Background
Nasopharyngeal carcinoma (NPC) is a rare pediatric cancer. Most children are first diagnosed with advanced locoregional disease. Identification of patients at higher risk of treatment ...failure is crucial as they may benefit from more aggressive initial treatment approaches. 18Fluorine‐labeled fluoro‐2‐deoxyglucose positron emission tomography (18F‐FDG PET) has shown promise as a prognostic tool for predicting outcomes.
Methods
Retrospective study of pediatric patients with locally advanced undifferentiated NPC who underwent 18F‐FDG PET/CT prior to intial treatment. Predictive significance of metabolic PET parameters on survival outcomes were estimated.
Results
Thirty‐two children were included, age range was 7.1–18 years at the time of diagnosis. The median follow‐up duration was 46.1 months. Three patients (9.4%) were classified as AJCC stage IIb, 13 patients (40.6%) as stage IIIa, eight patients (25%) as stage IIIb, and eight patients (25%) as stage IVa. Our findings revealed that high whole‐body metabolic tumor volume at the threshold of hepatic reference SUVmean (WB‐MTV‐HR) (>135 mL) was associated with significantly lower event‐free survival (EFS) compared to the low WB‐MTV‐HR group (≤135 mL) (3‐year EFS: 50% ± 18% vs. 82% ± 8%; p = .015). Additionally, the 3‐year overall survival (OS) rates differed significantly between the high whole‐body metabolic tumor volume at the threshold of an SUV of 2.5 isocontour (WB‐MTV‐2.5) group (MTV >74 mL) and the low WB‐MTV‐2.5 group (MTV ≤74 mL) (63% ± 18% vs. 100%; p = .021).
Conclusion
Our study suggests that WB‐MTV parameters could serve as significant prognostic factors for disease progression in pediatric patients with locally advanced undifferentiated NPC. However, further prospective studies with larger sample sizes are needed to validate these findings.
Background: In patients undergoing coronary intervention, different vasodilators are used to prevent the radial artery spasm (RAS). To date, no studies investigated the effect of these vasodilators ...in blood pressure (BP) reduction.
Aim: The study aimed to investigate and compare the effect of vasodilatory medications on BP reduction in patients undergoing transradial coronary angiography procedure.
Methods: We consecutively included 300 patients undergoing transradial coronary angiography procedures and randomly assigned them into three equal groups to compare the effect of verapamil (2.5 mg), nitroglycerin (200 μg), and combination (verapamil 2.5 mg with nitroglycerin 200 (μg) was diluted in 5 ml of normal saline and given through radial sheath. Changes in the BP, heart rate (HR), and other clinical parameters were assessed and presented as standardized mean differences (SMD) with 95% confidence intervals (CIs). ANOVA test was performed to analyze the differences in the BP and other clinical parameters between the three groups.
Results: Overall, the mean age of the study population was 53.26 years (standard deviation: 9.27), male patients (84%), with dyslipidemia (62.6%), and diabetes (45%). At baseline, the mean systolic BP (SBP) was 150.91 ± 31.66 mmHg, HR (72.34 ± 12.71 beats/min). After the administration of vasodilators, the combination group reduced SBP significantly (SMD: −33.35 95% CI: −40.27-−26.42, P < 0.001). There was a statistically significant difference between groups for the SBP (F2,296 =3.38, P = 0.035). Verapamil alone showed a significant decrease in the SBP by −27.23 mmHg and diastolic BP by −4.980 mmHg.
Conclusion: Intra-arterial administration of verapamil alone showed lower BP reduction compared to the combination of vasodilators. Verapamil could be a safer and effective alternative to prevent RAS with no deleterious effect on BP and HR in patients undergoing transradial coronary angiography.
In the present study, 200 Brown commercial egg-type layers (60 wk old) were used to study the effects of different levels of ecofriendly synthesis of calcium (Ca) nanoparticles (0.0, 0.50, 1.0, and ...1.5 g/kg diet) with biocompatible Sargassum latifolium algae extract (SL-CaNps) on exterior egg quality traits, electronic microscopic view of eggshells, Ca and phosphorus (P) retention, serum Ca and P concentrations, and the histology of the uterus. Hens fed with dietary SL-CaNps powder had higher egg weight and shell weight % values than those of the control group. All SL-CaNps treatment groups had the greatest values of shell weight per unit surface area and shell thickness. Dietary supplementation of SL-CaNps at graded levels up to 1.5 g/kg diet had higher serum Ca and inorganic P levels than that of the control. Laying hens fed with SL-CaNps-added diets had beneficial effects on shell ultrastructure in terms of well-developed palisade and mammillary layers. The numbers of apical cells along the branched tubular gland were greater in SL-CaNps-treated groups than those of control. Conclusively, supplementing SL-CaNps powder up to 1.5 g/kg to the diet of laying hens improved eggshell thickness, shell weight% and shell weight per unit surface and has no adverse effect on their eggshell quality or electronic microscopic view of their eggshell.
Growing evidence suggests the important role of IL-36 in the pathogenesis of psoriasis. Cathepsin G is a neutrophil-derived protease that can activate IL-36γ.
To assess the expression of IL-36γ and ...cathepsin G in psoriasis and to quantify the impact of treatment with narrow-band ultraviolet B phototherapy (NB-UVB) on their levels.
This case-control study involved 26 patients with moderate-severe psoriasis and 25 healthy volunteers. Psoriasis patients eligible for phototherapy received 24 NB-UVB sessions. Punch skin biopsies were obtained from all participants at recruitment and after phototherapy from patients. Real-time PCR was utilized for quantitative assessment of IL-36γ and cathepsin G expression in tissue samples.
The expression of IL-36γ and cathepsin G was significantly higher in psoriasis before NB-UVB therapy compared to controls (p < .001). Both proteins decreased significantly with clinical improvement following NB-UVB therapy compared to baseline (p < .001). However, their expression after treatment was still higher than controls (p < .001).
IL-36γ and cathepsin G expression is upregulated in psoriatic lesions, supporting their role as mediators of inflammation in psoriasis. Downregulation of IL-36γ and cathepsin G is a possible mechanism for psoriasis improvement after NB-UVB therapy. IL-36 and cathepsin G can be considered as therapeutic targets for psoriasis.
Diabetic nephropathy DN is one of the most prevalent microvascular complications of diabetes mellitus DM and it is considered a leading cause of kidney failure. In this study calycosin, an isoflavone ...that constitutes the major constituent in Radix Astragali with numerous pharmacological merits was investigated as reno-protective agent against DN and also the potential underlying mechanisms were investigated. Streptozotocin (STZ) (40 mg/kg) was injected in the peritoneal cavity of male Sprague-Dawely rats to induce DM. For ten weeks, calycosin (5 and 10 mg/kg), and NAC (500 mg/kg) were orally administered and they significantly lowered blood glucose levels, but significantly increased insulin levels. Calycosin improved the deteriorated kidney functions as evidenced in retracted serum creatinine, albuminuria, blood urea nitrogen, and proteinuria levels. Meanwhile, urine creatinine clearance significantly escalated. Furthermore, biomarkers of cell injury; LDH activity, significantly declined and kidney content of NO markedly decreased as well. Inflammation, fibrosis and oxidative stress were manifested by increased serum levels of IL-1β, renal NF-κBp65, NLRP3, TXNIP and MDA contents with declined levels of IL-10 and TAC and decreased Nrf2 expression. The above-mentioned biomarkers were significantly improved with calycosin treatment which modulated NF-κB/p65/NLRP3/TXNIP signaling, oxidative stress, inflammatory cytokines and fibrotic processes; Thus, implying a reno-protective impact. This was associated with improvement in renal histopathological and immune-histopathological parameters; H&E, Masson Trichrome and Nrf-2. Based on these findings, calycosin can be presumed to be a promising drug for hindering the development of DN through modulation of NF-κB/p65/NLRP3/TXNIP inflammasome signaling pathway.
Diabetic nephropathy (DN) is a diabetic complication characterized by disruption of renal microvasculature, reactive oxygen species accumulation and increased inflammation, all of which contribute to ...renal injury. Phenethyl isothiocyanate (PEITC) is a naturally occurring isothiocyanate well known for its antioxidant and anti-inflammatory effects, yet its reno-preventive effects against DN has not been investigated. The current study looked into the in vivo reno-protective effects of PEITC in STZ-induced DN in rats. PEITC (3, 10 and 30 mg/kg) was administered orally for 8 weeks post DM establishment. PEITC treatment significantly improved kidney and liver functions, renal histopathological features, tissue fibrosis, macrophage infiltration and blood glucose levels compared to DN control. Mechanistically, PEITC treatment alleviated DN-induced renal damage via modulating glycation and oxidative stresses and inflammatory response. As such, PEITC activated glyoxalase 1 (GLO1) that induced a retraction in renal tissue expression of advanced glycation end products (AGEs) and its receptor (RAGE). PEITC activated nuclear erythroid 2-related factor 2 (Nrf2) and increased expression of its downstream targets, hemeoxygenase-1 (HO-1) and gamma glutamate-cysteine (γ-GCS). Additionally, PEITC treatment decreased the expression of Nrf2 repressor protein, keap1. The anti-inflammatory effect of PEITC was driven, at least in part, via reducing the NLRP3 inflammasome activation as indicated by down regulation of NLRP3, TXNIP, capsase-1 and IL-1β, TNF-alpha and IL-6. In conclusion; PEITC attenuated DN progression in a dose dependent manner mainly via interruption of AGE/RAGE and NLPR3/TXNIP/NrF2 crosstalk.
Display omitted
•A series of hybridized benzothiazole pyrimidine-based on targeting EGFR/HER2 and TS enzymes was designed and synthesized.•They were submitted to NCI for preliminarily cytotoxic ...screening.•The (IC50) of the most active compounds was performed using the MTT assay method.•Enzyme inhibition assay for EGFR /HER2 enzymes was examined.•Enzyme inhibition assay for TS enzyme was performed.•Molecular docking into EGFR, HER2 and TS binding sites was performed.
Multi-targeted anticancer drugs are in focus as a promising research topic. A new series of benzothiazoles hybridized with pyrimidine moiety was designed and synthesized using the lead compound 4a. Various chemical modifications on the pyrimidine ring of 4a at four different positions were done in a trial to get new multi-targeted anticancer agents. The structures of the newly synthesized compounds were established on their elemental analyses and spectral data. All final synthesized derivatives were submitted to the National Cancer Institute (NCI), USA, to be screened for their in vitro anticancer activity. Further evaluation for the cytotoxic activity of the most active compounds was performed using the MTT assay method. Compounds 4d, 8d, 8h, 8i and 17 were then selected for examining their in vitro enzyme inhibitory activities against EGFR, HER2 and TS enzymes using lapatinib and 5FU as standards. Furthermore, cell cycle analysis and apoptosis induction detection were also evaluated. Finally, molecular docking studies were carried out for compounds 4d, 8d, 8h, 8i and 17 to interpret their observed enzymatic activities based on the ligand–protein interactions.
Breast cancer prevalence has been globally increasing, therefore, introducing novel interventions in cancer treatment is of a significant importance. The present study was designed to investigate the ...anti-cancer effect of Canagliflozin (CNG) in an experimental model of DMBA-induced mammary carcinoma in female rats.
18 female rats were divided into three experimental groups: Normal control, DMBA control, DMBA+ CNG treated group. DMBA (7.5 mg/kg) was injected subcutaneously in the mammary cells twice weekly for 4 weeks and CNG (10 mg/kg) was orally administered daily for an additional 3 weeks while DMBA control rats only received the vehicle for 3 weeks. Tumors’ weight and volume were measured, BRCA-1 and TAC were quantified in serum samples, mTOR, caspase-1, NFκB, IL-1β, NLRP3, GSDMD and MDA were quantified in tumors’ homogenates. Results: CNG treatment increased the BRCA-1 expression, suppressed mTOR inflammatory pathway, attenuated tumor inflammatory mediators; NLRP3, GSDMD, NFκB, IL-1β, suppressed the oxidative stress and inhibited tumor expression of the proliferation biomarker; Ki67.
CNG modulated mTOR-mediated signaling pathway and attenuated pyroptotic, inflammatory pathways, suppressed oxidative stress and eventually inhibited DMBA-induced mammary carcinoma proliferation.
Display omitted
•Crocin has chemo-preventive effect against experimentally-induced hepatocarcinogenesis.•Crocin modulated both intrinsic/extrinsic apoptotic pathways.•Crocin increased Nrf2 signaling pathway and HO-1 ...expression.•Crocin suppressed Keap-1 expression and hepatic content of c-JNK.
The results of the current study investigated the chemo-preventive effect of crocin against hepatocarcinogenesis in rats with particular focus on the evaluation of the modulatory impact of crocin on apoptotic and nuclear factor erythroid 2–related factor 2 (Nrf2) signaling pathways. Thioacetamide (TAA) (200 mg/kg, I.P.) was used for experimental induction of hepatocarcinogenesis in rats. Crocin administration significantly attenuated TAA-induced cancerous lesions with concomitant attenuation of impaired liver functions. This was associated with significant enhancement in hepatic Nrf2 and heme oxygenase-1 (HO-1) expression with parallel suppression in Keap-1 expression. Inline, crocin induced a significant improvement in hepatic oxidative status with enhanced antioxidant batteries. Crocin administration significantly suppressed the hepatic content of c-Jun N-terminal kinase (c-JNK) with significant upregulation in TNF-related apoptosis-inducing ligand (TRAIL) and caspase-8 protein expression as well as p53 gene expression; biomarkers of apoptosis. Moreover, hepatic expression of the apoptotic BAX significantly increased and the anti-apoptotic Bcl-2 significantly decreased in the liver specimen; biomarkers of intrinsic apoptosis. In conclusion; crocin attenuates experimentally induced hepato-carcinogenesis via modulation of oxidative/apoptotic signaling. Namely, crocin induced hepatic expression of Nrf2 with downstream modulation of endogenous HO-1 and Keap-1 signaling with modulation of various key players of apoptosis including; c-JNK, p53, TRAIL, caspase-8, BAX, and Bcl-2.
Diacerein (DIA) is an FDA approved anti‐inflammatory drug. Over the past few years, several studies reported its anti‐proliferative action against different types of cancers. However, the anti‐tumor ...effect against colon cancer remains obscure. Colon cancer is one of the top solid tumors diagnosed around the world. The current study aims to investigate DIA‐associated anti‐tumor effect In vivo and invitro and to further elaborate the potential underling molecular mechanism. In vitro, human Caco‐2 colon cancer cell lines were treated with serial dilution of DIA and were evaluated for cell viability and apoptotic percentages via MTT and Annexin V assays, respectively. In vivo, subcutaneous injection of 1,2‐dimethylhydrazine (DMH) (20 mg/kg for 15 weeks) was used to induce colon carcinogenesis. DIA oral administration at dose of 50 mg/kg/day for additional of 8 weeks was tested. This therapeutic regimen showed significant anti‐tumor effect and improvement of colonic tissue structure as evident by histopathological examination. Mechanistically, colon tissue samples were collected for ELISA and immunohistochemical analyses. Data showed that DIA treatment reduced colonic inflammatory status as evident by reduction of TLR4, NF‐κB and TNF‐α protein levels. In addition, DIA treatment reduced angiogenesis levels as evident by downregulation of VEGF tissue expression levels. Furthermore, DIA treatment modulated Wnt/β‐catenin pathway, induced caspase‐3 expression and interrupted IL‐6/STAT3/lncRNA HOTAIR axis. Altogether, this study provides evidence that DIA treatment might be beneficial in controlling colon cancer progression via multi pathways targeting mechanism.
PDF
