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1.
Plant Sci ; 314: 111065, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34895534

RESUMO

Sucrose-proton symporters play important roles in carbohydrate transport during plant growth and development. Their physiological functions have only been partly characterized and their regulation mechanism is largely unclear. Here we report that the knockout of a sucrose transporter gene, OsSUT1, by CRISPR-Cas9 mediated gene editing resulted in a slightly dwarf size and complete infertility of the gene's homozygous mutants. Observation of caryopsis development revealed that the endosperm of OsSUT1 mutants failed to cellularize and did not show any sign of seed-filling. Consistently, OsSUT1 was identified to express strongly in developing caryopsis of wild-type rice, particularly in the nucellar epidermis and aleurone which are critical for the uptake of nutrients into the endosperm. These results indicate that OsSUT1 is indispensable during the rice reproductive stage particularly for caryopsis development. Interestingly, OsSUT1 possesses at least 6 alternative splicing transcripts, including the 4 transcripts deposited previously and the other two identified by us. The differences among these transcripts primarily lie in their coding region of the 3' end and 3' UTR region. Real-time PCR showed that 4 of the 6 transcripts had different expressional patterns during rice vegetative and reproductive growth stages. Given the versatility of the gene, addressing its alternative splicing mechanism may expand our understanding of SUT's function substantially.


Assuntos
Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Fertilidade/genética , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Oryza/genética , Oryza/metabolismo , Sacarose/metabolismo , Processamento Alternativo , Produtos Agrícolas/genética , Produtos Agrícolas/metabolismo , Grão Comestível/genética , Grão Comestível/metabolismo , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Variação Genética , Genótipo , Sementes/crescimento & desenvolvimento
2.
Food Chem ; 367: 130664, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34343804

RESUMO

Cyclodextrin-based dispersive liquid-liquid microextraction (CD-DLLME) was developed for the determination of triazole and strobilurin fungicides in water, juice, and vinegar samples using high-performance liquid chromatography-diode-array detection (HPLC-DAD). Undecanol, which is a green solvent, was selected as the extraction solvent. A cyclodextrin aqueous solution was chosen as the dispersion solvent and demulsifier to avoid the use of a toxic dispersion solvent and eliminate the centrifugation step. Dispersion and phase separation were completed within 1 and 60 s, respectively. The linear range of this method was 1 to 100 µg L-1. The limits of detection were 0.3 µg L-1 along with the preconcentration factor of 133 and enrichment factor of 124. The recovery was 83.2% to 103.2%. This pretreatment method was fast, simple, and environmentally friendly and was successfully applied to the analysis of triazole and strobilurin fungicide residues in water, juice, and vinegar samples.


Assuntos
Ciclodextrinas , Fungicidas Industriais , Microextração em Fase Líquida , Poluentes Químicos da Água , Ácido Acético , Cromatografia Líquida de Alta Pressão , Fungicidas Industriais/análise , Solventes , Água , Poluentes Químicos da Água/análise
3.
Spectrochim Acta A Mol Biomol Spectrosc ; 266: 120412, 2022 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-34597870

RESUMO

A deep eutectic solvent (DES)-based extraction method is established to facilitate the determination of methomyl in grain via enzyme inhibition fluorescence. The environmentally-friendly DES was synthesized from proline and ethylene glycol and used as a green replacement for traditional extraction solvents that are generally toxic. The DES was added to grain samples and vortex extraction of methomyl, the supernatant was then collected for fluorescence detection. Biomass carbon quantum dots (CQDs) synthesized from millet were used as fluorescent probes. Acetylcholinesterase catalyzes the hydrolysis of acetylthiocholine iodide to thiocholine. The positively-charged thiocholine interacts electrostatically with the negatively-charged quantum dots resulting in the quenching of their fluorescent emission. The pesticide extract solution blocks the enzyme activity and thus recovers the fluorescent from the quantum dots. The fluorescence response was correlated with the amount of methomyl residue in the grain over the range 0.01 to 5 mg kg-1. The limit of detection was found to be 0.003 mg kg-1, and the limit of quantification 0.01 mg kg-1. Recoveries of 86.5% to 107.8% were obtained using real samples, including millet, rice, wheat, and barley, with a relative standard deviation of less than 3.8%. The method is efficient and convenient and has good application prospects for extracting and detecting pesticides in grain samples.


Assuntos
Metomil , Pontos Quânticos , Acetilcolinesterase , Grão Comestível , Limite de Detecção , Solventes
4.
Toxicol In Vitro ; 78: 105254, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34634291

RESUMO

Curcumin, a polyphenolic compound, is a well-known anticancer agent, although its poor bioavailability remains a big concern. Recent studies suggest that autophagy-targeted therapy may be a useful adjunct treatment for patients with thyroid cancer. Curcumin acts as an autophagy inducer on many cancer cells. However, little is known about the exact role of curcumin on thyroid cancer cells. In the present study, curcumin significantly inhibited the growth of thyroid cancer cells. Autophagy was markedly induced by curcumin treatment as evidenced by an increase in LC3-II conversion, beclin-1 accumulation, p62 degradation as well as the increased formation of acidic vesicular organelles (AVOs). 3-MA, an autophagy inhibitor, partially rescued thyroid cancer cells from curcumin-induced cell death. Additionally, curcumin was found to exert selective cytotoxicity on thyroid cancer cells but not normal epithelial cells and acted as an autophagy inducer through activation of MAPK while inhibition of mTOR pathways. Hyperactivation of the AKT/mTOR axis was observed in the majority of PTC samples we tested, and thyroid cancer cell lines along with cancer tissue specimens sustained a low basal autophagic activity. Taken together, our results provide new evidence that inducing autophagic cell death may serve as a potential anti-cancer strategy to handle thyroid cancer.

5.
Food Chem ; 370: 131360, 2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-34662796

RESUMO

A novel deep eutectic solvent-based extraction and sulfur-doped carbon quantum dots (S-CQDs) serving as fluorescence probes to detect pirimicarb in cereals were established. The deep eutectic solvent was synthesized using choline chloride and butanediol, achieving direct and efficient extraction of pirimicarb residue in the cereals. The fluorescence quenching of S-CQDs was caused by the electrostatic interaction between the negatively charged S-CQDs and positively charged thiocholine, which was the hydrolysate of acetylthiocholine. The fluorescence of S-CQDs was enhanced as the activity of acetylcholinesterase (AChE) was inhibited by pirimicarb, achieving the detection of pirimicarb in the cereal samples. The limit of detection (LOD) was 0.006 µg mL-1. The recovery ranged from 96.6% to 108.2%. This extraction and detection method of pirimicarb based on an environmentally friendly DES and S-CQD fluorescent sensor maintains good stability and convenience, offering a promising strategy for extracting and testing harmful substances in food samples.


Assuntos
Grão Comestível , Pontos Quânticos , Acetilcolinesterase , Carbamatos , Pirimidinas , Solventes
6.
J Affect Disord ; 297: 360-365, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34715187

RESUMO

OBJECTIVE: To examine the combined association of central obesity and depressive symptoms with risk of heart disease in a national prospective cohort study of the Chinese population. METHODS: Data came from 10,722 community-dwelling adults aged over 45 years, from the China Health and Retirement Longitudinal Study during 2011-2018. Central obesity was assessed with waist circumference (WC) in physical examinations (men with a WC of ≥ 90 cm and women with a WC of ≥ 80 cm). Depressive symptoms were assessed using the 10-item Center for Epidemiologic Studies Depression Scale (score ≥ 10). Participants were assigned to four groups according to central obesity (yes/no) and depressive symptoms (yes/no). Cox proportional hazard regression was used after adjusting for covariates. RESULTS: During 7 years of follow-up, we identified 1080 heart disease cases. Compared with people without central obesity and depressive symptoms, the multivariable-adjusted hazard ratios (95% confidence intervals) were 1.39 (1.18, 1.64) for those who had central obesity alone, 1.44 (1.18, 1.77) for those who had depressive symptoms alone, and 1.88 (1.55, 2.30) for those who had both central obesity and depressive symptoms. The combined association in men was more evident than that in women. CONCLUSIONS: Our study provided evidence that the coexistence of central obesity and depressive symptoms were associated with a substantially increased risk of heart disease compared to those without these two conditions.

7.
Front Med (Lausanne) ; 8: 771227, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34859019

RESUMO

Introduction: Few studies have addressed the genetic spectrum of NPHS1 variants in Chinese children with nephrotic syndrome. In this multicenter study, the clinical manifestations and features of NPHS1 variants in Chinese children with nephrotic syndrome were researched. Method: Genotypical and phenotypical data from 30 children affected by NPHS1 variants were collected from a multicenter registration system in China and analyzed retrospectively. Results: The patients were divided into two groups: congenital nephrotic syndrome (CNS [n = 24]) and non-CNS (early onset nephrotic syndrome [n = 6]). Renal biopsy was performed on four patients in the non-CNS group, revealing minimal change disease in three and focal segmental glomerulosclerosis in one. A total of 61 NPHS1 variants were detected, involving 25 novel variants. The "recurrent variants" included c.928G>A(p.Asp310Asn) in eight patients with CNS, followed by c.616C>A(p.Pro206Thr) in four, and c.2207T>C (p.Val736Ala) in three. Steroid treatment was applied in 29.2% (7/24)of the patients in the CNS group and 50% (3/6) of the patients in the non-CNS group. One patient in each group experienced complete remission but relapsed subsequently. Immunosuppressants were administered to three patients in the non-CNS group, eliciting an effective response. In the CNS group, three patients underwent renal transplantation and six died mainly from infection. Conclusion: Variants of NPHS1 cause CNS and early childhood-onset nephrotic syndrome. NPHS1 variants in Chinese individuals with nephrotic syndrome (NS) were mainly compound heterozygous variants, and c.928G>A(p.Asp310Asn) in exon 8 may act as a recurrent variant in the Chinese population, followed by c.616C>A(p.Pro206Thr) in exon 6. Steroids and immunosuppressants may be effective in selected patients.

8.
Foods ; 10(12)2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34945505

RESUMO

Foodborne Staphylococcus aureus (S. aureus) has attracted widespread attention due to its foodborne infection and food poisoning in human. Shikonin exhibits antibacterial activity against a variety of microorganisms, but there are few studies on its antibacterial activity against S. aureus. This study aims to explore the antibacterial activity and mechanism of shikonin against foodborne S. aureus. The results show that the minimum inhibitory concentrations (MICs) and the minimum bactericidal concentrations (MBCs) of shikonin were equal for all tested strains ranging from 35 µg/mL to 70 µg/mL. Shikonin inhibited the growth of S. aureus by reducing intracellular ATP concentrations, hyperpolarizing cell membrane, destroying the integrity of cell membrane, and changing cell morphology. At the non-inhibitory concentrations (NICs), shikonin significantly inhibited biofilm formation of S. aureus, which was attributed to inhibiting the expression of cidA and sarA genes. Moreover, shikonin also markedly inhibited the transcription and expression of virulence genes (sea and hla) in S. aureus. In addition, shikonin has exhibited antibacterial ability against both planktonic and biofilm forms of S. aureus. Importantly, in vivo results show that shikonin has excellent biocompatibility. Moreover, both the heat stability of shikonin and the antimicrobial activity of shikonin against S. aureus were excellent in food. Our findings suggest that shikonin are promising for use as a natural food additive, and it also has great potential in effectively controlling the contamination of S. aureus in food and reducing the number of illnesses associated with S. aureus.

9.
BMC Med Genomics ; 14(1): 298, 2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-34930241

RESUMO

BACKGROUND: Mutation processes leave different signatures in genes. For single-base substitutions, previous studies have suggested that mutation signatures are not only reflected in mutation bases but also in neighboring bases. However, because of the lack of a method to identify features of long sequences next to mutation bases, the understanding of how flanking sequences influence mutation signatures is limited. METHODS: We constructed a long short-term memory-self organizing map (LSTM-SOM) unsupervised neural network. By extracting mutated sequence features via LSTM and clustering similar features with the SOM, single-base substitutions in The Cancer Genome Atlas database were clustered according to both their mutation site and flanking sequences. The relationship between mutation sequence signatures and clinical features was then analyzed. Finally, we clustered patients into different classes according to the composition of the mutation sequence signatures by the K-means method and then studied the differences in clinical features and survival between classes. RESULTS: Ten classes of mutant sequence signatures (mutation blots, MBs) were obtained from 2,141,527 single-base substitutions via LSTM-SOM machine learning approach. Different features in mutation bases and flanking sequences were revealed among MBs. MBs reflect both the site and pathological features of cancers. MBs were related to clinical features, including age, sex, and cancer stage. The class of an MB in a given gene was associated with survival. Finally, patients were clustered into 7 classes according to the MB composition. Significant differences in survival and clinical features were observed among different patient classes. CONCLUSIONS: We provided a method for analyzing the characteristics of mutant sequences. Result of this study showed that flanking sequences, together with mutation bases, shape the signatures of SBSs. MBs were shown related to clinical features and survival of cancer patients. Composition of MBs is a feasible predictive factor of clinical prognosis. Further study of the mechanism of MBs related to cancer characteristics is suggested.

10.
Front Cell Infect Microbiol ; 11: 780959, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34956933

RESUMO

Glycosylphosphatidylinositol (GPI)-anchored proteins play important roles in maintaining the function of the cell wall and participating in pathogenic processes. The addition and removal of phosphoethanolamine (EtN-P) on the second mannose residue in the GPI anchor are vital for maturation and sorting of GPI-anchored proteins. Previously, we have shown that deletion of the gpi7, the gene that encodes an EtN-P transferase responsible for the addition of EtN-P to the second mannose residue of the GPI anchor, leads to the mislocalization of GPI-anchored proteins, abnormal polarity, reduced conidiation, and fast germination in Aspergillus fumigatus. In this report, the adherence and virulence of the A. fumigatus gpi7 deletion mutant were further investigated. The germinating conidia of the mutant exhibited an increased adhesion and a higher exposure of cell wall polysaccharides. Although the virulence was not affected, an increased adherence and a stronger inflammation response of the mutant were documented in an immunocompromised mouse model. An in vitro assay confirmed that the Δgpi7 mutant induced a stronger immune response and was more resistant to killing. Our findings, for the first time, demonstrate that in A. fumigatus, GPI anchoring is required for proper organization of the conidial cell wall. The lack of Gpi7 leads to fast germination, stronger immune response, and resistance to macrophage killing.

11.
Artigo em Inglês | MEDLINE | ID: mdl-34773498

RESUMO

BACKGROUND: The surgical resection of the pontomesencephalic junction (PMJ) glioma is difficult because the access is challenging due to nearby complicated neurovascular structures. METHOD: We report a left ventrolateral PMJ glioma successfully resected via the oculomotor-tentorial triangle (OTT), with improved right extremity weakness postoperatively while preserving the pyramidal tract, which resided laterally and posteriorly to the lesion. CONCLUSION: This case demonstrates the value of the OTT in brainstem surgery.

12.
Z Gerontol Geriatr ; 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34757468

RESUMO

OBJECTIVE: Frailty has a high prevalence in elders and impairs motor ability. This study aimed to investigate the influence caused by frailty in kinematic characteristics of walking and walking strategy adjustment from static standing to stable walking. METHODS: In this study, 80 community-dwelling elders performed tests. The Kihon checklist (KCL) was used to assess frailty. The timed up and go test (TUGT) and the 30-s chair stand test (30-s CST) were used to assess balance and muscle strength. The Xsens MVN BIOMECH Awinda was used to collect walking kinematic data. RESULTS: This study included 25 robust, 30 prefrail, and 25 frail elders. The TUGT completed time (P < 0.001) and the 30-s CST completed number (P = 0.002) had statistical differences among groups. The maximum peak of knee internal rotation showed an interaction between the frailty and the walking phase (P = 0.015). The peak angle of hip adduction, hip and knee flexion, and knee and ankle internal rotation were significantly lower in frail elders than others (P < 0.05). CONCLUSION: Frailty affects the kinematic characteristics of walking, resulting in the hip, knee, and ankle flexion, hip adduction, knee and ankle internal rotation reduced. Besides, frailty has a specific negative effect on the walking strategy adjustment from static standing to stable walking.

13.
14.
ACS Omega ; 6(42): 28394-28402, 2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34723036

RESUMO

The modification of cellulose with polycarboxylic acid is an important technology to functionalize the substrate. 1,2,3,4-Butanetetracarboxylic acid (BTCA) can significantly improve the anti-wrinkle performance of treated cotton fabrics by cross-linking with cellulose. However, the reaction site of BTCA carboxyl and the cellulose hydroxyl has not yet been clarified, which hinders the in-depth understanding about the reaction mechanism and the development of new cross-linking reagents. This study combines Fourier transform infrared and two-dimensional correlation spectroscopy to try to make it clear. Results confirmed that BTCA anhydride is an active intermediate (corresponding to the generally accepted theory) to esterify with cellulose hydroxyl, especially the O(6)-H(6) and O(2)-H(2). Cellobiose was taken as a model of cellulose to react with BTCA at variable temperatures, proving the above conclusion. In addition, the C14- or C11-containing carboxyl of BTCA showed a higher reactivity. Based on calculating reaction kinetics and thermodynamics with Gaussian 09W software, the most likely reaction route between BTCA and cellulose was as follows: BTCA → BTCA C5C14 anhydride → C14O15 ester → C14O15 ester C31C34 anhydride → C14O15C33O ester.

15.
J Mol Cell Biol ; 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34751390

RESUMO

Anaplastic thyroid cancer (ATC) is a rare but highly lethal disease. ATCs are resistant to standard therapies and are extremely difficult to manage. The stepwise cell dedifferentiation results in the impairment of the iodine-metabolizing machinery and the infeasibility of radioiodine treatment in ATC. Hence, re-inducing iodine-metabolizing gene expression to restore radioiodine avidity is considered as a promising strategy to fight against ATC. In the present study, capsaicin (CAP), a natural potent transient receptor potential vanilloid type 1 (TRPV1) agonist, was discovered to re-induce ATC cell differentiation and to increase the expression of thyroid transcription factors (TTFs including TTF-1, TTF-2, and PAX8) and iodine-metabolizing proteins, including thyroid stimulating hormone receptor (TSHR), thyroid peroxidase, and sodium iodine symporter (NIS), in two ATC cell lines, 8505C and FRO. Strikingly, CAP treatment promoted NIS glycosylation and its membrane trafficking, resulting in a significant enhancement of radioiodine uptake of ATC cells in vitro. Mechanistically, CAP activated TRPV1 channel and subsequently triggered Ca2+ influx, cyclic adenosine monophosphate (cAMP) generation, and cAMP responsive element binding protein (CREB) signal activation. Next, CREB recognized and bound to the promoter of SLC5A5 to facilitate its transcription. Moreover, the TRPV1 antagonist CPZ, the calcium chelator BAPTA, and the PKA inhibitor H-89 effectively alleviated the re-differentiation exerted by CAP, demonstrating that CAP might improve radioiodine avidity through the activation of the TRPV1‒Ca2+/cAMP/PKA/CREB signaling pathway. In addition, our study indicated that CAP might trigger a novel cascade to re-differentiate ATC cells and provide unprecedented opportunities for radioiodine therapy in ATC, bypassing canonical TSH‒TSHR pathway.

16.
Acta Biochim Biophys Sin (Shanghai) ; 53(11): 1450-1458, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34596216

RESUMO

Atrial fibrosis is a crucial mechanism responsible for atrial fibrillation (AF). Sex-determining region Y-box containing gene 9 (Sox9) plays a pivotal role in fibrosis of many organs such as the skin, kidney, and liver. However, there are few studies about the occurrence and maintenance of Sox9 in atrial fibrosis. In this study, we investigated the role of Sox9 in the fibrotic phenotype of human atrial tissues and rat atrial fibroblasts in vitro. In the human right atrial tissue, Masson's trichrome staining, immunofluorescence, real-time quantitative polymerase chain reaction, and western blot analysis were carried out to explore the relationship between Sox9 and atrial fibrosis at the morphological, functional, and molecular levels. In cultured atrial fibroblasts, Sox9 was overexpressed by adenovirus or depleted by siRNA, and then, recombinant human transforming growth factor (TGF)-ß1 was added. Immunofluorescence analysis, western blot analysis, Transwell assay, and scratch assay were used to analyze the cells. In patient atrial tissues, Sox9 was increased with worsened atrial fibrosis, and this increase was related to AF severity. In rat atrial fibroblasts, Sox9 was promoted by TGF-ß1, and the α-smooth muscle actin (α-SMA) protein level and the ability of cell migration were increased after Sox9 overexpression by adenovirus, while the α-SMA protein level and the cell migration ability were decreased after Sox9 depletion by siRNA. In conclusion, Sox9 is involved in the regulation of fibrosis in the atria and may be located downstream of TGF-ß1. Our findings may provide a new perspective to treat atrial fibrosis during AF.

17.
World Neurosurg ; 157: 91, 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34653707

RESUMO

Vertebral artery-posterior inferior cerebellar artery (VA-PICA) aneurysm is challenging owing to its variable anatomy and interference of lower cranial nerves. A recurrent ruptured VA-PICA aneurysm was successfully treated by occipital (OA)-PICA bypass with aneurysm trapping (Video 1). Informed consent was obtained from the patient. A ruptured right VA aneurysm was found in a 47-year-old man and treated by endovascular treatment. Follow-up angiography at 1 month revealed aneurysm recurrence with migration of endovascular materials. The patient was placed in a park-bench position for the far-lateral approach. A J-shaped incision was used for craniotomy. A 1-piece myocutaneous flap was raised, and the OA was skeletonized in a distal-to-proximal fashion. After craniotomy, the VA-PICA aneurysm with endovascular material inside was located under the vagoaccessory triangle. The tonsillomedullary segment or P3 of the PICA was robust and long enough as the recipient candidate for anastomosis. A linear arteriotomy was performed on the recipient artery, and an end-to-side OA-PICA bypass was achieved. Occlusion of the aneurysm was achieved by placing permanent clips on the VA proximal and distal to the aneurysm and the PICA next to the aneurysm sac without occluding the perforator. The postoperative course was uneventful with bypass patency. We believe this case demonstrates the surgical tenet of OA-PICA bypass for VA-PICA aneurysm.

18.
World J Pediatr ; 17(6): 643-652, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34716893

RESUMO

INTRODUCTION: To improve compliance with voiding diaries in children with primary monosymptomatic nocturnal enuresis (PMNE), a new modified 3-day weekend frequency-volume chart (FVC) was designed, and the compliance and validity of this modified FVC was evaluated by comparing with the International Children's Continence Society (ICCS) recommended voiding diary. METHODS: A total of 1200 patients with PMNE were enrolled in the study from 13 centers in China and were randomly assigned to record this modified FVC or the ICCS-recommended voiding diary. The primary outcome measure was the compliance, assessed by comparing the completing index and the quality score of diaries between two groups. The secondary outcome measure was the validity, evaluated by comparing the constituent of subtypes, micturition parameters and response rate to desmopressin. RESULTS: Among the 1200 participants enrolled in the study, 447 patients completed the ICCS-recommended voiding diary and 469 completed the modified diary. The diurnal completing index and the quality score of the modified FVC group were better than those of the ICCS group. In addition, there was no significant difference between these two groups in the subtype classification, or in the response rate to desmopressin. CONCLUSIONS: The modified FVC could be applied to obtain the voiding characteristics of children with PMNE as the ICCS-recommended voiding diary does and offers a reasonable and better choice for children with PMNE from the unselected population in the future.

19.
BMC Med Genomics ; 14(1): 250, 2021 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-34696790

RESUMO

BACKGROUND: Pathogenic variants of PAX2 cause autosomal-dominant PAX2-related disorder, which includes variable phenotypes ranging from renal coloboma syndrome (RCS), congenital anomalies of the kidney and urinary tract (CAKUT) to nephrosis. Phenotypic variability makes it difficult to define the phenotypic spectrum associated with genotype. METHODS: We collected the phenotypes in patients enrolled in the China national multicenter registry who were diagnosed with pathogenic variant in PAX2 and reviewed all published cases with PAX2-related disorders. We conducted a phenotype-based cluster analysis by variant types and molecular modeling of the structural impact of missense variants. RESULTS: Twenty different PAX2 pathogenic variants were identified in 32 individuals (27 families) with a diagnosis of RCS (9), CAKUT (11) and nephrosis (12) from the Chinese cohort. Individuals with abnormal kidney structure (RCS or CAKUT group) tended to have likely/presumed gene disruptive (LGD) variants (Fisher test, p < 0.05). A system review of 234 reported cases to date indicated a clear association of RCS to heterozygous loss-of-function PAX2 variants (LGD variants). Furthermore, we identified a subset of PAX2 missense variants in DNA-binding domain predicted to affect the protein structure or protein-DNA interaction associated with the phenotype of RCS. CONCLUSION: Defining the phenotypic spectrum combined with genotype in PAX2-related disorder allows us to predict the pathogenic variants associated with renal and ophthalmological development. It highlighted the approach of structure-based analysis can be applied to diagnostic strategy aiding precise and timely diagnosis.

20.
J Cardiovasc Pharmacol ; 78(2): 175-183, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34554674

RESUMO

ABSTRACT: Atrial fibrillation (AF) is a common arrhythmia in the clinic. Ablation failure and recurrence after cardioversion have become medical problems worldwide. An important pathological feature of AF is atrial fibrosis, which increases susceptibility to AF. As an important target of fibrosis signal integration, the signal transducer and activator of transcription 3 (STAT3) signaling pathway plays an important role in fibrosis. Caveolin-1 (CAV1), a cell membrane protein, is involved in a variety of the biological functions of cells. However, the role of CAV1 in atrial fibrosis remains unclear. In this study, Masson's trichrome staining was used to detect the degree of atrial fibrosis, and the expression of CAV1 in the human atrium was evaluated by immunohistochemistry. To further study the role of CAV1, its expression in cultured rat atrial fibroblasts was silenced using siRNAs. Atrial fibroblasts were treated with angiotensin II to observe the effects on CAV1 and the transforming growth factor-ß1 and STAT3 signaling pathways. We also detected the effects of CAV1 scaffolding domain (CSD) peptide on fibrosis through the addition of exogenous CSD peptide. The results showed that CAV1 expression decreased with the aggravation of atrial fibrosis and that this effect increased the incidence of AF. The depletion of CAV1 induced excessive extracellular matrix deposition by activating the STAT3 and transforming growth factor-ß1/SMAD2 signaling pathways, and this effect was exacerbated by stimulation with angiotensin II and improved by CSD peptide. These data suggested that CAV1 not only plays a critical role in fibrosis progression but also provides a target for the treatment of atrial fibrosis and AF.

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