Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 78
Filtrar
Más filtros

Banco de datos
País/Región como asunto
Tipo del documento
Intervalo de año de publicación
1.
Anal Chem ; 96(29): 11690-11698, 2024 07 23.
Artículo en Inglés | MEDLINE | ID: mdl-38991018

RESUMEN

Recent advances in single-cell proteomics have solved many bottlenecks, such as throughput, sample recovery, and scalability via nanoscale sample handling. In this study, we aimed for a sensitive mass spectrometry (MS) analysis capable of handling single cells with a conventional mass spectrometry workflow without additional equipment. We achieved seamless cell lysis and TMT labeling in a micro-HOLe Disc (microHOLD) by developing a mass-compatible single solution based on a zwitterionic detergent and a catalyst for single-cell lysis and tandem mass tag labeling without a heat incubation step. This method was developed to avoid peptide loss by surface adsorption and buffer or tube changes by collecting tandem mass tag-labeled peptide through microholes placed in the liquid chromatography injection vials in a single solution. We successfully applied the microHOLD single-cell proteomics method for the analysis of proteome reprogramming in hormone-sensitive prostate cells to develop castration-resistant prostate cancer cells. This novel single-cell proteomics method is not limited by cutting-edge nanovolume handling equipment and achieves high throughput and ultrasensitive proteomics analysis of limited samples, such as single cells.


Asunto(s)
Detergentes , Proteómica , Análisis de la Célula Individual , Proteómica/métodos , Humanos , Detergentes/química , Catálisis , Línea Celular Tumoral , Espectrometría de Masas en Tándem
2.
J Cell Mol Med ; 26(20): 5122-5134, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-36071453

RESUMEN

Nerve injury-induced protein 1 (Ninjurin1, Ninj1) is a membrane protein that mediates cell adhesion. The role of Ninj1 during inflammatory response has been widely investigated in macrophages and endothelial cells. Ninj1 is expressed in various tissues, and the liver also expresses high levels of Ninj1. Although the hepatic upregulation of Ninj1 has been reported in human hepatocellular carcinoma and septic mice, little is known of its function during the pathogenesis of liver diseases. In the present study, the role of Ninj1 in liver inflammation was explored using lipopolysaccharide (LPS)/D-galactosamine (D-gal)-induced acute liver failure (ALF) model. When treated with LPS/D-gal, conventional Ninj1 knock-out (KO) mice exhibited a mild inflammatory phenotype as compared with wild-type (WT) mice. Unexpectedly, myeloid-specific Ninj1 KO mice showed no attenuation of LPS/D-gal-induced liver injury. Whereas, Ninj1 KO primary hepatocytes were relatively insensitive to TNF-α-induced caspase activation as compared with WT primary hepatocytes. Also, Ninj1 knock-down in L929 and AML12 cells and Ninj1 KO in HepG2 cells ameliorated TNF-α-mediated apoptosis. Consistent with in vitro results, hepatocyte-specific ablation of Ninj1 in mice alleviated LPS/D-gal-induced ALF. Summarizing, our in vivo and in vitro studies show that lack of Ninj1 in hepatocytes diminishes LPS/D-gal-induced ALF by alleviating TNF-α/TNFR1-induced cell death.


Asunto(s)
Moléculas de Adhesión Celular Neuronal , Galactosamina , Fallo Hepático Agudo , Factores de Crecimiento Nervioso , Animales , Apoptosis , Caspasas/metabolismo , Moléculas de Adhesión Celular Neuronal/genética , Moléculas de Adhesión Celular Neuronal/metabolismo , Células Endoteliales/metabolismo , Hepatocitos/metabolismo , Humanos , Lipopolisacáridos , Hígado/metabolismo , Fallo Hepático Agudo/inducido químicamente , Fallo Hepático Agudo/genética , Fallo Hepático Agudo/metabolismo , Ratones , Ratones Noqueados , Factores de Crecimiento Nervioso/genética , Factores de Crecimiento Nervioso/metabolismo , Receptores Tipo I de Factores de Necrosis Tumoral , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo
3.
Int J Mol Sci ; 23(19)2022 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-36232665

RESUMEN

The global burden of chronic kidney disease is increasing, and the majority of these diseases are progressive. Special site-targeted drugs are emerging as alternatives to traditional drugs. Oligonucleotides (ODNs) have been proposed as effective therapeutic tools in specific molecular target therapies for several diseases. We designed ring-type non-coding RNAs (ncRNAs), also called mTOR ODNs to suppress mammalian target rapamycin (mTOR) translation. mTOR signaling is associated with excessive cell proliferation and fibrogenesis. In this study, we examined the effects of mTOR suppression on chronic renal injury. To explore the regulation of fibrosis and inflammation in unilateral ureteral obstruction (UUO)-induced injury, we injected synthesized ODNs via the tail vein of mice. The expression of inflammatory-related markers (interleukin-1ß, tumor necrosis factor-α), and that of fibrosis (α-smooth muscle actin, fibronectin), was decreased by synthetic ODNs. Additionally, ODN administration inhibited the expression of autophagy-related markers, microtubule-associated protein light chain 3, Beclin1, and autophagy-related gene 5-12. We confirmed that ring-type ODNs inhibited fibrosis, inflammation, and autophagy in a UUO mouse model. These results suggest that mTOR may be involved in the regulation of autophagy and fibrosis and that regulating mTOR signaling may be a therapeutic strategy against chronic renal injury.


Asunto(s)
Insuficiencia Renal Crónica , Obstrucción Ureteral , Actinas/metabolismo , Animales , Autofagia/genética , Beclina-1/metabolismo , Modelos Animales de Enfermedad , Fibronectinas/metabolismo , Fibrosis , Inflamación/metabolismo , Interleucina-1beta/metabolismo , Riñón/metabolismo , Mamíferos/metabolismo , Ratones , Proteínas Asociadas a Microtúbulos/metabolismo , Oligonucleótidos/farmacología , ARN no Traducido/metabolismo , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/tratamiento farmacológico , Insuficiencia Renal Crónica/genética , Sirolimus/farmacología , Sirolimus/uso terapéutico , Serina-Treonina Quinasas TOR/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Obstrucción Ureteral/complicaciones , Obstrucción Ureteral/genética , Obstrucción Ureteral/metabolismo
4.
Molecules ; 27(3)2022 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-35164031

RESUMEN

Renal fibrosis is a common process of various kidney diseases. Autophagy is an important cell biology process to maintain cellular homeostasis. In addition, autophagy is involved in the pathogenesis of various renal disease, including acute kidney injury, glomerular diseases, and renal fibrosis. However, the functional role of autophagy in renal fibrosis remains poorly unclear. The mammalian target of rapamycin (mTOR) plays a negative regulatory role in autophagy. Signal transducer and activator of transcription 3 (STAT3) is an important intracellular signaling that may regulate a variety of inflammatory responses. In addition, STAT3 regulates autophagy in various cell types. Thus, we synthesized the mTOR/STAT3 oligodeoxynucleotide (ODN) to regulate the autophagy. The aim of this study was to investigate the beneficial effect of mTOR/STAT3 ODN via the regulation of autophagy appearance on unilateral ureteral obstruction (UUO)-induced renal fibrosis. This study showed that UUO induced inflammation, tubular atrophy, and tubular interstitial fibrosis. However, mTOR/STAT3 ODN suppressed UUO-induced renal fibrosis and inflammation. The autophagy markers have no statistically significant relation, whereas mTOR/STAT3 ODN suppressed the apoptosis in tubular cells. These results suggest the possibility of mTOR/STAT3 ODN for preventing renal fibrosis. However, the role of mTOR/STAT3 ODN on autophagy regulation needs to be further investigated.


Asunto(s)
Autofagia/efectos de los fármacos , Fibrosis/prevención & control , Riñón/lesiones , Oligodesoxirribonucleótidos/antagonistas & inhibidores , Factor de Transcripción STAT3/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Animales , Modelos Animales de Enfermedad
5.
FASEB J ; 34(1): 333-349, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31914629

RESUMEN

Kidney fibrosis is a common process of various kidney diseases leading to end-stage renal failure irrespective of etiology. Myofibroblasts are crucial mediators in kidney fibrosis through production of extracellular matrix (ECM), but their origin has not been clearly identified. Many study proposed that epithelial and endothelial cells become myofibroblasts by epithelial dedifferentiation and endothelial-mesenchymal transition (EndoMT). TGF-ß1/Smad signaling plays a crucial role in partly epithelial-mensencymal transition (EMT) and EndoMT. Thus, we designed the TGF-ß1/Smad oligodeoxynucleotide (ODN), a synthetic short DNA containing complementary sequence for Smad transcription factor and TGF-ß1 mRNA. Therefore, this study investigated the anti-fibrotic effect of synthetic TGF-ß1/Smad ODN on UUO-induced kidney fibrosis in vivo model and TGF-ß1-induced in vitro model. To examine the effect of TGF-ß1/Smad ODN, we performed various experiments to evaluate kidney fibrosis. The results showed that UUO induced inflammation, ECM accumulation, epithelial dedifferentiation and EndoMT processes, and tubular atrophy. However, synthetic TGF-ß1/Smad ODN significantly suppressed UUO-induced fibrosis. Furthermore, synthetic ODN attenuated TGF-ß1-induced epithelial dedifferentiation and EndoMT program via blocking TGF-ß1/Smad signaling. In conclusion, this study demonstrated that administration of synthetic TGF-ß1/Smad ODN attenuates kidney fibrosis, epithelial dedifferentiation, and EndoMT processes. The findings propose the possibility of synthetic ODN as a new effective therapeutic tool for kidney fibrosis.


Asunto(s)
Desdiferenciación Celular , Células Epiteliales/patología , Transición Epitelial-Mesenquimal , Fibrosis/prevención & control , Enfermedades Renales/prevención & control , Oligodesoxirribonucleótidos/farmacología , Proteínas Smad/genética , Factor de Crecimiento Transformador beta1/genética , Animales , Células Epiteliales/metabolismo , Fibrosis/genética , Fibrosis/patología , Técnicas In Vitro , Enfermedades Renales/genética , Enfermedades Renales/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Obstrucción Ureteral/genética , Obstrucción Ureteral/patología , Obstrucción Ureteral/prevención & control
6.
J Nanobiotechnology ; 19(1): 458, 2021 Dec 28.
Artículo en Inglés | MEDLINE | ID: mdl-34963490

RESUMEN

Bio-inspired Topographically Mediated Surfaces (TMSs) based on high aspect ratio nanostructures have recently been attracting significant attention due to their pronounced antimicrobial properties by mechanically disrupting cellular processes. However, scalability of such surfaces is often greatly limited, as most of them rely on micro/nanoscale fabrication techniques. In this report, a cost-effective, scalable, and versatile approach of utilizing diamond nanotechnology for producing TMSs, and using them for limiting the spread of emerging infectious diseases, is introduced. Specifically, diamond-based nanostructured coatings are synthesized in a single-step fabrication process with a densely packed, needle- or spike-like morphology. The antimicrobial proprieties of the diamond nanospike surface are qualitatively and quantitatively analyzed and compared to other surfaces including copper, silicon, and even other diamond surfaces without the nanostructuring. This surface is found to have superior biocidal activity, which is confirmed via scanning electron microscopy images showing definite and widespread destruction of E. coli cells on the diamond nanospike surface. Consistent antimicrobial behavior is also observed on a sample prepared seven years prior to testing date.


Asunto(s)
Antibacterianos/química , Materiales Biocompatibles Revestidos/química , Diamante/química , Nanoestructuras/química , Antibacterianos/farmacología , Materiales Biocompatibles Revestidos/farmacología , Cobre/química , Cobre/farmacología , Diamante/farmacología , Escherichia coli/efectos de los fármacos , Escherichia coli/crecimiento & desarrollo , Nanoestructuras/ultraestructura , Nanotecnología , Propiedades de Superficie
7.
Int J Mol Sci ; 22(12)2021 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-34204534

RESUMEN

Leaky gut is a condition of increased paracellular permeability of the intestine due to compromised tight junction barriers. In recent years, this affliction has drawn the attention of scientists from different fields, as a myriad of studies prosecuted it to be the silent culprit of various immune diseases. Due to various controversies surrounding its culpability in the clinic, approaches to leaky gut are restricted in maintaining a healthy lifestyle, avoiding irritating factors, and practicing alternative medicine, including the consumption of supplements. In the current study, we investigate the tight junction-modulating effects of processed Aloe vera gel (PAG), comprising 5-400-kD polysaccharides as the main components. Our results show that oral treatment of 143 mg/kg PAG daily for 10 days improves the age-related leaky gut condition in old mice, by reducing their individual urinal lactulose/mannitol (L/M) ratio. In concordance with in vivo experiments, PAG treatment at dose 400 µg/mL accelerated the polarization process of Caco-2 monolayers. The underlying mechanism was attributed to enhancement in the expression of intestinal tight junction-associated scaffold protein zonula occludens (ZO)-1 at the translation level. This was induced by activation of the MAPK/ERK signaling pathway, which inhibits the translation repressor 4E-BP1. In conclusion, we propose that consuming PAG as a complementary food has the potential to benefit high-risk patients.


Asunto(s)
Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Preparaciones de Plantas/farmacología , Uniones Estrechas/efectos de los fármacos , Uniones Estrechas/metabolismo , Animales , Biomarcadores , Línea Celular , Permeabilidad de la Membrana Celular , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Femenino , Humanos , Masculino , Ratones , Modelos Biológicos , Transducción de Señal , Proteínas de Uniones Estrechas/genética , Proteínas de Uniones Estrechas/metabolismo
8.
Phytother Res ; 34(1): 126-138, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31512302

RESUMEN

Betula platyphylla (BP) is frequently administered in the treatment of various human diseases, including cancers. This study was undertaken to investigate the pharmacological function of the active components in BP and the underlying mechanism of its chemotherapeutic effects in human lung cancer cells. We observed that BP extracts and 1,7-bis(4-hydroxyphenyl)-4-hepten-3-one (BE1), one of the components of BP, effectively decreased the cell viability of several lung cancer cell lines. BE1-treated cells exhibited apoptosis induction and cell cycle arrest at the G2/M phase. Further examination demonstrated that BE1 treatment resulted in suppression of autophagy, as evidenced by increased protein expression levels of both LC3 II and p62/SQSTM1. Interestingly, the pharmacological induction of autophagy with rapamycin remarkably reduced the BE1-induced apoptosis, indicating that apoptosis induced by BE1 was associated with autophagy inhibition. Our data also demonstrated that BE1 exposure activated the p38 pathway resulting in regulation of the pro-apoptotic activity. Taken together, we believe that BE1 is a potential anticancer agent for human lung cancer, which exerts its effect by enhancing apoptosis via regulating autophagy and the p38 pathway.


Asunto(s)
Betula/química , Neoplasias Pulmonares/tratamiento farmacológico , Apoptosis , Autofagia , Línea Celular Tumoral , Proliferación Celular , Humanos , Transfección
9.
Int J Mol Sci ; 21(8)2020 Apr 13.
Artículo en Inglés | MEDLINE | ID: mdl-32295041

RESUMEN

Many studies have made clear that most of the genome is transcribed into noncoding RNAs, including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), both of which can affect different cell features. LncRNAs are long heterogeneous RNAs that regulate gene expression and a variety of signaling pathways involved in cellular homeostasis and development. Several studies have demonstrated that lncRNA is an important class of regulatory molecule that can be targeted to change cellular physiology and function. The expression or dysfunction of lncRNAs is closely related to various hereditary, autoimmune, and metabolic diseases, and tumors. Specifically, recent work has shown that lncRNAs have an important role in kidney pathogenesis. The effective roles of lncRNAs have been recognized in renal ischemia, injury, inflammation, fibrosis, glomerular diseases, renal transplantation, and renal-cell carcinoma. The present review focuses on the emerging role and function of lncRNAs in the pathogenesis of kidney inflammation and fibrosis as novel essential regulators. Although lncRNAs are important players in the initiation and progression of many pathological processes, their role in renal fibrosis remains unclear. This review summarizes the current understanding of lncRNAs in the pathogenesis of kidney fibrosis and elucidates the potential role of these novel regulatory molecules as therapeutic targets for the clinical treatment of kidney inflammation and fibrosis.


Asunto(s)
Enfermedades Renales/genética , ARN Largo no Codificante/genética , Animales , Biomarcadores , Fibrosis , Regulación de la Expresión Génica , Humanos , Enfermedades Renales/terapia , Factores de Transcripción/metabolismo
10.
Int J Mol Sci ; 21(2)2020 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-31963519

RESUMEN

Nerve injury-induced protein 1 (Ninjurin1, Ninj1) is a cell-surface adhesion molecule that regulates cell migration and attachment. This study demonstrates the increase in Ninj1 protein expression during development of intestinal inflammation. Ninj1-deficient mice exhibited significantly attenuated bodyweight loss, shortening of colon length, intestinal inflammation, and lesser pathological lesions than wild-type mice. Although more severe inflammation and serious lesions are observed in wild-type mice than Ninj1-deficient mice, there were no changes in the numbers of infiltrating macrophages in the inflamed tissues obtained from WT and Ninj1-deficient mice. Ninj1 expression results in activation of macrophages, and these activated macrophages secrete more cytokines and chemokines than Ninj1-deficient macrophages. Moreover, mice with conditional deletion of Ninj1 in myeloid cells (Ninj1fl/fl; Lyz-Cre+) alleviated experimental colitis compared with wild-type mice. In summary, we propose that the Ninj1 in myeloid cells play a pivotal function in intestinal inflammatory conditions.


Asunto(s)
Moléculas de Adhesión Celular Neuronal/fisiología , Adhesión Celular , Movimiento Celular , Colitis/prevención & control , Inflamación/prevención & control , Enfermedades Intestinales/prevención & control , Células Mieloides/metabolismo , Factores de Crecimiento Nervioso/fisiología , Animales , Células Cultivadas , Colitis/etiología , Colitis/metabolismo , Colitis/patología , Femenino , Inflamación/etiología , Inflamación/metabolismo , Inflamación/patología , Enfermedades Intestinales/etiología , Enfermedades Intestinales/metabolismo , Enfermedades Intestinales/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Transducción de Señal
11.
Biochem Biophys Res Commun ; 513(1): 49-55, 2019 05 21.
Artículo en Inglés | MEDLINE | ID: mdl-30935693

RESUMEN

Liver fibrosis is characterized by formation of scar tissue in the liver. The role of STAT3 signaling has been implicated on activating hepatic stellate cells (HSC) to myofibroblast-like cells in liver fibrosis. Major factors that activate STAT3 signaling are TGF-ß1 and IL-6, which are upregulated in the liver in patients afflicted with liver fibrosis. Recent reports indicate that not only IL-6, but also the non-canonical signaling pathway of TGF-ß1 is associated with STAT3 signaling. In this study, we demonstrate a new function of the STAT3 inhibitor, STX-0119, in liver fibrosis. STX-0119 is an inhibitor of STAT3 dimerization, which is required for nuclear localization of STAT3. We first investigated the anti-fibrotic effect of STX-0119 in in vitro experiments. Exposure to STX-0119 inhibited the nuclear localization of STAT3 in HSCs, resulting in decreased expression of its target genes, such as col1a1 and αSMA. In addition, STX-0119 also inhibited the TGF-ß1/IL-6-induced activation of HSCs. Next, we examined the in vivo effect of STX-0119 in the liver fibrosis mouse model using thioacetamide (TAA) and carbon tetrachloride (CCl4). STX-0119 attenuated the TAA-induced liver fibrosis by inhibiting activation of HSCs to myofibroblast-like cells. Consistent with the in vivo results using TAA-induced liver fibrosis model, treatment of STX-0119 similarly attenuated CCl4-induced liver fibrosis. In conclusion, we believe that STX-0119 inhibits the development of liver fibrosis by blocking the activation of hepatic stellate cells. These results indicate that STX-0119 is a potential new therapeutic strategy to prevent disease progression to cirrhosis.


Asunto(s)
Células Estrelladas Hepáticas/efectos de los fármacos , Cirrosis Hepática/tratamiento farmacológico , Oxadiazoles/uso terapéutico , Quinolinas/uso terapéutico , Factor de Transcripción STAT3/antagonistas & inhibidores , Animales , Proliferación Celular/efectos de los fármacos , Colágeno/análisis , Células Estrelladas Hepáticas/patología , Cirrosis Hepática/patología , Masculino , Ratones , Ratones Endogámicos C57BL
12.
Pediatr Cardiol ; 37(2): 290-4, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26433938

RESUMEN

Indications of sutureless repair (SR) for pulmonary vein anomalies have evolved from re-operational SR for pulmonary vein stenosis after the repair of total anomalous pulmonary venous drainage (TAPVD) to primary SR for TAPVD associated with right atrial isomerism or isolated TAPVD with small individual pulmonary veins (IPVs) and an unfavorable pulmonary vein anatomy. We sought to determine whether small IPVs outgrow somatic growth after primary SR. Between 2004 and 2013, 21 children underwent primary SR for TAPVD: 13 with a functionally single ventricle, 11 with right atrial isomerism, six with isolated TAPVD, and 13 with a pulmonary venous obstruction. TAPVD types were supracardiac in nine, infracardiac in 10, and mixed in two. Utilizing cardiac computed tomography (CT), the maximal diameter of each IPV was measured, and pulmonary vein index (PVI, summation of cross-sectional areas of all four IPVs divided by body surface area) was calculated. There were five early deaths after SR. Among survivors, 10 had both preoperative and postoperative cardiac CT at a 3.6-month median interval. On postoperative cardiac CT, IPVs were patent in all patients except one who developed a left lower pulmonary vein obstruction. There was a 71 ± 48 % postoperative increase in the actual diameter of all four IPVs, and PVI increased significantly from 215 ± 55 to 402 ± 117 mm(2)/m(2) (P value = 0.005). IPVs outgrew somatic growth after primary SR of TAPVD. Primary SR may be a useful measure in TAPVD patients whose IPVs are small.


Asunto(s)
Síndrome de Heterotaxia/cirugía , Venas Pulmonares/anomalías , Enfermedad Veno-Oclusiva Pulmonar/cirugía , Síndrome de Cimitarra/complicaciones , Síndrome de Cimitarra/cirugía , Procedimientos Quirúrgicos sin Sutura , Femenino , Humanos , Lactante , Recién Nacido , Modelos Lineales , Masculino , Complicaciones Posoperatorias , Circulación Pulmonar , Venas Pulmonares/cirugía , Reoperación , República de Corea , Resultado del Tratamiento , Cicatrización de Heridas
13.
Int J Urol ; 22(4): 400-3, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25586418

RESUMEN

OBJECTIVES: To evaluate the significance of a scrotum pulling maneuver during diagnostic laparoscopy for impalpable testis in order to determine whether an initial scrotal or inguinal incision should be carried out. METHODS: A total of 75 patients undergoing diagnostic laparoscopy were included in the present study. If the vas deferens and spermatic vessels were noted to enter the internal inguinal ring, the affected scrotum was pulled downwards and the movements of the cord structures were observed. If inferior movement of the cord structures at the internal inguinal ring were noted, a scrotal approach was preferred. In the absence of cord structure movement, an inguinal approach was carried out first. RESULTS: In 59 (76.6%) out of 77 impalpable testes, the spermatic vessels and vas deferens were noted to enter the internal inguinal ring. In 41 of the 59 cases (69.5%), the cord structures were observed to move inferiorly when the scrotum was pulled downwards. In these cases, a scrotal incision was carried out first. In 97% (40/41), a nubbin testis was found and was then excised. In 23% (18/59), the cord structures did not move on pulling the scrotum, and an inguinal approach was initially carried out on these cases. A viable testis was found on the inguinal canal in four cases, and a nubbin testis was excised in 14 cases. CONCLUSIONS: In patients with impalpable testis undergoing diagnostic laparoscopy, identification of spermatic cord movement along the internal inguinal ring while pulling the scrotum downwards determines the most appropriate surgical approach. This maneuver might also prevent inappropriately placed skin incisions.


Asunto(s)
Criptorquidismo/diagnóstico , Criptorquidismo/cirugía , Conducto Inguinal/cirugía , Laparoscopía/métodos , Escroto/cirugía , Niño , Preescolar , Técnicas de Diagnóstico Quirúrgico , Disgenesia Gonadal 46 XY/diagnóstico , Humanos , Lactante , Masculino , Movimiento (Física) , Estudios Prospectivos , Cordón Espermático , Testículo/anomalías , Conducto Deferente
14.
Drug Metab Dispos ; 42(9): 1493-7, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25008345

RESUMEN

A large set of Bacillus megaterium CYP102A1 mutants are known to metabolize various drugs to form human metabolites. Omeprazole (OMP), a proton pump inhibitor, has been widely used as an acid inhibitory agent for the treatment of gastric acid hypersecretion disorders. It is primarily metabolized by human CYP2C19 and CYP3A4 to 5'-OH OMP and a sulfone product, respectively. It was recently reported that several CYP102A1 mutants can oxidize racemic and S-OMP to 5'-OH OMP and that these mutants can further oxidize 5'-OH racemic OMP to 5'-COOH OMP. Here, we report that the S- and R-enantiomers of OMP are hydroxylated by 26 mutants of CYP102A1 to produce 1 major metabolite (5'-OH OMP) regardless of the chirality of the parent substrates. Although the binding of R-OMP to the CYP102A1 active site caused a more apparent change of heme environment compared with binding of S-OMP, there was no correlation between the spectral change upon substrate binding and catalytic activity of either enantiomer. The 5'-OH OMP produced from racemic, S-, and R-OMP could be obtained with a high conversion rate and high selectivity when the triple R47L/F87V/L188Q mutant was used. These results suggest that bacterial CYP102A1 mutants can be used to produce the human metabolite 5'-OH OMP from both the S- and R-enantiomers of OMP.


Asunto(s)
Proteínas Bacterianas/metabolismo , Sistema Enzimático del Citocromo P-450/metabolismo , Hidroxilación/fisiología , NADPH-Ferrihemoproteína Reductasa/metabolismo , Omeprazol/metabolismo , Bacillus megaterium/metabolismo , Proteínas Bacterianas/genética , Catálisis , Dominio Catalítico/fisiología , Sistema Enzimático del Citocromo P-450/genética , Hemo/metabolismo , Mutación/genética , NADPH-Ferrihemoproteína Reductasa/genética , Oxidación-Reducción , Estereoisomerismo
15.
Investig Clin Urol ; 65(1): 16-22, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38197747

RESUMEN

The Korean Association of Urogenital Tract Infection and Inflammation and the Korea Disease Control and Prevention Agency updated the Korean sexually transmitted infections (STIs) guidelines to respond to the changing epidemiologic trends, evolving scientific evidence, and advances in laboratory diagnostics and research. The main recommendations in the Mycoplasma genitalium infection parts of the Korean STIs guidelines 2023 revision are as follows: 1) For initial treatment: azithromycin 500 mg orally in a single dose, then 250 mg once daily for 4 days. 2) In case of treatment failure or recurrence, a macrolide susceptibility/resistance test is required, when susceptibility/resistance test is not feasible, doxycycline or minocycline 100 mg orally twice daily for 7 days, followed by azithromycin 1 g orally on the first day, then azithromycin 500 mg orally once daily for 3 days and then a test-of-cure should be considered 3 weeks after completion of therapy. 3) In case of macrolide sensitivity, doxycycline or minocycline 100 mg orally twice daily for 7 days, followed by azithromycin 1 g orally initial dose, then azithromycin 500 mg orally once daily for 3 days. 4) In case of macrolide resistance, doxycycline or minocycline 100 mg orally twice daily for 7 days, followed by moxifloxacin 400 mg orally once daily for 7 days. In the Korean STIs guideline 2023, macrolide resistance-guided antimicrobial therapy was emphasized due to the increased prevalence of macrolide resistance worldwide. Therefore, in case of treatment failure or recurrence, a macrolide susceptibility/resistance test is required.


Asunto(s)
Infecciones por Mycoplasma , Mycoplasma genitalium , Enfermedades de Transmisión Sexual , Humanos , Antibacterianos/uso terapéutico , Azitromicina/uso terapéutico , Macrólidos/uso terapéutico , Doxiciclina/uso terapéutico , Farmacorresistencia Bacteriana , Minociclina/uso terapéutico , Infecciones por Mycoplasma/tratamiento farmacológico , Enfermedades de Transmisión Sexual/tratamiento farmacológico , República de Corea/epidemiología
16.
World J Mens Health ; 42(1): 157-167, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37382279

RESUMEN

PURPOSE: To evaluate the anti-inflammatory and antioxidative effects of extracorporeal shockwave therapy (ESWT) on prostatitis and explore the mechanism of alleviating pain. MATERIALS AND METHODS: For in vitro testing, RWPE-1 cells were randomly divided into 5 groups: (1) RWPE-1 group (normal control), (2) LPS group (lipopolysaccharide inducing inflammation), (3) 0.1ESWT group (treated by 0.1 mJ/mm² energy level), (4) 0.2ESWT group (treated by 0.2 mJ/mm² energy level), and (5) 0.3ESWT group (treated by 0.3 mJ/mm² energy level). After ESWT was administered, cells and supernatant were collected for ELISA and western blot. For in vivo testing, Sprague-Dawley male rats were randomly divided into 3 groups: (1) normal group, (2) prostatitis group, and (3) ESWT group (n=12 for each). Prostatitis was induced by 17 beta-estradiol and dihydrotestosterone (DHT) administration. Four weeks after ESWT, the pain index was assessed for all groups and prostate tissues were collected for immunohistochemistry, immunofluorescence, apoptosis analysis and, western blot. RESULTS: Our in vitro studies showed that the optimal energy flux density of ESWT was 0.2 mJ/mm². In vivo, ESWT ameliorated discomfort in rats with prostatitis and inflammation symptoms were improved. Compared to normal rats, overexpressed NLRP3 inflammasomes triggered apoptosis in rats with prostatitis and this was improved by ESWT. TLR4-NFκB pathway was overactive after experimental prostatitis, compared to normal and ESWT groups, and prostatitis induced alterations in BAX/BAK pathway were inhibited by ESWT. CONCLUSIONS: ESWT improved CP/CPPS by reducing NLRP3 inflammasome and ameliorated apoptosis via inhibiting BAX/BAK pathway in a rat model. TLR4 may play a key role in bonding NLRP3 inflammasome and BAX/BAK pathways. ESWT might be a promising approach for the treatment of CP/CPPS.

17.
Brain Pathol ; 33(4): e13148, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-36623505

RESUMEN

The developmental functions of primary cilia and the downstream signaling pathways have been widely studied; however, the roles of primary cilia in the developing neurovascular system are not clearly understood. In this study, we found that ablation of genes encoding ciliary transport proteins such as intraflagellar transport homolog 88 (Ift88) and kinesin family member 3a (Kif3a) in cortical radial progenitors led to periventricular heterotopia during late mouse embryogenesis. Conditional mutation of primary cilia unexpectedly caused breakdown of both the neuroepithelial lining and the blood-choroid plexus barrier. Choroidal leakage was partially caused by enlargement of the choroid plexus in the cilia mutants. We found that the choroid plexus expressed platelet-derived growth factor A (Pdgf-A) and that Pdgf-A expression was ectopically increased in cilia-mutant embryos. Cortices obtained from embryos in utero electroporated with Pdgfa mimicked periventricular heterotopic nodules of the cilia mutant. These results suggest that defective ciliogenesis in both cortical progenitors and the choroid plexus leads to breakdown of cortical and choroidal barriers causing forebrain neuronal dysplasia, which may be related to developmental cortical malformation.


Asunto(s)
Cilios , Neuronas , Ratones , Animales , Cilios/genética , Cilios/metabolismo , Neuronas/metabolismo , Prosencéfalo , Transducción de Señal , Proteínas Portadoras/metabolismo
18.
Front Mol Biosci ; 10: 1250335, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37942288

RESUMEN

Alzheimer's disease (AD) is a brain disorder manifested by a gradual decline in cognitive function due to the accumulation of extracellular amyloid plaques, disruptions in neuronal substance transport, and the degeneration of neurons. In affected neurons, incomplete clearance of toxic proteins by neighboring microglia leads to irreversible brain inflammation, for which cellular signaling is poorly understood. Through single-cell transcriptomic analysis, we discovered distinct regional differences in the ability of microglia to clear damaged neurites. Specifically, microglia in the septal region of wild type mice exhibited a transcriptomic signature resembling disease-associated microglia (DAM). These lateral septum (LS)-enriched microglia were associated with dense axonal bundles originating from the hippocampus. Further transcriptomic and proteomic approaches revealed that primary cilia, small hair-like structures found on cells, played a role in the regulation of microglial secretory function. Notably, primary cilia were transiently observed in microglia, and their presence was significantly reduced in microglia from AD mice. We observed significant changes in the secretion and proteomic profiles of the secretome after inhibiting the primary cilia gene intraflagellar transport particle 88 (Ift88) in microglia. Intriguingly, inhibiting primary cilia in the septal microglia of AD mice resulted in the expansion of extracellular amyloid plaques and damage to adjacent neurites. These results indicate that DAM-like microglia are present in the LS, a critical target region for hippocampal nerve bundles, and that the primary ciliary signaling system regulates microglial secretion, affecting extracellular proteostasis. Age-related primary ciliopathy probably contributes to the selective sensitivity of microglia, thereby exacerbating AD. Targeting the primary ciliary signaling system could therefore be a viable strategy for modulating neuroimmune responses in AD treatments.

19.
Mol Neurobiol ; 2023 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-38049707

RESUMEN

Optical brain clearing combined with immunolabeling is valuable for analyzing molecular tissue structures, including complex synaptic connectivity. However, the presence of aberrant lipid deposition due to aging and brain disorders poses a challenge for achieving antibody penetration throughout the entire brain volume. Herein, we present an efficient brain-wide immunolabeling method, the immuno-active clearing technique (iACT). The treatment of brain tissues with a zwitterionic detergent, specifically SB3-12, significantly enhanced tissue permeability by effectively mitigating lipid barriers. Notably, Quadrol treatment further refines the methodology by effectively eliminating residual detergents from cleared brain tissues, subsequently amplifying volumetric fluorescence signals. Employing iACT, we uncover disrupted axonal projections within the mesolimbic dopaminergic (DA) circuits in 5xFAD mice. Subsequent characterization of DA neural circuits in 5xFAD mice revealed proximal axonal swelling and misrouting of distal axonal compartments in proximity to amyloid-beta plaques. Importantly, these structural anomalies in DA axons correlate with a marked reduction in DA release within the nucleus accumbens. Collectively, our findings highlight the efficacy of optical volumetric imaging with iACT in resolving intricate structural alterations in deep brain neural circuits. Furthermore, we unveil the compromised integrity of DA pathways, contributing to the underlying neuropathology of Alzheimer's disease. The iACT technique thus holds significant promise as a valuable asset for advancing our understanding of complex neurodegenerative disorders and may pave the way for targeted therapeutic interventions. The axonal projection of DA neurons in the septum and the NAc showed dystrophic phenotypes such as growth cone-like enlargement of the axonal terminus and aggregated neurites. Brain-wide imaging of structural defects in the neural circuits was facilitated with brain clearing and antibody penetration assisted with SB3-12 and Quadrol pre-treatment. The whole volumetric imaging process could be completed in a week with the robust iACT method. Created with https://www.biorender.com/ .

20.
Sci Rep ; 13(1): 207, 2023 01 05.
Artículo en Inglés | MEDLINE | ID: mdl-36604529

RESUMEN

This paper describes the fabrication of cicada-wing-inspired antimicrobial surfaces using Glancing Angle Deposition (GLAD). From the study of an annual cicada (Neotibicen Canicularis, also known as dog-day cicada) in North America, it is found that the cicada wing surfaces are composed of unique three-dimensional (3D) nanofeature arrays, which grant them extraordinary properties including antimicrobial (antifouling) and antireflective. However, the morphology of these 3D nanostructures imposes challenges in artificially synthesizing the structures by utilizing and scaling up the template area from nature. From the perspective of circumventing the difficulties of creating 3D nanofeature arrays with top-down nanofabrication techniques, this paper introduces a nanofabrication process that combines bottom-up steps: self-assembled nanospheres are used as the bases of the features, while sub-100 nm pillars are grown on top of the bases by GLAD. Scanning electron micrographs show the resemblance of the synthesized cicada wing mimicry samples to the actual cicada wings, both quantitatively and qualitatively. The synthetic mimicry samples are hydrophobic with a water contact angle of 125˚. Finally, the antimicrobial properties of the mimicries are validated by showing flat growth curves of Escherichia coli (E. coli) and by direct observation under scanning electron microscopy (SEM). The process is potentially suitable for large-area antimicrobial applications in food and biomedical industries.


Asunto(s)
Antiinfecciosos , Hemípteros , Nanoestructuras , Animales , Antiinfecciosos/farmacología , Escherichia coli , Hemípteros/anatomía & histología , Interacciones Hidrofóbicas e Hidrofílicas , Nanoestructuras/química , Propiedades de Superficie
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA