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1.
Proc Natl Acad Sci U S A ; 120(50): e2220496120, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-38064514

RESUMO

Massive GGGGCC (G4C2) repeat expansion in C9orf72 and the resulting loss of C9orf72 function are the key features of ~50% of inherited amyotrophic lateral sclerosis and frontotemporal dementia cases. However, the biological function of C9orf72 remains unclear. We previously found that C9orf72 can form a stable GTPase activating protein (GAP) complex with SMCR8 (Smith-Magenis chromosome region 8). Herein, we report that the C9orf72-SMCR8 complex is a major negative regulator of primary ciliogenesis, abnormalities in which lead to ciliopathies. Mechanistically, the C9orf72-SMCR8 complex suppresses the primary cilium as a RAB8A GAP. Moreover, based on biochemical analysis, we found that C9orf72 is the RAB8A binding subunit and that SMCR8 is the GAP subunit in the complex. We further found that the C9orf72-SMCR8 complex suppressed the primary cilium in multiple tissues from mice, including but not limited to the brain, kidney, and spleen. Importantly, cells with C9orf72 or SMCR8 knocked out were more sensitive to hedgehog signaling. These results reveal the unexpected impact of C9orf72 on primary ciliogenesis and elucidate the pathogenesis of diseases caused by the loss of C9orf72 function.


Assuntos
Esclerose Lateral Amiotrófica , Proteína C9orf72 , Cílios , Demência Frontotemporal , Animais , Camundongos , Esclerose Lateral Amiotrófica/metabolismo , Proteína C9orf72/genética , Proteína C9orf72/metabolismo , Cílios/metabolismo , Expansão das Repetições de DNA , Demência Frontotemporal/metabolismo , Proteínas Ativadoras de GTPase/metabolismo , Humanos , Células HEK293
2.
Small ; 20(15): e2307184, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38012533

RESUMO

Aqueous zinc-ion hybrid capacitors (ZIHCs), as ideal candidates for high energy-power supply systems, are restricted by unsatisfied energy density and poor cycling durability for further applications. The construction of a surface-functionalized carbon cathode is an effective strategy for improving the performance of ZIHCs. Herein, a high-performance ZIHC is achieved using oxygen-rich hierarchically porous carbon rods (MDPC-X) prepared by the pyrolysis of a metal-organic framework (MOF) assisted by KOH activation. The MDPC-X samples displayed high electric double-layer capacitance (EDLC) and pseudocapacitance owing to their oxygen-rich surfaces, abundant electroactive sites, and short ions/electron transfer lengths. The surface oxygen functional groups for the reversible chemical adsorption/desorption of Zn2+ are identified using ex situ X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM). Consequently, the as-assembled ZIHC exhibited a high capacity of 323.4 F g-1 (161.7 mA h g-1) at 0.5 A g-1 and a retention of 147 F g-1 (73.5 mA h g-1) at an ultrahigh current density of 50 A g-1, corresponding to high energy and power densities of 145.5 W h kg-1 and 45 kW kg-1, respectively. Furthermore, an excellent cycling life with 96.5% of capacity retention is also maintained after 10 000 cycles at 10 A g-1, demonstrating its promising potential for applications.

3.
Small ; 20(5): e2304047, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37752779

RESUMO

Microbial infections based on drug-resistant pathogenic organisms following surgery or trauma and uncontrolled bleeding are the main causes of increased mortality from trauma worldwide. The prevalence of drug-resistant pathogens has led to a significant increase in medical costs and poses a great threat to the normal life of people. This is an important issue in the field of biomedicine, and the emergence of new antimicrobial materials hydrogels holds great promise for solving this problem. Hydrogel is an important material with good biocompatibility, water absorption, oxygen permeability, adhesion, degradation, self-healing, corrosion resistance, and controlled release of drugs as well as structural diversity. Bacteria-disturbing hydrogels have important applications in the direction of surgical treatment, wound dressing, medical device coating, and tissue engineering. This paper reviews the classification of antimicrobial hydrogels, the current status of research, and the potential of antimicrobial hydrogels for one application in biomedicine, and analyzes the current research of hydrogels in biomedical applications from five aspects: metal-loaded hydrogels, drug-loaded hydrogels, carbon-material-loaded hydrogels, hydrogels with fixed antimicrobial activity and biological antimicrobial hydrogels, and provides an outlook on the high antimicrobial activity, biodegradability, biocompatibility, injectability, clinical applicability and future development prospects of hydrogels in this field.


Assuntos
Anti-Infecciosos , Hidrogéis , Humanos , Hidrogéis/química , Anti-Infecciosos/farmacologia , Bactérias , Bandagens , Antibacterianos/química
4.
Bioessays ; 44(12): e2100261, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36285664

RESUMO

The asymmetric distribution of lipids, maintained by flippases/floppases and scramblases, plays a pivotal role in various physiologic processes. Scramblases are proteins that move phospholipids between the leaflets of the lipid bilayer of the cellular membrane in an energy-independent manner. Recent studies have indicated that viral infection is closely related to cellular lipid distribution. The level and distribution of phosphatidylserine (PtdSer) in cells have been demonstrated to be critical regulators of viral infections. Previous studies have supported that the infection of human immunodeficiency virus (HIV), Zika virus, Ebola virus (EBOV), influenza virus, and dengue fever virus require the externalization of phospholipids mediated by scramblases, which are also involved in the pathogenicity of the pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this review, we review the relationship of scramblases with viruses and the potential viral effector proteins that might utilize host scramblases.


Assuntos
COVID-19 , Viroses , Infecção por Zika virus , Zika virus , Humanos , SARS-CoV-2 , Fosfatidilserinas/metabolismo , Fosfolipídeos/metabolismo
5.
Mikrochim Acta ; 191(4): 202, 2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38492117

RESUMO

Chiral self-assembly is the spontaneous organization of individual building blocks from chiral (bio)molecules to macroscopic objects into ordered superstructures. Chiral self-assembly is ubiquitous in nature, such as DNA and proteins, which formed the foundation of biological structures. In addition to chiral (bio) molecules, chiral ordered superstructures constructed by self-assembly have also attracted much attention. Chiral self-assembly usually refers to the process of forming chiral aggregates in an ordered arrangement under various non-covalent bonding such as H-bond, π-π interactions, van der Waals forces (dipole-dipole, electrostatic effects, etc.), and hydrophobic interactions. Chiral assembly involves the spontaneous process, which followed the minimum energy rule. It is essentially an intermolecular interaction force. Self-assembled chiral materials based on chiral recognition in electrochemistry, chiral catalysis, optical sensing, chiral separation, etc. have a broad application potential with the research development of chiral materials in recent years.

6.
Small ; 19(49): e2304172, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37563809

RESUMO

As a promising low-cost and high-safety energy storage candidate, zinc-ion hybrid capacitors (ZIHCs) have received extensive attention. For maximizing the advantages of ZIHC with high energy density and high power density, the structural engineering of the porous carbon materials is the crucial and effective strategy. Herein, an oxygen-enriched hierarchical porous carbon has been fabricated from the pyrolysis of olive leaves combing the chemical activation. The abundant interfacial active sites and short ions/electrons transfer length endow the hierarchical porous carbon cathode with high ions adsorption capacity and fast kinetic behaviors. Meanwhile, the oxygen-rich functional groups can provide extra pseudocapacitance and improve the wettability and conductivity of porous carbon. Benefiting from these advantages, an anti-self-discharge ZIHC device with a high energy-power feature has been assembled. The electrochemical process is studied by ex situ X-ray diffraction (XRD) and scanning electron microscope (SEM) methods. Finally, an excellent energy density of 136.3 W h kg-1 , and high power output of 20 kW kg-1 , as well as long cycle life with 91% capacity retention over 20 000 cycles at 10 A g-1 are realized by as-assembled ZIHC.

7.
Small ; 19(38): e2303059, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37217989

RESUMO

Chirality is a universal phenomenon in molecular and biological systems, denoting an asymmetric configurational property where an object cannot be superimposed onto its mirror image by any kind of translation or rotation, which is ubiquitous on the scale from neutrinos to spiral galaxies. Chirality plays a very important role in the life system. Many biological molecules in the life body show chirality, such as the "codebook" of the earth's biological diversity-DNA, nucleic acid, etc. Intriguingly, living organisms hierarchically consist of homochiral building blocks, for example, l-amino acids and d-sugars with unknown reason. When molecules with chirality interact with these chiral factors, only one conformation favors the positive development of life, that is, the chiral host environment can only selectively interact with chiral molecules of one of the conformations. The differences in chiral interactions are often manifested by chiral recognition, mutual matching, and interactions with chiral molecules, which means that the stereoselectivity of chiral molecules can produce changes in pharmacodynamics and pathology. Here, the latest investigations are summarized including the construction and applications of chiral materials based on natural small molecules as chiral source, natural biomacromolecules as chiral sources, and the material synthesized by design as a chiral source.

8.
FASEB J ; 36(6): e22340, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35524736

RESUMO

The prevention role of Lactiplantibacillus plantarum against the formation of kidney stones has been increasingly recognized; its mechanism, however, has mainly been focused on inhibiting the inflammation in the colon in the gastrointestinal (GI) system, and the intestinal metabolites from microflora have not been revealed fully with regarding to the stone formation. In this study, we investigated the effect of L. plantarum J-15 on kidney stone formation in renal calcium oxalate (CaOx) rats induced by ethylene glycol and monitored the changes of intestinal microflora and their metabolites detected by 16S rRNA sequencing and widely targeted analysis, followed by the evaluation of the intestinal barrier function and inflammation levels in the colon, blood and kidney. The results showed that L. plantarum J-15 effectively reduced renal crystallization and urinary oxalic acid. Ten microbial genera, including anti-inflammatory and SCFAs-related Faecalibaculum, were enriched in the J-15 treatment group. There are 136 metabolites from 11 categories significantly different in the J-15 supplementation group compared with CaOx model rats, most of which were enriched in the amino acid metabolic and secondary bile acid pathways. The expression of intestinal tight junction protein Occludin and the concentration of pro-inflammatory cytokines and prostaglandin were decreased in the intestine, which further reduced the translocated lipopolysaccharide and inflammation levels in the blood upon J-15 treatment. Thus, the inflammation and injury in the kidney might be alleviated by downregulating TLR4/NF-κB/COX-2 signaling pathway. It suggested that L. plantarum J-15 might reduce kidney stone formation by restoring intestinal microflora and metabolic disorder, protecting intestinal barrier function, and alleviating inflammation. This finding provides new insights into the therapies for renal stones.


Assuntos
Microbioma Gastrointestinal , Cálculos Renais , Animais , Oxalato de Cálcio/metabolismo , Feminino , Humanos , Inflamação/metabolismo , Cálculos Renais/induzido quimicamente , Cálculos Renais/prevenção & controle , Lactobacillaceae/genética , Lactobacillaceae/metabolismo , Masculino , RNA Ribossômico 16S/genética , Ratos
9.
World J Urol ; 41(10): 2659-2669, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37566142

RESUMO

OBJECTIVE: In recent years, the minimally invasive surgical treatment methods of ureteropelvic junctional obstruction (UPJO) have been diverse, but its approach and choice of surgical method are controversial. This network meta-analysis (NMA) aimed to compare the safety and effectiveness of minimally invasive surgeries for UPJO, which included robotic or laparoscopic pyeloplasty, via the retroperitoneal or transperitoneal approach. METHODS: We searched relevant RCTs in PubMed, Embase, Web of Science, the Cochrane Library, and CNKI. To assess the results of operative time, complications and success rate, pairwise, and NMA were carried out. The models for analyses were performed by Revman 5.3, Addis V1.16.8 and R software. RESULTS: A total of 6 RCTs were included in this study involving four types of surgeries: transperitoneal laparoscopic pyeloplasty (T-LP), retroperitoneal laparoscopic pyeloplasty (R-LP), robot-assisted transperitoneal pyeloplasty (T-RALP), and robot-assisted retroperitoneal pyeloplasty (R-RALP). This study consisted of 381 patients overall. T-RALP had a quicker operational duration (SMD = 1.67, 95% CI 0.27-3.07, P = 0.02) than T-LP. According to the NMA's consistency model, T-RALP improved the surgical success rate more than T-LP (RR = 6303.19, CI 1.28 to 1.47 × 1011). Ranking probabilities indicated that RALP could be the better option than LP and retroperitoneal approach was comparable to transperitoneal approach. All procedures had high surgical success rates and few complications. CONCLUSION: Outcomes for four surgical approaches used in the UPJO were comparable, with T-RALP being the most recommended approach. Selection between the transperitoneal and retroperitoneal approaches primarily depended on the surgeon's preference. Higher quality evidence is needed to further enhance the result.


Assuntos
Laparoscopia , Procedimentos Cirúrgicos Robóticos , Ureter , Obstrução Ureteral , Humanos , Pelve Renal/cirurgia , Metanálise em Rede , Laparoscopia/métodos , Procedimentos Cirúrgicos Urológicos/métodos , Ureter/cirurgia , Obstrução Ureteral/cirurgia , Procedimentos Cirúrgicos Robóticos/métodos , Resultado do Tratamento
10.
Proc Natl Acad Sci U S A ; 117(18): 9876-9883, 2020 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-32303654

RESUMO

A massive intronic hexanucleotide repeat (GGGGCC) expansion in C9ORF72 is a genetic origin of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Recently, C9ORF72, together with SMCR8 and WDR41, has been shown to regulate autophagy and function as Rab GEF. However, the precise function of C9ORF72 remains unclear. Here, we report the cryogenic electron microscopy (cryo-EM) structure of the human C9ORF72-SMCR8-WDR41 complex at a resolution of 3.2 Å. The structure reveals the dimeric assembly of a heterotrimer of C9ORF72-SMCR8-WDR41. Notably, the C-terminal tail of C9ORF72 and the DENN domain of SMCR8 play critical roles in the dimerization of the two protomers of the C9ORF72-SMCR8-WDR41 complex. In the protomer, C9ORF72 and WDR41 are joined by SMCR8 without direct interaction. WDR41 binds to the DENN domain of SMCR8 by the C-terminal helix. Interestingly, the prominent structural feature of C9ORF72-SMCR8 resembles that of the FLNC-FNIP2 complex, the GTPase activating protein (GAP) of RagC/D. Structural comparison and sequence alignment revealed that Arg147 of SMCR8 is conserved and corresponds to the arginine finger of FLCN, and biochemical analysis indicated that the Arg147 of SMCR8 is critical to the stimulatory effect of the C9ORF72-SMCR8 complex on Rab8a and Rab11a. Our study not only illustrates the basis of C9ORF72-SMCR8-WDR41 complex assembly but also reveals the GAP activity of the C9ORF72-SMCR8 complex.


Assuntos
Proteínas Relacionadas à Autofagia/ultraestrutura , Proteína C9orf72/ultraestrutura , Proteínas de Transporte/ultraestrutura , Complexos Multiproteicos/ultraestrutura , Sequência de Aminoácidos/genética , Esclerose Lateral Amiotrófica/genética , Arginina/genética , Autofagia/genética , Proteínas Relacionadas à Autofagia/genética , Proteína C9orf72/genética , Proteínas de Transporte/genética , Microscopia Crioeletrônica , Filaminas/genética , Filaminas/ultraestrutura , Demência Frontotemporal/genética , Proteínas Ativadoras de GTPase/genética , Proteínas Ativadoras de GTPase/ultraestrutura , Predisposição Genética para Doença , Humanos , Complexos Multiproteicos/genética , Alinhamento de Sequência , Proteínas rab de Ligação ao GTP/genética
11.
Mikrochim Acta ; 190(6): 230, 2023 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-37208529

RESUMO

Chiral materials have drawn the widespread attention for their its chiral recognition ability. The design and synthesis of chiral material are of importance owing to the unpredictability in controlling chirality during the synthesis process. To circumvent problems, a chiral MOF (D-His-ZIF-8) was synthesized by ligand exchange of 2-methylimidazole (Hmim) on ZIF-8 by D-histidine (D-His), which can be treated as chiral host to distinguish amino acid enantiomers. The obtained D-His-ZIF-8 can provide chiral nanochannels for amino acid guests. Meanwhile, polynary transition-metal ion (Co2+ and Fe3+) coordinating with polydopamine (PDA) wrapped on the surface of D-His-ZIF-8 can increase the active sites. The electrochemical chiral recognition behavior showed that D-His-ZIF-8@CoFe-PDA exhibited good recognition of the tryptophan enantiomer (L/D-Trp) (working potential of -0.2 V vs. Hg/HgCl2). The LOD and LOQ of L-Trp were 0.066 mM and 0.22 mM, respectively, while the LOD and LOQ of D-Trp were 0.15 mM and 0.50 mM, respectively. Finally, the usefulness of D-His-ZIF-8@CoFe-PDA/GCE was evaluated with a recovery of 94.4-103%. The analysis of real  samples shows that D-His-ZIF-8@CoFe-PDA/GCE is a feasible sensing platform for the detection of L-Trp and D-Trp.


Assuntos
Técnicas Biossensoriais , Polímeros , Polímeros/química , Triptofano/química , Histidina , Estereoisomerismo
12.
Mikrochim Acta ; 190(2): 61, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36662318

RESUMO

Chirality plays a key role in many fields of natural sciences as well as life sciences. Chiral materials are widely developed and used for electrochemical chiral recognition. In recent years, carbon quantum dots (CQDs) have been widely used as a novel carbon nanomaterial due to their excellent charge transfer properties, good biocompatibility, and low cost. The special structure of π-conjugated porphyrin attracts attention. Supramolecular self-assembly shows a way to construct chiral materials by self-assembling simple molecules into chiral composites. Herein, we demonstrate the self-assembly of achiral porphyrins induced by chiral carbon quantum dots assembled from L- and or D-tryptophan (L- and or D-Trp) with carbon quantum dots, resulting in 5,10,15,20-tetrakis (4-carboxyPheyl) (TCPP) self-assembled structure. The electrochemical chiral recognition of chiral self-assembled materials was studied using Phenylalanine (Phe) enantiomer as a chiral analyte. Electrochemical chiral recognition results showed that the chiral self-assembled materials induced by chiral templates have a good ability to discriminate Phe enantiomers. Therefore, this research provides a new idea for the synthesis of chiral composites and further expands applications to electrochemical chiral recognition.


Assuntos
Nanoestruturas , Porfirinas , Porfirinas/química , Fenilalanina/química , Triptofano , Carbono
13.
FASEB J ; 35(11): e21937, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34606628

RESUMO

Defective permeability barrier is considered to be an incentive of hyperuricemia, however, the link between them has not been proven. Here, we evaluated the potential preventive effects of Lactiplantibacillus plantarum N-1 (LPN1) on gut microbiota and intestinal barrier function in rats with hyperoxaluria-induced kidney stones. Male rats were supplied with 1% ethylene glycol (EG) dissolved in drinking water for 4 weeks to develop hyperoxaluria, and some of them were administered with LPN1 for 4 weeks before EG treatment as a preventive intervention. We found that EG not only resulted hyperoxaluria and kidney stone formation, but also promoted the intestinal inflammation, elevated intestinal permeability, and gut microbiota disorders. Supplementation of LPN1 inhibited the renal crystalline deposits through reducing urinary oxalic acid and renal osteopontin and CD44 expression and improved EG-induced intestinal inflammation and barrier function by decreasing the serum LPS and TLR4/NF-κB signaling and up-regulating tight junction Claudin-2 in the colon, as well as increasing the production of short-chain fatty acid (SCFAs) and the abundance of beneficial SCFAs-producing bacteria, mainly from the families of Lachnospiraceae and Ruminococcaceae. Probiotic LPN1 could prevent EG-induced hyperoxaluria by regulating gut microbiota and enhancing intestinal barrier function.


Assuntos
Etilenoglicol/efeitos adversos , Microbioma Gastrointestinal/genética , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Cálculos Renais/induzido quimicamente , Cálculos Renais/prevenção & controle , Lactobacillaceae , Permeabilidade , Probióticos/administração & dosagem , Animais , Colo/metabolismo , Colo/microbiologia , Ácidos Graxos Voláteis/análise , Ácidos Graxos Voláteis/biossíntese , Fezes/química , Fezes/microbiologia , Hiperoxalúria/induzido quimicamente , Hiperoxalúria/prevenção & controle , Hiperuricemia/induzido quimicamente , Hiperuricemia/prevenção & controle , Inflamação/metabolismo , Masculino , RNA Ribossômico 16S/genética , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Junções Íntimas/metabolismo
14.
World J Urol ; 40(1): 221-227, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34427737

RESUMO

PURPOSE: To predict the occurrence of calcium oxalate kidney stones based on clinical and gut microbiota characteristics. METHODS: Gut microbiota and clinical data from 180 subjects (120 for training set and 60 for validation) attending the West China Hospital (WCH) were collected between June 2018 and January 2021. Based on the gut microbiota and clinical data from 120 subjects (66 non-kidney stone individuals and 54 kidney stone patients), we evaluated eight machine learning methods to predict the occurrence of calcium oxalate kidney stones. RESULTS: With fivefold cross-validation, the random forest method produced the best area under the curve (AUC) of 0.94. We further applied random forest to an independent validation dataset with 60 samples (34 non-kidney stone individuals and 26 kidney stone patients), which yielded an AUC of 0.88. CONCLUSION: Our results demonstrated that clinical data combined with gut microbiota characteristics may help predict the occurrence of kidney stones.


Assuntos
Oxalato de Cálcio , Microbioma Gastrointestinal , Cálculos Renais/etiologia , Oxalato de Cálcio/análise , Estudos de Casos e Controles , Feminino , Humanos , Cálculos Renais/química , Masculino , Pessoa de Meia-Idade , Prognóstico
15.
Cell Mol Life Sci ; 78(5): 2131-2143, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32809042

RESUMO

Macroautophagy (hereafter referred to as autophagy) is a highly conserved catabolic eukaryotic pathway that is critical for stress responses and homeostasis. Atg18, one of the core proteins involved in autophagy, belongs to the PROPPIN family and is composed of seven WD40 repeats. Together with Atg2, Atg18 participates in the elongation of phagophores and the recycling of Atg9 in yeast. Despite extensive studies on the PROPPIN family, the structure of Atg18 from Saccharomyces cerevisiae has not been determined. Here, we report the structure of ScAtg18 at a resolution of 2.8 Å. Based on bioinformatics and structural analysis, we found that the 7AB loop of ScAtg18 is extended in Atg18, in comparison to other members of the PROPPIN family. Genetic analysis revealed that the 7AB loop of ScAtg18 is required for autophagy. Biochemical and biophysical experiments indicated that the 7AB loop of ScAtg18 is critical for interaction with ScAtg2 and the recruitment of ScAtg2 to the autophagy-initiating site. Collectively, our results show that the 7AB loop of ScAtg18 is a new binding site for Atg2 and is of functional importance to autophagy.


Assuntos
Autofagossomos/metabolismo , Proteínas Relacionadas à Autofagia/metabolismo , Proteínas de Membrana/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Sequência de Aminoácidos , Autofagossomos/genética , Autofagia/genética , Proteínas Relacionadas à Autofagia/química , Proteínas Relacionadas à Autofagia/genética , Sítios de Ligação/genética , Cristalografia por Raios X , Proteínas de Membrana/química , Proteínas de Membrana/genética , Microscopia de Fluorescência , Modelos Moleculares , Ligação Proteica , Domínios Proteicos , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/genética , Homologia de Sequência de Aminoácidos
16.
BMC Public Health ; 22(1): 1787, 2022 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-36127664

RESUMO

BACKGROUND: Growing number of studies have evidently shown that sleep disorders are associated with the recently increased risk of various diseases in general human population. However, the relationship between sleep quality and urolithiasis condition in humans is still unclear. The present study explored the relationship between quality of sleep and urolithiasis in Chinese population of population, western China and hence investigated the effects of sleep quality on urolithiasis disease. METHODS: A cross-sectional analysis was performed using data from the West China Natural Population Cohort Study (WCNPCS). The data was collected between May 2019 and June 2021. This study evaluated the association between the sleep quality and urolithiasis. The sleep quality was assessed using the Chinese version of the Pittsburgh Sleep Quality Index (PSQI) whereas urolithiasis, as the outcome was a binary variable. Multivariable logistic regression models that adjust the sociodemographic characteristics and health-related factors were used to assess the association between sleep quality and urolithiasis. Interaction was tested in prespecified subgroup of interest. RESULTS: After adjusting a series of confounding variables, the Pittsburgh Sleep Quality Index scores were found to have a significant positive correlation with the prevalence of urolithiasis (OR: 1.178; 95% CI = 1.083-1.282; p < 0.001). The risk of urolithiasis was significantly increased with an elevation of the component Pittsburgh Sleep Quality Index score in sleep latency, sleep duration, habitual sleep efficiency, and daytime dysfunction. CONCLUSIONS: It was evident that there is an association between sleep quality and prevalence of renal stones in natural population in western China regions. Poor sleep quality is related to urolithiasis. The findings of the current study hence highlighted the need for future public health guidelines to develop detailed strategies for improving sleep quality.


Assuntos
Qualidade do Sono , Urolitíase , China/epidemiologia , Estudos de Coortes , Estudos Transversais , Humanos , Urolitíase/epidemiologia
17.
Arch Biochem Biophys ; 702: 108674, 2021 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-33189652

RESUMO

Extracellular matrix (ECM) remodeling is strongly associated with pathological changes induced by bladder outlet obstruction (BOO). In this study, we investigated the role of interleukin-6 (IL-6) in mechanical stretch-induced ECM remodeling of bladder smooth muscle. To construct a BOO animal model, the urethras of female Sprague-Dawley rats were partially ligated. In addition, increased hydrostatic pressure and mechanical stretching were applied to human bladder smooth muscle cells (HBSMCs) as an in vitro model. The expression of rat inflammatory genes was analyzed using DNA microarrays. We used quantitative RT-PCR (qRT-PCR) and immunohistochemical staining to detect IL-6 in the bladder smooth muscle of rats. To determine the specificity of IL-6, small interfering ribonucleic acid (siRNA) transfection and IL-6 receptor inhibitor (SC144) were applied to HBSMCs. qRT-PCR with siRNA transfection was also used to determine the specificity of downstream signaling. Moreover, western blotting was conducted to verify the expression results. In the animal model, the expression of ECM components and inflammatory genes was significantly upregulated. The expression of IL-6 was increased at both the mRNA level and the protein level in BOO rats. In vitro, hydrostatic pressure, and mechanical stretching both promoted MMP7 and MMP11 expression. Additionally, downregulation of collagen III occurred in both the hydrostatic pressure group and the mechanical stretch group. However, the expression of fibronectin exhibited opposing patterns between the hydrostatic pressure and mechanical stretch groups. The application of targeted siRNA transfection and an inhibitor (SC144) that targeted IL-6 significantly reversed the changes in MMP7 and MMP11 under mechanical stress and partially increased the expression of collagen III and fibronectin. In summary, IL-6 participated in the ECM remodeling of HBSMCs under mechanical stress, indicating that IL-6 may play an essential role in BOO..


Assuntos
Matriz Extracelular/metabolismo , Interleucina-6/metabolismo , Músculo Liso/citologia , Receptores de Interleucina-6/metabolismo , Transdução de Sinais , Estresse Mecânico , Bexiga Urinária , Animais , Microambiente Celular , Colágeno/metabolismo , Matriz Extracelular/patologia , Feminino , Regulação Enzimológica da Expressão Gênica , Interleucina-6/genética , Metaloproteinases da Matriz/genética , Músculo Liso/patologia , Ratos , Ratos Sprague-Dawley , Obstrução do Colo da Bexiga Urinária/metabolismo , Obstrução do Colo da Bexiga Urinária/patologia
18.
FASEB J ; 34(8): 11200-11214, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32645241

RESUMO

The relationship of gut microbiota and calcium oxalate stone has been limited investigated, especially with no study of gut microbiota and short chain fatty acids (SCFAs) in nephrolithiasis. We provided Sprague Dawley rats of renal calcium oxalate stones with antibiotics and examined the renal crystals deposition. We also performed a case-control study by analyzing 16S rRNA microbial profiling, shotgun metagenomics and SCFAs in 153 fecal samples from non-kidney stone (NS) controls, patients with occasional renal calcium oxalate stones (OS) and patients with recurrent stones (RS). Antibiotics reduced bacterial load in feces and could promote the formation of renal calcium crystals in model rats. In addition, both OS and RS patients exhibited higher fecal microbial diversity than NS controls. Several SCFAs-producing gut bacteria, as well as metabolic pathways associated with SCFAs production, were considerably lower in the gut microbiota among the kidney stone patients compared with the NS controls. Representation of genes involved in oxalate degradation showed no significance difference among groups. However, fecal acetic acid concentration was the highest in RS patients with high level of urinary oxalate, which was positively correlated with genes involvement in oxalate synthesis. Administration of SCFAs reduced renal crystals. These results shed new light on bacteria and SCFAs, which may promote the development of treatment strategy in nephrolithiasis.


Assuntos
Oxalato de Cálcio/metabolismo , Ácidos Graxos Voláteis/metabolismo , Microbioma Gastrointestinal/fisiologia , Cálculos Renais/metabolismo , Cálculos Renais/microbiologia , Rim/metabolismo , Animais , Bactérias/genética , Estudos de Casos e Controles , Fezes/microbiologia , Microbioma Gastrointestinal/genética , Humanos , Masculino , Metagenômica/métodos , Pessoa de Meia-Idade , Nefrolitíase/metabolismo , Nefrolitíase/microbiologia , RNA Ribossômico 16S/genética , Ratos , Ratos Sprague-Dawley
19.
World J Urol ; 39(3): 897-905, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32430571

RESUMO

PURPOSE: Multiple studies have reported that preoperative positive urine culture is an independent risk factor for postoperative fever (POF) after ureteroscopy (URS). Urine nitrite is associated urinary tract infections (UTIs). However, none of studies has explored the role of urine nitrite in the prediction of POF after flexible URS (fURS). METHODS: Patients who underwent fURS by the same surgeon between 2009 and 2019 were screened. Sensitivity and specificity of urine culture and urine nitrite were calculated. Propensity score (PS) matching was performed to get a baseline-balanced retrospective cohort to avoid potential bias. Receiver operating characteristic-area under the curve (ROC-AUC) calculated was used to determine the predictive power of models. Decision curve analysis (DCA) was plotted to obtain the clinical benefit of the models. RESULTS: Poseoperative fever (POF) is defined as the temperature of the patient higher than 38 ℃ within 72 h after operation, with no sign of infection in other systems. 31(2.8%) of 1095 cases had POF after fURL. Urine nitrite had a better specificity than urine culture for POF diagnosis (P < 0.001). After the PS matching, a well-balanced cohort of 24 POF group and 96 no-POF group was produced. The mean AUC from the bootstrap resampling method for urine nitrite model (AUC: 0.8736; 95% CI: 0.8731-0.8743) was significantly increased than that of the urine culture model (AUC: 0.8385; 95% CI: 0.8378-0.8392). The application of two kinds of POF predicting models could bring clinical net benefit when the probability is < 35%. However, urine nitrite model showed a better clinical net benefit acquirement compared to the urine culture model. CONCLUSION: Preoperative positive urine nitrite may play a pivotal role in the prediction of POF after fURS and needs to be validated by future evidence.


Assuntos
Febre/microbiologia , Febre/urina , Cálculos Renais/cirurgia , Litotripsia/métodos , Nitritos/urina , Complicações Pós-Operatórias/microbiologia , Complicações Pós-Operatórias/urina , Ureteroscopia , Infecções Urinárias/urina , Adulto , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Período Pré-Operatório , Pontuação de Propensão , Estudos Retrospectivos , Urinálise , Urina/microbiologia
20.
World J Urol ; 39(11): 4227-4234, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34146123

RESUMO

PURPOSE: Many reconstructive urologists have observed that higher urethra injuries lead to potentially less successful repairs. This article introduces a novel prognostic factor for pelvic fracture caused urethral injury (PFUI) to predict stricture recurrence after delayed transperineal anastomotic urethroplasty (TAU) patients with PFUI based on urethra injury locations. MATERIALS AND METHODS: Patients who underwent suprapubic cystostomy tube placement and delayed TAU for PFUI by a single surgeon between 2009 and 2018 were screened. A total of 151 patients completed the follow-up. The relative location between the proximal urethra and the pubic ramus (PUE-PR), a novel stricture length classification method based on the anatomical landmark, was divided into a lower, middle, and upper group reflected by urethrogram. The nomogram was developed based on significant coefficients identified by multivariable Cox regression. RESULTS: Based on the relative position between the proximal urethra end and the pubic ramus (PUE-PR), 47 (31%), 66 (44%), and 38 (25%) patients were assigned to the lower, middle, and upper group, respectively. A total of 33 patients (22%) patients had a recurrence. The median (IQR) follow-up was 49 months (28-75). Smoking, endoscopic treatment history, and PUE-PR were identified as independent risk factors for stricture recurrence. The nomogram showed good discrimination with a C-index of 76.67%. The decision curve analysis (DCA) indicated that the model could bring more clinical net benefit when a threshold probability is larger than 8%. CONCLUSIONS: PUE-PR is a new prognostic factor for PFUI to predict stricture recurrence after TAU. A novel nomogram incorporating PUE-PR could be applied to facilitate the prediction of stricture recurrence after delayed TAU for PFUI.


Assuntos
Fraturas Ósseas/complicações , Nomogramas , Osso Púbico/lesões , Tempo para o Tratamento , Uretra/lesões , Uretra/cirurgia , Estreitamento Uretral/etiologia , Adulto , Anastomose Cirúrgica , Humanos , Masculino , Pessoa de Meia-Idade , Períneo , Prognóstico , Osso Púbico/anatomia & histologia , Estudos Retrospectivos , Uretra/anatomia & histologia , Procedimentos Cirúrgicos Urológicos/métodos
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