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1.
Adv Sci (Weinh) ; 11(14): e2307526, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38298064

RESUMO

Arginine and lysine, frequently appearing as a pair on histones, have been proven to carry diverse modifications and execute various epigenetic regulatory functions. However, the most context-specific and transient effectors of these marks, while significant, have evaded study as detection methods have thus far not reached a standard to capture these ephemeral events. Herein, a pair of complementary photo-arginine/δ-photo-lysine (R-dz/K-dz) probes is developed and involve these into histone peptide, nucleosome, and chromatin substrates to capture and explore the interactomes of Arg and Lys hPTMs. By means of these developed tools, this study identifies that H3R2me2a can recruit MutS protein homolog 6 (MSH6), otherwise repelDouble PHD fingers 2 (DPF2), Retinoblastoma binding protein 4/7 (RBBP4/7). And it is disclosed that H3R2me2a inhibits the chromatin remodeling activity of the cBAF complex by blocking the interaction between DPF2 (one component of cBAF) and the nucleosome. In addition, the novel pairs of H4K5 PTMs and respective readers are highlighted, namely H4K5me-Lethal(3)malignant brain tumor-like protein 2 (L3MBTL2), H4K5me2-L3MBTL2, and H4K5acK8ac-YEATS domain-containing protein 4 (YEATS4). These powerful tools pave the way for future investigation of related epigenetic mechanisms including but not limited to hPTMs.


Assuntos
Lisina , Nucleossomos , Lisina/metabolismo , Processamento de Proteína Pós-Traducional , Histonas/metabolismo , Cromatina , Arginina/metabolismo
2.
J Pain Res ; 16: 4015-4024, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38026459

RESUMO

Objective: The programmed intermittent bolus infusion (PIBI) of local anesthetic produces wider sensory blockade and better analgesia than continuous infusion (CI). We designed this trial to compare the effects of these two different infusion methods combined with Serratus Anterior Plane Blocks (cSAPBs) on postoperative pain relief in patients undergoing video-assisted thoracoscopic surgery. Methods: We randomly allocated 66 patients under going elective video-assisted thoracoscopic unilateral lung resection surgery to two groups (PIBI group and CI group, n=33 per group). After the surgical operation, the patients received ultrasound-guided ipsilateral SAPB, we randomized them to receive either automated intermittent boluses or continuous infusion of 0.3% ropivacaine. Tramadol consumption during the 48 hours following surgery was the primary outcome. Secondary outcomes included cumulative tramadol consumption during the first 24-h and the second 24-h periods after surgery, pain scores, patient satisfaction, blocked dermatomes, and adverse events. Results: During 48h, tramadol consumption in the PIBI group was significantly lower than in the CI group (190 mg [125, 305] vs 220 mg [170, 480], p= 0.034). As compared to the CI group, the PIBI group consumed less tramadol during the first 24 hours (145 mg [87.5, 210] vs 190 mg [140, 400], p=0.012). The dermatomes anesthetized to the pinprick and cold test were significantly more abundant in the PIBI group than in the CI group (3 [3,4] vs. 5 [4,5], p<0.001). Both groups had similar VAS scores at rest and when moving (p>0.05). Additionally, the PIBI group showed greater patient satisfaction. Both groups experienced similar adverse events (p>0.05). Conclusion: Compared with CI, PIBI administration regimen (0.3% ropivacaine 5 mL/h) for cSAPBs resulted in lower tramadol consumption, superior analgesia during the initial 12 h after the operation, and higher patient satisfaction. PIBI combined with cSAPBs was a better choice for postoperative analgesia in patients undergoing video-assisted thoracoscopic surgery.

3.
Biomed Pharmacother ; 167: 115533, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37748406

RESUMO

Overexpression of the hypoxia-induced transmembrane enzyme carbonic anhydrase IX (CA9) has been associated with poor prognosis and chemoresistance in aggressive breast cancer. This study aimed to investigate the involvement of CA9 in the anti-tumor activity of para-toluenesulfonamide (PTS) and elucidate its mechanism of action against breast cancer both in vitro and in vivo. MCF-7 and MDA-MB-231 breast cancer cells were treated with PTS or subjected to hypoxic conditions using cobalt chloride (CoCl2), with acetazolamide serving as a positive control. Additionally, 4T1 breast cancer cell allograft mice were co-treated with PTS and α-programmed cell death 1 (αPD-1) monoclonal antibody for one month. The results demonstrated that PTS effectively reduced cell viability and reversed migration ability in MCF-7 and MDA-MB-231 cells under CoCl2-induced hypoxia. Furthermore, PTS upregulated the expression of apoptosis-related proteins and downregulated CA9, hypoxia-inducible factor-1α (HIF-1α), and vascular endothelial growth factor (VEGF) proteins, possibly through modulation of p38 MAPK and ERK1/2 phosphorylated proteins. In the animal model, PTS100 inhibited tumor growth and lung metastasis in mammary tumor allograft mice, exhibiting synergistic effects when combined with αPD-1 therapy. Collectively, our findings suggest that PTS inhibits breast cancer growth and metastasis through the p38 MAPK/ERK1/2 pathway. Moreover, PTS may have the potential to prevent the development of resistance to αPD-1 therapy in breast cancer.


Assuntos
Neoplasias da Mama , Anidrases Carbônicas , Neoplasias de Mama Triplo Negativas , Humanos , Animais , Camundongos , Feminino , Inibidores da Anidrase Carbônica/farmacologia , Inibidores da Anidrase Carbônica/uso terapêutico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Anidrases Carbônicas/metabolismo , Anidrases Carbônicas/farmacologia , Sobrevivência Celular , Fator A de Crescimento do Endotélio Vascular/metabolismo , Antígenos de Neoplasias/metabolismo , Hipóxia/tratamento farmacológico , Hipóxia/metabolismo , Hipóxia Celular , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Linhagem Celular Tumoral , Neoplasias da Mama/patologia
4.
Shanghai Kou Qiang Yi Xue ; 32(2): 132-136, 2023 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-37153992

RESUMO

PURPOSE: To investigate whether resveratrol promotes odontogenic differentiation of human dental pulp stem cells(DPSCs) by up-regulating the expression of silent information regulator 1 (SIRT1) and activating ß-catenin signaling pathway. METHODS: Different concentrations of resveratrol(0, 10, 15, 20 and 50 µmol/L) were used to treat DPSCs for 7 days and 14 days, and cell proliferative activity was detected by CCK-8. After odontogenic differentiation induced by 15 µmol/L resveratrol for 7 days, alkaline phosphatase(ALP) staining was performed and real-time quantitative reverse transcription PCR(qRT-PCR) was used to detect the mRNA expression of Runt-related transcription factor 2 (Runx2), dentin sialophosphoprotein(DSPP) and dentin matrix protein-1(DMP-1) in DPSCs. Western blot was used to detect the expression of SIRT1 in DPSCs on a specific day (0, 3rd, 5th, 7th and 14th) after differentiation induction. Western blot was also used to detect the expression of SIRT1 and activated ß-catenin during odontogenic differentiation of DPSCs treated by 15 µmol/L resveratrol for 7 days. The experimental data was analyzed with GraphPad Prism 9 software package. RESULTS: 15 µmol/L resveratrol had no significant effect on proliferation of DPSCs on the 7th and 14th day; 15 µmol/L resveratrol promoted odontogenic differentiation of DPSCs and up-regulated mRNA expression of RUNX2, DSPP, and DMP-1 in DPSCs; the expression of SIRT1 was the highest on the 7th day during odontogenic differentiation induction. Resveratrol resulted in the increasing protein expressions of SIRT1 and activated ß-catenin when DPSCs was induced to odontogenic differentiation for 7 days. CONCLUSIONS: Resveratrol promotes odontogenic differentiation of human DPSCs by up-regulating the expression of SIRT1 protein and activating ß-catenin signaling pathway.


Assuntos
Subunidade alfa 1 de Fator de Ligação ao Core , beta Catenina , Humanos , Resveratrol/farmacologia , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , beta Catenina/metabolismo , beta Catenina/farmacologia , Polpa Dentária/metabolismo , Sirtuína 1/genética , Sirtuína 1/metabolismo , Sirtuína 1/farmacologia , Proliferação de Células , Diferenciação Celular , Odontogênese/genética , Células-Tronco/metabolismo , RNA Mensageiro/metabolismo , Células Cultivadas
5.
Biodivers Data J ; 11: e101468, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37215462

RESUMO

Background: Despite being the second largest group of vascular plants, ferns are scarcely reported being fed by insects when compared to angiosperms. Within these fern-feeding insects, lepidopterans are poorly represented and are restricted only to specific groups in this speciose order. The consumers specialising on fern spores are even scarcer in the order, with the majority being consumers of vegetative structures. Amongst the fern-spore-feeding Lepidoptera, Stathmopodidae is the family with the highest species diversity, even with a subfamily, Cyprininae Sinev, 2015, specialising on fern spores. However, fern-spore-feeding habit is not restricted to this subfamily. To understand the evolution of fern-spore-feeding within this family and to increase our knowledge of insect-fern evolution, detailed studies on fern-spore feeding stathmopodids are essential. New information: The present study rediscovered a rare, fern-spore-feeding, stathmopodid micro-moth, Stathmopodatacita (Meyrick, 1913), which has not been formally recorded or identified for more than 100 years. We documented the life history of this species and identified several species of Pyrrosia (Polypodiaceae, Platycerioideae) as host for the moth's larvae. A re-description of the fern-feeding moth is also provided as the original description is obscure in terms of character diagnosis.

6.
Biol Trace Elem Res ; 201(1): 139-148, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35066751

RESUMO

Cadmium (Cd) as a ubiquitous toxic heavy metal in the environment, causes severe hazards to human health, such as cellular stress and organ injury. Selenium (Se) was reported to reduce Cd toxicity and the mechanisms have been intensively studied so far. However, it is not yet crystal clear whether the protective effect of Se against Cd-induced cytotoxicity is related to selenoproteins in nerve cells or not. In this study, we found that Cd inhibited selenoprotein thioredoxin reductase 1 (TrxR1; TXNRD1) and decreased the expression level of TrxR1, resulting in cellular oxidative stress, and Se supplements ameliorated Cd-induced cytotoxicity in SH-SY5Y cells. Mechanistically, the detoxification of Se against Cd is attributed to the increase of the cellular TrxR activity and upregulated TrxR1 protein level, culminating in strengthened antioxidant capacity. Results showed that Se supplements attenuated the ROS production and apoptosis in SH-SY5Y cells, and significantly mitigated Cd-induced SH-SY5Y cell death. This study may be a valuable reference for shedding light on the mechanism of Cd-induced cytotoxicity and the role of TrxR1 in Se-mitigated cytotoxicity of Cd in neuroblast cells, which may be helpful for understanding the therapeutic potential of Cd and Se in treating or preventing neurodegenerative diseases, like Alzheimer's disease (AD) and Parkinson's disease (PD).


Assuntos
Neuroblastoma , Selênio , Humanos , Cádmio/toxicidade , Cádmio/metabolismo , Regulação para Baixo , Espécies Reativas de Oxigênio/metabolismo , Ácido Selenioso/metabolismo , Selênio/farmacologia , Selênio/metabolismo , Selenoproteínas/genética , Selenoproteínas/metabolismo , Tiorredoxina Redutase 1/metabolismo , Regulação para Cima
7.
ACS Sens ; 8(1): 289-296, 2023 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-36584336

RESUMO

As an important biomarker of lung cancer, n-propanol at the sub-ppm level is still challenging to be detected for a simple and immediate early diagnosis. In this work, a new n-propanol gas sensor with an ultralow detection limit down to 100 ppb is presented using AgCrO2 nanoparticles synthesized by a simple hydrothermal method. Compared with the congeneric CuCrO2 and commercial SnO2, AgCrO2 exhibits prevailing performances, including a higher selectivity, dynamic response, and logarithmical linearity but lower working temperature. The first-principles calculation and the energy band theoretical analysis are combined to elucidate the sensing mechanism, in which the chemical adsorption of gaseous molecules to silver followed by the dehydrogenation on chromium on the surface of AgCrO2 is responsible for the outstanding susceptibility toward n-propanol. The proposed metal oxide semiconductor gas sensor capable of sub-ppm n-propanol detection provides a route to design and optimize the sensitive material system for the advanced trace detection of the volatile organic compounds.


Assuntos
1-Propanol , Nanopartículas , Propanóis , Adsorção , Cromo , Gases
10.
World J Diabetes ; 13(8): 600-612, 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-36159226

RESUMO

BACKGROUND: Diabetic nephropathy (DN) is the principal cause of end-stage renal disease. Previous studies have shown that clopidogrel can prevent the early progression of renal injury. AIM: To elucidate whether clopidogrel is beneficial against DN by using a db/db mouse model. METHODS: db/db mice with a higher urinary albumin/creatinine ratio (ACR) relative to age- and sex-matched wild-type control mice were randomly allocated to clopidogrel and vehicle treatment groups. Clopidogrel was administered at doses of 5, 10, and 20 mg/kg by gavage for 12 wk. Body mass, blood glucose level, and urinary creatinine and albumin concentrations in each group were measured before and after the intervention. Renal fibrosis was evaluated using periodic acid-Schiff and Masson's trichrome staining. The renal protein expression of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and F4/80 was assessed using immunohistochemistry. Urinary TNF-α, monocyte chemoattractant protein-1 (MCP-1), and IL-6 levels were analyzed using enzyme-linked immunosorbent assay; TNF-α and IL-1ß mRNA expression was measured using real-time quantitative polymerase chain reaction. The protein expression of fibronectin (FN) and collagen I was assessed using immunohistochemistry. RESULTS: Clopidogrel treatment did not affect the body mass or blood glucose level of the db/db mice; however, it increased bleeding time and reduced urinary ACR in a dose-dependent manner. Immunohistochemical staining revealed an amelioration of renal fibrosis, significantly lower deposition of FN and collagen I, and significantly lower expression of the proinflammatory cytokines TNF-α and IL-1ß and lower levels of urinary TNF-α and MCP-1 in the clopidogrel-treated db/db mice (P < 0.05). Furthermore, clopidogrel significantly reduced macrophage infiltration into the glomeruli of the db/db mice. CONCLUSION: Clopidogrel significantly reduced renal collagen deposition and fibrosis and prevented renal dysfunction in db/db mice, most likely through inhibition of renal macrophage infiltration and the associated inflammation.

11.
Fish Shellfish Immunol ; 129: 127-136, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36055559

RESUMO

The present study evaluated the protective effect and the regulatory mechanism of taurine on growth inhibition and intestinal damage induced by glycinin in juvenile Rhynchocypris lagowskii Dybowski. The control diets had no glycinin and taurine, the glycinin diets contained only 80 g/kg glycinin, and the glycinin + taurine diets contained 80 g/kg glycinin+10 g/kg taurine. Juvenile Rhynchocypris lagowskii Dybowski (4.65 ± 0.03 g/tail) were respectively fed with these 3 diets for 8 weeks. The results showed that glycinin significantly decreased the final body weight, weight gain rate, specific growth rate, protein efficiency rate, feed efficiency rate and feeding rate of fish compared with the control group (P < 0.05). While taurine supplementation improved the growth performance and feed efficiency, but final body weight, weight gain rate, specific growth rate of the glycinin + taurine group were still significantly lower than the control group (P < 0.05). Compared with the glycinin group, taurine supplementation significantly increased whole-body and muscle crude protein content, and hepatopancreas and intestinal protease activities (P < 0.05). Distal intestinal villous dysplasia and mucosal damage, and increased intestinal mucosal permeability were observed in the glycinin group, while taurine supplementation alleviated these adverse effects. Usefully, taurine supplementation could also partially restore the impaired immune function and antioxidant capacity of fish fed glycinin diets. Compared with the glycinin group, taurine supplementation down-regulated pro-inflammatory cytokines TNF-α and IL-1ß mRNA levels, and up-regulated anti-inflammatory cytokines IL-10 and TGF-ß mRNA levels. Furthermore, taurine partially reversed the reduction of antioxidant genes Nrf2、HO-1, CAT and GPx mRNA levels in distal intestine induced by glycinin. Concluded, 80 g/kg glycinin led to intestinal damage, digestive dysfunction and increased intestinal mucosal permeability in juvenile Rhynchocypris lagowskii Dybowski, and these adverse effects were ultimately manifested in growth inhibition. But taurine supplementation could partially mitigate the negative effects induced by glycinin.


Assuntos
Interleucina-10 , Fator 2 Relacionado a NF-E2 , Ração Animal/análise , Animais , Anti-Inflamatórios , Antioxidantes/metabolismo , Peso Corporal , Dieta/veterinária , Suplementos Nutricionais/análise , Fator 2 Relacionado a NF-E2/metabolismo , Peptídeo Hidrolases , RNA Mensageiro/genética , Taurina/farmacologia , Fator de Crescimento Transformador beta , Fator de Necrose Tumoral alfa , Aumento de Peso
12.
Open Life Sci ; 17(1): 416-425, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35582623

RESUMO

Chromosomal abnormality is one of the important causes of dysplasia in children. However, due to regional and ethnic differences, the reported rates of chromosomal abnormalities in patients with dysplasia vary greatly. Moreover, the clinical manifestations in children with rare chromosomal diseases were heterogeneous. So, we retrospectively analyzed the karyotype results of 436 children with dysplasia and conducted a detailed analysis of rare chromosomal diseases. The results showed that chromosomal abnormalities were present in 181 of 436 cases. Intellectual disability, dysmorphology, congenital malformations, the disorder of sexual development, and short stature were the main five clinical symptoms in children with chromosomal abnormalities. Moreover, 136 cases of Trisomy 21 (Tri21) were detected, of which 130 were standard Tri21, 5 were robertsonian Tri21, and 1 was chimera type. In addition, 16 cases of rare abnormal karyotype, including complex Tri21, complex Turner syndrome, 4p-syndrome, 18q-syndrome, and 5p-syndrome, were also detected. In summary, chromosome abnormality is one of the important causes of dysplasia in children. Furthermore, prenatal screening and diagnosis could play a great significance in preventing dysplasia in children. In addition, the retrospective analysis of rare cases is valuable for clinical diagnosis and risk assessment of recurrence.

14.
Acta Biochim Pol ; 69(2): 399-407, 2022 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-35616622

RESUMO

Lipid droplets (LDs) are intracellular droplets containing phospholipids and neutral lipids. It is well known that LDs are organelles with a rich proteome. In the nervous system, these droplets may play an important role in maintaining the normal physiological function of nerve cells. Moreover, LDs may relate to the neurodegenerative disorders, such as Alzheimer's disease (AD). However, more information is still needed about the function of LDs. In the study presented here, we identified the protein composition of mouse neuroblastoma (N2a) cell LDs using immunodetection and high-performance liquid chromatography (HPLC) coupled with mass spectrometry (MS). Seventy three LDs proteins were identified. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to investigate the potential functions of these proteins. Subsequently, the relationships among the proteins were analyzed by constructing a protein-protein interaction (PPI) network. N2a cell LDs contain multiple Rab GTPases, chaperones, and proteins involved in ubiquitination and transport. Some of these proteins were known to modulate LD formation and were related to the function of nerve cells. This work presents the proteome of N2a cell LDs and will help to identify the role of LDs in the nervous system.


Assuntos
Neuroblastoma , Proteômica , Animais , Gotículas Lipídicas/metabolismo , Metabolismo dos Lipídeos/fisiologia , Camundongos , Proteoma/análise , Proteômica/métodos
15.
Artigo em Inglês | MEDLINE | ID: mdl-35559719

RESUMO

A novel obligate anaerobic organism, designated DONG20-135T, was isolated from human faeces collected in Beijing, PR China. Cells were Gram-stain-negative, rod-shaped, non-motile and non-spore-forming. Growth occurred at 25‒45 °C (optimum, 30‒35 °C), a pH range of 6-9 (optimum, pH 8) and in the presence of 0‒3.5 % (w/v) NaCl (optimum, 0.5‒1.5 %). The major fatty acids were C16 : 0, C18 : 1 ω9c and C10 : 0, the polar lipid profile consisted of diphosphatidylglycerol, phosphatidylglycerol, four glycolipids, six aminolipids, three aminophospholipids and four unidentified lipids. No respiratory quinones were detected. The cell-wall peptidoglycan of the strain was A1γ type, containing meso-diaminopimelic acid. The 16S rRNA gene sequences shared a lower identity (<92.7 % similarity) with the described species. The phylogenetic tree based on 16S rRNA gene sequences and the protein-concatamer tree showed that strain DONG20-135T formed a distinct lineage within the family Erysipelotrichaceae. The genomic DNA G + C content was 42.2 mol%. Based on the results of phenotypic, chemotaxonomic and genomic analyses, strain DONG20-135T represents a novel genus of the family Erysipelotrichaceae, for which the name Copranaerobaculum intestinale gen. nov., sp. nov. is proposed (=KCTC 15868T=CGMCC 1.17357T).


Assuntos
Ácidos Graxos , Fosfolipídeos , Anaerobiose , Técnicas de Tipagem Bacteriana , Composição de Bases , China , DNA Bacteriano/genética , Ácidos Graxos/química , Fezes , Humanos , Fosfolipídeos/química , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA
16.
J Pain Res ; 15: 1389-1399, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35592818

RESUMO

Objective: Continuous interscalene brachial plexus block (cIBPB) is an effective perioperative analgesic therapy for shoulder arthroscopic surgery (SAS) patients. This trial aimed to compare the effect of different cIBPB infusion methods on postoperative analgesia and respiratory function in patients undergoing SAS. Methods: After SAS, 88 patients were randomly assigned to four groups. Through interscalene catheter, all the patients received an initial dose of 10 mL 0.2% ropivacaine. The CI group received 0.2% ropivacaine 4 mL/h, and the PIBI1, PIBI2, and PIBI3 groups received intermittent 0.2% ropivacaine boluses at 4 mL/h, 8 mL/2 h, and 12 mL/3 h, respectively. The patients could also use a patient-controlled analgesia (PCA) pump to self-inject a tramadol bolus each time he/she felt pain. The primary outcome was the cumulative tramadol consumption over the 48 h after surgery. Secondary outcome measures included PCA frequency, pain (visual analogue scale, VAS) score, patient satisfaction, diaphragmatic excursion, pulmonary function, and adverse events. Results: The cumulative tramadol consumption and PCA frequency over the 48 h after surgery in groups PIBI2 and PIBI3 were lower than in both the CI and PIBI1 groups (p<0.001). The VAS scores (at rest and on movement) in groups PIBI2 and PIBI3 were lower than those in the CI and PIBI1 groups at 8 and 12 h after surgery (all p<0.001). Patient satisfaction scores were significantly higher in the PIBI2 group than in the other three groups (all p<0.001). Diaphragmatic excursion was significantly decreased in the PIBI3 group compared to the other three groups (p<0.05). The incidence of adverse events over the 48 h after surgery was significantly higher in the PIBI3 group compared to the other three groups (p<0.001). Conclusion: Programmed intermittent bolus infusion with 0.2% ropivacaine 8 mL/2 h for cIBPB can achieve lower tramadol consumption, along with better analgesia after surgery, lower reduction in diaphragmatic excursion, lower incidence of adverse events, and higher patient satisfaction.

17.
Acad Radiol ; 29(7): 1022-1028, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-34649781

RESUMO

AIM: To establish a predictive nomogram for malignancy risk stratification of micro-calcifications (MCCs) detected on mammography. MATERIALS AND METHODS: Consecutive mammograms from January 2017 to March 2021 were retrospectively reviewed. Traditional clinical features were recorded and mammographic features were estimated according to the 5th BI-RADS. A nomogram was developed to graphically predict the malignancy risk based on multivariate logistic regression analysis. The discrimination and calibration performance of the prediction model was assessed. RESULTS: There were 123 cases of suspicious MCCs with final pathological results identified with a malignancy rate of 55.2%. The malignancy rates of subgroups divided according to the morphology and distribution of MCCs, age, menopausal status and the maximum diameter of MCCs were significantly different. Multivariate logistic analysis showed that a menopause status of postmenopausal, maximum diameters of MCCs ≥2 cm, the morphology of MCCs as fine pleomorphic or fine linear or branching, and the distribution of MCCs as linear or segmental were predictive of a higher probability of malignancy. A prediction nomogram was developed based on four risk factors, including menopausal status as well as the maximum diameters, distribution and morphology of the MCCs. The AUC of that nomogram was 0.839 (95%CI:0.771-0.903). CONCLUSION: In mammography, the morphology, distribution and maximum diameter of MCCs, and the menopausal status are independent predictors of malignant suspicious MCCs and are readily available in the clinical setting. The nomogram developed in this study for individualized malignancy risk stratification of suspicious MCCs shows a reliable discrimination performance.


Assuntos
Doenças Mamárias , Neoplasias da Mama , Calcinose , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Calcinose/diagnóstico por imagem , Calcinose/patologia , Feminino , Humanos , Mamografia/métodos , Nomogramas , Estudos Retrospectivos
18.
Cancer Drug Resist ; 4(3): 517-542, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34888495

RESUMO

Triple-negative breast cancer (TNBC) is a pathological term used to identify invasive breast cancers that lack expression of estrogen and progesterone receptors and do not have pathologic overexpression of the HER2 receptor or harbor ERBB2 gene amplification. TNBC includes a collection of multiple distinct disease entities based upon genomic, transcriptomic and phenotypic characterization. Despite improved clinical outcomes with the development of novel therapeutics, TNBC still yields the worst prognosis among all clinical subtypes of breast cancer. We will systematically review evidence of the genomic evolution of TNBC, as well as potential mechanisms of disease progression and treatment resistance, defined in part by advances in next-generation DNA sequencing technology (including single cell sequencing), providing a new perspective on treatment strategies, and promise to reveal new potential therapeutic targets. Moreover, we review novel therapies aimed at homologous recombination deficiency, PI3 kinase/AKT/PTEN pathway activation, androgen receptor blockade, immune checkpoint inhibition, as well as antibody-drug conjugates engaging novel cell surface targets, including recent progress in pre-clinical and clinical studies which further validate the role of targeted therapies in TNBC. Despite major advances in treatment for TNBC, including FDA approval of 2 PARP inhibitors for metastatic TNBC, the crossing of the superiority boundary in a phase 3, placebo-controlled study of adjuvant olaparib in early-stage patients with germline BRCA-mutated high-risk HER2-negative early breast cancer, the FDA approval of 2 PD-(L)1 checkpoint antibodies for metastatic TNBC, and the FDA approval of the first antibody drug conjugate for TNBC, significant challenges remain. For example, despite the dawn of immunotherapy in metastatic TNBC, durable responses are limited to a small subset of patients, definitive biomarkers for patient selection are lacking, and the Oncology Drug Advisory Committee to the FDA has recently voted against approval of an anti-PD-1 checkpoint antibody high risk early-stage TNBC in the neoadjuvant setting. Also, despite early positive randomized phase 2 studies of AKT inhibition in metastatic TNBC, a recent phase 3 registration trial failed to validate earlier phase 2 data. Finally, we note that level one evidence for clinical efficacy of androgen receptor blockade in TNBC is still lacking. To meet these and other challenges, we will catalogue the ongoing exponential increase in interest in basic, translational, and clinical research to develop new treatment paradigms for TNBC.

19.
Ying Yong Sheng Tai Xue Bao ; 32(12): 4370-4380, 2021 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-34951278

RESUMO

Mechanisms underlying leaf photosynthetic acclimation in winter wheat under elevation of CO2 concentration ([CO2]) remain unclear. The aim of the study was to investigate the effects of source-sink variation on photosynthetic acclimation induced by drought under elevated [CO2]. A winter wheat (Triticum aestivum L. 'Zhengmai 9023') pot experiment was conducted in open top climate chambers with [CO2] of 400µmol·mol-1 or 600 µmol·mol-1 and soil water content at 80%±5% or 55%±5% of field capacity. The parameters of chlorophyll fluorescence, electron transport rate, photosynthetic curve, leaf nitrogen content, and grain yield were measured at the elongation and heading stages. Under drought condition, leaf PSⅡ photochemical efficiency was not affected by elevated [CO2], but the maximum electron transport rate and the ratio of electron partitioned to carboxylation reaction in Calvin cycle was increased at the elongation stage, and thus the Rubisco carboxylation rate and maximum photosynthetic rate were increased. Although the maximum electron transportation rate and partitioning ratio of electron to carboxylation reaction in Calvin cycle remained high at the heading stage, the PSⅡ photochemical efficiency, Rubisco carboxylation rate, and triose phosphate utilization rate were decreased by elevated [CO2], which consequently reduced the maximum photosynthetic rate for plant under drought stress. Under drought condition, elevated [CO2] increased wheat tiller biomass, kernel number, and kernel weight per ear, but decreased infertile kernel number, resulting in an overall increase in grain weight. In conclusion, the elevated [CO2]-induced increase in wheat grain yield per tiller under drought condition was mainly caused by enhanced photosynthetic performance at the elongation stage. The photosynthetic acclimation in source leaves during the heading stage under elevated [CO2] was mainly attributed to the reduction in PSⅡ photochemical efficiency and triose phosphate utilization rate, but not to the maximum electron transportation rate, ratio of electron partitioned to carboxylation in Calvin cycle or sink leaf strength.


Assuntos
Secas , Triticum , Aclimatação , Dióxido de Carbono , Fotossíntese , Folhas de Planta
20.
PeerJ ; 9: e12418, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34754629

RESUMO

BACKGROUND: Hawthorn species (Crataegus L.; Rosaceae tribe Maleae) form a well-defined clade comprising five subgeneric groups readily distinguished using either molecular or morphological data. While multiple subsidiary groups (taxonomic sections, series) are recognized within some subgenera, the number of and relationships among species in these groups are subject to disagreement. Gametophytic apomixis and polyploidy are prevalent in the genus, and disagreement concerns whether and how apomictic genotypes should be recognized taxonomically. Recent studies suggest that many polyploids arise from hybridization between members of different infrageneric groups. METHODS: We used target capture and high throughput sequencing to obtain nucleotide sequences for 257 nuclear loci and nearly complete chloroplast genomes from a sample of hawthorns representing all five currently recognized subgenera. Our sample is structured to include two examples of intersubgeneric hybrids and their putative diploid and tetraploid parents. We queried the alignment of nuclear loci directly for evidence of hybridization, and compared individual gene trees with each other, and with both the maximum likelihood plastome tree and the nuclear concatenated and multilocus coalescent-based trees. Tree comparisons provided a promising, if challenging (because of the number of comparisons involved) method for visualizing variation in tree topology. We found it useful to deploy comparisons based not only on tree-tree distances but also on a metric of tree-tree concordance that uses extrinsic information about the relatedness of the terminals in comparing tree topologies. RESULTS: We obtained well-supported phylogenies from plastome sequences and from a minimum of 244 low copy-number nuclear loci. These are consistent with a previous morphology-based subgeneric classification of the genus. Despite the high heterogeneity of individual gene trees, we corroborate earlier evidence for the importance of hybridization in the evolution of Crataegus. Hybridization between subgenus Americanae and subgenus Sanguineae was documented for the origin of Sanguineae tetraploids, but not for a tetraploid Americanae species. This is also the first application of target capture probes designed with apple genome sequence. We successfully assembled 95% of 257 loci in Crataegus, indicating their potential utility across the genera of the apple tribe.

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