RESUMO
BACKGROUND: Fritillaria ussuriensis is an endangered medicinal plant known for its notable therapeutic properties. Unfortunately, its population has drastically declined due to the destruction of forest habitats. Thus, effectively protecting F. ussuriensis from extinction poses a significant challenge. A profound understanding of its genetic foundation is crucial. To date, research on the complete mitochondrial genome of F. ussuriensis has not yet been reported. RESULTS: The complete mitochondrial genome of F. ussuriensis was sequenced and assembled by integrating PacBio and Illumina sequencing technologies, revealing 13 circular chromosomes totaling 737,569 bp with an average GC content of 45.41%. A total of 55 genes were annotated in this mitogenome, including 2 rRNA genes, 12 tRNA genes, and 41 PCGs. The mitochondrial genome of F. ussuriensis contained 192 SSRs and 4,027 dispersed repeats. In the PCGs of F. ussuriensis mitogenome, 90.00% of the RSCU values exceeding 1 exhibited a preference for A-ended or U-ended codons. In addition, 505 RNA editing sites were predicted across these PCGs. Selective pressure analysis suggested negative selection on most PCGs to preserve mitochondrial functionality, as the notable exception of the gene nad3 showed positive selection. Comparison between the mitochondrial and chloroplast genomes of F. ussuriensis revealed 20 homologous fragments totaling 8,954 bp. Nucleotide diversity analysis revealed the variation among genes, and gene atp9 was the most notable. Despite the conservation of GC content, mitogenome sizes varied significantly among six closely related species, and colinear analysis confirmed the lack of conservation in their genomic structures. Phylogenetic analysis indicated a close relationship between F. ussuriensis and Lilium tsingtauense. CONCLUSIONS: In this study, we sequenced and annotated the mitogenome of F. ussuriensis and compared it with the mitogenomes of other closely related species. In addition to genomic features and evolutionary position, this study also provides valuable genomic resources to further understand and utilize this medicinal plant.
Assuntos
Espécies em Perigo de Extinção , Fritillaria , Genoma Mitocondrial , Filogenia , Plantas Medicinais , Edição de RNA , Fritillaria/genética , Plantas Medicinais/genética , Composição de Bases , RNA de Transferência/genética , Anotação de Sequência MolecularRESUMO
Objective: The purpose of this study was to explore the clinical benefits of establishing an enteral nutrition (EN) pathway via percutaneous transhepatic cholangiography drainage (PTCD) catheterization in patients with late-stage malignant obstructive jaundice (MOJ).Methods: We selected 30 patients diagnosed as having late-stage MOJ with malnutrition. A dual-lumen biliary-enteral nutrition tube was placed via PTCD along with a biliary stent implantation. Postoperative EN was provided, and we observed the time taken for tube placement, its success rate, complications, and therapeutic efficacy.Results: Tube placement was successful in all 30 patients with an average procedural time of 5.7 ± 1.4 min with no tube placement complications. Compared to preoperative measures, there was a significant improvement in postoperative jaundice reduction and nutritional indicators one month after the procedure (p < 0.05). Post-placement complications included tube perileakage in 5 cases, entero-biliary reflux in 4 cases, tube blockage in 6 cases, tube displacement in 4 cases, accidental tube removal in 3 cases, and tube replacement due to degradation in 8 cases, with tube retention time ranging from 42 to 314 days, averaging 124.7 ± 37.5 days. All patients achieved the parameters for effective home-based enteral nutrition with a noticeable improvement in their quality of life.Conclusion: In this study, we found that the technique of establishing an EN pathway via PTCD catheterization was minimally invasive, safe, and effective; the tube was easy to maintain; and patient compliance was high. It is, thus, suitable for long-term tube retention in patients with late-stage MOJ.
Assuntos
Colangiografia , Drenagem , Nutrição Enteral , Icterícia Obstrutiva , Humanos , Icterícia Obstrutiva/etiologia , Icterícia Obstrutiva/terapia , Icterícia Obstrutiva/cirurgia , Masculino , Feminino , Drenagem/métodos , Nutrição Enteral/métodos , Pessoa de Meia-Idade , Idoso , Colangiografia/métodos , Stents , Resultado do Tratamento , Cateterismo/métodos , Complicações Pós-Operatórias/etiologia , Desnutrição/etiologia , Desnutrição/terapia , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: We investigated the presence of Chlamydia psittaci in poultry and the environment in live poultry wholesale markets in Changsha during 2021-2022 and conducted a phylogenetic analysis to understand its distribution in this market. METHODS: In total, 483 samples were analyzed using real-time polymerase chain reaction and 17 C. psittaci-positive samples using high-throughput sequencing, BLAST similarity, and phylogenetic analysis. RESULTS: Twenty-two out of 483 poultry and environmental samples were positive for C. psittaci (overall positivity rate: 4.55%) with no difference in positivity rates over 12 months. Chlamydia psittaci was detected at 11 sampling points (overall positivity rate: 27.5%), including chicken, duck, and pigeon/chicken/duck/goose shops, with pigeon shops having the highest positivity rate (46.67%). The highest positivity rates were found in sewage (12.5%), poultry fecal (7.43%), cage swab (6.59%), avian pharyngeal/cloacal swab (3.33%), and air (2.29%) samples. The ompA sequences were identified in two strains of C. psittaci, which were determined to bear genotype B using phylogenetic analysis. Thus, during monitoring, C. psittaci genotype B was detected in the poultry and environmental samples from the poultry wholesale market in Changsha. CONCLUSIONS: To address the potential zoonotic threat, C. psittaci monitoring programs in live poultry markets should be enhanced.
Assuntos
Chlamydophila psittaci , Filogenia , Doenças das Aves Domésticas , Aves Domésticas , Psitacose , Animais , Chlamydophila psittaci/genética , Chlamydophila psittaci/isolamento & purificação , Chlamydophila psittaci/classificação , China/epidemiologia , Psitacose/microbiologia , Psitacose/veterinária , Psitacose/epidemiologia , Aves Domésticas/microbiologia , Doenças das Aves Domésticas/microbiologia , Doenças das Aves Domésticas/epidemiologia , Galinhas/microbiologia , Patos/microbiologia , Fezes/microbiologia , Reação em Cadeia da Polimerase em Tempo RealRESUMO
Non-healing diabetic wounds (DW) are a serious clinical problem that remained poorly understood. We recently found that topical application of growth differentiation factor 11 (GDF11) accelerated skin wound healing in both Type 1 DM (T1DM) and genetically engineered Type 2 diabetic db/db (T2DM) mice. In the present study, we elucidated the cellular and molecular mechanisms underlying the action of GDF11 on healing of small skin wound. Single round-shape full-thickness wound of 5-mm diameter with muscle and bone exposed was made on mouse dorsum using a sterile punch biopsy 7 days following the onset of DM. Recombinant human GDF11 (rGDF11, 50 ng/mL, 10 µL) was topically applied onto the wound area twice a day until epidermal closure (maximum 14 days). Digital images of wound were obtained once a day from D0 to D14 post-wounding. We showed that topical application of GDF11 accelerated the healing of full-thickness skin wounds in both type 1 and type 2 diabetic mice, even after GDF8 (a muscle growth factor) had been silenced. At the cellular level, GDF11 significantly facilitated neovascularization to enhance regeneration of skin tissues by stimulating mobilization, migration and homing of endothelial progenitor cells (EPCs) to the wounded area. At the molecular level, GDF11 greatly increased HIF-1É expression to enhance the activities of VEGF and SDF-1É, thereby neovascularization. We found that endogenous GDF11 level was robustly decreased in skin tissue of diabetic wounds. The specific antibody against GDF11 or silence of GDF11 by siRNA in healthy mice mimicked the non-healing property of diabetic wound. Thus, we demonstrate that GDF11 promotes diabetic wound healing via stimulating endothelial progenitor cells mobilization and neovascularization mediated by HIF-1É-VEGF/SDF-1É pathway. Our results support the potential of GDF11 as a therapeutic agent for non-healing DW.
Assuntos
Diabetes Mellitus Experimental , Células Progenitoras Endoteliais , Fatores de Diferenciação de Crescimento , Cicatrização , Animais , Humanos , Camundongos , Proteínas Morfogenéticas Ósseas/metabolismo , Quimiocina CXCL12/efeitos dos fármacos , Quimiocina CXCL12/metabolismo , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Células Progenitoras Endoteliais/metabolismo , Células Progenitoras Endoteliais/patologia , Fatores de Diferenciação de Crescimento/uso terapêutico , Fatores de Diferenciação de Crescimento/metabolismo , Neovascularização Fisiológica , Fator A de Crescimento do Endotélio Vascular/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/metabolismo , Cicatrização/efeitos dos fármacos , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/uso terapêutico , Subunidade alfa do Fator 1 Induzível por Hipóxia/efeitos dos fármacos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismoRESUMO
BACKGROUND: Typhoid fever and paratyphoid fever are one of the most criticial public health issues worldwide, especially in developing countries. The incidence of this disease may be closely related to socio-economic factors, but there is a lack of research on the spatial level of relevant determinants of typhoid fever and paratyphoid fever. METHODS: In this study, we took Hunan Province in central China as an example and collected the data on typhoid and paratyphoid incidence and socio-economic factors in 2015-2019. Firstly spatial mapping was made on the disease prevalence, and again using geographical probe model to explore the critical influencing factors of typhoid and paratyphoid, finally employing MGWR model to analysis the spatial heterogeneity of these factors. RESULTS: The results showed that the incidence of typhoid and paratyphoid fever was seasonal and periodic and frequently occurred in summer. In the case of total typhoid and paratyphoid fever, Yongzhou was the most popular, followed by Xiangxi Tujia and Miao Autonomous Prefecture, Huaihua and Chenzhou generally focused on the south and west. And Yueyang, Changde and Loudi had a slight increase trend year by year from 2015 to 2019. Moreover, the significant effects on the incidence of typhoid and paratyphoid fever from strong to weak were as follows: gender ratio(q = 0.4589), students in ordinary institutions of higher learning(q = 0.2040), per capita disposable income of all residents(q = 0.1777), number of foreign tourists received(q = 0.1697), per capita GDP(q = 0.1589), and the P values for these factors were less than 0.001. According to the MGWR model, gender ratio, per capita disposable income of all residents and Number of foreign tourists received had a positive effect on the incidence of typhoid and paratyphoid fever. In contrast, students in ordinary institutions of higher learning had a negative impact, and per capita GDP shows a bipolar change. CONCLUSIONS: The incidence of typhoid and paratyphoid fever in Hunan Province from 2015 to 2019 was a marked seasonality, concentrated in the south and west of Hunan Province. Attention should be paid to the prevention and control of critical periods and concentrated areas. Different socio-economic factors may show other directions and degrees of action in other prefecture-level cities. To summarize, health education, entry-exit epidemic prevention and control can be strengthened. This study may be beneficial to carry out targeted, hierarchical and focused prevention and control of typhoid fever and paratyphoid fever, and provide scientific reference for related theoretical research.
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Febre Paratifoide , Febre Tifoide , Humanos , Febre Tifoide/epidemiologia , Febre Paratifoide/epidemiologia , Febre Paratifoide/prevenção & controle , Estações do Ano , China/epidemiologia , Incidência , Fatores SocioeconômicosRESUMO
Rapeseed straw, bagasse, and walnut peel have a large amount of resource reserves, but there are few technologies for high value-added utilization. In the research of biochar, walnut green husk is rarely used as raw material. In addition, the three main components of biomass (lignin, cellulose, and hemicellulose) are present in similar proportions, and the differences between the physical and chemical properties of biochar prepared with similar amounts of biomass raw materials are not clear. Using three kinds of biomass of the same quality as raw materials, biochar was prepared via pyrolysis at 400 °C, and activated carbon was prepared via CO2 activation at 800 °C. The results showed that the pore numbers of the three kinds of biochar increased after activation, resulting in the increase of the specific surface area. The resulting numbers were 352.99 m2/g for sugarcane bagasse biochar (SBB)-CO2, 215.04 m2/g for rapeseed straw biochar (RSB)-CO2, and 15.53 m2/g for walnut green husk biochar (WGB)-CO2. Ash increased the amount of carbon formation, but a large amount of ash caused biochar to form a perforated structure and decreased the specific surface area (e.g., WGB), which affected adsorption ability. When the three main components were present in similar proportions, a high content of cellulose and lignin was beneficial to the preparation of biochar. The adsorption value of MB by biochar decreased with the increase of biomass ash content. After activation, the maximum adsorption value of MB for bagasse biochar was 178.17 mg/g, rapeseed straw biochar was 119.25 mg/g, and walnut peel biochar was 85.92 mg/g when the concentration of methene blue solution was 300 mg/L and the biochar input was 0.1 g/100 mL at room temperature. The adsorption of MB by biochar in solution occurs simultaneously with physical adsorption and chemical adsorption, with chemical adsorption being dominant. The optimal MB adsorption by SBB-CO2 was dominated by multimolecular-layer adsorption. This experiment provides a theoretical basis for the preparation of biochar and research on its applications in the future.
Assuntos
Brassica napus , Brassica rapa , Juglans , Saccharum , Celulose , Lignina , Adsorção , Biomassa , Dióxido de Carbono , Carvão Vegetal , Azul de Metileno , Grão ComestívelRESUMO
The structural revision of four Stemona alkaloids from Stemona tuberosa is reported. The misassignment of the tuberostemonine O structure (1) was recognized when a new alkaloid, tuberostemonine P, was isolated and unambiguously assigned structure 1 in this work. Reinvestigation of the spectroscopic data and NMR calculations led to the revised structure 1a for tuberostemonine O. The structural misassignment of dehydrocroomine A as 2 was corrected by reinterpreting the X-ray crystal structure, which was consistent with 2a. The structural reassignments of dehydrocroomine B (3 to 3a) and dehydrocroomine (4 to 4a) were confirmed by X-ray crystallography and NMR calculations, respectively.
Assuntos
Alcaloides , Stemonaceae , Alcaloides/química , Estrutura Molecular , Stemonaceae/químicaRESUMO
In the task of image instance segmentation, semi-supervised instance segmentation algorithms have received constant research attention over recent years. Among these algorithms, algorithms based on transfer learning are better than algorithms based on pseudo-label generation in terms of segmentation performance, but they can not make full use of the relevant characteristics of source tasks. To improve the accuracy of these algorithms, this work proposes a semi-supervised instance segmentation model AFT-Mask (attention-based feature transfer Mask R-CNN) based on category attention. The AFT-Mask model takes the result of object-classification prediction as "attention" to improve the performance of the feature-transfer module. In detail, we designed a migration-optimization module for connecting feature migration and classification prediction to enhance segmentation-prediction accuracy. To verify the validity of the AFT-Mask model, experiments were conducted on two types of datasets. Experimental results show that the AFT-Mask model can achieve effective knowledge transfer and improve the performance of the benchmark model on semi-supervised instance segmentation.
Assuntos
AlgoritmosRESUMO
This study aimed to investigate the role of truncated growth differentiation factor 11 (GDF11), in which the recognition site of Furin from wild-type GDF11 was deleted to enhance the cellular stability, in skin wound healing in the setting of diabetes mellitus (DM) and the underlying mechanisms. Our study found that both truncated and natural GDF11s effectively accelerated wound healing processes in both T1DM and T2DM mice with a potency compatible to PDGF, bFGF, and EGF, but being much higher than GDF8. At the cellular level, GDF11 stimulated the proliferation and suppressed HG-induced apoptosis of HSFs. Further study revealed that GDF11 activated the YAP-Smad2/3-CTGF fibrotic signaling pathway by reversing HG-induced upregulation of phosphorylated form of YAP (p-YAP), increases p-Smad2/3 levels, and restoring HG-induced repression of CTGF expression by GDF11. Overall, the study shows that both natural and truncated GDF11s promote the healing process of skin wound in mice of both T1DM and T2DM partly via stimulating dermal fibrosis via the YAP-Smad2/3-CTGF pathway, suggesting it a potential agent for treating skin wound in diabetic population.
Assuntos
Proteínas Morfogenéticas Ósseas/administração & dosagem , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Fatores de Diferenciação de Crescimento/administração & dosagem , Cicatrização/efeitos dos fármacos , Administração Tópica , Animais , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Proteínas Morfogenéticas Ósseas/fisiologia , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/fisiologia , Células Cultivadas , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Experimental/fisiopatologia , Diabetes Mellitus Tipo 1/patologia , Diabetes Mellitus Tipo 1/fisiopatologia , Diabetes Mellitus Tipo 2/patologia , Diabetes Mellitus Tipo 2/fisiopatologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/patologia , Fatores de Diferenciação de Crescimento/fisiologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Pele/efeitos dos fármacos , Pele/lesões , Pele/patologia , Cicatrização/fisiologiaRESUMO
BACKGROUND: Few studies have focused on cesarean delivery (CD) trends among primipara under the one-child and the two-child policies. This study aimed to explore the trends in CD rates among primipara during 1995-2019 and the associated factors with CD risk. METHODS: This study obtained clinical data on primiparous mothers and newborns from 1995 to 2019 at a large tertiary hospital in Wuhan, China. Trends in CD rates were calculated using the joinpoint regression analysis. The Chi-square tests and log-binomial regression analyses were used to evaluate the associations between primary variables and CD risk. RESULTS: CD rates showed a significant upward trend with an average annual percentage change (APC) of 2.2% (95% CI: 0.6, 3.8%) during the study period. In 1995-2006, the CD rates continued to increase with an APC of 7.8% (95% CI: 4.8, 10.9%). After 2006, the CD rates started to decline by an APC of - 4.1% (95% CI: - 5.5, - 2.6%). The CD rates non-significantly increased from 36.2% in 2016 to 43.2% in 2019. Moreover, the highest CD rate during 2015-2019 was observed on August 30 (59.2%) and the lowest on September 1 (29.7%). Primipara of older age and those with >3pregnancies had higher risks of CD. Furthermore, primipara who gave birth to newborns with low birth weight and macrosomia had higher risks of CD. CONCLUSIONS: Maternal and fetal as well as social and cultural factors may contribute to the rising trend of CD rates. Effective measures should be taken to control CD under the two-child policy, especially for primipara.
Assuntos
Cesárea/tendências , Peso Fetal , Idade Materna , Paridade , Adulto , Distribuição de Qui-Quadrado , China/epidemiologia , Política de Planejamento Familiar , Feminino , Macrossomia Fetal/epidemiologia , Humanos , Recém-Nascido , Masculino , Gravidez , Análise de Regressão , Fatores de Risco , Centros de Atenção Terciária , Adulto JovemRESUMO
INTRODUCTION: Nonsurgical treatments that can prevent or reduce the extent of the mandibular excess at an early stage are desirable. A single botulinum toxin (BTX) injection into the unilateral and bilateral masseter can regulate mandibular contour and condylar cartilage. However, BTX injection is frequency dependent when used in facelifts. This study aimed to evaluate the effect of BTX injection into the bilateral masseter at different frequencies on the mandibular contour and condylar cartilage. METHODS: In the present study, 24 female Sprague Dawley rats (4 weeks old) were divided into 3 groups: control, single injection, and triple injection. Contour measurement of the mandible was carried out by radiographic imaging. Microcomputerized tomography was performed to determine the change in bone volume in the subchondral bone. Hematoxylin and eosin staining was used to observe the morphologic changes of condylar cartilage. Immunohistochemistry was performed to detect the expression level of biomechanically sensitive factors, including transforming growth factor-ß1, parathyroid hormone-related protein, SRY-box 9, and type II collagen. RESULTS: Bone volume and/or total volume, trabecular number, and trabecular thickness of the mineralized cartilage and subchondral bone significantly decreased in the triple injection group when compared with the single injection group. Mandibular contour also diminished after increased BTX injection frequencies. Chondrocyte proliferation ability and the expression levels of transforming growth factor-ß1, parathyroid hormone-related protein, SRY-box 9, and type II collagen significantly decreased in all BTX injection groups and more in the triple injection group. CONCLUSIONS: Morphologic changes of the mandible and condylar cartilage become more obvious after increased BTX injection frequencies, suggesting that multiple BTX injections into the masseter of patients may relieve the severity of mandibular deformity at an early stage.
Assuntos
Toxinas Botulínicas , Côndilo Mandibular/diagnóstico por imagem , Animais , Cartilagem , Feminino , Humanos , Mandíbula/diagnóstico por imagem , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND AND PURPOSE: Kaposi's sarcoma-associated herpes virus (KSHV) vIL-6 is sufficient to induce lymphatic reprogramming of vascular endothelial cells, which is a key event in Kaposi's sarcoma (KS) development. This study was aimed to investigate the effect of Chinese herb oroxylin A on lymphatic reprogramming and neovascularization by KSHV vIL-6 in vitro and in vivo. METHODS: The lymphatic-phenotype endothelial cell line was generated by lentiviral KSHV vIL-6 infection. Cell viability and apoptosis were determined by MTT assay or flow cytometry with annexin V/propidium iodide staining. Migration, invasion, and neovascularization of the vIL-6-expressing lymphatic-phenotype endothelial cells were determined by wound healing assay, transwell chamber assay, microtubule formation assay, and chick chorioallantoic membrane assay, respectively. Quantitative polymerase chain reaction and Western blot analysis were used to test the expression of Prox1, VEGFR3, podoplanin, LYVE-1, and PPARγ in cells. Co-localization of Prox1 and PPARγ was determined by immunofluorescence. Ubiquitination of Prox1 was detected by in vivo ubiquitination assay. RESULTS: The lymphatic-phenotype endothelial cell line expressing KSHV vIL-6 was successfully generated. Oroxylin A induced cellular invasion abrogation, apoptosis induction, and neovascularization inhibition of the vIL-6-expressing endothelial cells. Mechanically, oroxylin A elevated PPARγ expression, which in turn interacted with and facilitated Prox1 to undergo ubiquitinational degradation, and subsequently leads to VEGFR3, LYVE-1, and podoplanin reduction. CONCLUSION: Through modulating PPARγ/Prox1 axis, oroxylin A inhibits lymphatic reprogramming and neovascularization of KSHV vIL-6. Thus, oroxylin A may serve as a candidate for the treatment of KS as well as other aggressive angiomas.
Assuntos
Reprogramação Celular , Células Endoteliais/efeitos dos fármacos , Flavonoides/farmacologia , Herpesvirus Humano 8/efeitos dos fármacos , PPAR gama/imunologia , Sarcoma de Kaposi/imunologia , Sarcoma de Kaposi/virologia , Animais , Diferenciação Celular , Linhagem Celular , Embrião de Galinha , Medicamentos de Ervas Chinesas/farmacologia , Células Endoteliais/imunologia , Humanos , Interleucina-6/imunologia , Neovascularização Patológica/imunologia , Transdução de Sinais , Fatores de TranscriçãoRESUMO
BACKGROUND: The surgical approach of the zygomaticomaxillary complex fracture is usually performed with preauricular coronal incision assisted with intraoral maxillary sulcus incision. There will be preauricular scars postoperatively. METHODS: The authors introduce a postauricular hemicoronal incision to avoid the formation of scars in front of the ear. RESULTS AND DISCUSSION: The postauricular hemicoronal incision can avoid vascular damage caused by careless operation in the preauricular approach. It eliminates the possibility of dissection or ligation of the superficial arteries and veins when preauricular approach was used. It results in no scar in front of ear, while reducing suture time and complexity.
Assuntos
Fraturas Maxilares/cirurgia , Fraturas Zigomáticas/cirurgia , Adolescente , Cicatriz , Humanos , Masculino , Fraturas Maxilares/diagnóstico por imagem , Fraturas Zigomáticas/diagnóstico por imagemRESUMO
PURPOSE: Pamidronate disodium-associated bone necrosis is poorly understood at the cellular and molecular levels. This study proposes a pathway leading to the pamidronate disodium-mediated inhibition of osteogenic differentiation of human bone marrow mesenchymal stem cells (BMMSCs) derived from the mandible in vitro. MATERIALS AND METHODS: Primary human BMMSCs were isolated from the mandible and marrow tissue. A proliferation assay was performed to determine the experimental concentration of pamidronate disodium. Alkaline phosphatase (ALP) activity, ALP staining, and Alizarin red S (ARS) staining were assessed after treatment with pamidronate disodium (0, 0.1, 0.5, 1, 5, 10 µg/mL). Quantitative real-time polymerase chain reaction and western blotting specific for Wnt and ß-catenin signaling genes or proteins were performed after treatment with pamidronate disodium 0.5 µg/mL. Wnt3a was used to observe the osteogenic differentiation of BMMSCs during treatment with pamidronate disodium 0.5 µg/mL. RESULTS: As expected, pamidronate disodium 1, 5, and 10 µg/ml were unfavorable for BMMSC growth (P < .05), whereas 0.1 and 0.5 µg/mL did not affect BMMSC growth (P ≥ .05). BMMSCs treated with pamidronate disodium 0.5 µg/mL had lower ALP activity, ALP staining, and ARS staining (P < .05), and BMMSCs treated with low concentrations (<0.5 µg/mL) of pamidronate disodium had the same levels of ALP activity, ALP staining, and ARS staining as the control (0 µg/mL). Pamidronate disodium 0.5 µg/mL decreased the expression of genes and proteins involved in Wnt and ß-catenin signaling. BMMSCs with Wnt3a and pamidronate disodium 0.5 µg/mL had higher ALP activity, ALP staining, and ARS staining (P < .05). CONCLUSIONS: Pamidronate disodium inhibited Wnt and ß-catenin signaling, which controls osteogenic differentiation in BMMSCs. Wnt3a, a Wnt and ß-catenin signaling activator, reversed the negative effects caused by pamidronate disodium to salvage the osteogenic defect in BMMSCs.
Assuntos
Difosfonatos/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Osteonecrose/etiologia , Via de Sinalização Wnt/efeitos dos fármacos , Via de Sinalização Wnt/fisiologia , Células Cultivadas , Humanos , Mandíbula , Osteogênese , PamidronatoRESUMO
We aimed to investigate the association between dihydropyrimidine dehydrogenase (DPYD) gene polymorphisms and the risk of pediatric acute lymphoblastic leukemia (ALL) and its prognosis after chemotherapy. A total of 147 pediatric ALL patients diagnosed by our hospital between January 2011 and December 2014 were included in the case group, and 102 healthy people who received a physical examination during the same time frame in our hospital were included in the control group. DNA sequencing was applied for site determination and genotyping of the DPYD 85T > C, 2194G > A, 1156G > T, and IVS14 + 1G > A polymorphisms. The genotype and allele frequencies of the two groups were compared. A significant difference was found in the comparison of the mutant gene and allele frequencies of the 85T > C polymorphism between the case and control groups (P < 0.05). The CT and CC genotypes in the 85T > C polymorphism were associated with the risk of the disease (OR = 1.592, 95 % CI = 1.010-2.509), suggesting that the recessive gene (85C) was more likely to lead to the occurrence of ALL compared with the dominant gene (85T) (P < 0.05). Patients carrying the C allele of the 85T > C polymorphism presented higher damage of their liver functions and higher infection rates compared with patients carrying the non-C allele (P < 0.05). A higher proportion of liver function damage and a higher infection rate were found in patients with the GA genotype in the IVS14 + 1G > A polymorphism compared with the GG genotype (P < 0.05). The complete remission (CR) rate in patients with the GG genotype in the IVS14 + 1G > A polymorphism was higher than in patients with the GA genotype (P = 0.020). After 5-fluorouracil/calcium folinate (5-FU/CF)-based chemotherapy, the event-free survival (EFS) rate of patients with the TT genotype was higher than patients with the CT and CC genotypes (P < 0.05). Our results revealed that the C allele of the 85T > C polymorphism might be associated with susceptibility to pediatric ALL. Patients carrying the C allele may have an increased risk of ALL. Thus, the 85T > C polymorphism may be a predictor of CR for pediatric ALL patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Di-Hidrouracila Desidrogenase (NADP)/genética , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Frequência do Gene , Genótipo , Humanos , Estimativa de Kaplan-Meier , Leucovorina/administração & dosagem , Masculino , Reação em Cadeia da Polimerase , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Prognóstico , Fatores de RiscoRESUMO
OBJECTIVE: Human umbilical cord mesenchymal stem cells (hUCMSCs) have renoprotective effects but the influence of the microenvironment on characteristics of hUCMSCs has not been well studied. Here, we investigate the effects of injury conditions on properties of hUCMSCs. RESULTS: hUCMSCs were treated in vitro under conditions mimicking the injury microenvironment of acute kidney injury. Cells stimulated with factor-treated medium proliferated slowly at first but quickly afterwards their morphology subsequently changed from spindle to stellate shape. Increased number of cells with strong expression of thymine-1 (Thy-1) or α-smooth muscle actin (α-SMA) was detected at 1 or 2 weeks after stimulation. Hepatocyte growth factor (HGF) level markedly increased after culture for 6 h under hypoxia condition. The expressions of HGF and insulin growth factor-1 (IGF-1) were significantly up-regulated from 0.22 ± 0.03 to 0.9 ± 0.02 and 0.07 ± 0.03 to 0.19 ± 0.01 in H/R-treated hUCMSCs respectively. Co-culture with injured renal tubular epithelial cells significantly promoted the expression of HGF (1.19 ± 0.21) and IGF-1 (0.24 ± 0.03) in hUCMSCs. CONCLUSION: The characteristics of hUCMSCs change in response to inured conditions, which may enhance the efficacy of stem cell therapy and provide novel strategies in maximizing biological and functional properties of hUCMSCs.
Assuntos
Meios de Cultura/farmacologia , Células Epiteliais/citologia , Túbulos Renais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Cordão Umbilical/citologia , Actinas/metabolismo , Injúria Renal Aguda/terapia , Animais , Hipóxia Celular , Proliferação de Células , Células Cultivadas , Técnicas de Cocultura , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Fator de Crescimento de Hepatócito/metabolismo , Humanos , Técnicas In Vitro , Fator de Crescimento Insulin-Like I/metabolismo , Células-Tronco Mesenquimais/citologia , Gravidez , Ratos , Antígenos Thy-1/metabolismoRESUMO
Primary cilia have versatile functions, such as receiving signals from the extracellular microenvironment, mediating signaling transduction, and transporting ciliary substances, in tissue and organ development and clinical disease pathogenesis. During early development (embryos within 10 weeks) in the oral and maxillofacial region, defects in the structure and function of primary cilia can result in severe craniofacial malformations. For example, mice with mutations in the cilia-related genes Kif3a and IFT88 exhibit midline expansion and cleft lip/palate, which occur due to abnormalities in the fusion of the single frontonasal prominence and maxillary prominences. In the subsequent development of the oral and maxillofacial region, we discussed the regulatory role of primary cilia in the development of the maxilla, mandible, Meckel cartilage, condylar cartilage, lip, tongue, and tooth, among others. Moreover, primary cilia are promising regulators in some oral and maxillofacial diseases, such as tumors and malocclusion. We also summarize the regulatory mechanisms of primary cilia in oral and maxillofacial development and related diseases, including their role in various signaling transduction pathways. For example, aplasia of submandibular glands in the Kif3a mutant mice is associated with a decrease in SHH signaling within the glands. This review summarizes the similarities and specificities of the role of primary cilia in tissue and organ development and disease progression in the oral and maxillofacial region, which is expected to contribute several ideas for the treatment of primary cilia-related diseases.
Assuntos
Cílios , Cílios/metabolismo , Cílios/patologia , Animais , Humanos , Desenvolvimento Maxilofacial/genética , Camundongos , Transdução de Sinais , Cinesinas/metabolismo , Cinesinas/genéticaRESUMO
We aimed to evaluate the influence of sirtuin1 (sirt1) on the ESCC chemotherapeutic sensitivity to cisplatin. We used ESCC cell ablation sirt1 for establishing a xenograft mouse tumor model. The tumor volume was then detected. sirt1 was over-expressed significantly in ESCC patients and cells. Moreover, sirt1 knockdown raised ESCC sensitivity to cisplatin. Besides, glycolysis was associated with ESCC cell chemotherapy resistance to cisplatin. Furthermore, sirt1 increased ESCC cells' cisplatin chemosensitivity through HK2. Sirt1 enhanced in vivo ESCC chemosensitivity to cisplatin. Overall, these findings suggested that sirt1 knockdown regulated the glycolysis pathway and raised the ESCC chemotherapeutic sensitivity.
Assuntos
Cisplatino , Resistencia a Medicamentos Antineoplásicos , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Glicólise , Sirtuína 1 , Sirtuína 1/metabolismo , Sirtuína 1/genética , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Humanos , Glicólise/efeitos dos fármacos , Animais , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/metabolismo , Carcinoma de Células Escamosas do Esôfago/genética , Camundongos , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/genética , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , Ensaios Antitumorais Modelo de Xenoenxerto , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Feminino , Masculino , Camundongos NusRESUMO
Climate change and human activities escalate the frequency and intensity of wildfires, threatening amphibian habitats and survival; yet, research on these impacts remains limited. Wildfire ash alters water quality, introduces contaminants, and may disrupt microbial communities, impacting gut and skin microbiota; however, the effects on gut and skin microbiota remain unclear. Rana dybowskii were exposed to five concentrations (0 g L-1, 1.25 g L-1, 2.5 g L-1, 5 g L-1, and 10 g L-1) of aqueous extracts of wildfire ashes (AEAs) for 30 days to assess AEAs' metal content, survival, and microbiota diversity via Illumina sequencing. Our results showed that the major elements in ash were Ca > K > Mg > Al > Fe > Na > Mn, while in AEA they were K > Ca > Na > Mg > As > Al > Cu. A significant decrease in amphibian survival rates with increased AEA concentration was shown. The beta diversity analysis revealed distinct shifts in microbiota composition. Notably, bacterial genera associated with potential health risks showed increased abundance in skin microbiota, emphasising the potential for ash exposure to affect amphibian health. Functional prediction analyses revealed significant shifts in metabolic pathways related to health and disease, indicating that wildfire ash exposure may influence amphibian health through changes in microbial functions. This study highlights the urgent need for strategies to mitigate wildfire ash impacts on amphibians, as it significantly alters microbiota and affects their survival and health.
Assuntos
Microbioma Gastrointestinal , Ranidae , Pele , Incêndios Florestais , Animais , Pele/efeitos dos fármacos , Pele/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Ranidae/microbiologia , Microbiota/efeitos dos fármacos , Bactérias/genética , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/metabolismo , Metais/toxicidadeRESUMO
Objective: Brucellosis has a considerable impact on human health and the economy in developing countries. In China, the biggest developing country, brucellosis shifted spread of the epidemic from northern to southern regions. Understanding the transmission characteristic of brucellosis on Hunan province, located in central China, is of great significance for successful control. Methods: We developed a multi-population and multi-route dynamic model (MPMRDM), which is an animal-human-environment coupled model. The model is an extension of the SEIR model, taking into account direct transmission and indirect transmission. We used the model to explore the spread of brucellosis and evaluate the effectiveness of various intervention strategies. Results: The animal-to-animal transmission rate was the highest at 5.14 × 10-8, while the environment-to-person transmission rate was the lowest at 9.49 × 10-12. The mean R0 was 1.51. The most effective intervention was taking personal protection, followed by shortening the infection period. Shortening the infection period combined with personal protection is the most effective two-combined intervention strategy. After any comprehensive intervention strategy was implemented, TAR dropped by 90% or more. Conclusion: The results demonstrate that animal transmission route is essential for controlling human brucellosis. Strengthening personal protection, early detection, and early treatment can effectively control the trend of brucellosis. These results can provide an important reference for optimizing brucellosis intervention plans.