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1.
Discov Med ; 36(185): 1280-1288, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38926114

RESUMEN

BACKGROUND: Kinesin family member 26B (KIF26B) has been closely linked to the occurrence and progression of various tumors. However, there is limited research on its role in oral squamous cell carcinoma (OSCC). This article aims to investigate the expression levels and mechanisms of KIF26B in OSCC. METHODS: Real time quantity polymerase chain reaction (RT-qPCR) and Western blot analyses were conducted to assess the expression levels of KIF26B in 35 OSCC specimens and their corresponding non-cancerous tissues. Overexpression and silencing of KIF26B were achieved in HSC6 and SCC25 cells, respectively, resulting in the establishment of KIF26B-overexpressing and si-KIF26B cell lines, designated as the KIF26B group and si-KIF26B group. Proliferation assays using 5-Ethynyl-2'-deoxyuridine (EdU) labeling and clone formation were performed to evaluate the proliferative capacity of cells in these groups. The invasive and migratory abilities of cells in the KIF26B and si-KIF26B groups were assessed using Transwell assay. Additionally, the influence of KIF26B on the glycogen synthase kinase (GSK)-3ß/ß-catenin pathway was investigated through Western blot analysis. RESULTS: According to the results of RT-qPCR and Western blot analyses, the expression of KIF26B was predominantly higher in OSCC tissues compared to normal tissues (p < 0.01). Overexpression of KIF26B notably accelerated cell migration, invasion, and proliferation (p < 0.01), whereas knockdown of KIF26B significantly inhibited these processes (p < 0.01). Additionally, KIF26B overexpression led to increased levels of active ß-catenin, p-GSK-3, and c-myc (p < 0.01), while KIF26B silencing decreased the levels of these proteins (p < 0.01). CONCLUSION: Our findings suggest that KIF26B may play a role in the pathogenesis and progression of OSCC as an oncogene. This study establishes a foundation for the identification of potential therapeutic targets for OSCC.


Asunto(s)
Biomarcadores de Tumor , Carcinoma de Células Escamosas , Proliferación Celular , Cinesinas , Neoplasias de la Boca , Humanos , Cinesinas/genética , Cinesinas/metabolismo , Neoplasias de la Boca/genética , Neoplasias de la Boca/patología , Neoplasias de la Boca/metabolismo , Línea Celular Tumoral , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/metabolismo , Proliferación Celular/genética , Femenino , Masculino , Persona de Mediana Edad , Regulación Neoplásica de la Expresión Génica , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Glucógeno Sintasa Quinasa 3 beta/genética , Movimiento Celular/genética , Anciano , Vía de Señalización Wnt/genética , beta Catenina/metabolismo , beta Catenina/genética
2.
Polymers (Basel) ; 15(4)2023 Feb 11.
Artículo en Inglés | MEDLINE | ID: mdl-36850189

RESUMEN

Quercetin, as one of the most biologically active natural flavonoids, is widely found in various vegetables, fruits and Chinese herbs. In this work, molecularly imprinted polymer (MIP) was synthesized through surface molecular imprinting technology with sol-gel polymerization mechanism on SiO2 at room temperature using quercetin as the template, SiO2 as the supporter, 3-aminopropyltriethoxysilane (APTES) as the functional monomer, and tetraethoxysilane (TEOS) as the cross-linker. The prepared MIP was characterized via scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FT-IR) and nitrogen adsorption measurements to validate its surface morphology, structure and functionality. SEM images revealed that the morphology of MIP was rough and spherical with the particle size of 260 nm larger than that of the support SiO2. In the FTIR spectra of MIP, the band around 1499 cm-1 and 2932 cm-1 were assigned to N-H and C-H groups, respectively. The results indicated that the imprinted polymer layers were grafted on the surface of SiO2 and the MIP had been successfully prepared. Since the specific surface area and pore volume of MIP were markedly higher than those of NIP and SiO2 and were 52.10 m2 g-1 and 0.150 cm3 g-1, respectively, it was evident that the imprinting process created corresponding imprinted cavities and porosity. The MIP for adsorbing quercetin was evaluated by static adsorption experiment. The results indicated that the adsorption equilibrium could be reached within 90 min and the maximum adsorption capacity was as high as 35.70 mg/g. The mechanism for adsorption kinetics and isotherm of MIP for quercetin was proved to conform the pseudo-second-order kinetics model (R2 = 0.9930) and the Freundlich isotherm model (R2 = 0.9999), respectively, revealing that chemical adsorption and heterogeneous surface with multilayer adsorption dominated. In contrast to non-imprinted polymer (NIP), the MIP demonstrated high selectivity and specific recognition towards quercetin whose selectivity coefficients for quercetin relative to biochanin A were 1.61. Furthermore, the adsorption capacity of MIP can be maintaining above 90% after five regeneration cycles, indicating brilliant reusability and potential application for selective adsorption of quercetin.

3.
Exp Neurol ; 228(2): 206-14, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21238453

RESUMEN

Sex-associated differences in the perception and modulation of pain have widely been reported in humans as well as animals. The aim of the present study performed in conscious rats of both sexes was to systematically investigate the role of sex in endogenous descending controls of nociceptive paw withdrawal reflex during experimental muscle pain elicited by intramuscular (i.m.) injection with different doses (0.1-0.4 ml of 0.9-5.8%) of saline. Ipsilateral i.m. injection of 0.2-0.4 ml, but not 0.1 ml, isotonic (0.9%, IT) saline elicited long lasting (about 7d), secondary and contralateral mechanical hyperalgesia in female rats, whereas male rats exhibited a bilateral, short-term (less than 1d) mechanical hyperalgesia only during the exposure to 0.4 ml IT saline injection (P < 0.05). A bolus of 0.4 ml, but not 0.1-0.2 ml, IT saline significantly induced a one-week, secondary and contralateral heat hypoalgesia in both male and female rats (P < 0.05). In contrast to the IT saline injection, 0.1 ml hypertonic (5.8%, HT) saline started to evoke bilateral mechanical hyperalgesia in male and female rats. During the HT saline induced muscle nociception, mechanical hyperalgesia in female rats was greater in magnitude and longer in duration than that of in male rats (P < 0.05). Heat hypoalgesia was bilaterally found in male rats receiving either 0.2 ml or 0.4 ml HT saline injection, whereas female rats showed heat hypoalgesia, subjected only to the 0.4 ml HT saline injection (P < 0.05 and P < 0.001). Intrathecal (i.th.) administration of either 6-hydroxydopamine hydrobromide (6-OHDA) or 5,7-dihydroxytryptamine (5,7-DHT) significantly attenuated the HT saline induced heat hypoalgesia, not mechanical hyperalgesia, in male rats. By contrast, in female rats i.th. 6-OHDA markedly blocked heat hypoalgesia, and mechanical hyperalgesia was prevented by 5,7-DHT treatment. It is suggested that i.m. injection of saline dose-dependently elicits ipsilateral secondary and contralateral mechanical hyperalgesia and heat hypoalgesia, which are differently modulated by descending noradrenaline (NA) and serotonin (5-HT) pathways in rats of both sexes. Importantly, the present findings here are not only consistent with our previous study indicating a supraspinal nociception discriminator with different triggering thresholds to govern peripheral A-δ and C-fiber mediated responses (You et al., 2010), but further strengthen this hypothesis that compared with male rats, supraspinal nociception discriminator in female rats exhibits a lower facilitatory threshold and a higher inhibitory threshold. This may bring our attention to better understand why females are commonly reported to be more sensitive and less tolerant to noxious stimulation. In conclusion, sex-related differences are important in descending modulations of pain and anesthesia. Less noxious stimuli could activate descending inhibition in males but not females, whereas less noxious afferents may elicit descending facilitation in female, but not male rats. Central noradrenergic and serotonergic pathways are differently involved in the action of descending modulations of nociception in rats of both sexes.


Asunto(s)
Músculo Esquelético/fisiopatología , Norepinefrina/fisiología , Dolor/inducido químicamente , Reflejo/fisiología , Serotonina/fisiología , Caracteres Sexuales , Cloruro de Sodio/toxicidad , Médula Espinal/fisiología , Animales , Femenino , Calor , Inyecciones Intramusculares , Masculino , Músculo Esquelético/efectos de los fármacos , Dolor/metabolismo , Dimensión del Dolor/métodos , Umbral del Dolor/efectos de los fármacos , Umbral del Dolor/fisiología , Ratas , Ratas Sprague-Dawley , Tiempo de Reacción/efectos de los fármacos , Tiempo de Reacción/fisiología , Reflejo/efectos de los fármacos , Médula Espinal/efectos de los fármacos
4.
J Physiol ; 588(Pt 21): 4177-88, 2010 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-20837643

RESUMEN

In conscious rats, we investigated the change of nociceptive paw withdrawal reflexes elicited by mechanical and heat stimuli during intramuscular (i.m.) 5.8% hypertonic (HT) saline elicited muscle nociception. i.m. injection of HT saline caused rapid onset, long lasting (around 7 days), bilateral mechanical hyperalgesia, while it induced bilateral, slower onset (1 day after the HT saline injection), long-term (about 1-2 weeks) heat hypoalgesia. Ipsilateral topical pre-treatment of the sciatic nerve with 1% capsaicin significantly prevented the occurrence of both the bilateral mechanical hyperalgesia and the contralateral heat hypoalgesia. Intrathecal administration of either 6-hydroxydopamine hydrobromide (6-OHDA) or 5,7-dihydroxytryptamine (5,7-DHT), and intraperitoneal injection of naloxone all markedly attenuated the HT saline induced bilateral heat hypoalgesia, but not the mechanical hyperalgesia. Combined with experiments with lesioning of the rostroventral medulla with kainic acid, the present data indicate that unilateral i.m. injection of HT saline elicits time-dependent bilateral long-term mechanical hyperalgesia and heat hypoalgesia, which were modulated by descending facilitatory and inhibitory controls, respectively. We hypothesize that supraspinal structures may function to discriminate between afferent noxious inputs mediated by Aδ- and C-fibres, either facilitating Aδ-fibre mediated responses or inhibiting C-fibre mediated activities. However, this discriminative function is physiologically silent or inactive, and can be triggered by stimulation of peripheral C-fibre afferents. Importantly, in contrast to the rapid onset of descending facilitation, the late occurrence of descending inhibition suggests a requirement of continuous C-fibre input and temporal summation. Thus, a reduction of C-fibre input using exogenous analgesic agents, i.e. opioids, may counteract the endogenous descending inhibition.


Asunto(s)
Calor , Hiperalgesia/fisiopatología , Músculo Esquelético/fisiopatología , Nociceptores/fisiología , Animales , Capsaicina/farmacología , Dihidroxitriptaminas/farmacología , Masculino , Modelos Animales , Músculo Esquelético/inervación , Naloxona/farmacología , Fibras Nerviosas Amielínicas/fisiología , Nociceptores/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Reflejo/efectos de los fármacos , Reflejo/fisiología , Solución Salina Hipertónica/farmacología , Nervio Ciático/efectos de los fármacos , Nervio Ciático/fisiología , Factores de Tiempo
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