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1.
Cell ; 187(1): 204-215.e14, 2024 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-38070508

RESUMO

Mounting evidence suggests metabolism instructs stem cell fate decisions. However, how fetal metabolism changes during development and how altered maternal metabolism shapes fetal metabolism remain unexplored. We present a descriptive atlas of in vivo fetal murine metabolism during mid-to-late gestation in normal and diabetic pregnancy. Using 13C-glucose and liquid chromatography-mass spectrometry (LC-MS), we profiled the metabolism of fetal brains, hearts, livers, and placentas harvested from pregnant dams between embryonic days (E)10.5 and 18.5. Our analysis revealed metabolic features specific to a hyperglycemic environment and signatures that may denote developmental transitions during euglycemic development. We observed sorbitol accumulation in fetal tissues and altered neurotransmitter levels in fetal brains isolated from hyperglycemic dams. Tracing 13C-glucose revealed disparate fetal nutrient sourcing depending on maternal glycemic states. Regardless of glycemic state, histidine-derived metabolites accumulated in late-stage fetal tissues. Our rich dataset presents a comprehensive overview of in vivo fetal tissue metabolism and alterations due to maternal hyperglycemia.


Assuntos
Diabetes Mellitus , Diabetes Gestacional , Feto , Animais , Feminino , Camundongos , Gravidez , Diabetes Mellitus/metabolismo , Feto/metabolismo , Glucose/metabolismo , Placenta/metabolismo , Diabetes Gestacional/metabolismo
2.
Nat Chem Biol ; 20(3): 314-322, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37537378

RESUMO

Glycolysis is a universal metabolic process that breaks down glucose to produce adenosine triphosphate (ATP) and biomass precursors. The Entner-Doudoroff (ED) pathway is a glycolytic pathway that parallels textbook glycolysis but yields half as much ATP. Accordingly, in organisms that possess both glycolytic pathways (for example, Escherichia coli), its raison d'être remains a mystery. In this study, we found that the ED pathway provides a selective advantage during growth acceleration. Upon carbon and nitrogen upshifts, E. coli accelerates growth faster with than without the ED pathway. Concurrent isotope tracing reveals that the ED pathway flux increases faster than that of textbook glycolysis. We attribute the fast response time of the ED pathway to its strong thermodynamic driving force and streamlining of glucose import. Intermittent nutrient supply manifests the evolutionary advantage of the parallel glycolysis; thus, the dynamic nature of an ostensibly redundant pathway's role in promoting rapid adaptation constitutes a metabolic design principle.


Assuntos
Escherichia coli , Glicólise , Trifosfato de Adenosina , Glucose , Aceleração
3.
Proc Natl Acad Sci U S A ; 120(42): e2308373120, 2023 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-37816063

RESUMO

A hybrid approach combining water-splitting electrochemistry and H2-oxidizing, CO2-fixing microorganisms offers a viable solution for producing value-added chemicals from sunlight, water, and air. The classic wisdom without thorough examination to date assumes that the electrochemistry in such a H2-mediated process is innocent of altering microbial behavior. Here, we report unexpected metabolic rewiring induced by water-splitting electrochemistry in H2-oxidizing acetogenic bacterium Sporomusa ovata that challenges such a classic view. We found that the planktonic S. ovata is more efficient in utilizing reducing equivalent for ATP generation in the materials-biology hybrids than cells grown with H2 supply, supported by our metabolomic and proteomic studies. The efficiency of utilizing reducing equivalents and fixing CO2 into acetate has increased from less than 80% of chemoautotrophy to more than 95% under electroautotrophic conditions. These observations unravel previously underappreciated materials' impact on microbial metabolism in seemingly simply H2-mediated charge transfer between biotic and abiotic components. Such a deeper understanding of the materials-biology interface will foster advanced design of hybrid systems for sustainable chemical transformation.


Assuntos
Dióxido de Carbono , Proteômica , Dióxido de Carbono/metabolismo , Luz Solar , Acetatos/metabolismo , Água/química
4.
Xenotransplantation ; 31(2): exen12855, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38602029

RESUMO

Carbohydrate-antigens widely existed on glycoproteins and glycosphingolipids of all mammalian cells play a crucial role in self-defense and immunity. Xeno-reactive antibodies included in natural human sera play a protecting role in an acute phase-rejection of xenotransplantation. In this study, we investigated the effect of an alteration of glycosylation-pattern, caused by human sialyltransferases such as hST3Gal II or hST6GalNAc IV, on human serum mediated cytotoxicity in pig kidney PK15 cells. From LDH cytotoxicity assay, cytotoxicity to human serum was significantly increased in hST3Gal II and hST6GalNAc IV-transfected PK15 cells, as compared to the control. In the hST6Gal I-carrying cells, the cytotoxicity to human serum was rather decreased. Moreover, flow cytometry analysis revealed that an alteration of pig glycosylation-pattern by hST3Gal II or hST6GalNAc IV influences on a binding of human IgM or IgG, respectively, in pig kidney cells, regardless of Gal antigen alteration. Finally, we found that hST6GalNAc IV contributed to increase of terminal disialylated tetrasaccharide structure, disialyl T antigen, as evidenced by increase of the MAL II lectin binding capacity in the hST6GalNAc IV-transfected PK15 cells, compared with control. Therefore, our results suggest that carbohydrate antigens, such as disialyl T antigen, newly synthesized by the ST3Gal II- and ST6GalNAc IV are potentially believed to be new xeno-reactive elements.


Assuntos
Sialiltransferases , Transplante Heterólogo , beta-Galactosídeo alfa-2,3-Sialiltransferase , Animais , Humanos , Antígenos Virais de Tumores , Carboidratos , Mamíferos/metabolismo , Sialiltransferases/genética , Sialiltransferases/química , Sialiltransferases/metabolismo , Suínos
5.
Int J Med Sci ; 21(8): 1552-1558, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38903925

RESUMO

Background: Continuous intravenous infusion of remimazolam may be suitable for sedation in patients undergoing regional anaesthesia. However, there have been no studies comparing remimazolam and dexmedetomidine for this purpose. This study compared emergence from sedation between dexmedetomidine and remimazolam following continuous intravenous infusion in patients undergoing spinal anaesthesia. Methods: This double-blinded, randomised controlled trial assessed the sedative effects of dexmedetomidine and remimazolam. Following spinal anaesthesia, patients were sedated using continuous intravenous infusion of either dexmedetomidine (D group) or remimazolam (R group).The D group received dexmedetomidine administered at 6 mL/kg/h (6 µg/kg/h) for 10 minutes, followed by 1 mL/kg/h (1 µg/kg/h). The R group received remimazolam administered at 6 mL/kg/h (6 mg/kg/h) for 10 minutes, followed by 1 mL/kg/h (1 mg/kg/h). Sedation levels were evaluated using the Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scale. The time to reach MOAA/S ≤ 3 from the start of drug infusion and the time to reach MOAA/S = 5 from the end of infusion were recorded. Hemodynamic parameters and respiratory rate were also monitored. Results: The R group reached MOAA/S ≤ 3 significantly faster than the D group during induction of sedation (4 ± 1 minutes and 11 ± 3 minutes, respectively, p < 0.001). The R group also reached MOAA/S = 5 significantly faster than the D group during emergence from sedation (11 ± 3 minutes and 16 ± 5 minutes, respectively, p < 0.001). Both groups maintained stable hemodynamic parameters and respiratory rate without any significant differences, although the mean heart rate was significantly lower in the D group than in the R group after the start of infusion. Conclusion: Remimazolam demonstrated significantly faster induction of and emergence from sedation compared to dexmedetomidine, with no significant differences in haemodynamics or respiratory depression.


Assuntos
Raquianestesia , Dexmedetomidina , Hipnóticos e Sedativos , Humanos , Dexmedetomidina/administração & dosagem , Dexmedetomidina/efeitos adversos , Raquianestesia/métodos , Masculino , Feminino , Adulto , Hipnóticos e Sedativos/administração & dosagem , Pessoa de Meia-Idade , Método Duplo-Cego , Infusões Intravenosas , Benzodiazepinas/administração & dosagem , Benzodiazepinas/efeitos adversos , Período de Recuperação da Anestesia , Hemodinâmica/efeitos dos fármacos , Sedação Consciente/métodos
6.
Ecotoxicol Environ Saf ; 274: 116213, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38493702

RESUMO

Antibacterial films have gained attention since the outbreak of the COVID-19 pandemic; however, the impact of metals contained in antibacterial films on human safety have not been sufficiently investigated. This study reports on the important features that must be considered when assessing the bioaccessibility of Ag, Cu, and Zn in antibacterial films. Specifically, the effects of the artificial sweat component (i.e., amino acid and pH), surface weathering of antibacterial films, wipe sampling, and sebum were carefully examined. Our findings suggest that amino acids greatly affect bioaccessibility as amino acids act as ligands to facilitate metal ion leaching. In addition, constant exposure to ultraviolet C causes the film surface to oxidize, which significantly increases metal bioaccessibility due to the electrostatic repulsion between metal oxides and organic substrates. The presence of sebum in artificial sweat and physical damage to the film surface had no significant effects. Furthermore, the wipe sampling used to mimic the realistic dermal contact suggests the feasibility of applying this method for the assessment of bioaccessibility of metals in antibacterial films. The method offers significant advantages for evaluating the human safety aspects of skin contact with consumer products in future research.


Assuntos
Metais Pesados , Pandemias , Humanos , Metais/análise , Pele/metabolismo , Antibacterianos/farmacologia , Antibacterianos/metabolismo , Aminoácidos/metabolismo , Metais Pesados/análise , Monitoramento Ambiental/métodos
7.
J Cell Biochem ; 124(9): 1423-1434, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37642132

RESUMO

Tuberculosis (TB) is caused by Mycobacterium tuberculosis (Mtb) and is still one of the global health burdens. The occurrence of various cases and multidrug resistance confirm that TB has not been completely conquered. For these reasons, the present research has been conducted to explore TB vaccine and drug candidate possibility using Mtb-secreted proteins. Among these proteins, MPT32 is known to have antigenicity and immunogenicity. There has not been a report on the host immune responses and regulation in macrophage cells. The present study was conducted with MPT32 in RAW 264.7 murine macrophage cells that control immune responses by sensing pathogen invasion and environmental change. We have found that MPT32 could activate lipopolysaccharide (LPS)-induced gene expression of metalloproteinase-9 (MMP-9) and inflammation in RAW 264.7 cells. After treating cells with MPT32, the increase in pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß (IL-1ß) and IL-6, was observed. In addition, activated macrophages expressed inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) to generate various inflammatory mediator molecules, such as nitric oxide (NO). The increase in iNOS and COX-2 levels, which are up-regulators of MMP-9 expression, was also confirmed. The biochemical events are involved in the downstream of activated MAPK signaling and translocation of NF-κ B transcription factor. The present results prove the immunomodulatory effect of MPT32 in the RAW 264.7 murine macrophage cells. it claims the possibility of a TB vaccination and drug candidate using MPT32, contributing to the prevention of TB.


Assuntos
Proteínas de Bactérias , Mycobacterium tuberculosis , Animais , Camundongos , Ciclo-Oxigenase 2/genética , Inflamação , Macrófagos , Metaloproteinase 9 da Matriz , NF-kappa B , Regulação para Cima , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Tuberculose/metabolismo , Tuberculose/microbiologia
8.
Plant Physiol ; 190(4): 2366-2379, 2022 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-35944218

RESUMO

Virus-induced gene silencing (VIGS) is a powerful tool for high-throughput analysis of gene function. Here, we developed the VIGS vector pCF93, from which expression of the cucumber fruit mottle mosaic virus genome is driven by the cauliflower mosaic virus 35S promoter to produce viral transcripts in inoculated plants. To test the utility of the pCF93 vector, we identified candidate genes related to male sterility (MS) in watermelon (Citrullus lanatus), which is recalcitrant to genetic transformation. Specifically, we exploited previously reported reference-based and de novo transcriptome data to define 38 differentially expressed genes between a male-sterile line and its fertile near-isogenic line in the watermelon cultivar DAH. We amplified 200- to 300-bp fragments of these genes, cloned them into pCF93, and inoculated DAH with the resulting VIGS clones. The small watermelon cultivar DAH enabled high-throughput screening using a small cultivation area. We simultaneously characterized the phenotypes associated with each of the 38 candidate genes in plants grown in a greenhouse. Silencing of 8 of the 38 candidate genes produced male-sterile flowers with abnormal stamens and no pollen. We confirmed the extent of gene silencing in inoculated flowers using reverse transcription-qPCR. Histological analysis of stamens from male-fertile and male-sterile floral buds and mature flowers revealed developmental defects and shrunken pollen sacs. Based on these findings, we propose that the pCF93 vector and our VIGS system will facilitate high-throughput analysis for the study of gene function in watermelons.


Assuntos
Citrullus , Tobamovirus , Tobamovirus/genética , Citrullus/genética , Flores/genética , Fenótipo , Inativação Gênica , Regulação da Expressão Gênica de Plantas
9.
Ann Surg Oncol ; 30(8): 5295-5303, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37160804

RESUMO

BACKGROUND: Radical cystectomy is a major urological procedure with high morbidity and mortality. The chart-derived frailty index (CFI), a measure of preoperative frailty, can be calculated by using demographic and routine laboratory variables. We assessed the impact of CFI on 1-year mortality after radical cystectomy. METHODS: This retrospective study included patients with bladder cancer who underwent radical cystectomy between 2007 and 2021. The CFI was calculated as the sum of the presence of the following parameters: age > 70 years, body mass index < 18.5 kg/m2, hematocrit < 35%, albumin < 3.4 g/dL, and creatinine > 2.0 mg/dL. Patients were divided into those with low (0-2) and high (3-5) CFI. The 1-year, all-cause and cancer-specific mortalities after radical cystectomy were evaluated. RESULTS: Of the 1004 patients, 914 (91.0%) had a low CFI and 90 (9.0%) had a high CFI. The 1-year, all-cause mortality in the low and high CFI groups was 12.0% and 27.8%, respectively (P < 0.001). Multivariate Cox regression analysis revealed that high CFI (P < 0.001), tumor stage (P = 0.003), and red blood cell transfusion amount (P < 0.001) were significantly associated with 1-year, all-cause mortality after radical cystectomy. Kaplan-Meier survival analysis demonstrated significantly different 1-year, all-cause and cancer-specific mortalities after radical cystectomy between patients with a high CFI and those with a low CFI (log-rank test, both P < 0.001). CONCLUSIONS: High CFI is associated with higher 1-year mortality after radical cystectomy, suggesting that the CFI can effectively predict mortality after radical cystectomy.


Assuntos
Fragilidade , Neoplasias da Bexiga Urinária , Humanos , Idoso , Cistectomia , Estudos Retrospectivos , Fragilidade/complicações , Taxa de Sobrevida , Neoplasias da Bexiga Urinária/patologia
10.
J Nanobiotechnology ; 21(1): 12, 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36635755

RESUMO

Despite the development of therapeutic modalities to treat cancer, multidrug resistance (MDR) and incomplete destruction of deeply embedded lung tumors remain long-standing problems responsible for tumor recurrence and low survival rates. Therefore, developing therapeutic approaches to treat MDR tumors is necessary. In this study, nanodrugs with enhanced intracellular drug internalization were identified by the covalent bonding of carbon nanotubes of a specific nano size and doxorubicin (DOX). In addition, carbon nanotube conjugated DOX (CNT-DOX) sustained in the intracellular environment in multidrug-resistant tumor cells for a long time causes mitochondrial damage, suppresses ATP production, and results in the effective therapeutic effect of drug-resistant tumors. This study identified that H69AR lung cancer cells, an adriamycin (DOX) drug-resistant tumor cell line, did not activate drug resistance function on designed nano-anticancer drugs with a specific nano size. In summary, this study identified that the specific size of the nanodrug in combination with DOX overcame multidrug-resistant tumors by inducing selective accumulation in tumor cells and inhibiting ATP by mitochondrial damage.


Assuntos
Neoplasias Pulmonares , Nanopartículas , Nanotubos de Carbono , Humanos , Resistencia a Medicamentos Antineoplásicos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Linhagem Celular Tumoral , Nanopartículas/uso terapêutico , Trifosfato de Adenosina
11.
Sensors (Basel) ; 23(11)2023 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-37299765

RESUMO

Prestressed girders reduce cracking and allow for long spans, but their construction requires complex equipment and strict quality control. Their accurate design depends on a precise knowledge of tensioning force and stresses, as well as monitoring the tendon force to prevent excessive creep. Estimating tendon stress is challenging due to limited access to prestressing tendons. This study utilizes a strain-based machine learning method to estimate real-time applied tendon stress. A dataset was generated using finite element method (FEM) analysis, varying the tendon stress in a 45 m girder. Network models were trained and tested on various tendon force scenarios, with prediction errors of less than 10%. The model with the lowest RMSE was chosen for stress prediction, accurately estimating the tendon stress, and providing real-time tensioning force adjustment. The research offers insights into optimizing girder locations and strain numbers. The results demonstrate the feasibility of using machine learning with strain data for instant tendon force estimation.


Assuntos
Aprendizado de Máquina , Tendões , Estresse Mecânico , Análise de Elementos Finitos
12.
Int J Mol Sci ; 24(9)2023 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-37175965

RESUMO

Currently, there are three major assaying methods used to validate in vitro whitening activity from natural products: methods using mushroom tyrosinase, human tyrosinase, and dopachrome tautomerase (or tyrosinase-related protein-2, TRP-2). Whitening agent development consists of two ways, melanin synthesis inhibition in melanocytes and downregulation of melanocyte stimulation. For melanin levels, the melanocyte cell line has been used to examine melanin synthesis with the expression levels of TRP-1 and TRP-2. The proliferation of epidermal surfaced cells and melanocytes is stimulated by cellular signaling receptors, factors, or mediators including endothelin-1, α-melanocyte-stimulating hormone, nitric oxide, histamine, paired box 3, microphthalmia-associated transcription factor, pyrimidine dimer, ceramide, stem cell factors, melanocortin-1 receptor, and cAMP. In addition, the promoter region of melanin synthetic genes including tyrosinase is upregulated by melanocyte-specific transcription factors. Thus, the inhibition of growth and melanin synthesis in gene expression levels represents a whitening research method that serves as an alternative to tyrosinase inhibition. Many researchers have recently presented the bioactivity-guided fractionation, discovery, purification, and identification of whitening agents. Melanogenesis inhibition can be obtained using three different methods: tyrosinase inhibition, copper chelation, and melanin-related protein downregulation. There are currently four different types of inhibitors characterized based on their enzyme inhibition mechanisms: competitive, uncompetitive, competitive/uncompetitive mixed-type, and noncompetitive inhibitors. Reversible inhibitor types act as suicide substrates, where traditional inhibitors are classified as inactivators and reversible inhibitors based on the molecule-recognizing properties of the enzyme. In a minor role, transcription factors can also be downregulated by inhibitors. Currently, the active site copper iron-binding inhibitors such as kojic acid and chalcone exhibit tyrosinase inhibitory activity. Because the tyrosinase catalysis site structure is important for the mechanism determination of tyrosinase inhibitors, understanding the enzyme recognition and inhibitory mechanism of inhibitors is essential for the new development of tyrosinase inhibitors. The present review intends to classify current natural products identified by means of enzyme kinetics and copper chelation to exhibit tyrosinase enzyme inhibition.


Assuntos
Melaninas , Monofenol Mono-Oxigenase , Humanos , Melaninas/metabolismo , Monofenol Mono-Oxigenase/metabolismo , Cobre/metabolismo , Cinética , Melanócitos/metabolismo , Fatores de Transcrição/metabolismo , Fator de Transcrição Associado à Microftalmia/genética , Fator de Transcrição Associado à Microftalmia/metabolismo , Inibidores Enzimáticos/farmacologia
13.
Cleft Palate Craniofac J ; 60(10): 1326-1330, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-35473400

RESUMO

Patau syndrome (trisomy 13) is a severe disorder associated with multiple systemic defects. Patau syndrome is commonly associated with ocular abnormalities but rarely associated with congenital glaucoma. To obtain a better surgical view, palatoplasty requires neck extension during surgery. The intraocular pressure (IOP) of patients with Patau syndrome can increase owing to the neck extension position while undergoing palatoplasty, particularly in those with congenital glaucoma. Here, we describe a case with increased IOP measured using a rebound tonometer during palatoplasty in a pediatric patient with Patau syndrome and congenital glaucoma. This case shows that it may be important to reduce the degree of neck extension and shorten the operation time to minimize any increase in the IOP during palatoplasty in pediatric patients with Patau syndrome accompanied by congenital glaucoma.


Assuntos
Fissura Palatina , Glaucoma , Humanos , Criança , Pressão Intraocular , Síndrome da Trissomia do Cromossomo 13 , Tonometria Ocular , Glaucoma/cirurgia , Glaucoma/congênito , Fissura Palatina/cirurgia
14.
J Cell Biochem ; 123(4): 772-781, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35060178

RESUMO

Mycobacterium tuberoculosis (Mtb) is a contagious pathogen that causes human tuberculosis (TB). TB is a major global health threat that causes 9.6 million illnesses and 1.5 million deaths per year. Recent studies have suggested Mtb-secreted proteins as new candidates for therapeutic drugs and vaccines. LprG is a Mtb-secreted surface glycolipoprotein encoded by lprG (Rv1411c), which forms an operon with Rv1410c, where Rv1410c encodes P55, an efflux pump membrane protein. Various in vitro and in vivo studies have reported on the target-binding activity, cell envelope biosynthesis, and mycobacterial virulence of LprG. However, the anti-inflammatory effect of LprG in macrophages has not yet been investigated. In this study, we demonstrated that LprG can suppress lipopolysaccharide (LPS)-induced inflammation in a macrophage model. LprG inhibited LPS-stimulated nitric oxide (NO) production. LprG also suppressed expression of inducible cyclooxygenase-2 (COX-2) and nitric oxide synthase (iNOS) at the transcriptional and protein levels. In addition, LprG decreased mRNA expression of the pro-inflammatory cytokines interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor-α (TNF-α). Furthermore, LprG attenuated nuclear factor kappa-B (NF-κB) translocation and IκB phosphorylation. Moreover, LprG specifically inhibited phosphorylated kinases such as c-Jun N-terminal kinase (p-JNK) and extracellular signal-regulated kinase 1/2 (p-ERK1/2), but not p-p38. Taken together, these results suggest that LprG inhibits LPS-stimulated inflammation via downregulation of NO, COX-2, iNOS, and pro-inflammatory cytokines through the NF-κB, AP-1, and MAPK signaling pathways. The present study will aid in the development of anti-inflammatory medications using Mtb. The organism, which has long been regarded as a human pathogenic or human health-threating agent, can be utilized as a future medical resource.


Assuntos
Lipopolissacarídeos , Mycobacterium tuberculosis , Animais , Anti-Inflamatórios/farmacologia , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Citocinas/metabolismo , Humanos , Inflamação/induzido quimicamente , Inflamação/metabolismo , Lipopolissacarídeos/toxicidade , Sistema de Sinalização das MAP Quinases , Macrófagos/metabolismo , Camundongos , Proteína Quinase 3 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Mycobacterium tuberculosis/metabolismo , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo
15.
Biochem Biophys Res Commun ; 635: 136-143, 2022 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-36274363

RESUMO

Enhancer of zeste homolog 2 (EZH2), with EED and SUZ12, forms the polycomb repressive complex 2 (PRC2), which catalyzes histone H3 lysine 27 (H3K27) methylation. Canonically, EZH2 is well known to repress transcription by mediating H3K27 tri-methylation (H3K27me3) at target gene promoters. In this study, we report that EZH2 non-canonically regulates transcription of SET/TAF-Iß, known as a subunit of inhibitor of acetyltransferases (INHAT) complex and as a proto-oncogene. Importantly, transcriptional regulation of SET/TAF-Iß by EZH2 was independent of PRC2 and its methyltransferase activity. Moreover, EZH2 and SET/TAF-Iß levels were positively correlated, and both genes were highly expressed in various cancers including colon cancer as indicated by the analysis of TCGA database. Taken together, our study suggests the non-canonical role of EZH2 as a transcriptional activator of SET/TAF-Iß independent of methyltransferase function in colon cancer.


Assuntos
Neoplasias do Colo , Proteína Potenciadora do Homólogo 2 de Zeste , Humanos , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Acetiltransferases , Complexo Repressor Polycomb 2/genética , Complexo Repressor Polycomb 2/metabolismo , Regulação da Expressão Gênica
16.
Ann Surg Oncol ; 29(8): 5321-5329, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35368220

RESUMO

BACKGROUND: During robot-assisted partial nephrectomy (RAPN), renal artery clamping is necessary to optimize the surgical field. However, renal artery clamping can induce renal blood flow reduction and postoperative renal dysfunction. Papaverine is used as a potent vasodilator agent. We determined if periarterial administration of papaverine after renal artery clamping improved intraoperative renal artery blood flow and early postoperative glomerular filtration rate (GFR) compared with placebo in RAPN. PATIENTS AND METHODS: In this randomized controlled trial, 96 patients who underwent RAPN were enrolled between November 2019 and December 2020. Patients were administered periarterial normal saline as a placebo (placebo group) or papaverine (papaverine group) just after renal artery declamping. The primary outcome was renal artery blood flow by Doppler ultrasound 2 min after periarterial administration of papaverine or placebo after renal artery declamping. The secondary outcome was GFR estimated by renal scan 3 months after RAPN. RESULTS: Renal artery blood flow and GFR were significantly higher in the papaverine group than in the placebo group (538.0 [376.6-760.0] mL/min versus 338.8 [205.8-603.4] mL/min, P = 0.002 and 93.5 ± 17.1 mL/min/1.73 m2 versus 85.9 ± 15.8 mL/min/1.73 m2, P = 0.033, respectively). CONCLUSIONS: Periarterial papaverine administration increased intraoperative renal artery blood flow and early postoperative GFR in RAPN, suggesting that papaverine administration has beneficial effects on renal perfusion after renal artery clamping and could be a valuable option for improving renal function after RAPN.


Assuntos
Neoplasias Renais , Procedimentos Cirúrgicos Robóticos , Robótica , Humanos , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/cirurgia , Nefrectomia , Papaverina/farmacologia , Artéria Renal/cirurgia , Circulação Renal , Estudos Retrospectivos , Resultado do Tratamento
17.
J Surg Res ; 279: 453-463, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35841814

RESUMO

INTRODUCTION: Burns can cause multiple organ systemic derangements, particularly in respiratory systems. The prognostic nutritional index (PNI) can predict postoperative outcomes. We evaluated the incidence and risk factors, including PNI, for postoperative pulmonary complications (PPCs) in patients with major burns. METHODS: PNI was calculated as 10 × (serum albumin level) + 0.005 × (total lymphocyte count). Major burn patients admitted to the ICU without burn-induced lung injuries were retrospectively included. The incidence of PPCs was measured within 1 wk of burn surgery. A multivariable logistic regression analysis was performed to evaluate the risk factors for PPCs. Receiver operating characteristic curve analysis and propensity-score matched analysis were conducted to estimate the influence of PNI on PPCs. Outcomes after burn surgery were also assessed. RESULTS: Of 444 major burn patients, 138 (31.1%) showed PPCs. Risk factors for PPCs were PNI, gender, total body surface area burned, interval between burn and surgery, and red blood cell transfusion rate. The area under the curve of PNI for predicting PPCs was 0.709 (cutoff value = 31.5). The incidence of PPCs was significantly higher in the PNI ≤ 31.5 group than in the PNI > 31.5 group (55.7% versus 22.8%, P < 0.001) after propensity-score matching. The intensive care unit stay duration was longer and 90-d mortality was higher in patients who developed PPCs (19 [9-27] d versus 8 [4-17] d, P < 0.001; 11.6% versus 0.3%, P < 0.001). CONCLUSIONS: The prevalence of PPCs in patients with major burns was 31.1% and preoperative PNI was a predictor of PPCs in these patients. PNI ≤ 31.5 was significantly related to a higher incidence of PPCs.


Assuntos
Queimaduras , Avaliação Nutricional , Queimaduras/complicações , Queimaduras/cirurgia , Humanos , Estado Nutricional , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Albumina Sérica
18.
Phys Chem Chem Phys ; 24(47): 28903-28912, 2022 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-36440632

RESUMO

Hyperstoichiometric (p-type) misfit-layered calcium cobaltites have been studied as components in various high-temperature electrochemical devices. Multiple studies have reported their applications or physical properties, but systematic studies on their defect structures and thermodynamic quantities are still insufficient. In this study, the oxygen nonstoichiometry and the electrical conductivity of Gd-Cu co-doped misfit cobalt oxide were measured as functions of temperature and oxygen partial pressure, along with thermodynamic quantities. The behavior of oxygen nonstoichiometry could not be explained by a defect structure assuming the ideal solution, as it showed a positive deviation in Raoult's law. The redesigned nonideal proposed defect structure, considering that the deviation originated from the high concentration of degenerate holes, could describe the oxygen nonstoichiometry precisely; and in this process, the values of , , Nv, , γh, and were quantitatively extracted. These values were compared with those obtained for the undoped system. The total electrical conductivity was measured using a dense specimen obtained via spark plasma sintering, and the anisotropic nature of the material was confirmed.

19.
Sensors (Basel) ; 22(11)2022 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-35684809

RESUMO

Non-carious cervical lesions (NCCLs) are saucer-shaped abrasions of a tooth. NCCLs can form due to various etiologies, including toothbrushing wear, acid erosion, and mechanical stress. Owing to this complex interplay, the mechanism of NCCLs in tooth abrasion has not been established. This study aims to develop a numerical method using a computational toothbrush to simulate NCCLs. The forces acting on the teeth and the amount of abrasion generated were evaluated. The discrete element method using in-house code, connected particle model, and Archard wear model were applied for brushing. In the toothbrush model, 42 acrylic tufts were fixed into a toothbrush head. The teeth models with enamel properties comprised four flat plates and two grooves to simulate the anterior teeth and NCCLs. The brushing speed and depth for one cycle were established as simulation parameters. The force applied within the ununiform plane was concentrated on several bristles as the toothbrush passed through the interproximal space. The brushing force (depth) had a greater effect on tooth abrasion than the brushing speed. Toothbrushing abrasion was mainly concentrated in the interproximal space. Therefore, forceful tooth brushing can cause NCCLs from the interproximal space to the cervical area of the tooth.


Assuntos
Abrasão Dentária , Escovação Dentária , Simulação por Computador , Humanos , Projetos de Pesquisa , Estresse Mecânico , Abrasão Dentária/etiologia , Abrasão Dentária/patologia , Escovação Dentária/efeitos adversos
20.
Int J Mol Sci ; 23(3)2022 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-35163392

RESUMO

Microorganisms, such as bacteria, viruses, and fungi, and host cells, such as plants and animals, have carbohydrate chains and lectins that reciprocally recognize one another. In hosts, the defense system is activated upon non-self-pattern recognition of microbial pathogen-associated molecular patterns. These are present in Gram-negative and Gram-positive bacteria and fungi. Glycan-based PAMPs are bound to a class of lectins that are widely distributed among eukaryotes. The first step of bacterial infection in humans is the adhesion of the pathogen's lectin-like proteins to the outer membrane surfaces of host cells, which are composed of glycans. Microbes and hosts binding to each other specifically is of critical importance. The adhesion factors used between pathogens and hosts remain unknown; therefore, research is needed to identify these factors to prevent intestinal infection or treat it in its early stages. This review aims to present a vision for the prevention and treatment of infectious diseases by identifying the role of the host glycans in the immune response against pathogenic intestinal bacteria through studies on the lectin-glycan interaction.


Assuntos
Microbioma Gastrointestinal , Trato Gastrointestinal/metabolismo , Trato Gastrointestinal/microbiologia , Lectinas/metabolismo , Polissacarídeos/metabolismo , Animais , Infecções Bacterianas/metabolismo , Humanos , Lectinas/química , Modelos Biológicos , Polissacarídeos/química
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