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1.
Neurourol Urodyn ; 43(2): 486-493, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38149696

RESUMO

AIMS: To examine the association between testosterone deficiency (TD) and nocturia in males, with specific attention to age and cardiovascular disease (CVD) comorbidity. METHODS: This cross-sectional study utilized the National Health and Nutrition Examination Survey (NHANES) data from 2011 to 2016, assessing 6137 adult male participants. TD was defined by a serum total testosterone (TT) concentration less than 300 ng/dL. Nocturia was determined based on participants' responses to a standard NHANES question regarding the frequency of urination during the night. RESULTS: The study observed a significant association between TD and nocturia (adjusted odds ratio [95% confidence interval] = 1.211 [1.060-1.384], p = 0.005). Moreover, a U-shape pattern was noted in the relationship between serum TT concentration and the relative odds of nocturia. Subgroup analysis revealed a robust correlation between TD and nocturia in those over 60 years old, and those with hypertension, dyslipidemia, and CVDs. CONCLUSION: Our findings suggest a positive correlation between TD and nocturia, particularly among elderly individuals with CVD. This association underscores the potential therapeutic significance of addressing TD in the management of nocturia. Furthermore, longitudinal studies are needed to establish a causal relationship between TD and nocturia.


Assuntos
Doenças Cardiovasculares , Noctúria , Adulto , Humanos , Masculino , Idoso , Pessoa de Meia-Idade , Noctúria/epidemiologia , Inquéritos Nutricionais , Estudos Transversais , Testosterona
2.
Am J Emerg Med ; 80: 178-184, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38613987

RESUMO

OBJECTIVES: Out-of-hospital cardiac arrest (OHCA) survival differences due to sex remain controversial. Previous studies adjusted for prehospital variables, but not sex-based in-hospital management disparities. We aimed to investigate age and sex-related differences in survival outcomes in OHCA patients after adjustment for sex-based in-hospital management disparities. METHODS: This retrospective observational study used a prospective multicenter OHCA registry to review data of patients from October 2015 to December 2020. The primary outcome was good neurological outcome defined as cerebral performance category score 1 or 2. We performed multivariable logistic regression and restricted cubic spline analysis according to age. RESULTS: Totally, 8988 patients were analyzed. Women showed poorer prehospital characteristics and received fewer coronary angiography, percutaneous coronary interventions, targeted temperature management, and extracorporeal membrane oxygenation than men. Good neurological outcomes were lower in women than in men (5.8% vs. 12.2%, p < 0.001). After adjustment for age, prehospital variables, and in-hospital management, women were more likely to have good neurological outcomes than men (adjusted odds ratio [aOR] 1.37, 95% confidence interval [CI] 1.07-1.74, p = 0.012). The restricted cubic spline curve showed a reverse sigmoid pattern of adjusted predicted probability of outcomes and dynamic associations of sex and age-based outcomes. CONCLUSIONS: Women with OHCA were more likely to have good neurological outcome after adjusting for age, prehospital variables, and sex-based in-hospital management disparities. There were non-linear associations between sex and survival outcomes according to age and age-related sex-based differences.


Assuntos
Parada Cardíaca Extra-Hospitalar , Humanos , Parada Cardíaca Extra-Hospitalar/terapia , Parada Cardíaca Extra-Hospitalar/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Fatores Sexuais , Fatores Etários , Disparidades em Assistência à Saúde/estatística & dados numéricos , Sistema de Registros , Reanimação Cardiopulmonar/estatística & dados numéricos
3.
Molecules ; 29(3)2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38338475

RESUMO

The global increase in antibiotic consumption is related to increased adverse effects, such as antibiotic-associated diarrhea (AAD). This study investigated the chemical properties of Zingiber officinale Rosc (ZO) extract and its ameliorative effects using a lincomycin-induced AAD mouse model. Intestinal tissues were evaluated for the expression of lysozyme, claudin-1, and α-defensin-1, which are associated with intestinal homeostasis. The cecum was analyzed to assess the concentration of short-chain fatty acids (SCFAs). The chemical properties analysis of ZO extracts revealed the levels of total neutral sugars, acidic sugars, proteins, and polyphenols to be 86.4%, 8.8%, 4.0%, and 0.8%, respectively. Furthermore, the monosaccharide composition of ZO was determined to include glucose (97.3%) and galactose (2.7%). ZO extract administration ameliorated the impact of AAD and associated weight loss, and water intake also returned to normal. Moreover, treatment with ZO extract restored the expression levels of lysozyme, α-defensin-1, and claudin-1 to normal levels. The decreased SCFA levels due to induced AAD showed a return to normal levels. The results indicate that ZO extract improved AAD, strengthened the intestinal barrier, and normalized SCFA levels, showing that ZO extract possesses intestinal-function strengthening effects.


Assuntos
Zingiber officinale , alfa-Defensinas , Camundongos , Animais , Muramidase , Claudina-1/genética , Diarreia/induzido quimicamente , Diarreia/tratamento farmacológico , Antibacterianos/efeitos adversos , Açúcares
4.
Electrophoresis ; 44(21-22): 1698-1703, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37650251

RESUMO

We present a novel method for fabricating round cross-sectional channels for autoregulatory pressure regulators. The application of previously reported methods in multilayered soft lithography using three-dimensional printed molds is challenging. Herein, we used a thermal expansion technique to create round cross-sectional channels in replica layers using air in the cavity space of a master mold. The width and height of the round channel in the replica could be adjusted in the range of 80-300 and 3-57 µm, respectively, by varying the precuring time of the replica in the gel state and adjusting the cavity size of the master mold. We successfully fabricated a pressure regulator with a round cross-sectional channel, achieving a constant output pressure at a low threshold input pressure. Our device exhibited superior performance, with a constant output pressure at a threshold input pressure of less than 77%, compared to a device with a rectangular cross-sectional channel. Our method has significant potential for application in the fabrication of integrated microfluidic systems with round cross-sectional channels.


Assuntos
Microfluídica , Estudos Transversais , Microfluídica/métodos
5.
Mar Drugs ; 21(10)2023 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-37888444

RESUMO

Xinghamide A (1), a new nonapeptide, was discovered in Streptomyces xinghaiensis isolated from a halophyte, Suaeda maritima (L.) Dumort. Based on high-resolution mass and NMR spectroscopic data, the planar structure of 1 was established, and, in particular, the sequence of nine amino acids was determined with ROESY and HMBC NMR spectra. The absolute configurations of the α-carbon of each amino acid residue were determined with 1-fluoro-2,4-dinitrophenyl-l-and -d-leucine amide (Marfey's reagents) and 2,3,4,6-tetra-O-acetyl-ß-d-glucopyranosyl isothiocyanate, followed by LC-MS analysis. The anti-inflammatory activity of xinghamide A (1) was evaluated by inhibitory abilities against the nitric oxide (NO) secretion and cyclooxygenase-2 (COX-2) expression in lipopolysaccharide (LPS)-stimulated RAW264.7 cells.


Assuntos
Aminoácidos , Streptomyces , Aminoácidos/química , Streptomyces/metabolismo , Espectroscopia de Ressonância Magnética , Cromatografia Líquida
6.
Int J Urol ; 30(11): 1036-1043, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37522563

RESUMO

OBJECTIVE: To preoperative factors that could predict the persisting storage symptoms after Holmium laser enucleation of the prostate (HoLEP). METHODS: Medical records of 257 patients who underwent HoLEP between December 2014 and January 2021 were reviewed. Participants with a follow-up period exceeding 6 months were included. Preoperative data, including International Prostate Symptom Score (IPSS), uroflowmetry, prostate size, and prostate-specific antigen, were collected. All participants underwent a preoperative urodynamic study. The correlation between perioperative variables and postoperative medication therapy (antimuscarinics or beta-3 agonists) was assessed. RESULTS: Out of 257 participants in the study, 46 (18.6%) were allocated to the medication group, of which 25 (54.3%) initiated medication therapy postoperatively. The medication group showed worse postoperative IPSS storage symptom score and quality of life score compared to the medication-free group (p = 0.048 and p = 0.002, respectively), but no significant differences were observed in complications or operative variables. In the de-novo medication group, patients had lower preoperative Qmax , larger prostate volume, and smaller maximum cystometric capacity (MCC) compared to the persisting medication group (p = 0.020, p = 0.009, and p = 0.008, respectively). Overactive bladder (OAB) history, terminal detrusor overactivity (DO), and IPSS urgency item were identified as possible predictive factors for post-HoLEP medication use. CONCLUSIONS: Preoperative factors such as OAB history, terminal DO, and IPSS urgency item may predict the need for post-HoLEP medication therapy. Further follow-up studies are warranted to understand the characteristics of the de-novo medication group due to the significant discomfort it can cause to patients.


Assuntos
Terapia a Laser , Lasers de Estado Sólido , Hiperplasia Prostática , Ressecção Transuretral da Próstata , Bexiga Urinária Hiperativa , Masculino , Humanos , Próstata/cirurgia , Bexiga Urinária Hiperativa/etiologia , Bexiga Urinária Hiperativa/complicações , Hiperplasia Prostática/complicações , Hiperplasia Prostática/tratamento farmacológico , Hiperplasia Prostática/cirurgia , Lasers de Estado Sólido/uso terapêutico , Qualidade de Vida , Resultado do Tratamento , Ressecção Transuretral da Próstata/efeitos adversos , Terapia a Laser/efeitos adversos
7.
Int J Mol Sci ; 24(3)2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36768389

RESUMO

This study aimed to synthesize and evaluate the anti-inflammatory activity of 3-substituted-indolin-2-one derivatives. Cell viability of 3-substituted-indolin-2-one derivatives was measured with the EZ-Cytox reagent; interleukin (IL)-6, tumor necrosis factor (TNF)-α, and inducible NOS mRNA levels were measured using Taqman qRT-PCR; pro-inflammatory cytokine IL-6 and TNF-α levels were determined using ELISA kits; the phosphorylation of Akt, JNK, ERK, p38, p65, and IκB protein levels were measured by immunoblotting. Among the nineteen 3-substituted-indolin-2-one derivatives synthesized, 3-(3-hydroxyphenyl)-indolin-2-one showed the highest anti-inflammatory activity, inhibiting the nitric oxide production related to inflammation, suppressing the production of TNF-α and IL-6 in a concentration-dependent manner and mRNA expression. Moreover, 3-(3-hydroxyphenyl)-indolin-2-one significantly inhibited lipopolysaccharide (LPS)-induced signal pathways such as the Akt, MAPK, and NF-κB signaling pathways. Our findings revealed that a 3-substituted-indolin-2-one derivative, 3-(3-hydroxyphenyl)-indolin-2-one, possesses excellent anti-inflammatory activity and can be considered for future research.


Assuntos
Interleucina-6 , Fator de Necrose Tumoral alfa , Interleucina-6/genética , Interleucina-6/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Macrófagos/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/metabolismo , NF-kappa B/metabolismo , RNA Mensageiro/metabolismo , Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo
8.
Molecules ; 28(18)2023 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-37764519

RESUMO

Ten traditional herbal extracts effective against diarrhea, infectious diseases, and bacterial activity were selected and analyzed for Peyer's patch cell-mediated intestinal immunomodulatory activity in vitro and in vivo. Among the 10 herbal extracts, Zingiber officinale Rosc. (ZO) extract induced the highest secretion of immunoglobulin A (IgA) and granulocyte macrophage colony-stimulating factor (GM-CSF) in the cells of Peyer's patches. Furthermore, animal experiments showed that IA production was enhanced with the oral administration of ZO extract (100 mg/kg and 300 mg/kg) for 10 days. In addition, 6-, 8-, 10-gingerol, and 6-, 8-, 10-shogaol, the six major index compounds of ZO extract, were analyzed using HPLC. Our study findings confirm the intestinal immunomodulatory activity of ZO extract and lay a strong foundation for future analytical studies aimed at determining the active components of ZO extracts.

9.
Anal Chem ; 94(37): 12884-12889, 2022 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-36069050

RESUMO

In this study, we present a fluidic dispensing system that can automate the sequential fluidic delivery of multiple reagents for lateral flow assays. Highly sensitive assays typically require multiple solution-based sequences, including washing steps and signal amplification. However, implementation of these types of sequences on an automated and highly sensitive point-of-care testing (POCT) platform remains challenging. Our platform consists of two disposable cartridges with reagent chambers and a test strip and an instrument that has a mechanical timer to actuate the cam-follower-gear components. The timer rotation sequentially shifts the position of the chambers and loads the reagents to the test paper strip. The dispensing intervals are controlled at a variation of <1% within a total actuation time of 60 min. Unlike other POCT devices, the timing of fluid delivery in our timer-actuated platform is not dependent on the selection of substrates and reagents, and the unique approach to fluidic delivery results in no reagent overlap or carryover, minimal reagent loss, and highly accurate fluidic timing control for highly sensitive solution-based assays. As a model application, the proposed platform applies a gold enhancement solution to amplify the detection signal and detect prostate-specific antigen with a limit of detection of 86 pg/mL within 27 min. This platform provides an opportunity for solution-based POCT applications with high sensitivity, thereby satisfying the requirement for user-friendly operations in resource-limited settings.


Assuntos
Testes Imunológicos , Antígeno Prostático Específico , Ouro , Humanos , Imunoensaio/métodos , Indicadores e Reagentes , Masculino , Testes Imediatos
10.
Chirality ; 34(7): 999-1007, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35417058

RESUMO

A class of carbonyl extractors, (R)-3, (R)-4, and (R)-5, with nonaxial chirality containing asymmetric carbons has been synthesized and studied for their efficiencies in enantioselective liquid-liquid extraction for underivatized amino acids. The bulky t-butyl ketone extractors, (R)-4 and (R)-5, showed the stereoselectivities ranging 5.4-9.4 of l/d ratio much better than those of the aldehyde extractor, (R)-3, ranging 2.4-5.2. The imine formation rates and yields of the t-butyl ketones were not significantly affected by their bulkiness and even in the absence of resonance-assisted hydrogen bond. This work confirms that a bulky t-butyl ketone can be a good choice in the development of an extractor not only with axial chirality but also with nonaxial chirality for the enantioselective extraction of unprotected amino acids.


Assuntos
Aminoácidos , Cetonas , Aminoácidos/química , Ligação de Hidrogênio , Cetonas/química , Extração Líquido-Líquido , Estereoisomerismo
11.
Int J Clin Oncol ; 27(2): 403-410, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34714459

RESUMO

BACKGROUND: Previous studies have shown a relationship between the occurrence and recurrence of prostate cancer; however, this relationship remains controversial. We investigated the relationship between obesity and biochemical recurrence in patients with prostate cancer. METHODS: Clinicopathological factors were analyzed after dividing the patient population according to the Asian population-specific body mass index (BMI) criteria for "normal" (< 23 kg/m2), "overweight" (23-27.5 kg/m2), and "obese" (≥ 27.5 kg/m2). Among the 389 patients included in this study, 108 were classified as normal, while 227 and 54 patients were classified as overweight and obese, respectively. The relationships between clinicopathological factors and biochemical recurrence were analyzed by univariate and multivariate Cox ≤ proportional hazard models. Biochemical recurrence was defined as two consecutive prostate-specific antigen (PSA) measurements ≥ 0.2 ng/mL. RESULTS: In univariate analysis, the categorical variables of "overweight" and "obese" were significant prognostic factors for biochemical recurrence. In multivariate analysis models including PSA density [hazard ratio (HR) 1.8, p = 0.01], extraprostatic extension (HR 2.0, p < 0.001), Gleason score (HR 1.7, p = 0.01), surgical margin positivity (HR 2.46, p < 0.001), and lymphovascular invasion (HR 2.53, p < 0.001), the categorical variables of "overweight" (HR 1.6, p = 0.03) and "obese" (HR 1.76, p = 0.035) were prognostic factors for biochemical recurrence. CONCLUSION: The obesity status of patients with prostate cancer as "overweight" and "obese" was a risk factor for biochemical recurrence after adjusting for other clinicopathological factors.


Assuntos
Sobrepeso , Neoplasias da Próstata , Humanos , Masculino , Recidiva Local de Neoplasia , Obesidade/complicações , Sobrepeso/complicações , Antígeno Prostático Específico , Prostatectomia , Neoplasias da Próstata/cirurgia , Estudos Retrospectivos , Fatores de Risco
12.
J Korean Med Sci ; 37(22): e78, 2022 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-35668683

RESUMO

BACKGROUND: We analyzed the differences between clinical characteristics and computed tomography (CT) findings in patients with coronavirus disease 2019 (COVID-19) to establish potential relationships with mediastinal lymphadenopathy and clinical outcomes. METHODS: We compared the clinical characteristics and CT findings of COVID-19 patients from a nationwide multicenter cohort who were grouped based on the presence or absence of mediastinal lymphadenopathy. Differences between clinical characteristics and CT findings in these groups were analyzed. Univariate and multivariate analyses were performed to determine the impact of mediastinal lymphadenopathy on clinical outcomes. RESULTS: Of the 344 patients included in this study, 53 (15.4%) presented with mediastinal lymphadenopathy. The rate of diffuse alveolar damage pattern pneumonia and the visual CT scores were significantly higher in patients with mediastinal lymphadenopathy than in those without (P < 0.05). A positive correlation between the number of enlarged mediastinal lymph nodes and visual CT scores was noted in patients with mediastinal lymphadenopathy (Spearman's ρ = 0.334, P < 0.001). Multivariate analysis showed that mediastinal lymphadenopathy was independently associated with a higher risk of intensive care unit (ICU) admission (odds ratio, 95% confidence interval; 3.25, 1.06-9.95) but was not significantly associated with an increased risk of in-hospital death in patients with COVID-19. CONCLUSION: COVID-19 patients with mediastinal lymphadenopathy had a larger extent of pneumonia than those without. Multivariate analysis adjusted for clinical characteristics and CT findings revealed that the presence of mediastinal lymphadenopathy was significantly associated with ICU admission.


Assuntos
COVID-19 , Linfadenopatia , COVID-19/complicações , Estudos de Coortes , Mortalidade Hospitalar , Humanos , Linfadenopatia/diagnóstico por imagem , Linfadenopatia/patologia , Estudos Retrospectivos
13.
Sensors (Basel) ; 22(23)2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36501854

RESUMO

We proposed the statistical misalignment model and the power-efficient configuration of transceivers for bi-directional multi-input and multi-output (MIMO) based vertical free space optical (FSO) links. Spatial diversity based MIMO FSO systems could be used to mitigate atmospheric fading issues. However, the increased number of channels can cause additional pointing error in pointing, acquisition and tracking (PAT) systems. The statistical misalignment model for detecting misalignment error is derived from the multiple transceivers. For the bi-directional characteristics of non-terrestrial back-haul networks, transmission performance is down-leveled to the worse in the asymmetric MIMO configuration of transceivers. The symmetric structure can mitigate the effect of increased pointing error to improve transmission performance. The proposed technique can be applied to the design of power-efficient FSO systems for non-terrestrial wireless back-haul networks.

14.
Sensors (Basel) ; 22(14)2022 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-35891072

RESUMO

A proposed prototype of a 10-bit 1 MS/s single-ended asynchronous Successive Approximation Register (SAR) Analog-to-Digital Converter (ADC) with an on-chip bandgap reference voltage generator is fabricated with 130 nm technology. To optimize the power consumption, static, and dynamic performance, several techniques have been proposed. A dual-path bootstrap switch was proposed to increase the linearity sampling. The Voltage Common Mode (VCM)-based Capacitive Digital-to-Analog Converter (CDAC) switching technique was implemented for the CDAC part to alleviate the switching energy problem of the capacitive DAC. The proposed architecture of the two-stage dynamic latch comparator provides high speed and low power consumption. Moreover, to achieve faster bit conversion with an efficient time sequence, asynchronous SAR logic with an internally generated clock is implemented, which avoids the requirement of a high-frequency external clock, as all conversions are carried out in a single clock cycle. The proposed error amplifier-based bandgap reference voltage generator provides a stable reference voltage to the ADC for practical implementation. The measurement results of the proposed SAR ADC, including an on-chip bandgap reference voltage generator, show an Effective Number of Bits (ENOB) of 9.49 bits and Signal-to-Noise and Distortion Ratio (SNDR) of 58.88 dB with 1.2 V of power supply while operating with a sampling rate of 1 MS/s.

15.
Sensors (Basel) ; 22(6)2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-35336447

RESUMO

This paper presents a Dual-Port-15-Throw (DP15T) antenna switch module (ASM) Radio Frequency (RF) switch implemented by a branched antenna technique which has a high linearity for wireless communications and various frequency bands, including a low- frequency band of 617-960 MHz, a mid-frequency band of 1.4-2.2 GHz, and a high-frequency band of 2.3-2.7 GHz. To obtain an acceptable Insertion Loss (IL) and provide a consistent input for each throw, a branched antenna technique is proposed that distributes a unified magnetic field at the inputs of the throws. The other role of the proposed antenna is to increase the inductance effects for the closer ports to the antenna pad in order to decrease IL at higher frequencies. The module is enhanced by two termination modes for each antenna path to terminate the antenna when the switch is not operating. The module is fabricated in the silicon-on-insulator CMOS process. The measurement results show a maximum IMD2 and IMD3 of -100 dBm, while for the second and third harmonics the maximum value is -89 dBc. The module operates with a maximum power handling of 35 dBm. Experimental results show a maximum IL of 0.34 and 0.92 dB and a minimum isolation of 49 dB and 35.5 dB at 0.617 GHz and 2.7 GHz frequencies, respectively. The module is implemented in a compact way to occupy an area of 0.74 mm2. The termination modes show a second harmonic of 75 dBc, which is desirable.

16.
Int J Mol Sci ; 23(16)2022 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-36012363

RESUMO

Crystalline metal-organic frameworks (MOFs) are extensively used in areas such as gas storage and small-molecule drug delivery. Although Cu-BTC (1, MOF-199, BTC: benzene-1,3,5-tricarboxylate) has versatile applications, its NO storage and release characteristics are not amenable to therapeutic usage. In this work, micro-sized Cu-BTC was prepared solvothermally and then processed by ball-milling to prepare nano-sized Cu-BTC (2). The NO storage and release properties of the micro- and nano-sized Cu-BTC MOFs were morphology dependent. Control of the hydration degree and morphology of the NO delivery vehicle improved the NO release characteristics significantly. In particular, the nano-sized NO-loaded Cu-BTC (NO⊂nano-Cu-BTC, 4) released NO at 1.81 µmol·mg-1 in 1.2 h in PBS, which meets the requirements for clinical usage. The solid-state structural formula of NO⊂Cu-BTC was successfully determined to be [CuC6H2O5]·(NO)0.167 through single-crystal X-ray diffraction, suggesting no structural changes in Cu-BTC upon the intercalation of 0.167 equivalents of NO within the pores of Cu-BTC after NO loading. The structure of Cu-BTC was also stably maintained after NO release. NO⊂Cu-BTC exhibited significant antibacterial activity against six bacterial strains, including Gram-negative and positive bacteria. NO⊂Cu-BTC could be utilized as a hybrid NO donor to explore the synergistic effects of the known antibacterial properties of Cu-BTC.


Assuntos
Cobre , Óxido Nítrico , Antibacterianos/farmacologia , Benzeno , Cobre/química , Ácidos Tricarboxílicos
17.
J Biol Chem ; 295(33): 11584-11601, 2020 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-32565424

RESUMO

The biochemical activities of dirigent proteins (DPs) give rise to distinct complex classes of plant phenolics. DPs apparently began to emerge during the aquatic-to-land transition, with phylogenetic analyses revealing the presence of numerous DP subfamilies in the plant kingdom. The vast majority (>95%) of DPs in these large multigene families still await discovery of their biochemical functions. Here, we elucidated the 3D structures of two pterocarpan-forming proteins with dirigent-like domains. Both proteins stereospecifically convert distinct diastereomeric chiral isoflavonoid precursors to the chiral pterocarpans, (-)- and (+)-medicarpin, respectively. Their 3D structures enabled comparisons with stereoselective lignan- and aromatic terpenoid-forming DP orthologs. Each protein provides entry into diverse plant natural products classes, and our experiments suggest a common biochemical mechanism in binding and stabilizing distinct plant phenol-derived mono- and bis-quinone methide intermediates during different C-C and C-O bond-forming processes. These observations provide key insights into both their appearance and functional diversification of DPs during land plant evolution/adaptation. The proposed biochemical mechanisms based on our findings provide important clues to how additional physiological roles for DPs and proteins harboring dirigent-like domains can now be rationally and systematically identified.


Assuntos
Glycyrrhiza/metabolismo , Ligases/metabolismo , Pisum sativum/metabolismo , Proteínas de Plantas/metabolismo , Pterocarpanos/metabolismo , Cristalografia por Raios X , Glycyrrhiza/química , Indolquinonas/metabolismo , Ligases/química , Simulação de Acoplamento Molecular , Pisum sativum/química , Proteínas de Plantas/química , Conformação Proteica , Domínios Proteicos , Multimerização Proteica
18.
Mol Cancer ; 20(1): 78, 2021 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-34039363

RESUMO

BACKGROUND: Distant metastasis is the major cause of death in patients with colorectal cancer (CRC). Previously, we identified KITENIN as a metastasis-enhancing gene and suggested that the oncogenic KITENIN complex is involved in metastatic dissemination of KITENIN-overexpressing CRC cells. Here, we attempted to find substances targeting the KITENIN complex and test their ability to suppress distant metastasis of CRC. METHODS: We screened a small-molecule compound library to find candidate substances suppressing the KITENIN complex in CRC cells. We selected a candidate compound and examined its effects on the KITENIN complex and distant metastasis through in vitro assays, a molecular docking model, and in vivo tumor models. RESULTS: Among several compounds, we identified DKC1125 (Disintegrator of KITENIN Complex #1125) as the best candidate. DKC1125 specifically suppressed KITENIN gain of function. After binding KH-type splicing regulatory protein (KSRP), DKC1125 degraded KITENIN and Dvl2 by recruiting RACK1 and miRNA-124, leading to the disintegration of the functional KITENIN-KSRP-RACK1-Dvl2 complex. A computer docking model suggested that DKC1125 specifically interacted with the binding pocket of the fourth KH-domain of KSRP. KITENIN-overexpressing CRC cells deregulated certain microRNAs and were resistant to 5-fluorouracil, oxaliplatin, and cetuximab. DKC1125 restored sensitivity to these drugs by normalizing expression of the deregulated microRNAs, including miRNA-124. DKC1125 effectively suppressed colorectal liver metastasis in a mouse model. Interestingly, the combination of DKC1125 with 5-fluorouracil suppressed metastasis more effectively than either drug alone. CONCLUSION: DKC1125 targets the KITENIN complex and could therefore be used as a novel therapeutic to suppress liver metastasis in CRC expressing high levels of KITENIN.


Assuntos
Antineoplásicos/farmacologia , Proteínas de Transporte/efeitos dos fármacos , Neoplasias Colorretais/patologia , Proteínas de Membrana/efeitos dos fármacos , Proteínas de Ligação a RNA/efeitos dos fármacos , Proteínas de Ligação a RNA/metabolismo , Transativadores/efeitos dos fármacos , Transativadores/metabolismo , Animais , Antineoplásicos/química , Descoberta de Drogas , Humanos , Camundongos , Simulação de Acoplamento Molecular , Metástase Neoplásica/patologia , Proteínas de Ligação a RNA/antagonistas & inibidores , Transativadores/antagonistas & inibidores
19.
Neurourol Urodyn ; 40(6): 1569-1575, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34036656

RESUMO

AIMS: To investigate the association of nocturia with the prevalence of cardiovascular disease (CVD) using the National Health and Nutrition Examination Survey (NHANES) data. METHODS: Among the 40 790 individuals who participated in NHANES from 2005 to 2012, 14 114 adults were analyzed in this study. A participant was considered to have nocturia if they have two or more voiding episodes nightly. In addition, participants with nocturia more than four times in a day were considered to have severe nocturia. A multivariate logistic regression analysis with adjustment for confounding variables, including age, sex, race, body mass index (BMI), smoking status, alcohol consumption, sleeping time, dyslipidemia, hypertension, and diabetes mellitus was performed with 1:1 propensity score matching (PSM). RESULTS: Nocturia occurred in 4610 individuals (32.7%). The prevalence of CVD was significantly higher in men, older individuals, those with higher BMI, smokers, and those with diabetes, hypertension, and hyperlipidemia. There was also a significantly higher prevalence of nocturia in the participants with CVD. Multivariate analysis showed that odds ratios (ORs) of mild and severe nocturia for CVD were 1.23 (95% confidence interval [CI]: 1.08-1.39) and 1.74 (95% CI: 1.39-2.17), respectively. After 1:1 PSM, the ORs of mild and severe nocturia were 1.27 (95% CI: 1.10-1.48) and 1.73 (95% CI: 1.33-2.26), respectively, showing statistical significance. CONCLUSION: Data from the NHANES indicate that CVD was significantly associated with the prevalence of nocturia, after taking major confounding factors into account. Furthermore, the risk for CVD increases with increasing nocturia severity.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus , Noctúria , Adulto , Doenças Cardiovasculares/epidemiologia , Humanos , Masculino , Noctúria/epidemiologia , Inquéritos Nutricionais , Prevalência
20.
Am J Emerg Med ; 50: 120-125, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34343760

RESUMO

OBJECTIVE: Clinical research on drug intoxication is necessary for appropriate action in emergency departments (EDs). However, currently, there are no evident biomarkers for predicting adverse events (AEs) in patients with drug intoxication. We aimed to evaluate the prognostic value of serum lactate concentrations and lactate kinetics for AEs such as cardiogenic or respiratory failure in patients admitted to the ED with acute drug overdose. METHODS: We conducted a single-center retrospective study by reviewing the prospective suicide registry of patients visiting the ED. The primary outcome was composite AEs at any point during the ED visit or hospital stay. RESULTS: A total of 566 patients with acute drug overdose were enrolled in this study. Of these, 62 patients had AEs, whereas 363 patients did not, yielding an AE rate of 14.6%. The median 0 h lactate concentrations in the AE and non-AE groups were 2.7 [2.1-5.1] mmol/L and 2.1 [1.4-2.9] mmol/L, respectively (p < 0.001). The median 6 h lactate concentrations in the AE and non-AE groups were 2.0 [1.5-3.9] mmol/L and 1.3 [0.9-2.2] mmol/L, respectively (p < 0.001). The area under the curve of lactate at 0 h for predicting AEs was 0.705 (95% CI: 0.659-0.748). The optimal lactate cutoff point was 4.2 mmol/L (37.1% sensitivity, 92.8% specificity). Multivariable analysis using a stepwise backward method showed that the 0 h lactate concentration was associated with AEs in acute drug intoxication after adjusting for confounders (adjusted OR of 0 h lactate, 1.47; 95% CI, 1.23-1.77). However, the 6 h lactate concentrations, lactate clearance, and delta lactate levels did not predict the outcomes. CONCLUSION: Lactate concentrations and kinetics in patients admitted to the ED with an acute drug overdose exhibited limited prognostic utility in predicting AEs and should be interpreted with caution when considered for clinical decision-making.


Assuntos
Overdose de Drogas/sangue , Serviço Hospitalar de Emergência , Lactatos/sangue , Adulto , Feminino , Humanos , Lactatos/farmacocinética , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Sistema de Registros , Estudos Retrospectivos
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