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PURPOSE: The purpose of this in vitro study was to evaluate the trueness of removable partial denture clasps fabricated with titanium (Ti) through the selective laser melting (SLM) technique compared to cobalt-chromium alloys (CoCr). MATERIALS AND METHODS: A virtual Aker clasp was designed on a scanned tooth, and SLM printers were used to print 20 claps using cobalt chromium (n = 10) and titanium alloy (n = 10). The deviation between the printed clasps and reference design was measured using the surface matching software (Geomagic control x) at rest, retentive tip, reciprocal tip, retentive shoulder, and reciprocal shoulder. An Independent t-test was used to determine the influence of 3D-printed material on the trueness (a = 0.05). RESULTS: The gap distance in mm between the reference design and printed in titanium showed an average of 0.0001 ±0.0544, 0.0256 ±0.1309, 0.0230 ±0.1028, 0.0701 ±0.1234, and 0.0013 ±0.0735 mm in rest, reciprocal arm tip, retentive arm tip, retentive arm shoulder, and reciprocal arm shoulder, respectively. The gap distance in mm between the reference design and printed clasps in CoCr alloy showed an average of 0.0316 ±0.0692, 0.2783 ±0.1678, 0.1446 ±0.1528, 0.0315 ±0.0906, and 0.0419 ±0.1088 mm in rest, reciprocal arm tip, retentive arm tip, retentive arm shoulder, and reciprocal arm shoulder, respectively. The difference between titanium and CoCr alloys at each observation site was significant. CONCLUSION: Clasps fabricated from titanium with SLM printing have the least deviation and better trueness compared to those fabricated from cobalt chromium.
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BACKGROUND: The most widely used substance in the fabrication of dental prosthesis is poly (methyl methacrylate), or PMMA, and the development of biofilm is frequently associated with its use. To enhance the mechanical properties of heat-polymerized PMMA, this study prepared PMMA/gold nanoparticles (AuNps). The occlusal vertical dimension and tooth movement were examined in the current study. The occlusal vertical dimension was assessed using an electronic digital calliper measuring device, and tooth movement was measured using a CAD Star digital scanner. RESULTS: Tooth movement and occlusal vertical dimension of a PMMA/gold nanoparticles (AuNps) were decreased for all groups containing AuNps. Statistical analysis was performed by means of the SPSS 16 software package. CONCLUSIONS: Incorporation of AuNps into heat- polymerized PMMA resin led to increase dimensional stability of complete denture base material.
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Nanopartículas del Metal , Polimetil Metacrilato , Humanos , Resinas Acrílicas , Oro , Dentadura Completa , Ensayo de Materiales , Propiedades de SuperficieRESUMEN
Objectives: To determine the efficacy of whole-body vibration in the treatment of postnatal constipation. METHODS: The prospective, randomised, single-blind, pre-post, controlled trial was conducted from December 2020 to May 2021 at the outpatient clinic of the Obstetrics and Gynaecology Department, Kafrelsheikh University Hospital, Egypt, and comprised women with complaint of postnatal constipation. They were randomised into two groups. Group A was subjected to whole-body vibration in addition to diet instructions, pelvic floor exercises and static abdominal exercisesforsix weeks. Group B wassubjected to pelvic floor exercises,static abdominal exercises and diet instructions. Constipation symptom questionnaire and patient assessment of constipation quality of life questionnaire were used at baseline and post-intervention. Data was analysed using SPSS 25. RESULTS: Of the 40 women, 20(50%) were in each of the 2 groups. Group A mean age was 24.88±2.22 years, while it was 24±2.25 years in Group B. Age, height and body mass index were not significantly different between the groups (p>0.05). There was significant improvement in Group A quality of life and constipation severity (p<0.05). CONCLUSIONS: Whole-body vibration had positive impact on postpartum women's constipation symptoms and quality of life. RCT registration: NCT05286476, Link: https://clinicaltrials.gov/ct2/show/NCT05286476.
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Calidad de Vida , Vibración , Embarazo , Humanos , Femenino , Adulto Joven , Adulto , Vibración/uso terapéutico , Método Simple Ciego , Estudios Prospectivos , Diafragma Pélvico , Estreñimiento/terapia , Terapia por EjercicioRESUMEN
Non-small cell lung cancer (NSCLC) is an important sub-type of lung cancer associated with poor diagnosis and therapy. Innovative multi-functional systems are urgently needed to overcome the invasiveness of NSCLC. Carbon quantum dots (CQDs) derived from natural sources have received interest for their potential in medical bio-imaging due to their unique properties, which are characterized by their water solubility, biocompatibility, simple synthesis, and low cytotoxicity. In the current study, ethylene-diamine doped CQDs enhanced their cytotoxicity (98 ± 0.4%, 97 ± 0.38%, 95.8 ± 0.15%, 86 ± 0.15%, 12.5 ± 0.14%) compared to CQDs alone (99 ± 0.2%, 98 ± 1.7%, 96 ± 0.8%, 93 ± 0.38%, 91 ± 1.3%) at serial concentrations (0.1, 1, 10, 100, 1000 µg/mL). In order to increase their location in a specific tumor site, folic acid was used to raise their functional folate recognition. The apoptotic feature of A549 lung cells exposed to N-CQDs and FA-NCQDs was characterized by a light orange-red color under fluorescence microscopy. Additionally, much nuclear fragmentation and condensation were seen. Flow cytometry results showed that the percentage of cells in late apoptosis and necrosis increased significantly in treated cells to (19.7 ± 0.03%), (27.6 ± 0.06%) compared to untreated cells (4.6 ± 0.02%), (3.5 ± 0.02%), respectively. Additionally, cell cycle arrest showed a strong reduction in cell numbers in the S phase (14 ± 0.9%) compared to untreated cells (29 ± 0.5%). Caspase-3 levels were increased significantly in A549 exposed to N-CQDs (2.67 ± 0.2 ng/mL) and FA-NCQDs (3.43 ± 0.05 ng/mL) compared to untreated cells (0.34 ± 0.04 ng/mL). The functionalization of CQDs derived from natural sources has proven their potential application to fight off non-small lung cancer.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Puntos Cuánticos , Humanos , Carbono , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/tratamiento farmacológico , Microscopía Fluorescente , Ácido FólicoRESUMEN
BACKGROUND: Cancer-related pain is a complicated symptom that often coincides with fatigue, depression, and anxiety. Although many safe treatments are available, inadequate control of Cancer-related pain continues to lead to suffering in cancer patients. This study's aim is to describe pain control, and the pattern of change in opioid and adjuvant medication prescriptions, before and after referral to the Palliative Care Center. METHODS: We conducted a prospective cohort study in adult cancer patients the Palliative Care Center between January 1, 2016 and December 30, 2017. We measured pain intensity and other associated symptoms via the Revised Edmonton Symptom Assessment System (ESAS-r) and documented detailed analgesics and adjuvant medication history before starting any palliative care and on days 0, 3, 6, and 14. RESULTS: The analysis included 240 patients whose cancer-related pain, anxiety, and depression scores meaningfully improved by day 6. The changes in the median (interquartile ranges) of Cancer-related pain, anxiety, and depression scores from day 0 to day 6 were: 6 (4-8) to 3 (1-4); 6 (4-9) to 2 (1-4); and 3 (2-6) to 2 (1-4), respectively, with p < 0.001 for all. Morphine was the most common opioid administered; the percentage using it increased from 20.4% (n = 49) before referral to 49.6% (n = 119) on day 6 (p < 0.001). The median morphine equivalent daily dose decreased from a median (interquartile ranges) of 60(31-93) mg/day before referral to 34(22-66) mg/day on day 6 (p < 0.001). There was also a statistically significant increase in the percentage of patients taking adjuvant medications, from 38.8% before referral to 84.2% on day 6 (p < 0.001). Comparing D0 to D6, the number of patients using Gabapentinoids significantly increased from 57(23.75%) to 79(32.9%) (p < 0.001), amitriptyline dramatically increased from 14 (5.8%) to 44 (18.3%) (p < 0.001), and other antidepressant drugs increased from 15 (6.2%) to 34 (14.1%) (p < 0.001). CONCLUSION: After referral to the Palliative Care Center, patients' pain and other symptoms scores decreased significantly, even with lower median morphine equivalent daily doses, arguably through more appropriately directed opioid use. This is evidence for the effectiveness of the comprehensive program at the Palliative Care Center in Kuwait.
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Dolor en Cáncer , Neoplasias , Adulto , Analgésicos Opioides/uso terapéutico , Dolor en Cáncer/tratamiento farmacológico , Humanos , Kuwait , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Cuidados Paliativos , Prescripciones , Estudios Prospectivos , Derivación y ConsultaRESUMEN
BACKGROUND: The primary aim of the study is to evaluate the functional outcome following AMIC procedure in patients with osteochondral injury of the talus. The secondary aim is to evaluate if size of the lesion and patient's age influence outcome. MATERIALS AND METHODS: This is a retrospective study of 25 patients who underwent AMIC procedure of the talus treated by a single surgeon. Functional outcomes were evaluated using pre and post operative AOFAS and VAS scores. RESULTS: The mean lesion size was 1.74 cms with 88% of lesions in the study more than 1.4 cms. There was a significant improvement in AOFAS score with mean improvement of 49.40 (p < 0.05) and VAS score of 5.36 (p < 0.05). We could not find any correlation between either age or lesion size with functional outcome for AMIC procedure. CONCLUSION: AMIC procedure seems to be a reliable treatment method for larger diameter osteochondral lesions of the talus up to 2.5 cms in diameter.
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Traumatismos del Tobillo/cirugía , Matriz Ósea/trasplante , Condrogénesis , Cartílago Auricular/lesiones , Astrágalo/lesiones , Adolescente , Adulto , Anciano , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Tiempo , Trasplante Autólogo , Resultado del Tratamiento , Adulto JovenRESUMEN
Steroid cell tumors occur usually in the ovaries with very few reported cases of extra-ovarian origin. Our patient was a fifteen year old female, complaining from secondary amenorrhea and voice deepening. Values of serum cortisol, DHEA, FSH & LH were normal. Serum Testosterone was elevated while ACTH-pm was markedly elevated. MRI described bilateral solid para-ovarian masses. Exploration revealed two bilateral tubal extraluminal cysts & a right broad ligament cyst which were all excised. Pathological examination led to the diagnosis of steroid cell tumor. Serum testosterone & ACTH returned to normal levels after surgery with subsequent regression of the virilizing symptoms. We can conclude that extra-ovarian steroid cell tumors are extremely rare. They are usually presented with virilizing symptoms and hormonal abnormalities. Surgery is the main line of treatment.
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Síndrome de ACTH Ectópico/diagnóstico , Ligamento Ancho/patología , Neoplasias de las Trompas Uterinas/diagnóstico , Neoplasias Pélvicas/diagnóstico , Tumores de los Cordones Sexuales y Estroma de las Gónadas/diagnóstico , Síndrome de ACTH Ectópico/etiología , Síndrome de ACTH Ectópico/metabolismo , Adolescente , Hormona Adrenocorticotrópica/metabolismo , Ligamento Ancho/metabolismo , Egipto , Neoplasias de las Trompas Uterinas/complicaciones , Neoplasias de las Trompas Uterinas/metabolismo , Neoplasias de las Trompas Uterinas/patología , Femenino , Humanos , Neoplasias Pélvicas/complicaciones , Neoplasias Pélvicas/metabolismo , Neoplasias Pélvicas/patología , Tumores de los Cordones Sexuales y Estroma de las Gónadas/complicaciones , Tumores de los Cordones Sexuales y Estroma de las Gónadas/metabolismo , Tumores de los Cordones Sexuales y Estroma de las Gónadas/patología , Virilismo/diagnóstico , Virilismo/etiología , Virilismo/metabolismoRESUMEN
The present study aimed to explore the relationship between cyber-bullying and psychological security, psychological loneliness, and age. In other words, it sought to identify the predictive power of these three variables on cyber-bullying among university students. Participants were 426 male and female Saudi university students aged between 18 and 36 years (M = 21.00, SD = 2.42). Three scales were used to probe cyber-bullying and psychological security and loneliness. Data analysis revealed that 17.6% of the participants were cyber-bullies. Significant differences in cyber-bullying were found by gender (in favor of males). A significant positive correlation was found between cyber-bullying on one hand and psychological security and loneliness and age on the other. The findings also revealed that cyber-bullying among university students can be predicted by psychological loneliness and age. Psychological loneliness is the best predictor of cyber-bullying. It explained .284 of cyber-bullying, while age, psychological loneliness explained .339 of cyber-bullying. These findings shed more light on the psychological aspects included in cyber-bullying. It is a significant contribution in that it identified the motives beyond cyber-bullying and its adverse effects on individuals.
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Acoso Escolar , Víctimas de Crimen , Ciberacoso , Adolescente , Adulto , Femenino , Humanos , Internet , Soledad , Masculino , Estudiantes , Universidades , Adulto JovenRESUMEN
There are an increasing number of studies on smartphone addiction (SA) among students, and also a number of cross-cultural ones. We add to this body of research by presenting, for the first time, a cross-cultural study comparing students in four Middle Eastern countries: Sudan, Jordan, Saudi Arabia, and Yemen. In this context, we also attempt to replicate findings-in other studies-that there are differences in smartphone addiction prevalence along the lines of sex, culture and subject of study. These findings were indeed replicated in a Middle Eastern context. We found significant differences between the Jordanian sample and the other three samples, with Jordanians displaying higher SA. The Sudanese displayed higher SA than the Yemenis, and the Saudis higher than the Sudanese or the Yemeni. We also found that females displayed greater SA than males and humanities students greater SA than science students.
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Conducta Adictiva , Teléfono Inteligente , Estudiantes/psicología , Adolescente , Adulto , Comparación Transcultural , Cultura , Femenino , Humanos , Masculino , Medio Oriente , Factores Sexuales , Adulto JovenRESUMEN
This case involves a 53-year-old male who was diagnosed with stenotic ascending colon cancer and peritoneal metastatic deposits. He was initially planned for cytoreductive surgery and heated intraperitoneal chemotherapy (CRS and HIPEC), along with resection of the primary tumor in the form of right hemicolectomy. Intraoperatively, the disease was found to be more extensive than anticipated. Consequently, the plan was modified to include debulking right hemicolectomy with hand-sewn ileocolic anastomosis and extensive peritoneal procedures. Postoperatively, he experienced an anastomotic leak, leading to another laparotomy. However, due to anatomical challenges, creating a stoma was considered unsafe. Therefore, innovative interventions were performed, including controlling the anastomotic defect with a 30Fr Foley catheter without disrupting the anastomosis. A collaborative effort from various medical teams facilitated the patient's discharge home after an extended stay in the critical care unit (CCU).
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Common bile duct (CBD) stones are a common biliary tract disease. For asymptomatic CBD stones, stone removal by endoscopic retrograde cholangiopancreatography (ERCP) is recommended in available guidelines. Because asymptomatic CBD stones is a benign disease with no noticeable symptoms, the risk vs benefit strategy should be thoroughly considered before performing ERCP in these patients. Clinical care review, technical aspects of the procedure, and patient preferences should also be considered.
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A cyst of the canal of Nuck is an uncommon disorder in females. It results from the failure of obliteration of the peritoneal fold that runs along the round ligament. This case report details a unique and rare presentation of a 38-year-old female who presented with a right groin swelling. Although her preoperative images showed only the right canal of the Nuck cyst, the intraoperative diagnosis was established as a femoral hernia containing a canal of the Nuck cyst. She underwent an elective cyst excision with repair of the femoral hernia. She had an uneventful post-operative recovery. A femoral hernia that contains a cyst of the canal of Nuck is a rare manifestation of this uncommon condition. The most effective treatment options are surgical cyst excision and repair of the femoral hernia.
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AIM: Cardiac fibrosis is characterized by excessive accumulation of fibrous tissue, particularly collagens, in the myocardium. Accumulated fibrous tissue renders myocardium stiffer and reduces its contractility. Empagliflozin is an oral hypoglycemic agent with extra-diabetic functional profile toward maintaining cardiac functions. The present study aimed to examine protective effect of empagliflozin against an in-vivo model of cardiac fibrosis induced by isoprenaline and targeting TGF-ß/SMAD signaling as a possible pathway responsible for such effect. MAIN METHODS: Sixty animals were divided into six groups; the first was normal, and the second was treated with isoprenaline only (5 mg/kg/day I.P.) as a control. The third received pirfenidone (500 mg/kg/day P.O.), and the remaining groups received graded doses (5, 10, 20 mg/kg respectively) of empagliflozin for 14 days before fibrosis induction by isoprenaline (5 mg/kg/day) for 30 days. KEY FINDINGS: Isoprenaline increased cardiac enzymes, and cardiac tissues revealed elevated concentrations of transforming growth factor ß (TGF-ß1), monocyte chemoattractant protein 1 (MCP-1), tumor necrosis factor α (TNF-α), and c-jun N-terminal kinase (JNK) proteins. Expression of nuclear factor kappa B (NF-κB), alpha smooth muscle actin (α-SMA), collagens, suppressor of mothers against decapentaplegic (SMADs), connective tissue growth factor (CTGF), and fibronectin was upregulated. Empagliflozin improved the histological picture of heart tissue in comparison to fibrosis developed in controls, and protected against fibrosis through significant modulation of all mentioned parameters' concentrations and expressions. SIGNIFICANCE: Empagliflozin demonstrated a promising protective approach against biological model of cardiac fibrosis through an anti-fibrotic effect through targeting TGF-ß signaling pathways.
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Transducción de Señal , Factor de Crecimiento Transformador beta , Ratas , Animales , Factor de Crecimiento Transformador beta/metabolismo , Isoproterenol/toxicidad , Factor de Crecimiento Transformador beta1/metabolismo , Fibrosis , Colágeno/farmacologíaRESUMEN
Background: Vascular endothelial growth factor (VEGF) is the primary substance involved in retinal barrier breach. VEGF overexpression may cause diabetic macular edema (DME). Laser photocoagulation of the macula is the standard treatment for DME; however, recently, intravitreal anti-VEGF injections have surpassed laser treatment. Our aim was to evaluate the efficacy of intravitreal injections of aflibercept or ranibizumab for managing treatment-naive DME. Methods: This single-center, retrospective, interventional, comparative study included eyes with visual impairment due to treatment-naive DME that underwent intravitreal injection of either aflibercept 2 mg/0.05 mL or ranibizumab 0.5 mg/0.05 mL at Al-Azhar University Hospitals, Egypt between March 2023 and January 2024. Demographic data and full ophthalmological examination results at baseline and 1, 3, and 6 months post-injection were collected, including the best-corrected distance visual acuity (BCDVA) in logarithm of the minimum angle of resolution (logMAR) notation, slit-lamp biomicroscopy, dilated fundoscopy, and central subfield thickness (CST) measured using spectral-domain optical coherence tomography. Results: Overall, the 96 eyes of 96 patients with a median (interquartile range [IQR]) age of 57 (10) (range: 20-74) years and a male-to-female ratio of 1:2.7 were allocated to one of two groups with comparable age, sex, diabetes mellitus duration, and presence of other comorbidities (all P >0.05). There was no statistically significant difference in baseline diabetic retinopathy status or DME type between groups (both P >0.05). In both groups, the median (IQR) BCDVA significantly improved from 0.7 (0.8) logMAR at baseline to 0.4 (0.1) logMAR at 6 months post-injection (both P = 0.001), with no statistically significant difference between groups at all follow-up visits (all P >0.05). The median (IQR) CST significantly decreased in the aflibercept group from 347 (166) µm at baseline to 180 (233) µm at 6 months post-injection, and it decreased in the ranibizumab group from 360 (180) µm at baseline to 190 (224) µm at 6 months post-injection (both P = 0.001), with no statistically significant differences between groups at all follow-up visits (all P >0.05). No serious adverse effects were documented in either group. Conclusions: Ranibizumab and aflibercept were equally effective in achieving the desired anatomical and functional results in patients with treatment-naïve DME in short-term follow-up without significant differences in injection counts between both drugs. Larger prospective, randomized, double-blinded trials with longer follow-up periods are needed to confirm our preliminary results.
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Membrane sweeping is considered a simple and effective method for initiating spontaneous onset of labor. Despite the widely accepted membrane sweeping use to prevent post-term birth, the optimal frequency has not been estimated. We aimed to assess the effectiveness and safety of twice-weekly versus once-weekly membrane sweeping in post-term pregnancy prevention. Four different databases were searched for available clinical trials from inception to October 2022. We selected randomized controlled trials (RCTs) that compared twice-weekly membrane sweeping in intervention group versus once-weekly membrane sweeping in control group among pregnant women with singleton pregnancy at ≥ 39 gestational weeks. Our primary outcomes were the rate of spontaneous onset of labor and the requirement for formal methods of labor induction. Our secondary outcomes were sweeping to delivery interval in days, gestational age at delivery in weeks, Bishop score at admission, chorioamnionitis, and premature rupture of membranes. Three RCTs (596 patients) were included. Twice-weekly membrane sweeping was associated with significant increase in the rate of spontaneous onset of labor and significant decline in labor induction rate in comparison with once-weekly group. Duration from sweeping to delivery was significantly shorter among the twice-weekly group (p<0.001). Furthermore, gestational age at delivery was significantly earlier in the twice-weekly group. A significantly higher Bishop score at admission was observed in the twice-weekly group (p=0.02). There were no significant differences across both groups in chorioamnionitis and premature rupture of membranes. In conclusion, twice-weekly membrane sweeping is more effective in preventing post-maturity pregnancy than once-weekly sweeping without added adverse events.
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Trabajo de Parto , Obstetricia , Femenino , Humanos , Embarazo , Corioamnionitis/etiología , Trabajo de Parto Inducido/métodos , Resultado del Embarazo , Nacimiento Prematuro/etiología , Ensayos Clínicos Controlados Aleatorios como Asunto , Obstetricia/métodosRESUMEN
In this case report, we present a case of antisynthetase syndrome which is a rare disease that can be easily missed, if not specifically looked for in adults, whose initial presentation is combination of myopathic and respiratory symptoms. In clinical practice, patients presenting with coronavirus disease 2019 (COVID-19) symptoms, whose computed tomography (CT) imaging is consistent with COVID-19, were accordingly isolated and treated as COVID-19 awaiting reverse transcription polymerase chain reaction (RT-PCR) results. However, there are many COVID-19 mimics on chest CT, which can make the CT-based diagnosis of COVID-19 unsafe.
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OBJECTIVE: the aim of this study is to evaluate immunohistochemically the expression of ezrin, and moesin, in endometrial lesion cases in order to detect EC at early stages which will have an important implication on the patients' outcome. METHOD: 100 stored, formalin-fixed, paraffin-embedded tissue blocks of endometrial curettage obtained due to abnormal uterine bleeding or postmenopausal bleeding were collected. Each paraffin block was re-cut by rotatory microtome at 4 µm thickness then mounted on a glass slide and stained by hematoxylin and eosin for routine histopathological examination and on charged slides for immunohistochemistry using an automated staining system (Dako autostainer link 48) with antibodies against Moesin and Ezrin. Cytoplasmic staining was evaluated for both Moesin and Ezrin based on the intensity and extent of staining and scored for each sample. RESULT: Both Moesin and Ezrin were significantly higher in atypical endometrial hyperplasia compared to benign hyperplasia and significantly higher in endometrial carcinoma compared to atypical hyperplasia. Moesin also significantly correlated with higher tumor grades while Ezrin was significantly higher in postmenopausal women denoting their role in tumor progression and poor prognosis. CONCLUSION: Both Moesin and Ezrin could be potentially used as predictive markers for endometrial carcinoma screening programmes as well as indicators for cancer progression.
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Detección Precoz del Cáncer , Neoplasias Endometriales , Humanos , Femenino , Hiperplasia , Neoplasias Endometriales/diagnósticoRESUMEN
Disturbance in glucose metabolism was proposed to be a pathogenetic mechanism of breast cancer. Trimetazidine (TMZ) inhibits ß-oxidation of fatty acids through blocking the activity of 3-ketoacylCoA thiolase enzyme, leading to enhancement of glucose oxidation and metabolic respiration. The present study aimed to examine the cytotoxic effect of TMZ in both in vivo and in vitro models of breast cancer, focusing on its impact on the expression of some glycolytic enzymes and AKT signaling. The cytotoxic effect of TMZ was screened against breast (MCF-7) cancer cell line at different concentrations [0.01-100 µM]. In vivo, graded doses (10, 20, 30 mg/kg) of TMZ were tested against solid Ehrlich carcinoma (SEC) in mice. Tumor tissues were isolated for assessment of the expression of glucose transporter-1 (GLUT-1) and glycolytic enzymes by quantitative PCR. The protein expression of AKT and cellular myelocytomatosis (c-Myc) was determined by western blotting, while p53 expression was evaluated by immunohistochemistry. Molecular docking study of TMZ effect on AKT and c-Myc was performed using Auto-Dock Vina docking program. TMZ showed a cytotoxic action against MCF-7 cells, having IC50 value of 2.95 µM. In vivo, TMZ reduced tumor weight, downregulated the expression of glycolytic enzymes, suppressed AKT signaling, but increased p53 expression. Molecular docking and in silico studies proposed that TMZ is an AKT and c-Myc selective inhibitor. In conclusion, TMZ demonstrated a viable approach to suppress tumor proliferation in biological models of breast cancer.
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Carcinoma , Trimetazidina , Animales , Ratones , Proteínas Proto-Oncogénicas c-akt , Trimetazidina/farmacología , Trimetazidina/uso terapéutico , Simulación del Acoplamiento Molecular , Proteína p53 Supresora de TumorRESUMEN
OBJECTIVE: the aim of this study is evaluation of Topo IIa expression in laryngeal squamous cell carcinomas and correlation of this expression with various clinicopathological parameters. METHODS: ninety cases of laryngeal squamous cell carcinoma archived paraffin blocks were collected in the form of total laryngectomies. Each paraffin block was re-cut by rotatory microtome at 4 µm thickness and stained by hematoxylin and eosin for routine histopathological examination and on charged slides for immunohistochemistry using an automated staining system with antibodies against Topo IIa. Mainly nuclear and slightly cytoplasmic staining was considered positive. Percentage of positive Topo IIa cells was graded then grouped into low expression and overexpression. RESULTS: Topo IIa overexpression was seen in 91.1% of cases, while low expression was noticed in the remaining 8.9% of cases. There were statistically significant correlations between Topo IIa expression and tumor histological grade, lymph node metastasis and T stage as well as statistically significant positive correlation between Topo IIa expression as we progress from normal to dysplastic/in situ up to malignant transformation. CONCLUSION: High expression of Topo IIa may indicate more aggressive tumor and may play a role in tumorogenesis in laryngeal squamous cell carcinoma.
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Proteínas de Unión al ADN , Neoplasias de Cabeza y Cuello , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello , Proteínas de Unión al ADN/metabolismo , Parafina , Antígenos de Neoplasias/metabolismo , ADN-Topoisomerasas de Tipo II/metabolismoRESUMEN
Diabetic retinopathy (DRET) triggers vision loss in adults, however, little therapeutic options are existing. Memantine is an anti-Alzheimer drug that antagonizes the activity of glutamate at N-methyl-D-aspartate (NMDA) receptors. Glutamate and thioredoxin-interacting protein (TXNIP) are known to be overexpressed in diabetic retinas and can produce activation of NOD-like receptor protein 3 (NLRP3) with subsequent secretion of interlukin-1ß. This study repurposed memantine for its neuroprotective effect in experimental DRET and tested its impact on ROS/TXNIP/NLRP3. In addition, KEGG pathway database and STRING database identified the protein-protein interaction between glutamate receptors and TXNIP/NLRP3. Male Swiss albino mice received alloxan (180 mg/kg) to induce DRET. After 9 weeks, we divided the mice into groups: (a) saline, (ii) DRET, (iii and iv) DRET + oral memantine (5 or 10 mg per kg) for 28 days. Then, mice were euthanized, and eyeballs were removed. Retinal samples were utilized for biochemical, histopathological, and electron microscopy studies. Retinal levels of glutamate, TXNIP, NLRP3 and interlukin-1ß were estimated using ELISA technique as well as retinal malondialdehyde. Histopathological and ultrastructural examination demonstrated that oral memantine attenuated vacuolization and restored normal retinal cell layers. Moreover, memantine reduced TXNIP, NLRP3, interleukin-1ß and MDA concentrations. These results provide evidence demonstrating memantine' efficacy in alleviating DRET via suppressing reactive oxygen species/TXNIP/NLRP3 signaling cascade. Therefore, memantine might serve as a potential therapy for retinopathy after adequate clinical research.