Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 166
Filtrar
1.
Clin Exp Dermatol ; 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38699954

RESUMEN

BACKGROUND: Seeking health information online has drastically increased. Isotretinoin is one of the agents used to treat acne. OBJECTIVES: In this study, we aimed to investigate the reliability and quality of YouTube videos related to acne treatment, which have been misconception to increase suicide. METHODS: We used the terms "isotretinoin suicide" and "acne treatment suicide" to search YouTube videos. Videos that were not in English, irrelevant, or devoid of audio were not included. The information in the videos was primarily categorized as reliable or unreliable based on its scientific validation. DISCERN and the Global Quality Score were used to evaluate the videos' overall quality. RESULTS: 200 videos in total were examined. 112 videos were included in the study. 39 videos (34.8 %) were found to be reliable, and 73 videos (65.2%) were found to be unreliable. DISCERN values of videos uploaded by physicians or professional organizations and health information websites were found to be significantly higher. There was a statistically significant negative correlation between DISCERN score and video length and the length of time the video was on YOUTUBE, while a positive correlation was observed between DISCERN score and subscriber. CONCLUSION: Although videos created by dermatologists have become widespread in recent years, it is still insufficient. Patient experience videos mostly contain information which does not reflect the reality and emphasize that isotretinoin increases the risk of suicide without evidence. As the number of dermatologists posting videos on YouTube increases, the chances of people accessing correct information will increase.

2.
Br J Radiol ; 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38775658

RESUMEN

OBJECTIVES: Our aim is to estimate the long-term neurological sequelae and prognosis in term neonatal asphyxia treated with hypothermia via volumetric apparent diffusion coefficient (ADC) map histogram analysis (HA). METHODS: Brain MRI studies of eighty-three term neonates with asphyxia who received whole-body hypothermia treatment and examined between postnatal (PN) 4 to 6th days were retrospectively re-evaluated by two radiologists. Volumetric HA was performed for the areas frequently affected in deep and superficial asphyxia (thalamus, lentiform nucleus, posterior limb of internal capsule, corpus callosum forceps major and perirolandic cortex-subcortical white matter) on ADC map. The quantitative ADC values were obtained separately for each region. Qualitative-visual (conventional) MRI findings were also re-evaluated. Neonates were examined neurodevelopmentally according to the Revised Brunet-Lezine scale. The distinguishability of long-term neurodevelopmental outcomes was statistically investigated. RESULTS: With HA, the adverse neurodevelopmental outcomes could only be distinguished from mild-moderated impairment and normal development at the thalamus with 10th percentile ADC (p = 0.02 and p = 0.03; respectively) and ADCmin (p = 0.03 and p = 0.04; respectively). Also with the conventional MRI findings, adverse outcome could be distinguished from mild-moderated impairment (p = 0.04) and normal development (p = 0.04) via cytotoxic edema of the thalamus, corpus striatum and diffuse cerebral cortical. CONCLUSION: The long-term adverse neurodevelopmental outcomes in newborns with asphyxia who received whole-body hypothermia treatment can be estimate similarly with volumetric ADC-HA and the conventional assessment of the ADC map. ADVANCES IN KNOWLEDGE: This study compare early MRI ADC-HA with neurological sequelae in term newborns with asphyxia who received whole-body hypothermia treatment. We couldn't find any significant difference in predicting adverse neurological sequelae between the visual-qualitative evaluation of the ADC map and HA.

3.
J Tissue Viability ; 33(2): 160-164, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38622036

RESUMEN

BACKGROUND: In discharge phase process, supporting patients to develop their own self-care strategies will increase their self-management skills and reduce complications and other health problems that may arise. AIM: The aim of the study is to examine the learning needs of individuals with burns regarding pre-discharge care and treatment and the factors affecting them. METHOD: Data from this cross-sectional study was collected with the "Descriptive Characteristics Form" and "Patient Learning Needs Scale (PLNS)". The study population consisted of patients hospitalized in the adult burn unit of a university hospital in eastern Turkey between May and October 2021. RESULTS: In the present study, it was observed that the pre-discharge learning needs of the patients were at a high level according to the mean score of the general score of the PLNS. Education level, marital status, companion experience and body mass index effected PLNS. CONCLUSIONS: In light of the results, it is recommended that discharge training be planned individually and determined according to the individual's learning needs and affecting factors.


Asunto(s)
Quemaduras , Alta del Paciente , Humanos , Estudios Transversales , Femenino , Masculino , Quemaduras/terapia , Quemaduras/psicología , Adulto , Turquía , Alta del Paciente/estadística & datos numéricos , Alta del Paciente/normas , Persona de Mediana Edad , Encuestas y Cuestionarios , Anciano , Evaluación de Necesidades/estadística & datos numéricos
4.
Turk J Ophthalmol ; 54(2): 116-119, 2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38646410

RESUMEN

Merkel cell carcinoma (MCC) is an unusual skin tumor that has a significant rate of distant and local metastases. It is known that primary MCC of the eyelid usually occurs at the upper eyelid. Here we report an unusual case of MCC metastasis to the eyelid. A 63-year-old male was diagnosed with MCC three years earlier after initially presenting with a mass in his right thigh. After histopathological diagnosis, the patient received medical therapy. During treatment, he developed multiple distant metastases and a firm, purple, vascularized lesion on the upper eyelid. We confirmed the lesion was an eyelid metastasis of MCC by histopathological examination and imaging methods. This case shows that extraocular MCC can metastasize to the eyelids, particularly the upper eyelid, where primary periocular MCC usually appears.


Asunto(s)
Carcinoma de Células de Merkel , Neoplasias de los Párpados , Neoplasias Cutáneas , Humanos , Masculino , Carcinoma de Células de Merkel/secundario , Carcinoma de Células de Merkel/diagnóstico , Persona de Mediana Edad , Neoplasias de los Párpados/secundario , Neoplasias de los Párpados/diagnóstico , Neoplasias Cutáneas/secundario , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/patología , Biopsia , Párpados/patología
5.
ACS Omega ; 9(10): 12175-12183, 2024 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-38497028

RESUMEN

Indole-chalcone hybrids have burst into prominence as potent weapons in the battle against pain and inflammation due to their unique features, allowing these ligands to form pivotal interactions with biological targets. In this context, the base-catalyzed Claisen-Schmidt condensation of 3',4'-(methylenedioxy)acetophenone with heteroaromatic aldehydes carrying an indole scaffold yielded new chalcones (1-7). The central and peripheral antinociceptive activities of all chalcones (compounds 1-7) at the dose of 10 mg/kg (i.p.) were evaluated by hot plate (supraspinal response), tail immersion (spinal response), and acetic acid-induced writhing tests in mice. The anti-inflammatory activities of compounds 1-7 were also investigated by means of a carrageenan-induced mouse paw edema model. The results revealed that compounds 1-7 extended the latency of response to thermal stimulus significantly in a hot-plate test similar to dipyrone (300 mg/kg; i.p.), the positive control drug. However, only compounds 2-7 were found to be significantly effective in the tail-immersion test. Compounds 1-7 also significantly showed analgesic effect by reducing the number of writhes and anti-inflammatory activity by inhibiting edema formation at different time intervals and levels. 1-(1,3-Benzodioxol-5-yl)-3-(1-methyl-1H-indol-2-yl)prop-2-en-1-one (4) drew attention by providing the highest efficacy results in both acute analgesia and inflammation models. Based on the in silico data acquired from the QikProp module, compound 4 was predicted to possess favorable oral bioavailability and drug-like properties. Taken together, it can be concluded that chalcones (1-7), especially compound 4, are outstanding candidates for further research to investigate their potential use in the management of pain and inflammation.

6.
Eur J Pediatr ; 183(3): 1153-1162, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37971516

RESUMEN

To investigate coronavirus disease 2019 (COVID-19) in infants aged 0 to 3 months because there is currently a significant gap in the literature on the subject. A cross-sectional study was conducted with the involvement of 19 medical centers across Turkey and 570 infants. The majority of the patients were male (58.2%), and the three most common symptoms were fever (78.2%), cough (44.6%), and feeding intolerance (39.9%). The results showed that a small percentage of infants had positive blood (0.9%) or urine cultures (10.2%). Most infants presented with fever (78.2%). Children without underlying conditions (UCs) had mostly a complicated respiratory course and a normal chest radiography. Significant more positive urine culture rates were observed in infants with fever. A higher incidence of respiratory support requirements and abnormal chest findings were seen in infants with chronic conditions. These infants also had a longer hospital stay than those without chronic conditions.  Conclusions: Our study discloses the clinical observations and accompanying bacterial infections found in infants aged under 3 months with COVID-19. These findings can shed light on COVID-19 in infancy for physicians because there is limited clinical evidence available. What is Known: • COVID-19 in infants and older children has been seen more mildly than in adults. • The most common symptoms of COVID-19 in infants are fever and cough, as in older children and adults. COVID-19 should be one of the differential diagnoses in infants with fever. What is New: • Although most infants under three months had fever, the clinical course was uneventful and respiratory complications were rarely observed in healthy children. • Infants with underlying conditions had more frequent respiratory support and abnormal chest radiography and stayed longer in the hospital.


Asunto(s)
COVID-19 , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Enfermedad Crónica , Tos/etiología , COVID-19/epidemiología , COVID-19/complicaciones , Estudios Transversales , Turquía/epidemiología
7.
ANZ J Surg ; 93(12): 2964-2968, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38093462

RESUMEN

BACKGROUND: This study was designed to examine the effect of guided imagery applied to geriatric orthopaedic patients on preoperative anxiety and comfort. METHODS: This study was conducted as a randomized controlled trial. The population of the study consisted of geriatric patients treated in the orthopaedics and traumatology clinic of a university hospital. The sample consisted of 80 patients, including the experimental group (n = 40) and the control group (n = 40). Personal Descriptive Form, The State-Trait Anxiety Inventory (STAI) and General Comfort Scale were used as data collection tools. RESULTS: After the guided imagery application, it was determined that the anxiety of the experimental group decreased statistically significantly, and their comfort improved (P < 0.05). CONCLUSION: After the imagery, it was determined that the patients in the experimental group had a decrease in their anxiety level and an improvement in their comfort. Since it is a low-cost and easily accessible method, applying imagery in the preoperative period is recommended.


Asunto(s)
Imágenes en Psicoterapia , Ortopedia , Humanos , Anciano , Imágenes en Psicoterapia/métodos , Ansiedad/prevención & control , Trastornos de Ansiedad , Periodo Preoperatorio
8.
ACS Omega ; 8(45): 42867-42877, 2023 Nov 14.
Artículo en Inglés | MEDLINE | ID: mdl-38024728

RESUMEN

In an attempt to identify small molecules for the treatment of leukemia, 12 new pyrazolines (2a-l) were synthesized efficiently. WST-1 assay was performed to examine their cytotoxic features on HL-60 human acute promyelocytic leukemia (APL), K562 human chronic myeloid leukemia (CML), and THP-1 human acute monocytic leukemia cells. Four compounds (2e, 2f, 2g, and 2h) were determined as promising antileukemic agents on HL-60 and K562 cells. IC50 values of compounds 2f, 2h, 2e, 2g, and bortezomib for the HL-60 cell line were found as 33.52, 42.89, 48.02, 62.34, and 31.75 µM, while IC50 values of compounds 2h, 2g, 2f, 2e, and bortezomib for K562 cells were determined as 33.61, 50.23, 57.28, 76.90, and 42.69 µM, respectively. Further studies were carried out to shed light on the mechanism of antileukemic action. According to the data obtained by in vitro experiments, 1-(4-fluorophenyl)-3-(thiophen-3-yl)-5-(4-(4-methylpiperazin-1-yl)phenyl)-2-pyrazoline (2f) and 1-(3-bromophenyl)-3-(thiophen-3-yl)-5-(4-(4-methylpiperazin-1-yl)phenyl)-2-pyrazoline (2h) have proved to be potential antileukemic agents with remarkable cytotoxicity against HL-60 and K562 cells by activation of caspase 3, thereby inducing apoptosis.

9.
ACS Omega ; 8(22): 20056-20065, 2023 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-37305321

RESUMEN

In an endeavor to identify small molecules for the management of non-small-cell lung carcinoma, 10 new hydrazone derivatives (3a-j) were synthesized. MTT test was conducted to examine their cytotoxic activities against human lung adenocarcinoma (A549) and mouse embryonic fibroblast (L929) cells. Compounds 3a, 3e, 3g, and 3i were determined as selective antitumor agents on A549 cell line. Further studies were conducted to figure out their mode of action. Compounds 3a and 3g markedly induced apoptosis in A549 cells. However, both compounds did not show any significant inhibitory effect on Akt. On the other hand, in vitro experiments suggest that compounds 3e and 3i are potential anti-NSCLC agents acting through Akt inhibition. Furthermore, molecular docking studies revealed a unique binding mode for compound 3i (the strongest Akt inhibitor in this series), which interacts with both hinge region and acidic pocket of Akt2. However, it is understood that compounds 3a and 3g exert their cytotoxic and apoptotic effects on A549 cells via different pathway(s).

11.
ANZ J Surg ; 93(5): 1207-1213, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36898959

RESUMEN

BACKGROUND: The purpose of this study is to investigate the effects of guided imagery on postoperative pain and comfort in geriatric orthopedics patients. METHODS: This study was carried out with a randomized-controlled true experimental design. The population of the study included geriatric patients receiving treatment at the orthopedics and traumatology inpatient clinic of a university hospital. Based on random selection, the sample consisted of total of 102 patients, including 40 patients in the experimental group and 40 in the control group. The data were collected using a Personal Information Form, the Visual Analog Scale, and the General Comfort Questionnaire. RESULTS: After the guided imagery intervention, the pain levels of the experimental group significantly decreased compared to their baseline pain levels (t = 4.002, P = 0.00). Their perceived comfort was also significantly improved (t = -5.428, P = 0.00). Although the perceived comfort of the control group decreased, this decrease was not statistically significant (t = 0.698, P = 0.489). CONCLUSION: It is recommended that guided imagery, which is an inexpensive and accessible method, be integrated into the nursing care process to reduce the pain and increase the comfort of geriatric orthopedics patients.


Asunto(s)
Procedimientos Ortopédicos , Ortopedia , Humanos , Anciano , Imágenes en Psicoterapia/métodos , Dolor Postoperatorio/prevención & control , Dimensión del Dolor
12.
Turk Neurosurg ; 33(3): 509-513, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36951037

RESUMEN

AIM: To evaluate the optimal timing and outcome of fluoroscopically guided transforaminal epidural steroid injections (TFESI) for the management of radicular pain due to extruded lumbar disc herniation (LDH). MATERIAL AND METHODS: In this clinical study, 305 individuals received fluoroscopically guided TFESI for the management of radicular pain due to extruded LDH. Preprocedural and 12-week postprocedural Visual Analog Scale (VAS) scores measuring radicular pain were statistically compared. The neurological conditions of the patients and the complications of the procedure were also recorded. RESULTS: The intensity of radicular pain evaluated by the mean preprocedural and 12-week postprocedural VASs were 8.765 ± 0.559 and 2.281 ± 0.401, respectively (p=0.001, and t=119.01). A correlation was noted between the short duration of symptoms before the procedure and the effectiveness of the procedure. After 12 weeks of the procedure, 32 of the 58 patients showed improvement in terms of neurological deficit. There was no major complication. Nine patients required lumbar disc surgery after the procedure. CONCLUSION: This clinical research demonstrated that TFESI for the management of extruded LDH may alleviate radicular pain and may decrease the neurological deficit and that it is more effective when performed at the earliest possible time point.


Asunto(s)
Desplazamiento del Disco Intervertebral , Región Lumbosacra , Humanos , Desplazamiento del Disco Intervertebral/complicaciones , Dolor , Esteroides
13.
Int J Mol Sci ; 24(3)2023 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-36768971

RESUMEN

Targeted therapies have come into prominence in the ongoing battle against non-small cell lung cancer (NSCLC) because of the shortcomings of traditional chemotherapy. In this context, indole-based small molecules, which were synthesized efficiently, were subjected to an in vitro colorimetric assay to evaluate their cyclooxygenase (COX) inhibitory profiles. Compounds 3b and 4a were found to be the most selective COX-1 inhibitors in this series with IC50 values of 8.90 µM and 10.00 µM, respectively. In vitro and in vivo assays were performed to evaluate their anti-NSCLC and anti-inflammatory action, respectively. 2-(1H-Indol-3-yl)-N'-(4-morpholinobenzylidene)acetohydrazide (3b) showed selective cytotoxic activity against A549 human lung adenocarcinoma cells through apoptosis induction and Akt inhibition. The in vivo experimental data revealed that compound 3b decreased the serum myeloperoxidase and nitric oxide levels, pointing out its anti-inflammatory action. Moreover, compound 3b diminished the serum aminotransferase (particularly aspartate aminotransferase) levels. Based on the in vitro and in vivo experimental data, compound 3b stands out as a lead anti-NSCLC agent endowed with in vivo anti-inflammatory action, acting as a dual COX-1 and Akt inhibitor.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Inhibidores de la Angiogénesis/farmacología , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Antiinflamatorios no Esteroideos/farmacología , Ciclooxigenasa 2/metabolismo , Inhibidores de la Ciclooxigenasa 2/farmacología , Inhibidores de la Ciclooxigenasa 2/uso terapéutico , Simulación del Acoplamiento Molecular , Estructura Molecular , Proteínas Proto-Oncogénicas c-akt , Relación Estructura-Actividad , Ciclooxigenasa 1/metabolismo
14.
Arch Pharm (Weinheim) ; 356(4): e2200570, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36603162

RESUMEN

In the search for small-molecule aldose reductase (AR) inhibitors, new tetrazole-hydrazone hybrids (1-15) were designed. An efficient procedure was employed for the synthesis of compounds 1-15. All hydrazones were subjected to an in vitro assay to assess their AR inhibitory profiles. Compounds 1-15 caused AR inhibition with Ki values ranging between 0.177 and 6.322 µM and IC50 values ranging between 0.210 and 0.676 µM. 2-[(1-(4-Hydroxyphenyl)-1H-tetrazol-5-yl)thio]-N'-(4-fluorobenzylidene)acetohydrazide (4) was the most potent inhibitor of AR in this series. Compound 4 markedly inhibited AR (IC50 = 0.297 µM) in a competitive manner (Ki = 0.177 µM) compared to epalrestat (Ki = 0.857 µM, IC50 = 0.267 µM). Based on the in vitro data obtained by applying the MTT test, compound 4 showed no cytotoxic activity toward normal (NIH/3T3) cells at the tested concentrations, indicating its safety as an AR inhibitor. Compound 4 exhibited proper interactions with crucial amino acid residues within the active site of AR. In silico QikProp data of all hydrazones (1-15) were also determined to assess their pharmacokinetic profiles. Taken together, compound 4 stands out as a promising inhibitor of AR for further in vivo studies.


Asunto(s)
Aldehído Reductasa , Hidrazonas , Hidrazonas/farmacología , Relación Estructura-Actividad , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Aminoácidos , Simulación del Acoplamiento Molecular
15.
Turk Neurosurg ; 33(2): 265-271, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36622190

RESUMEN

AIM: To assess anterior gradient protein 2 (AGR2) gene expression in patients with human glioblastoma (GBM) in comparison to levels in healthy brain tissues. MATERIAL AND METHODS: We evaluated the expression levels of AGR2 gene in 34 tissue samples: 29 of them were derived from patients with glioblastoma (GBM group) and 5 were derived from patients with mesial temporal lobe epilepsy (control group). Moreover, in order to demonstrate the AGR2 gene expression, we performed RNA isolation from tissue samples, cDNA acquisition from RNA via reverse transcription and the demonstration of gene expression via real-time polymerase chain reaction. We therefore confirmed findings of both groups. RESULTS: The mean age of the GBM and control groups were 53.1 ± 12.82 years and 40.4 ± 10.92 years respectively. AGR2 gene expression levels of the GBM group were significantly higher than those of the control group (p < 0.01). There were no significant differences of AGR2 gene expression levels across age groups, levels of glucose, urea, creatinine, white blood cell count (WBC), neutrophil, lymphocyte, hemoglobin, platelet, thyroid-stimulating hormone (TSH), T3 and T4 in GBM group (p > 0.05). CONCLUSION: AGR2 gene expression was significantly higher in patients with GBM. Thus, AGR2 gene can be considered as a potential therapeutic target.


Asunto(s)
Glioblastoma , Proteínas Oncogénicas , Humanos , Adulto , Persona de Mediana Edad , Anciano , Proteínas Oncogénicas/genética , Mucoproteínas/genética , Glioblastoma/diagnóstico , Glioblastoma/genética , Glioblastoma/terapia , Expresión Génica , ARN , Línea Celular Tumoral
16.
Nat Struct Mol Biol ; 30(1): 107-114, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36536104

RESUMEN

The double-strand break (DSB) repair pathway called microhomology-mediated end-joining (MMEJ) is thought to be dependent on DNA polymerase theta (Polθ) and occur independently of nonhomologous end-joining (NHEJ) factors. An unresolved question is whether MMEJ is facilitated by a single Polθ-mediated end-joining pathway or consists of additional undiscovered pathways. We find that human X-family Polλ, which functions in NHEJ, additionally exhibits robust MMEJ activity like Polθ. Polλ promotes MMEJ in mammalian cells independently of essential NHEJ factors LIG4/XRCC4 and Polθ, which reveals a distinct Polλ-dependent MMEJ mechanism. X-ray crystallography employing in situ photo-induced DSB formation captured Polλ in the act of stabilizing a microhomology-mediated DNA synapse with incoming nucleotide at 2.0 Å resolution and reveals how Polλ performs replication across a DNA synapse joined by minimal base-pairing. Last, we find that Polλ is semisynthetic lethal with BRCA1 and BRCA2. Together, these studies indicate Polλ MMEJ as a distinct DSB repair mechanism.


Asunto(s)
Roturas del ADN de Doble Cadena , Reparación del ADN , Animales , Humanos , Reparación del ADN por Unión de Extremidades , ADN , Mamíferos
17.
Drug Dev Res ; 84(2): 185-199, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36469421

RESUMEN

In an attempt to identify potent antitumor agents for the fight against non-small cell lung cancer, new thiazolyl hydrazones (2a-n) were synthesized and examined for their in vitro cytotoxic effects on A549 human lung adenocarcinoma and L929 mouse embryonic fibroblast cells by means of the MTT assay. Furthermore, the effects of the most potent anticancer agents on apoptosis and Akt inhibition were investigated. 2-[2-((Isoquinolin-5-yl)methylene)hydrazinyl]-4-(4-methylsulfonylphenyl)thiazole (2k) (IC50 = 1.43 ± 0.12 µM) and 2-[2-((isoquinolin-5-yl)methylene)hydrazinyl]-4-(1,3-benzodioxol-5-yl)thiazole (2l) (IC50 = 1.75 ± 0.07 µM) displayed more pronounced anticancer activity than cisplatin (IC50 = 3.90 ± 0.10 µM) on A549 cell lines; 2-[2-((isoquinolin-5-yl)methylene)hydrazinyl]-4-(4-methoxyphenyl)thiazole (2j) (IC50 = 3.93 ± 0.06 µM) showed anticancer activity close to cisplatin. These compounds were found to induce apoptosis in A549 cells. Compound 2j (IC50 = 3.55 ± 0.64 µM) showed stronger Akt inhibitory activity than GSK690693 (IC50 = 4.93 ± 0.06 µM), while compounds 2k and 2l did not cause Akt inhibition at IC50 concentrations (1.43 and 1.75 µM, respectively). To comprehensively elucidate the binding pose of compound 2j and to provide a detailed understanding on the ligand' binding mechanism, induced-fit docking calculations were also conducted. Both in vitro and in silico studies suggest that compound 2j shows its cytotoxic and apoptotic effects on A549 cell lines via Akt inhibition. However, it is understood that compounds 2k and 2l exert their strong anticancer effects on A549 cells through different pathways.


Asunto(s)
Antineoplásicos , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Animales , Ratones , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Cisplatino/farmacología , Proteínas Proto-Oncogénicas c-akt , Tiazoles/farmacología , Tiazoles/química , Hidrazonas/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Ensayos de Selección de Medicamentos Antitumorales , Fibroblastos , Antineoplásicos/farmacología , Antineoplásicos/química , Proliferación Celular , Relación Estructura-Actividad , Simulación del Acoplamiento Molecular , Estructura Molecular , Línea Celular Tumoral
18.
Eur J Med Chem ; 244: 114851, 2022 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-36270087

RESUMEN

In an attempt to identify small molecules for targeted therapy of non-small cell lung carcinoma (NSCLC) and prostate cancer (PCa), new arylidene indanones (1-10) were synthesized via the Claisen-Schmidt condensation of 5,6-methylenedioxy-1-indanone with p-substituted benzaldehyde. Compounds 1-10 were assessed for their cytotoxic effects on human lung adenocarcinoma (A549) and human pancreatic ductal carcinoma (PANC-1) cells as well as human normal lung fibroblast (CCD-19Lu) and human normal pancreatic ductal epithelial (hTERT-HPNE) cells. Among them, compounds 2, 4 and 10 were more effective on A549 and PANC-1 cells than cisplatin. Compounds 1 and 9 also showed more potent cytotoxic activity towards PANC-1 cells than cisplatin. In vitro assays were performed to assess their effects on DNA synthesis, apoptosis, caspase-3, mitochondrial membrane potential, intracellular calcium levels, morphological changes in cancer cells. Furthermore, all compounds were investigated for their inhibitory effects on cathepsin L (CatL) and cathepsin D (CatD). Compounds 2 and 4 exerted potent anti-NSCLC action through caspase-independent apoptosis induced by an increase in intracellular calcium level and correspondingly the disruption of the ΔΨm. These compounds also caused apoptotic morphological alterations in A549 cells. Compound 4 also inhibited both cathepsins but its inhibitory potency on CatL was more significant. Based on in vitro mechanistic assays, compound 4 was identified as a promising anticancer agent for targeted therapy of NSCLC. On the other hand, the marked anti- PCa activity of compound 1 mediated by apoptotic cell death is also noteworthy, but further enzymatic assays are required to elucidate its main mechanism of action.


Asunto(s)
Antineoplásicos , Carcinoma de Pulmón de Células no Pequeñas , Diseño de Fármacos , Indanos , Neoplasias Pulmonares , Terapia Molecular Dirigida , Neoplasias de la Próstata , Humanos , Masculino , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Apoptosis/efectos de los fármacos , Calcio , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Línea Celular Tumoral , Proliferación Celular , Cisplatino/farmacología , Indanos/química , Indanos/farmacología , Indanos/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias de la Próstata/tratamiento farmacológico
19.
Constr Build Mater ; 337: 127576, 2022 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-35493028

RESUMEN

Recently, COVID-19 has appeared as an international pandemic, leading to serious risks for humans. Using face masks is one of the most common measures in a wide-ranging prevention program that could control the COVID-19 dissemination. Face masks are typically composed of non-biodegradable and non-renewable polymers based on petroleum, which are harmful to nature and lead to health problems. In the present study, disposable face masks, the use of which has increased due to the Covid-19 pandemic throughout the world and which cause environmental pollution, were divided into very small pieces and utilized as a modifier in the bitumen binder. Therefore, this study aimed to provide a solution to such a significant environmental problem. Five different ratios of waste mask and the single ratio of styrene-butadienestyrene (SBS) were added to the pure binder and the rheological, physical, and chemical properties of the modified binders were compared. The result showed that adding a waste mask and SBS to the pure bitumen caused increases in binders' softening point and viscosity and reductions in the penetration value. Waste mask modifications were able to better maintain its elastic properties both at low stress and high-stress levels with increasing temperature. 3% SBS was the binder most affected by temperature rise. As a result, it has been determined that binders containing more than 2% waste mask have better performance characteristics than binders containing 3% SBS in terms of physical and rheological properties.

20.
Arch Pharm (Weinheim) ; 355(9): e2200136, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35606682

RESUMEN

In an endeavor to identify potent anti-inflammatory agents, new thiosemicarbazones (TSCs) incorporated into a diaryl ether framework (2a-2l) were prepared and screened for their in vitro inhibitory effects on cyclooxygenases (COXs). 4-[4-(Piperidin-1-ylsulfonyl)phenyl]-1-[4-(4-cyanophenoxy)benzylidene]thiosemicarbazide (2c) was the most potent and selective COX-1 inhibitor in this series, with an IC50 value of 1.89 ± 0.04 µM. On the other hand, 4-[4-(piperidin-1-ylsulfonyl)phenyl]-1-[4-(4-nitrophenoxy)benzylidene]thiosemicarbazide (2b) was identified as a nonselective COX inhibitor (COX-1 IC50 = 13.44 ± 0.65 µM, COX-2 IC50 = 12.60 ± 0.78 µM). Based on molecular docking studies, the diaryl ether and the TSC groups serve as crucial moieties for interactions with pivotal amino acid residues in the active sites of COXs. According to MTT test, compounds 2b and 2c showed low cytotoxic activity toward NIH/3T3 cells. Their in vivo anti-inflammatory and antioxidant potencies were also assessed using the lipopolysaccharide-induced sepsis model. Compounds 2b and 2c diminished high-sensitivity C-reactive protein, myeloperoxidase, nitric oxide, and malondialdehyde levels. Both compounds also caused a significant decrease in aspartate aminotransferase levels as well as alanine aminotransferase levels. In silico pharmacokinetic studies suggest that compounds 2b and 2c possess favorable drug-likeness and oral bioavailability. It can be concluded that these compounds may act as orally bioavailable anti-inflammatory and antioxidant agents.


Asunto(s)
Tiosemicarbazonas , Animales , Antiinflamatorios/farmacología , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/farmacología , Antioxidantes/farmacología , Ciclooxigenasa 1/metabolismo , Ciclooxigenasa 2/metabolismo , Inhibidores de la Ciclooxigenasa 2/química , Inhibidores de la Ciclooxigenasa 2/farmacología , Inhibidores de la Ciclooxigenasa/química , Inhibidores de la Ciclooxigenasa/farmacología , Éteres , Ratones , Simulación del Acoplamiento Molecular , Estructura Molecular , Relación Estructura-Actividad , Tiosemicarbazonas/farmacología
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...