby EPAS1 and CYP4F2 showing reduced transcriptional activity in Tibetan pigs. A high-frequency missense mutation is found in THSD7A (Lys561Arg) in Tibetan pigs. The selective sweeps in Tibetan pigs was found in association with selection against non-coding variants, indicating an important role of regulatory mutations in Tibetan pig evolution. This study is important in understanding the evolution of Tibetan pigs and advancing our knowledge on animal adaptation to high-altitude environments.


Assuntos
Aclimatação/genética , Resistência à Doença/genética , Hipóxia/veterinária , Seleção Genética , Sus scrofa/fisiologia , Altitude , Animais , Genética Populacional , Genoma , Genômica , Hipóxia/genética , Mutação , Filogenia , Tibet
20.
Sci Rep ; 8(1): 637, 2018 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-29330453

RESUMO

Aimed to investigate the characteristics of CS-induced membrane in comparison with the PMMA-induced membrane. Cellular components, histological changes, growth factor expressions of IL-6, VEGF, BMP-2, and TGF-ß1 in the two induced membranes were compared at 2, 4, 6 and 8 weeks, respectively. We also compared the histological changes at the bone defects between CS and PMMA groups. The structural characteristics of induced membrane were similar between CS and PMMA. Endochondral ossification took place in the CS-induced membrane at 8 week. Levels of VEGF, BMP-2 and TGF-ß1 in CS-induced membrane were insignificantly higher than those in PMMA-induced membrane at different time points. The expression of IL-6 was significantly higher in PMMA-induced membranes at 2nd week. In addition, osteogenic and neovascular activities of induced membranes increased with time and peaked at 6 weeks. CS promoted endochondral ossification at the broken ends of the bone defect than PMMA did. CS-induced membrane has a better capacity of generating VEGF, BMP-2 and TGF-ß1.osteogenic and neovascular activities achieve highest level at 6 week. CS may have the potential to replace PMMA as a novel spacer in Masquelet technique.


Assuntos
Proteína Morfogenética Óssea 2/genética , Sulfato de Cálcio/farmacologia , Fraturas do Fêmur/terapia , Polimetil Metacrilato/farmacologia , Fator de Crescimento Transformador beta1/genética , Fator A de Crescimento do Endotélio Vascular/genética , Animais , Modelos Animais de Doenças , Fraturas do Fêmur/diagnóstico por imagem , Fraturas do Fêmur/etiologia , Fraturas do Fêmur/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Membranas Artificiais , Osteogênese/efeitos dos fármacos , Ratos , Microtomografia por Raio-X
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