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Background@#Glioblastoma is the most aggressive primary malignant brain tumor in adults and is characterized by poor prognosis. Immune evasion occurs via programmed death-ligand 1 (PD-L1)/programmed death receptor 1 (PD-1) interaction. Some malignant tumors have responded to PD-L1/PD-1 blockade treatment strategies, and PD-L1 has been described as a potential predictive biomarker. This study discussed the expression of PD-L1 and CD8 in glioblastomas. @*Methods@#Thirty cases of glioblastoma were stained immunohistochemically for PD-L1 and CD8, where PD-L1 expression in glioblastoma tumor tissue above 1% is considered positive and CD-8 is expressed in tumor infiltrating lymphocytes. The expression of each marker was correlated with clinicopathologic parameters. Survival analysis was conducted to correlate progression-free survival (PFS) and overall survival (OS) with PD-L1 and CD8 expression. @*Results@#Diffuse/fibrillary PD-L1 was expressed in all cases (mean expression, 57.6%), whereas membranous PD-L1 was expressed in six of 30 cases. CD8-positive tumor-infiltrating lymphocytes (CD8+ TILs) had a median expression of 10%. PD-L1 and CD8 were positively correlated (p = .001). High PD-L1 expression was associated with worse PFS and OS (p = .026 and p = .001, respectively). Correlation of CD8+ TILs percentage with age, sex, tumor site, laterality, and outcomes were statistically insignificant. Multivariate analysis revealed that PD-L1 was the only independent factor that affected prognosis. @*Conclusions@#PD-L1 expression in patients with glioblastoma is robust; higher PD-L1 expression is associated with lower CD8+ TIL expression and worse prognosis.
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BACKGROUND@#Lung fibrosis is considered as an end stage for many lung diseases including lung inflammatory disease, autoimmune diseases and malignancy. There are limited therapeutic options with bad prognostic outcome. The aim of this study was to explore the effect of mesenchymal stem cells (MSCs) derived from bone marrow on Bleomycin (BLM) induced lung fibrosis in albino rats. @*METHODS@#30 adult female albino rats were distributed randomly into 4 groups; negative control group, Bleomycin induced lung fibrosis group, lung fibrosis treated with bone marrow-MSCs (BM-MSCs) and lung fibrosis treated with cell free media. Lung fibrosis was induced with a single dose of intratracheal instillation of BLM. BM-MSCs or cell free media were injected intravenously 28 days after induction and rats were sacrificed after another 28 days for assessment. Minute respiratory volume (MRV), forced vital capacity (FVC) and forced expiratory volume 1 (FEV1) were recorded using spirometer (Power lab data acquisition system). Histological assessment was performed by light microscopic examination of H&E, and Masson’s trichrome stained sections and was further supported by morphometric studies. In addition, electron microscopic examination to assess ultra-structural changes was done. Confocal Laser microscopy and PCR were used as tools to ensure MSCs homing in the lung. @*RESULTS@#Induction of lung fibrosis was confirmed by histological examination, which revealed disorganized lung architecture, thickened inter-alveolar septa due excessive collagen deposition together with inflammatory cellular infiltration. Moreover, pneumocytes depicted variable degenerative changes. Reduction in MRV, FVC and FEV1 were recorded. BM-MSCs treatment showed marked structural improvement with minimal cellular infiltration and collagen deposition and hence restored lung architecture, together with lung functions. @*CONCLUSION@#MSCs are promising potential therapy for lung fibrosis that could restore the normal structure and function of BLM induced lung fibrosis.
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BACKGROUND@#Lung fibrosis is considered as an end stage for many lung diseases including lung inflammatory disease, autoimmune diseases and malignancy. There are limited therapeutic options with bad prognostic outcome. The aim of this study was to explore the effect of mesenchymal stem cells (MSCs) derived from bone marrow on Bleomycin (BLM) induced lung fibrosis in albino rats. @*METHODS@#30 adult female albino rats were distributed randomly into 4 groups; negative control group, Bleomycin induced lung fibrosis group, lung fibrosis treated with bone marrow-MSCs (BM-MSCs) and lung fibrosis treated with cell free media. Lung fibrosis was induced with a single dose of intratracheal instillation of BLM. BM-MSCs or cell free media were injected intravenously 28 days after induction and rats were sacrificed after another 28 days for assessment. Minute respiratory volume (MRV), forced vital capacity (FVC) and forced expiratory volume 1 (FEV1) were recorded using spirometer (Power lab data acquisition system). Histological assessment was performed by light microscopic examination of H&E, and Masson’s trichrome stained sections and was further supported by morphometric studies. In addition, electron microscopic examination to assess ultra-structural changes was done. Confocal Laser microscopy and PCR were used as tools to ensure MSCs homing in the lung. @*RESULTS@#Induction of lung fibrosis was confirmed by histological examination, which revealed disorganized lung architecture, thickened inter-alveolar septa due excessive collagen deposition together with inflammatory cellular infiltration. Moreover, pneumocytes depicted variable degenerative changes. Reduction in MRV, FVC and FEV1 were recorded. BM-MSCs treatment showed marked structural improvement with minimal cellular infiltration and collagen deposition and hence restored lung architecture, together with lung functions. @*CONCLUSION@#MSCs are promising potential therapy for lung fibrosis that could restore the normal structure and function of BLM induced lung fibrosis.
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OBJECTIVE@#Nutraceutical products are widely used for their claimed therapeutic benefits. However, falsified or adulterated nutraceuticals present a major health threat to consumers. This study investigates the pharmaceutical quality, safety and anti-inflammatory effects of six male enhancement nutraceuticals that claim to be 100% natural.@*METHODS@#Three batches of six male enhancement products were tested to detect the presence and levels of adulterants via high-performance liquid chromatography (HPLC). The pharmaceutical quality of the selected nutraceuticals was tested with near infrared spectroscopy (NIR) and SeDeM. The cytotoxic effects of these products on HepG2 cells were determined through cell proliferation (XTT) and lactate dehydrogenase (LDH) cytotoxicity assays. Lastly, the in vitro inflammatory effects of these products were investigated using murine J774 macrophages through cytokine release analysis.@*RESULTS@#HPLC analysis detected the presence of sildenafil citrate, a vasodilator, and the active ingredient in Viagra and Revatio, in all batches of the products we analyzed. Amount of sildenafil citrate ranged from 0.45 mg to 51.85 mg among different batches. NIR assessment showed inter- and intra-batch heterogeneity in product composition. Results of the XTT and LDH assays showed significant cytotoxic effects of the analyzed products. XTT analysis revealed that the viability of HepG2 treated with tested products varied from 27.57% to 41.43%. Interestingly, the male enhancement products also showed anti-inflammatory effects.@*CONCLUSION@#Despite their labeling as 100% natural, all products tested in this study contained levels of sildenafil citrate, which was not reported on the packaging. There was a lack of pharmaceutical uniformity among products of the same batch and across different batches. Additionally, the products we tested had cytotoxic effects. These study findings highlight the adulteration, poor quality and hazard of these nutraceuticals. Therefore, strict regulation of these products and standardization of the definition of nutraceuticals are urgently needed. Further, these falsely advertised products should be withdrawn from the market due to potential adverse effects on the health of their consumers.
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OBJECTIVE@#This study investigated cytotoxicity and induction of apoptosis in human cervical cancer cells (HELA) and prostate cancer cells (PC-3) using the most active fraction of Moringa peregrina seed extract.@*METHODS@#Dried and powdered seeds were extracted using 95% ethanol. The total ethanolic extract was further dissolved in distilled water and separated into petroleum ether, chloroform, ethyl acetate and aqueous extracts. Based on the results of in vitro anticancer studies of all extracts, the most highly active extract was selected for evaluation of apoptosis induction and cell cycle analysis on HELA and PC-3 cells at its half maximal inhibitory concentration using flow cytometry; DNA fragmentation by agarose gel electrophoresis and the expression of protein were measured by Western blot.@*RESULTS@#The chloroform fraction from the ethanolic extract of M. peregrina (CFEE) was the most active antitumor fraction. The selectivity index, determined using the normal Vero cell line, indicated that CFEE had a high degree of selectivity against HELA and PC-3 cells. CFEE induced apoptosis, confirmed by cell cycle arrest at sub-G phase and DNA fragmentation. CFEE induced an increase in mRNA expression of caspase-3, a decrease in Bcl-2 mRNA expression, and decreased ATP levels. CFEE increased protein expression of caspase-3 and decreased protein expression of poly-ADP-ribose polymerase-1 (PARP-1). Flow cytometric analysis showed an appreciable increase in the number of cells in the early apoptotic stage in CFEE-treated HELA and PC-3 cells. CFEE treatment significantly increased lipid peroxidation (malondialdehyde level) in HELA and PC-3 cells.@*CONCLUSION@#Seed extract of M. peregrina displayed a significant antitumor effect through apoptosis induction in HELA and PC-3 cells.
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An association between obesity and cardiac mass has been recognized for almost two decades, whereas the precise nature of the association remains elusive Theoretical consideration have long suggested that it may be mediated at least in part by insulin resistance [Mc, Nutly ,2003].Several studies have found an association between insulin resistance and left ventricular hypertrophy. [Lacobellis et al, 2003]. In human, production of leptin[ an adipocyte - derived peptide], has been linked to obesity, insulin and insulin sensitivity [Leyva et al, 1998]. It was considered that alteration in plasma concentration could constitute an additional component of metabolic syndrome of cardio-vascular risk[Leyva et al, 1998]. The aim of this work was to evaluate the relationship between obesity, insulin resistance, leptin and left ventricular mass and function in young obese females with insulin resistance. Sixty five premenopausal females aged 25-45 years with no history of diabetes or hypertension was participated in this study. Twenty were non obese and forty five were obese .Fasting serum glucose, insulin and leptin were assessed and homeostatic model assessment HOMA-IR score was calculated. According to HOMA-IR obese premenopausal females were divided into 2 subgroups: - Subgroups 1: [Insulin sensitive group or IS group] included 20 obese females with HOMA-IR <3.8.And Subgroup 2: [insulin resistance group or IR group] included 25 obese females with HOMA-IR>/=3.8.Echocardiography was done for all females participated in the study to evaluate L.V mass and function. Waist circumference [WC], serum insulin, serum leptin and HOMA-IR were significantly higher in obese group compared to non obese group [p<0.05, <0.05, <0.001 and <0.00l respectively] and between IR and IS subgroups [p<0.05, <0.05, <0.001 and <0.00l respectively].As regard Echocardiographic studies left ventricular mass[LVM] and left ventricular mass corrected t height 2.7 [LVM/h2.7 ]were significantly higher in obese group compared to non obese group [p<0.05] and between IR and IS subgroups [p<0.05 for both],while the ratio between peak transmitral E and A wave velocity[E/A ratio] was lower in obese group compared to non obese group [<0.05], it was also lower in IR subgroup compared to IS subgroup [p<0.05].There was positive significant correlation between LVM and LVM/H2.7 and serum insulin [p<0.05]and serum leptin [p<0.05] in IS subgroup while the correlation was highly significant between both and fasting leptin [p<0.001] in IR subgroup. Obesity is a clinical syndrome associated with hyperinsulinemia, hyperleptinemia and insulin resistance Abnormalities of LV diastolic function and mass occur frequently in obese patients. Hyperleptinemia can be an early sign for left ventricular dysfunction in obese females
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Humanos , Femenino , Adulto , Persona de Mediana Edad , Leptina/sangre , Función Ventricular Izquierda , Obesidad , Premenopausia , Hipertensión , Diabetes Mellitus , GlucemiaRESUMEN
To determine the histological and immunohistochemical alterations of human penile cavernosal tissue in venogenic erectile dysfunction [ED] compared with potent controls regarding collagen fibres, elastic fibres, smooth muscle content and inducible nitric oxide synthase [i-NOS] expression. Cavernous biopsies were obtained from four potent men [two with penile fracture and two with congenital penile curvature] regarded as controls and from 15 patients with venogenic ED undergoing implantation of penile prosthesis. The specimens obtained were subjected to haematoxylin and eosin, Masson's trichrome and orcein stains and antismooth muscle alpha-actin and i-NOS immunostaining. Evaluation was carried out using computerized morphometric analysis and results were statistically compared. A significant increase of collagen fibres with reduced smooth muscle and elastic fibre content was shown in patients with venogenic ED compared with controls. There was also an increased expression of i-NOS immuonoreactivity. Histological alterations of cavernosal tissue structure in venogenic ED point to progressive fibrosis. Early diagnosis by penile biopsy may help to combat fibrosis and preserve the integrity of erectile tissue and accordingly the penile erection
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Humanos , Masculino , Disfunción Eréctil , InmunohistoquímicaRESUMEN
Preterm neonates comprise the most heavily transfused group of patients, and about 85% of extremely low birth weight newborns receive a transfusion by the end of their hospital stay. The aim of this study was to assess the possible metabolic effects of RBC transfusion on preterm infants especially during the first 2 weeks of life, and its relation to blood volume. This study was conducted on 40 preterm neonates with gestational age of less than or equal to 34 weeks. They received RBCs transfusion during first 2 weeks of life. Venous blood samples of infants were collected 2 to 4 hours before and 1 hour after the end of transfusion to evaluate hemoglobin [Hb] level, hematocrit, acid-base, electrolytes, and glucose status. Then infants were classified into two main groups: those who received RBCs volume less than or 20 ml/kg and those who received RBCs volume more than 20 ml/kg. Infants received a mean volume of 20.38 +/- 3.2 ml per kg RBCs [range 10.9 -26.6 ml/kg] at a median age of 9.8 +/- 3.6 days. After transfusion, a significant increase of mean Hb [p<0.001], mean Hct [p<0.001], pH [p<0.001], pO2 [p<0.05] and a significant decrease of the pCO2 [41.46 +/- 8.8torr vs. 35.4 +/- 9.34torr; p<0.001] were observed. In addition, there was a significant increase of serum K[+] [p<0.001], and a significant decrease of Ca[+2] [p<0.001].A positive correlation was found between the K[+] intake and the changes of kalemia [r=0.99; p=0-00]. Furthermore we observed an inverse correlation between the patients calcium intake and the changes of calcemia [r=-0.35; p=0.02]. On comparing the changes in clinical and biochemical variables between two groups after transfusion, we observed a significant increase in mean Hb and Hct associated with a significant decrease in mean serum Ca[+2] [p<0.001] in the group receiving the larger blood volume. RBCs transfusion was effective in improving anemia, oxygenation, increasing pH and decreasing CO2 and Ca[+2]. However, from a more clinically relevant point of view we demonstrated the development of hyperkalemia, especially in infants with a previously borderline hyperkalemia
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Humanos , Masculino , Femenino , Transfusión Sanguínea/efectos adversos , Equilibrio Ácido-Base , Glucemia , Electrólitos , HiperpotasemiaRESUMEN
Objectiver lnterstitial cells of Cajal [ICC] are c-kit positive immunoreactive cells which are thought to play an important role in the control of gut motility. The work aimed at studying the morphology of ICC and precisely localize their regional and transmural pattern of distribution in normal human alimentary tract. The study included 102 normal human alimentary tract specimens obtained from male patients with a mean age 37.92 +/- 8.53. All sections were stained with hematoxylin and eosin and c-kit immunohistochemical staining. Immunohistochemically stained sections were submitted for a computer aided image analytical study to detect the area percent of immunoreactive cells. The data obtained was statistically analyzed. ICC could not be demonstrated in H and E stained sections. Immunohistochemically, two morphological subtypes of ICC were recognized, a spindle bipolar and stellate multipolar forms. ICC were detected in the myenteric plexus layer of the esophagus, corpus, pylorus, small intestine, colon and rectum. Intramuscular ICC could be demonstrated in the esophagus, fundus, corpus, pylorus, colon, rectum and anal canal. ICC at the deep muscular plexus were found only in the small intestine. In the pylorus, colon and rectum, ICC were also found at the submucosal border of the circular muscle layer. The wide distribution of ICC all over the human alimentary tract is compatible with their physiological role being important mediators of gut motility
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Humanos , Masculino , Células Intersticiales de Cajal/patología , Neoplasias del Sistema Digestivo , Inmunohistoquímica , /métodos , Biopsia/estadística & datos numéricosRESUMEN
Bronchopulmonary dysplasia [BPD] or chronic lung disease [CLD] is a disorder of lung injury and repair originally ascribed to positive pressure mechanical ventilation and oxygen toxicity. Matrix metalloproteinases [MMPs] including MMP9 act in remodeling and destruction of extracelluar lung matrix and basement membranes. Tissue inhibitor metalloproteinase 1 [TIMP1] is the specific tissue inhibitor of MMP9. Imbalance in the level of MMP9 relative to its inhibitor TIMP1 has been implicated in matrix disruption and remodeling with further development of [CLD]. to study the value of rising ratio MMP9/ TIMP1 in serial TAF samples in prediction of CLD in neonates needing mechanical ventilation for a long duration. A prospective study conducted on 48 preterm neonates having respiratory distress syndrome [RDS] recruited from NICU of Kasr El Eini Hospital. They were all receiving mechanical ventilation. Their mean gestational age [GA] was 32.03 +/- 1.07 weeks and mean birth weight [BW] was 1118 +/- 93.38 gm. They were subjected to 3 serial tracheal aspirate fluid collections [TAF] during the routine tracheal lavage. 1st sample was collected during the 1st 24 hours of life, 2nd sample during the period from the 8th to the 11th day postnatal and the 3rd sample during the period from the 12th to the 16th day postnatal. Levels of MMP9 and TIMP1, were measured using ELISA technique. Ratio MMP9/TIMP1 was calculated. Patients who completed the 3 serial samples were subdivided into 2 groups: Group I: including patients who developed CLD and Group II including patients who did not develop CLD. Ratio of MMP9/TIMP1 was compared in the 3 serial samples in both groups. 18 neonates died before they completed the 3 successive samples and were excluded from the final analysis of the study. The results of the present study showed that MMP9/TIMP1 ratio was rising over the 3 successive samples in CLD group. In 1st sample ratio in CLD group was 3.6 +/- 0.92 versus 3.32 +/- 0.8 in no CLD group P Value 0.426 non significant but ratio rises in 2nd samples to reach 5.12 +/- 1.44 in CLD group versus 3.30 +/- 0.82 in no CLD group p value 0.002 highly significant. In the 3rd sample the ratio rises more to be 6.50 +/- 1.79 in CLD group versus 3.09 +/- 0.78 in no CLD group P Value 0.001 very highly significant. A rising ratio MMP9/ TIMP1 in TAF in early life might be of use as a predictor for the development of CLD in ventilated neonates. Supplementation of tissue inhibitor [TIMP1] when available could be an effective strategy in the prophylaxis and treatment of CLD