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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.
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Adaptación Fisiológica , Animales , Porcinos , Filogenia , Especificidad de la Especie , Adaptación Fisiológica/genética , ÁfricaRESUMEN
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.
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Braquiuros/genética , Genoma Mitocondrial , Animales , Braquiuros/clasificación , Proteínas Mitocondriales/genética , Filogenia , ARN de Transferencia/genéticaRESUMEN
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.
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Predisposición Genética a la Enfermedad , Interleucina-1beta/genética , Interleucinas/genética , Osteomielitis/genética , Polimorfismo Genético , Accidentes de Tránsito , Adulto , Calcáneo , China , Femenino , Fémur , Genotipo , Homocigoto , Humanos , Proteína Antagonista del Receptor de Interleucina 1/genética , Interleucina-6/genética , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Osteomielitis/etnología , Staphylococcus aureus , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/genéticaRESUMEN
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.
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Articulación Acromioclavicular/lesiones , Articulación Acromioclavicular/cirugía , Luxaciones Articulares/cirugía , Procedimientos de Cirugía Plástica/métodos , Técnicas de Sutura/efectos adversos , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Procedimientos de Cirugía Plástica/efectos adversos , Factores de RiesgoRESUMEN
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.
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Articulación Acromioclavicular/lesiones , Articulación Acromioclavicular/cirugía , Luxaciones Articulares/cirugía , Procedimientos Ortopédicos/métodos , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Procedimientos Ortopédicos/efectos adversos , Complicaciones Posoperatorias/etiología , Técnicas de Sutura/instrumentación , Suturas , Adulto JovenRESUMEN
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.
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Dispositivos de Fijación Ortopédica/estadística & datos numéricos , Fracturas del Radio/terapia , Adolescente , Vendajes/efectos adversos , Vendajes/estadística & datos numéricos , Moldes Quirúrgicos/efectos adversos , Moldes Quirúrgicos/estadística & datos numéricos , Niño , Preescolar , Manejo de la Enfermedad , Femenino , Humanos , Masculino , Dispositivos de Fijación Ortopédica/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Férulas (Fijadores)/efectos adversos , Férulas (Fijadores)/estadística & datos numéricos , Resultado del TratamientoRESUMEN
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.
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Proteína con Dominio Pirina 3 de la Familia NLR , Osteomielitis , Humanos , Estudios de Casos y Controles , China , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Osteomielitis/genética , Polimorfismo de Nucleótido SimpleRESUMEN
Introduction: Pathogens causing diabetic foot infections (DFIs) vary by region globally; however, knowledge of the causative organism is essential for effective empirical treatment. We aimed to determine the incidence and antibiotic susceptibility of DFI pathogens worldwide, focusing on Asia and China. Methods: Through a comprehensive literature search, we identified published studies on organisms isolated from DFI wounds from January 2000 to December 2020. Results: Based on our inclusion criteria, we analyzed 245 studies that cumulatively reported 38,744 patients and 41,427 isolated microorganisms. DFI pathogens varied according to time and region. Over time, the incidence of Gram-positive and Gram-negative aerobic bacteria have decreased and increased, respectively. America and Asia have the highest (62.74%) and lowest (44.82%) incidence of Gram-negative bacteria, respectively. Africa has the highest incidence (26.90%) of methicillin-resistant Staphylococcus aureus. Asia has the highest incidence (49.36%) of Gram-negative aerobic bacteria with species infection rates as follows: Escherichia coli, 10.77%; Enterobacter spp., 3.95%; and Pseudomonas aeruginosa, 11.08%, with higher local rates in China and Southeast Asia. Linezolid, vancomycin, and teicoplanin were the most active agents against Gram-positive aerobes, while imipenem and cefoperazone-sulbactam were the most active agents against Gram-negative aerobes. Discussion: This systematic review showed that over 20 years, the pathogens causing DFIs varied considerably over time and region. This data may inform local clinical guidelines on empirical antibiotic therapy for DFI in China and globally. Regular large-scale epidemiological studies are necessary to identify trends in DFI pathogenic bacteria. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023447645.
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Antibacterianos , Pie Diabético , Humanos , Pie Diabético/microbiología , Pie Diabético/epidemiología , China/epidemiología , Antibacterianos/uso terapéutico , Incidencia , Infecciones Bacterianas/epidemiología , Infecciones Bacterianas/microbiología , Infecciones Bacterianas/tratamiento farmacológicoRESUMEN
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.
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Calcio/metabolismo , Músculo Liso/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Tráquea/metabolismo , Animales , Ratones , Músculo Liso/citología , Ovalbúmina/administración & dosificación , Tráquea/citologíaRESUMEN
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.
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Calcio/fisiología , Cilios/fisiología , Microscopía Confocal/métodos , Tráquea/fisiología , Adenosina Trifosfato/metabolismo , Animales , Calcio/metabolismo , Cilios/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Tráquea/metabolismoRESUMEN
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.
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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.
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Péptidos y Proteínas de Señalización Intracelular/antagonistas & inhibidores , Osteogénesis/efectos de los fármacos , Factor de Necrosis Tumoral alfa/farmacología , Células 3T3 , Animales , Calcificación Fisiológica/efectos de los fármacos , Calcificación Fisiológica/fisiología , Diferenciación Celular/efectos de los fármacos , Diferenciación Celular/genética , Diferenciación Celular/fisiología , Línea Celular , Bases de Datos Farmacéuticas , Evaluación Preclínica de Medicamentos , Marcadores Genéticos , Técnicas In Vitro , Péptidos y Proteínas de Señalización Intracelular/química , Ligandos , Ratones , Modelos Moleculares , Simulación del Acoplamiento Molecular , Osteoblastos/citología , Osteoblastos/efectos de los fármacos , Osteoblastos/metabolismo , Osteogénesis/genética , Osteogénesis/fisiología , Unión Proteica , Relación Estructura-Actividad , Resonancia por Plasmón de Superficie , Interfaz Usuario-ComputadorRESUMEN
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.
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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.
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Antineoplásicos Fitogénicos/farmacología , Autofagia/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Inhibidores de la Angiogénesis/administración & dosificación , Inhibidores de la Angiogénesis/farmacología , Animales , Antineoplásicos Fitogénicos/administración & dosificación , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Medicamentos Herbarios Chinos/administración & dosificación , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Glucuronidasa/genética , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Neovascularización Patológica/tratamiento farmacológico , Neovascularización Patológica/patología , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/patología , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
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/.
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Cromosomas/genética , Sondas de ADN/genética , Genómica/métodos , Programas Informáticos , Animales , HumanosRESUMEN
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.
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Secuencia de Bases , Secuencia Conservada , Estudio de Asociación del Genoma Completo/métodos , Genoma , Ratones/genética , Sus scrofa/genética , Animales , Estudio de Asociación del Genoma Completo/veterinaria , HumanosRESUMEN
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.
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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.
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Pueblo Asiatico , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Interleucina-1beta/genética , Osteomielitis , Polimorfismo de Nucleótido Simple , Adulto , Pueblo Asiatico/etnología , Pueblo Asiatico/genética , China/etnología , Enfermedad Crónica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Osteomielitis/etnología , Osteomielitis/genéticaRESUMEN
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 15,345â¯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 Aâ¯+â¯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.
Asunto(s)
Genoma Mitocondrial , Genómica , Lepidópteros/clasificación , Lepidópteros/genética , Filogenia , Animales , Composición de Base , Secuencia de Bases , Genómica/métodos , Sistemas de Lectura Abierta , Secuencias Reguladoras de Ácidos NucleicosRESUMEN
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.