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1.
Genes Dev ; 32(15-16): 1085-1100, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-30018102

RESUMO

Continuous formation of somatic tissues in plants requires functional stem cell niches where undifferentiated cells are maintained. In Arabidopsis thaliana, PLETHORA (PLT) and SCARECROW (SCR) genes are outputs of apical-basal and radial patterning systems, and both are required for root stem cell specification and maintenance. The WUSCHEL-RELATED HOMEOBOX 5 (WOX5) gene is specifically expressed in and required for functions of a small group of root stem cell organizer cells, also called the quiescent center (QC). PLT and SCR are required for QC function, and their expression overlaps in the QC; however, how they specify the organizer has remained unknown. We show that PLT and SCR genetically and physically interact with plant-specific teosinte-branched cycloidea PCNA (TCP) transcription factors to specify the stem cell niche during embryogenesis and maintain organizer cells post-embryonically. PLT-TCP-SCR complexes converge on PLT-binding sites in the WOX5 promoter to induce expression.


Assuntos
Proteínas de Arabidopsis/metabolismo , Raízes de Plantas/genética , Nicho de Células-Tronco , Fatores de Transcrição/metabolismo , Arabidopsis/citologia , Arabidopsis/embriologia , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Proteínas de Arabidopsis/química , Proteínas de Arabidopsis/genética , Expressão Gênica , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Mutação , Raízes de Plantas/citologia , Raízes de Plantas/embriologia , Raízes de Plantas/crescimento & desenvolvimento , Domínios e Motivos de Interação entre Proteínas , Fatores de Transcrição/química , Fatores de Transcrição/genética
2.
Plant J ; 117(3): 856-872, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37983569

RESUMO

Sorbitol is a critical photosynthate and storage substance in the Rosaceae family. Sorbitol transporters (SOTs) play a vital role in facilitating sorbitol allocation from source to sink organs and sugar accumulation in sink organs. While prior research has addressed gene duplications within the SOT gene family in Rosaceae, the precise origin and evolutionary dynamics of these duplications remain unclear, largely due to the complicated interplay of whole genome duplications and tandem duplications. Here, we investigated the synteny relationships among all identified Polyol/Monosaccharide Transporter (PLT) genes in 61 angiosperm genomes and SOT genes in representative genomes within the Rosaceae family. By integrating phylogenetic analyses, we elucidated the lineage-specific expansion and syntenic conservation of PLTs and SOTs across diverse plant lineages. We found that Rosaceae SOTs, as PLT family members, originated from a pair of tandemly duplicated PLT genes within Class III-A. Furthermore, our investigation highlights the role of lineage-specific and synergistic duplications in Amygdaloideae in contributing to the expansion of SOTs in Rosaceae plants. Collectively, our findings provide insights into the genomic origins, duplication events, and subsequent divergence of SOT gene family members. Such insights lay a crucial foundation for comprehensive functional characterizations in future studies.


Assuntos
Magnoliopsida , Rosaceae , Rosaceae/genética , Filogenia , Magnoliopsida/genética , Genoma de Planta/genética , Sorbitol , Evolução Molecular , Duplicação Gênica
3.
Cell Biol Toxicol ; 40(1): 67, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39110362

RESUMO

BACKGROUND: Titanium dioxide nanoparticles (TiO2NPs) are widely used in medical application. However, the relevant health risk has not been completely assessed, the potential of inducing arterial thrombosis (AT) in particular. METHODS: Alterations in platelet function and susceptibility to arterial thrombosis induced by TiO2NPs were examined using peripheral blood samples from healthy adult males and an in vivo mouse model, respectively. RESULTS: Here, using human platelets (hPLTs) freshly isolated from health volunteers, we demonstrated TiO2NP treatment triggered the procoagulant activity of hPLTs through phosphatidylserine exposure and microvesicles generation. In addition, TiO2NP treatment increased the levels of glycoprotein IIb/IIIa and P-selectin leading to aggregation and activation of hPLTs, which were exacerbated by providing physiology-mimicking conditions, including introduction of thrombin, collagen, and high shear stress. Interestingly, intracellular calcium levels in hPLTs were increased upon TiO2NP treatment, which were crucial in TiO2NP-induced hPLT procoagulant activity, activation and aggregation. Moreover, using mice in vivo models, we further confirmed that TiO2NP treatment a reduction in mouse platelet (mPLT) counts, disrupted blood flow, and exacerbated carotid arterial thrombosis with enhanced deposition of mPLT. CONCLUSIONS: Together, our study provides evidence for an ignored health risk caused by TiO2NPs, specifically TiO2NP treatment augments procoagulant activity, activation and aggregation of PLTs via calcium-dependent mechanism and thus increases the risk of AT.


Assuntos
Plaquetas , Ativação Plaquetária , Agregação Plaquetária , Trombose , Titânio , Titânio/toxicidade , Animais , Humanos , Agregação Plaquetária/efeitos dos fármacos , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Masculino , Trombose/induzido quimicamente , Camundongos , Ativação Plaquetária/efeitos dos fármacos , Adulto , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/metabolismo , Coagulação Sanguínea/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Selectina-P/metabolismo , Cálcio/metabolismo , Cálcio/sangue , Nanopartículas/toxicidade , Nanopartículas Metálicas/toxicidade
4.
Clin Chem Lab Med ; 62(4): 690-697, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-37855253

RESUMO

OBJECTIVES: Automated hematology analysis is expected to improve the performance of platelet counting. We evaluated the performance of a new platelet counting, hybrid (PLT-H) and also impedance (PLT-I) and optical (PLT-O) on the BC-780 automated hematology analyzer compared to the international reference method (IRM) in blood samples with thrombocytopenic and platelet interference. METHODS: The basic platelet count performance of the BC-780 automated hematology analyzer was evaluated according to the requirements of the Clinical Laboratory and Standards Institute (CLSI) Document H26-A2. Additionally, the thrombocytopenic (low PLT count) blood samples and the platelet interference blood samples including fragmented red blood cells (RBCs), microcytes or small RBCs, and giant platelets were determined with the BC-780 hematology analyzer compared to the IRM. RESULTS: Blank counting and the carry-over contamination rate of platelet count using the BC-780 both met the manufacturers' claim. For both 123 thrombocytopenic and 232 platelet interference blood samples (72 fragmented RBCs, 91 microcytes and 51 giant platelets), all three platelet counting methods exhibited high comparability with the IRM (the lowest correlation (r)=0.916). Interestingly, the comparability of PLT-H (r=0.928-0.986) with the IRM was better than that of PLT-I (r=0.916-0.979). CONCLUSIONS: The performance of PLT-H in the BC-780 met the manufacturer's specifications. PLT-H exhibits better reproducibility than did PLT-I, correlates well with the PLT-O for thrombocytopenic samples and demonstrates good anti-interference ability. PLT-H counting is therefore recommended as a zero-cost alternative platelet counting method for platelet interference samples in clinical settings.


Assuntos
Agmatina/análogos & derivados , Hematologia , Ácido Oxâmico/análogos & derivados , Humanos , Contagem de Plaquetas/métodos , Reprodutibilidade dos Testes , Hematologia/métodos , Plaquetas
5.
Clin Exp Nephrol ; 28(7): 636-646, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38402503

RESUMO

BACKGROUND: Iron deficiency anemia (IDA) increases levels of C-terminal fibroblast growth factor 23 (cFGF23) and platelet count (PLT), each of which is associated with cardiovascular events. Therefore, we hypothesized that iron replacement with ferric citrate hydrate (FC) would decrease cFGF23 levels and PLT in patients with IDA. METHODS: In a randomized, open-label, multicenter, 24-week clinical trial, patients with non-dialysis-dependent chronic kidney disease (CKD) and non-CKD complicated by IDA (8.0 ≤ hemoglobin < 11.0 g/dL; and serum ferritin < 50 ng/mL [CKD]; < 12 ng/mL [non-CKD]) were randomized 1:1 to FC-low (500 mg: approximately 120 mg elemental iron/day) or FC-high (1000 mg: approximately 240 mg elemental iron/day). If sufficient iron replacement had been achieved after week 8, further treatment was discontinued. RESULTS: Seventy-three patients were allocated to FC-low (CKD n = 21, non-CKD n = 15) and FC-high (CKD n = 21, non-CKD n = 16). Regardless of CKD status, FC increased serum ferritin and transferrin saturation, did not change intact FGF23 or serum phosphorus, but decreased cFGF23. In FC-low group, median changes in cFGF23 from baseline to week 8 were -58.00 RU/mL in CKD and -725.00 RU/mL in non-CKD; in FC-high group, the median changes were -66.00 RU/mL in CKD and -649.50 RU/mL in non-CKD. By week 8, FC treatment normalized PLT in all patients with high PLT at baseline (>35.2 × 104/µL; FC-low: 1 CKD, 8 non-CKD; FC-high: 3 CKD, 8 non-CKD). CONCLUSION: Regardless of CKD status, iron replacement with FC decreased elevated cFGF23 levels and normalized elevated PLT in patients with IDA. CLINICAL TRIAL REGISTRATION NUMBER: jRCT2080223943.


Assuntos
Anemia Ferropriva , Compostos Férricos , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos , Insuficiência Renal Crônica , Humanos , Fatores de Crescimento de Fibroblastos/sangue , Compostos Férricos/uso terapêutico , Compostos Férricos/administração & dosagem , Masculino , Feminino , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Anemia Ferropriva/tratamento farmacológico , Anemia Ferropriva/sangue , Pessoa de Meia-Idade , Idoso , Contagem de Plaquetas , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Ferritinas/sangue , Hematínicos/uso terapêutico , Resultado do Tratamento , Adulto
6.
Plant Mol Biol ; 113(1-3): 75-88, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37606746

RESUMO

Three members of the Arabidopsis AINTEGUMENTA-LIKE/PLETHORA (AIL/PLT) transcription factor family, AIL5/PLT5, AIL6/PLT3, and AIL7/PLT7, exhibit partially overlapping roles with AINTEGUMENTA (ANT) during flower development. Loss of ANT function alone results in smaller floral organs and female sterility indicating that some ANT functions cannot be provided by these related transcription factors. Previously, we showed that expression of AIL6 at the same levels and spatial pattern as ANT could largely rescue the defects of ant mutants. This suggested that the functional differences between ANT and AIL6 were primarily a consequence of expression differences. Here, we investigated the functional differences between ANT and both AIL5 and AIL7 by expressing these two AILs under the control of the ANT promoter. We found that only ANT:gAIL5 lines with much higher amounts of AIL5 mRNA as compared with ANT could compensate for loss of ANT function. ANT:gAIL7 lines with AIL7 mRNA levels similar to those of ANT were able to rescue some but not all aspects of the ant mutant phenotype. Thus, expression differences alone cannot explain the functional differences between ANT and these two related proteins. Studies in yeast show that AIL5 and AIL7 have lower transcriptional activation activities as compared with ANT and AIL6 when bound to the consensus ANT DNA binding site. Our results suggest that differences in both expression and protein activity contribute to the functional specificity of ANT compared with AIL5 and AIL7.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Flores , Regulação da Expressão Gênica de Plantas , RNA Mensageiro/metabolismo , Fatores de Transcrição/metabolismo
7.
Development ; 147(6)2020 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-32108025

RESUMO

Aerial organs of plants, being highly prone to local injuries, require tissue restoration to ensure their survival. However, knowledge of the underlying mechanism is sparse. In this study, we mimicked natural injuries in growing leaves and stems to study the reunion between mechanically disconnected tissues. We show that PLETHORA (PLT) and AINTEGUMENTA (ANT) genes, which encode stem cell-promoting factors, are activated and contribute to vascular regeneration in response to these injuries. PLT proteins bind to and activate the CUC2 promoter. PLT proteins and CUC2 regulate the transcription of the local auxin biosynthesis gene YUC4 in a coherent feed-forward loop, and this process is necessary to drive vascular regeneration. In the absence of this PLT-mediated regeneration response, leaf ground tissue cells can neither acquire the early vascular identity marker ATHB8, nor properly polarise auxin transporters to specify new venation paths. The PLT-CUC2 module is required for vascular regeneration, but is dispensable for midvein formation in leaves. We reveal the mechanisms of vascular regeneration in plants and distinguish between the wound-repair ability of the tissue and its formation during normal development.


Assuntos
Arabidopsis , Redes Reguladoras de Genes/fisiologia , Folhas de Planta/fisiologia , Caules de Planta/fisiologia , Feixe Vascular de Plantas/fisiologia , Regeneração/genética , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/fisiologia , Regulação da Expressão Gênica de Plantas , Ácidos Indolacéticos/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Oxigenases de Função Mista/genética , Oxigenases de Função Mista/metabolismo , Desenvolvimento Vegetal/fisiologia , Folhas de Planta/genética , Folhas de Planta/crescimento & desenvolvimento , Caules de Planta/genética , Caules de Planta/crescimento & desenvolvimento , Feixe Vascular de Plantas/genética , Plantas Geneticamente Modificadas , Regiões Promotoras Genéticas , Transdução de Sinais/genética , Fatores de Transcrição/fisiologia , Cicatrização/genética
8.
Planta ; 259(1): 8, 2023 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-38019301

RESUMO

MAIN CONCLUSION: This study reveals that mutations in BRIP1/2 subunits of the BAS complex disrupt root meristem development by decreasing PIN genes expression, affecting auxin transport, and downregulating essential root genes PLT. Switch defective/sucrose non-fermentable (SWI/SNF) chromatin remodeling complexes play vital roles in plant development. BRAHMA-interacting proteins1 (BRIP1) and BRIP2 are subunits of BRAHMA (BRM)-associated SWI/SNF complex (BAS) in plants; however, their role and underlying regulatory mechanism in root development are still unknown. Here, we show that brip1 brip2 double mutants have a significantly shortened root meristem and an irregular arrangement in a portion of the root stem cell niche. The mutations in BRIP1 and BRIP2 cause decreased expression of the PIN-FORMED (PIN) genes, which in turn reduces the transport of auxin at the root tip, leading to the disruption of the accurate establishment of normal auxin concentration gradients in the stem cells. Chromatin immunoprecipitation (ChIP) experiments indicated that BRIP1 and BRIP2 directly bind to the PINs. Furthermore, we found a significant down-regulation in the expression of key root development genes, PLETHORA (PLT), in brip1 brip2. The brip1 brip2 plt1 plt2 quadruple mutations do not show further exacerbation in the short-root phenotype compared to plt1 plt2 double mutants. Using a dexamethasone (DEX)-inducible PLT2 transgenic line, we showed that acute overexpression of PLT2 partially rescues root meristem defects of brip1 brip2, suggesting that BRIP1 and BRIP2 act in part through the PLT1/2 pathway. Taken together, our results identify the critical role and the underlying mechanism of BRIP1/2 in maintaining the development of root meristem through the regulation of auxin output and expression of PLTs.


Assuntos
Ácidos Indolacéticos , Meristema , Proteínas de Plantas , Transporte Biológico , Regulação para Baixo , Expressão Gênica , Meristema/genética , Proteínas de Plantas/genética
9.
Bioorg Chem ; 130: 106256, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36371822

RESUMO

The novel Palmatine (PLT)-based supramolecular salt palmatine-sulfosalicylic acid (PLT-SSA) was designed and synthesized, and its structures was determined by the single crystal X-ray diffraction. It is found that PLT-SSA exhibited enhancing thermodynamic stability, fluorescence intensity and emission lifetime in crystal state, which indicated that these structures and aromatic rings may give more overlap between the host-guest units and give rise to a long-lived charge-separated state. In addition, the dyeing properties and toxicity of these protoberberine alkaloid (BBC and PLTCl) and their supramolecular salts will be developed in this work used as yellow dyes for development multifunctional fabrics.


Assuntos
Alcaloides de Berberina , Alcaloides/farmacologia , Alcaloides/química , Corantes , Termodinâmica , Alcaloides de Berberina/química , Alcaloides de Berberina/farmacologia
10.
Pediatr Nephrol ; 38(6): 1811-1820, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36449101

RESUMO

BACKGROUND: Primary hyperoxaluria type 1 (PH1) is an autosomal recessive disease caused by the liver defect of oxalate metabolism, which leads to kidney failure and systemic manifestations. Until recently, liver transplantation was the only definitive treatment. The timing of liver transplantation can be early, while kidney function is still normal (pre-emptive liver transplantation-PLT), or when the patient reaches stage 5 chronic kidney disease (CKD) and needs combined liver-kidney transplantation. We aimed to determine the long-term kidney outcomes of PLT in PH1 patients. METHODS: A retrospective single-center study of PH1 patients who were followed in our center between 1997 and 2017. We compared the kidney outcomes of patients who underwent PLT to those who presented with preserved kidney function and did not undergo PLT. RESULTS: Out of 36 PH1 patients, 18 patients were eligible for PLT (eGFR > 40 mL/min/1.73 m2 at the time of diagnosis). Seven patients underwent PLT (PLT group), while 11 continued conservative treatments (PLTn group). In the PLT group, the median eGFR at the time of PLT and at the end of the follow-up period (14-20 years) was 72 (range 50-89) and 104 (range 86-108) mL/min/1.73 m2, respectively, and no patient died or reached stage 5 CKD. In the PLTn group, eight patients (72.7%) reached stage 5 CKD (median time to kidney replacement therapy was 11 years), and two patients died from disease complications (18.2%). CONCLUSIONS: Pre-emptive liver transplantation preserved kidney function in patients with PH1 in our cohort. Early intervention can prevent kidney failure and systemic oxalosis in PH1. A higher resolution version of the Graphical abstract is available as Supplementary information.


Assuntos
Hiperoxalúria Primária , Falência Renal Crônica , Transplante de Fígado , Insuficiência Renal , Humanos , Transplante de Fígado/efeitos adversos , Estudos Retrospectivos , Hiperoxalúria Primária/complicações , Hiperoxalúria Primária/cirurgia , Falência Renal Crônica/etiologia , Insuficiência Renal/complicações
11.
Platelets ; 34(1): 2287064, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38031975

RESUMO

The hybrid-channel platelet counting method (PLT-H) is a new platelet counting technique proposed by Mindray of China. In this study, we aimed to evaluate the accuracy of this technique in various situations and its reliability in platelet transfusion decision-making. A total of 378 venous blood samples were tested. Using the immunological PLT counting method recommended by the International Council for Standardization in Hematology as the reference method (PLT-IRM), Passing-Bablok regression and Bland-Altman analysis were performed on the PLT-H results. The anti-interference performance of PLT-H under different interference levels was explored using intergroup comparisons, and confusion matrices were analyzed at various transfusion cutoff values. In the absence of interference, there was a strong correlation between PLT-H and PLT-IRM (r = 0.993, 95% CI: 0.990-0.996). Under various interference conditions, the correlation between PLT-H and PLT-IRM was between 0.963 and 0.992, with an average deviation of -14.56 to -2.02. The performance of PLT-H against interference did not change significantly with increasing levels of small RBCs, large PLTs, and RBC fragments (P = .5704, 0.0832, 0.9893). In low-value samples (PLT <100 × 109/L), the coefficient of variation (CV) for PLT-H was less than 7.6%, regardless of the presence or absence of interfering substances. In addition, there was a high agreement between PLT-H and PLT-IRM (ICC = 0.972). Confusion matrice analysis at each medical decision level showed similarity to methods using the fluorescence channel (PLT-O) and superiority to the impedance channel (PLT-I). Compared with PLT-I, PLT-H has higher accuracy in PLT counting, stronger anti-interference ability, better performance in low-value samples at no extra economic cost and can be more useful for platelet transfusion decision-making. PLT-H is a novel method for platelet counting that offers higher accuracy, providing physicians with the ability to make better medical decisions, particularly in cases where values are low, or interference is present. As it does not require additional reagents, it is highly likely to replace PLT-I and become the mainstream method for platelet counting in the future.


Assuntos
Plaquetas , Transfusão de Plaquetas , Humanos , Reprodutibilidade dos Testes , Contagem de Plaquetas/métodos
12.
BMC Surg ; 23(1): 117, 2023 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-37165423

RESUMO

BACKGROUND: Prognositic nutritional index (PNI), monocyte-to-lymphocyte ratio (MLR) and platelet (PLT) are associated with tumor survival in many human malignancies. Whereas, no study combined PNI-MLR-PLT score and indicated its predictive significance on the prognosis of patients with non-metastatic clear cell renal cell carcinoma (ccRCC). METHODS: In this study, we retrospectively collected the clinicopathological characteristics and prognostic data from 164 cases of non-metastatic ccRCC and aimed to determine the clinical significance of PNI-MLR-PLT score on patients' outcomes after surgery. The optimal cut-off values of PNI (PNI > 47.40 vs PNI < 47.40), MLR (MLR > 0.31 vs MLR < 0.31) and PLT (PLT > 245 vs PLT < 245) were identified with relative operating characteristic (ROC) curve analysis. The PNI-MLR-PLT score system was established by the value of three indexes, each indication was assigned a score of 0 or 1. Overall survival (OS) and metastasis-free survival (MFS) were analyzed using Kaplan-Meier estimate and Cox regression models. RESULTS: The mean follow-up period was 85.67 months. Eight (5.0%) patients died, 4 (2.0%) relapsed, and 7 (4.0%) developed metastasis after surgery. The 3-year OS and MFS rates were 98.2% and 97.6%, and the 5-year OS and MFS rates were both 90.2%. Our results suggested that PNI-MLR-PLT score negatively correlated with pathological T stage and tumor grade. Survival outcomes revealed that lower PNI-MLR-PLT score is associated with inferior OS (P < 0.001) and MFS (P < 0.001) after surgery. Subgroup analysis regarding pathological T stage, tumor grade and surgical modalities obtained consistent results. univariable and multivariable Cox analysis showed that high PNI-MLR-PLT score was the independent protective factor of tumor survival in non-metastatic ccRCC patients. CONCLUSIONS: Our data suggested that PNI-MLR-PLT score could serve as a promising independent prognostic factor in patients with non-metastatic ccRCC.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Avaliação Nutricional , Prognóstico , Carcinoma de Células Renais/cirurgia , Estudos Retrospectivos , Relevância Clínica , Monócitos , Linfócitos , Neoplasias Renais/cirurgia
13.
Niger J Clin Pract ; 26(9): 1297-1302, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37794542

RESUMO

Background: Inflammation biomarkers known as acute phase reactants (APRs) show significant variations in serum concentrations during inflammation brought on by both viral and noninfectious diseases. The erythrocyte sedimentation rate (ESR), the C-reactive protein (CRP), the lactate dehydrogenase (LDH), the ferritin, the fibrinogen, the procalcitonin, the D-dimer, and the troponin I are all significant APRs. During inflammation, the serum levels of each of these positive APRs rise. The sensitivity and specificity of hematologic parameters and indices are as high as the inflammatory biomarkers mentioned above for monitoring disease severity and treatment response. Aim: We aimed to evaluate the differences in hematological parameters and indices, and to reveal their treatment and prognostic values, especially in deceased patients with COVID-19. Materials and Methods: The hemogram parameters of 169 critical patients with COVID-19 (125 males and 44 females) who received inpatient treatment at ….between 1 March 2020 and 31 December 2021 were analyzed retrospectively. The patients were divided into two groups-deceased (77) and surviving (92)-noting demographic data such as age and gender. All analyses were performed using SPSS 25.0. Results: Analyses of the hematological parameters used during the treatment processes revealed statistically significant differences between the two patient groups. White blood cell (WBC), neutrophil, and neutrophil-to-lymphocyte ratio (NLR) values were significantly higher (P = 0.019, P = 0.000 and P = 0.000, respectively) for deceased subjects, while lymphocyte, platelet and plateletcrit (PCT) values were significantly lower (for all values, P = 0.000). Platelet volume (MPV) and platelet distribution width (PDW), as well as MPV/PLT, PDW/PLT, MPV/PCT, and PDW/PCT, levels were significantly higher in deceased subjects (P = 0.000). Particularly in our deceased cases, receiver operating characteristic analyses were performed to reveal the importance of such analyses in prognostic status evaluation in COVID-19 since the hematological parameters are quite different. Cut-off values were determined for each parameter, and sensitivity and specificity ratios were calculated. While the sensitivities of MPV/PLT, PDW/PLT, MPV/PCT, and PDW/PCT indices are over 80%, neutrophil and white blood cell sensitivities were found to be lower (74%, 68.8%, respectively). Conclusion: In addition to NLR, which is an important biomarker, the hematological indices MPV/PLT, PDW/PLT, MPV/PCT, and PDW/PCT can be used to determine the risk of death in patients with severe COVID-19.


Assuntos
COVID-19 , Masculino , Feminino , Humanos , Estudos Retrospectivos , Contagem de Plaquetas , Plaquetas , Prognóstico , Biomarcadores , Inflamação
14.
Plant Biotechnol J ; 20(8): 1622-1635, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35524453

RESUMO

Plant genetic transformation is a crucial step for applying biotechnology such as genome editing to basic and applied plant science research. Its success primarily relies on the efficiency of gene delivery into plant cells and the ability to regenerate transgenic plants. In this study, we have examined the effect of several developmental regulators (DRs), including PLETHORA (PLT5), WOUND INDUCED DEDIFFERENTIATION 1 (WIND1), ENHANCED SHOOT REGENERATION (ESR1), WUSHEL (WUS) and a fusion of WUS and BABY-BOOM (WUS-P2A-BBM), on in planta transformation through injection of Agrobacterium tumefaciens in snapdragons (Antirrhinum majus). The results showed that PLT5, WIND1 and WUS promoted in planta transformation of snapdragons. An additional test of these three DRs on tomato (Solanum lycopersicum) further demonstrated that the highest in planta transformation efficiency was observed from PLT5. PLT5 promoted calli formation and regeneration of transformed shoots at the wound positions of aerial stems, and the transgene was stably inherited to the next generation in snapdragons. Additionally, PLT5 significantly improved the shoot regeneration and transformation in two Brassica cabbage varieties (Brassica rapa) and promoted the formation of transgenic calli and somatic embryos in sweet pepper (Capsicum annum) through in vitro tissue culture. Despite some morphological alternations, viable seeds were produced from the transgenic Bok choy and snapdragons. Our results have demonstrated that manipulation of PLT5 could be an effective approach for improving in planta and in vitro transformation efficiency, and such a transformation system could be used to facilitate the application of genome editing or other plant biotechnology application in modern agriculture.


Assuntos
Brassica , Capsicum , Solanum lycopersicum , Agrobacterium tumefaciens/genética , Brassica/genética , Capsicum/genética , Solanum lycopersicum/genética , Plantas Geneticamente Modificadas/genética , Transformação Genética , Transgenes
15.
New Phytol ; 233(4): 1780-1796, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34913488

RESUMO

Peptide-receptor signaling is an important system for intercellular communication, regulating many developmental processes. A single process can be controlled by several distinct signaling peptides. However, since peptide-receptor modules are usually studied separately, their mechanistic interactions remain largely unexplored. Two phylogenetically unrelated peptide-receptor modules, GLV6/GLV10-RGI and TOLS2/PIP2-RLK7, independently described as inhibitors of lateral root initiation, show striking similarities between their expression patterns and gain- and loss-of-function phenotypes, suggesting a common function during lateral root spacing and initiation. The GLV6/GLV10-RGI and TOLS2/PIP2-RLK7 modules trigger similar transcriptional changes, likely in part via WRKY transcription factors. Their overlapping set of response genes includes PUCHI and PLT5, both required for the effect of GLV6/10, as well as TOLS2, on lateral root initiation. Furthermore, both modules require the activity of MPK6 and can independently trigger MPK3/MPK6 phosphorylation. The GLV6/10 and TOLS2/PIP2 signaling pathways seem to converge in the activation of MPK3/MPK6, leading to the induction of a similar transcriptional response in the same target cells, thereby regulating lateral root initiation through a (partially) common mechanism. Convergence of signaling pathways downstream of phylogenetically unrelated peptide-receptor modules adds an additional, and hitherto unrecognized, level of complexity to intercellular communication networks in plants.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas , Quinases de Proteína Quinase Ativadas por Mitógeno/genética , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Peptídeos/metabolismo , Transdução de Sinais
16.
BMC Cancer ; 22(1): 311, 2022 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-35321670

RESUMO

INTRODUCTION: Immunotherapy has become a new therapy for advanced hepatocellular carcinoma (HCC); however, its treatment results are considerably different. CD4+ T cells (CD4+) are the key to immunotherapy, but patients with HCC that have low CD4+ are rarely observed for clinical evidence. Hepatitis B virus-related HCC is often accompanied by cirrhosis and portal hypertension; therefore, CD4+ tend to be relatively low in number. TACE is the standard treatment for Barcelona Clinic Liver Cancer (BCLC)-B HCC, which may further reduce the number of CD4 + . METHODS: This retrospective cohort study further reduced CD4+ by including patients with human immunodeficiency virus (HIV) to observe the relationship between CD4+ and Chronic hepatitis B virus (CHB) induced HCC. A total of 170 BCLC-B HCC patients (42 HIV+) were included. Univariate and multivariate analyses, and artificial neural networks (ANNs) were used to evaluate the independent risk factors for the two-year survival. RESULTS: The statistical analysis of the two-year survival rate showed that the main factors influencing survival were liver function and immune indices, including CD4+, platelet, alanine aminotransferase, aspartate aminotransferase, aspartate aminotransferase-to-platelet ratio index, and fibrosis-4 (FIB-4) (P < 0.05). Compared with that in other indices, in logistic and ANN multivariate analysis, CD4 + -to-FIB-4 ratio (CD4+/FIB-4) had the highest importance with 0.716 C-statistic and 145.93 cut-off value. In terms of overall survival rate, HIV infection was not a risk factor (P = 0.589); however, CD4+/FIB-4 ≤ 145.93 significantly affected patient prognosis (P = 0.002). CONCLUSION: HIV infection does not affect the prognosis of BCLC-B HCC, but CD4+ have a significant predictive value. CD4+ played a vital role in HCC and this deserves the attention from physicians. Further, the CD4+/FIB-4 is a clinically valuable effective prognostic indicator for these patients.


Assuntos
Carcinoma Hepatocelular , Infecções por HIV , Hepatite B Crônica , Neoplasias Hepáticas , Linfócitos T CD4-Positivos/patologia , Carcinoma Hepatocelular/patologia , Infecções por HIV/complicações , Infecções por HIV/patologia , Hepatite B Crônica/complicações , Humanos , Cirrose Hepática/patologia , Neoplasias Hepáticas/patologia , Contagem de Plaquetas , Prognóstico , Estudos Retrospectivos
17.
Hepatol Res ; 52(4): 352-363, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35040549

RESUMO

AIM: Accurate detection of the hepatic fibrosis stage is essential to estimate the outcome of patients with non-alcoholic fatty liver disease (NAFLD). Many formulas, biomarkers, and imaging tests are being developed to predict advanced liver fibrosis without performing a liver biopsy. However, these tests do not have high efficiency in detecting early-stage hepatic fibrosis. Therefore, we aimed to detect the presence of hepatic fibrosis (≥F1) merely by using only standard clinical markers. METHODS: A total of 436 patients with NAFLD who underwent liver biopsy were retrospectively enrolled as the discovery cohort (316 patients) and the validation cohort (120 patients). Liver biopsy and laboratory data were matched to extract simple parameters for identifying ≥F1. RESULTS: We developed a novel simplified ≥F1 detecting system, designated as 2-Step PLT16-AST44 method, where (1) PLT of 16 × 104 /µl or less, or (2) PLT greater than 16 × 104 /µl and AST greater than 44 U/L is determined as having ≥F1 fibrosis. The 2-Step PLT16-AST44 method had a sensitivity of 68%, a specificity of 90%, a positive predictive value (PPV) of 97%, a negative predictive value (NPV) of 40%, and an accuracy of 72% to detect ≥F1 fibrosis in the discovery cohort. Validation studies further supported these results. Despite its simplicity, the 2-Step PLT16-AST44 method's power to detect ≥F1 fibrosis in total NAFLD patients was comparable to hyaluronic acid, type 4 collagen 7S, FIB-4, and APRI. CONCLUSIONS: We propose the 2-Step PLT16-AST44 method as a simple and beneficial early-stage hepatic fibrosis detection system.

18.
Andrologia ; 54(3): e14345, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34879434

RESUMO

The present study investigated the sperm quality parameters and platelet indices in adolescent and adult varicocele rats. Twenty male Wistar rats were distributed into four groups (n = 5): I-sham adolescent group, II-sham adult group, III-varicocele adolescent group, and IV-varicocele adult group. Rats were sacrificed on the 61st day of the experiment. Sperm count (×106  ml-1 ), sperm motility and viability (%) were significantly (p < 0.05) different between varicocele and sham groups in adolescent and adult rats. Varicocele adults had significant (p < 0.05) lower platelet count (PLT) than sham adolescents and adults. The mean platelet volume (MPV), the MPV/PLT ratio, plateletcrit (PCT) and platelet distribution width (PDW) differ significantly (p < 0.05) between varicocele and sham groups of adolescent and adult rats. It is the first time the ratio MPV/PLT was evaluated in association with other platelet indices in adolescent and adult varicocele rats. Based on the results, it would appear these indicators can become a promising tool in varicocele diagnosis.


Assuntos
Volume Plaquetário Médio , Varicocele , Adolescente , Animais , Plaquetas , Humanos , Masculino , Contagem de Plaquetas , Ratos , Ratos Wistar , Motilidade dos Espermatozoides , Varicocele/complicações
19.
Int J Mol Sci ; 23(20)2022 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-36293031

RESUMO

Cell surface receptors play essential roles in perceiving and processing external and internal signals at the cell surface of plants and animals. The receptor-like protein kinases (RLK) and receptor-like proteins (RLPs), two major classes of proteins with membrane receptor configuration, play a crucial role in plant development and disease defense. Although RLPs and RLKs share a similar single-pass transmembrane configuration, RLPs harbor short divergent C-terminal regions instead of the conserved kinase domain of RLKs. This RLP receptor structural design precludes sequence comparison algorithms from being used for high-throughput predictions of the RLP family in plant genomes, as has been extensively performed for RLK superfamily predictions. Here, we developed the RLPredictiOme, implemented with machine learning models in combination with Bayesian inference, capable of predicting RLP subfamilies in plant genomes. The ML models were simultaneously trained using six types of features, along with three stages to distinguish RLPs from non-RLPs (NRLPs), RLPs from RLKs, and classify new subfamilies of RLPs in plants. The ML models achieved high accuracy, precision, sensitivity, and specificity for predicting RLPs with relatively high probability ranging from 0.79 to 0.99. The prediction of the method was assessed with three datasets, two of which contained leucine-rich repeats (LRR)-RLPs from Arabidopsis and rice, and the last one consisted of the complete set of previously described Arabidopsis RLPs. In these validation tests, more than 90% of known RLPs were correctly predicted via RLPredictiOme. In addition to predicting previously characterized RLPs, RLPredictiOme uncovered new RLP subfamilies in the Arabidopsis genome. These include probable lipid transfer (PLT)-RLP, plastocyanin-like-RLP, ring finger-RLP, glycosyl-hydrolase-RLP, and glycerophosphoryldiester phosphodiesterase (GDPD, GDPDL)-RLP subfamilies, yet to be characterized. Compared to the only Arabidopsis GDPDL-RLK, molecular evolution studies confirmed that the ectodomain of GDPDL-RLPs might have undergone a purifying selection with a predominance of synonymous substitutions. Expression analyses revealed that predicted GDPGL-RLPs display a basal expression level and respond to developmental and biotic signals. The results of these biological assays indicate that these subfamily members have maintained functional domains during evolution and may play relevant roles in development and plant defense. Therefore, RLPredictiOme provides a framework for genome-wide surveys of the RLP superfamily as a foundation to rationalize functional studies of surface receptors and their relationships with different biological processes.


Assuntos
Arabidopsis , Proteínas de Plantas , Animais , Proteínas de Plantas/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Plastocianina/genética , Plastocianina/metabolismo , Teorema de Bayes , Leucina/metabolismo , Plantas/metabolismo , Proteínas Quinases/genética , Proteínas Quinases/metabolismo , Receptores de Superfície Celular/metabolismo , Aprendizado de Máquina , Hidrolases/metabolismo , Diester Fosfórico Hidrolases/metabolismo , Lipídeos , Filogenia
20.
Plant J ; 103(2): 752-768, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32279407

RESUMO

Understanding how flowers form is an important problem in plant biology, as human food supply depends on flower and seed production. Flower development also provides an excellent model for understanding how cell division, expansion and differentiation are coordinated during organogenesis. In the model plant Arabidopsis thaliana, floral organogenesis requires AINTEGUMENTA (ANT) and AINTEGUMENTA-LIKE 6 (AIL6)/PLETHORA 3 (PLT3), two members of the Arabidopsis AINTEGUMENTA-LIKE/PLETHORA (AIL/PLT) transcription factor family. Together, ANT and AIL6/PLT3 regulate aspects of floral organogenesis, including floral organ initiation, growth, identity specification and patterning. Previously, we used RNA-Seq to identify thousands of genes with disrupted expression in ant ail6 mutant flowers, indicating that ANT and AIL6/PLT3 influence a vast transcriptional network. The immediate downstream targets of ANT and AIL6/PLT3 in flowers are unknown, however. To identify direct targets of ANT regulation, we performed an RNA-Seq time-course experiment in which we induced ANT activity in transgenic plants bearing an ANT-glucocorticoid receptor fusion construct. In addition, we performed a ChIP-Seq experiment that identified ANT binding sites in developing flowers. These experiments identified 200 potential ANT target genes based on their proximity to ANT binding sites and differential expression in response to ANT. These 200 candidate target genes were involved in functions such as polarity specification, floral organ development, meristem development and auxin signaling. In addition, we identified several genes associated with lateral organ growth that may mediate the role of ANT in organ size control. These results reveal new features of the ANT transcriptional network by linking ANT to previously unknown regulatory targets.


Assuntos
Proteínas de Arabidopsis/fisiologia , Arabidopsis/metabolismo , Flores/crescimento & desenvolvimento , Ácidos Indolacéticos/metabolismo , Reguladores de Crescimento de Plantas/metabolismo , Fatores de Transcrição/fisiologia , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Proteínas de Arabidopsis/metabolismo , Flores/anatomia & histologia , Flores/metabolismo , Regulação da Expressão Gênica de Plantas , Genes de Plantas/genética , Reguladores de Crescimento de Plantas/fisiologia , Plantas Geneticamente Modificadas , Transdução de Sinais , Fatores de Transcrição/metabolismo
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