Aboul Ella Hassanien (Abo)

Cancer extracellular vesicles (EVs), or exosomes, promote tumor progression through enhancing tumor growth, initiating epithelial-to-mesenchymal transition, remodeling the tumor microenvironment, and preparing metastatic niches. Three-dimensionally (3D) cultured tumoroids / spheroids aim to reproduce some aspects of tumor behavior in vitro and show increased cancer stem cell properties. These properties are transferred to their EVs that promote tumor growth. Moreover, recent tumoroid models can be furnished with aspects of the tumor microenvironment, such as vasculature, hypoxia, and extracellular matrix. This review summarizes tumor tissue culture and engineering platforms compatible with EV research. For example, the combination experiments of 3D-tumoroids and EVs have revealed multifunctional proteins loaded in EVs, such as metalloproteinases and heat shock proteins. EVs or exosomes are able to transfer their cargo molecules to recipient cells, whose fates are often largely altered. In addition, the review summarizes approaches to EV labeling technology using fluorescence and luciferase, useful for studies on EV-mediated intercellular communication, biodistribution, and metastatic niche formation.

BACKGROUND: Multiple myeloma (MM) is a hematological bone marrow malignancy that can be treated but is usually fatal. Medication resistance is the major cause of relapses due to cancer stem cells (CSCs). As a result, this study aimed to identify multiple myeloma cancer stem cells (MMCSCs) in the bone marrow of twelve MM patients with pathological complete response (pCR) after chemotherapy and to investigate the potential effect of Curcumin/Piperine (C/P) extract as an anti-MMCSCs treatment in twenty newly diagnosed patients.

METHODS: This study included twenty bone marrow (BM) samples from newly diagnosed MM patients and twelve BM samples from pCR patients after a year of treatment. The MTT test was performed to assess the treatment's effective dosage. A flow cytometer was used to identify MMCSCs, cell cycle profile, extract's apoptotic activity, and proliferation marker in the selected samples. Also,  a colony formation test and stemness protein were investigated.

RESULTS: In newly diagnosed MM patients, the C/P extract suppressed MMCSCs by 64.71% for CD138-/CD19- and 38.31% for CD38++. In MM patients' samples obtained after one year of treatment, the MMCSCs inhibition percentage reached 44.71% (P < 0.008) for CD138-/CD19- and 36.94% (P < 0.221) for CD38++. According to cell cycle analyses, the number of cells treated with C/P extract was significantly reduced in the S and G0/G1 phases (87.38%: 35.15%, and 4.83%: 2.17% respectively), with a rapid increase in the G2/M phases (1.1%: 2.2%.). MMCSCs apoptosis was identified using a flow cytometer and Annexin-V. Multiple myeloma stem cell (MMCSC) proliferation was inhibited. Clonogenicity was suppressed by 60%, and stemness protein expression was reduced by 70%.

CONCLUSION: MMCSCs in the bone marrow of MM-pCR patients can be utilized as a prognostic tool to predict recurrent multiple myeloma incidence. Also, the therapeutic potential of C/P extract as a prospective anti-MM drug targeting MMCSCs.

This observational study evaluates three-dimensionally the relation between the root of maxillary canine and overlying labial cortical plate of bone during orthodontic canine retraction. Eighty-four bilateral maxillary canines in 42 patients were retracted in the extraction space of first premolars, using conventional orthodontic NiTi retraction spring delivering 150gm. Three-dimensional evaluation at the cusp tip, root apex, and the overlying cortical bone was done based on Classification of Root/Cortical bone relation (CRCR) before and after canine retraction. 168 observations of the canines pre- and post-retraction showed a mean distal movement of the canine cusp tip of 3.78(± 2.05) mm, while the canine root apex was almost stationary. Scarcely, 5.4% of the canine roots and root apices persisted in the medullary bone during retraction, while 16.1% contacted the overlying cortical bone. Fenestration of the overlying cortical bone by the canine roots or root apices occurred in 78.6% of the sample. The unembellished intimacy between the canine root and apex to the overlying thick dense cortical bone might have the decelerating effect on the maxillary canine retraction. The natural bone plate labial to the maxillary canine root did not yield infront nor enlarge due to canine retraction, but else defeated the current orthodontic biomechanical implementation.

In July 2019, the National Institute for Health and Care Excellence (NICE) initiated a major review of its health technology evaluation methods to update its methods guide. This update has recently concluded with the publication of its health technology evaluation manual in January 2022. This paper reports the methods and findings of the review in relation to the recommended approach to use for the measurement and valuation of health-related quality of life (HRQoL) in submissions to NICE. Issues related to (i) the methods to use when NICE's preferred measure (EQ-5D) is not appropriate or not available; (ii) adjusting health state utility values over time to account for age; (iii) measuring and valuing HRQoL in children and young people; and (iv) including carers' QoL in economic evaluations were included in this review. This commentary summarises the methods used to undertake the review, its findings, and the changes to NICE methods that were proposed based on these findings. It also outlines topics where further research is needed before definitive methods guidance can be issued. The broad proposals described here were subject to a public consultation in 2020 and a further consultation on the updated methods guidance was completed in October 2021 before the publication of the manual in January 2022.

BACKGROUND: Familial Mediterranean fever (FMF) is an autoinflammatory disease that can have conduction disturbances and cardiac rhythm disorders as manifestations of cardiac involvement. The aim of the study is to assess the susceptibility of children with FMF to cardiac repolarization abnormalities and therefore arrhythmia in children with FMF.

METHODS: A cross sectional study conducted on 60 children had FMF and 40 age and sex matched healthy controls. Cardiac repolarization markers, cardiac dimensions and functions were assessed by electrocardiogram (ECG) and conventional echocardiography in patients and controls.

RESULTS: The mean ± SD age of the patients was 10.43 ± 3.472 years, corrected QT (QTc) and the ratio of peak to end T wave (Tpe) over QTc interval (Tpe /QTc) increased significantly in FMF patients more than healthy control (p value 0.023 and 0.022 respectively). P wave dispersion (Pd) was significantly higher in FMF patients with amyloidosis (p value 0.030). No significant difference was found in cardiac dimensions and functions between the two groups. We found a statistically negative correlation between Pd and age of patients at time of study, age of disease onset and age at diagnosis. On the other hand, we found a statistically significant positive correlation between Pd with number of attacks per year and disease severity score. Furthermore, Tpe/QTc ratio correlated with FMF 50 score, QTc correlated with 24 hours proteinuria. QT, JT intervals correlated with fibrinogen.

CONCLUSIONS: FMF Patients may have increased risk of arrhythmia and should be monitored on regular basis. Compliance to colchicine therapy and better disease control might play a role in decreasing this risk.

Aim: The current study was conducted to evaluate the caries prevention potential of pearl powder against Casein Phosphopeptide-Amorphous Calcium Phosphate (CPP-ACP) in enamel white spot lesions. Methodology: Thirty subjects were randomized into two equal groups (n=15). Group 1 (intervention group) received pearl powder gel, while group 2 (Control group) received Casein Phosphopeptide-Amorphous Calcium Phosphate (GC Tooth-Mousse). The participants were instructed to use pea size amount of pearl powder gel or GC Tooth-Mousse on the teeth surfaces using their finger twice daily after brushing with fluoride-free toothpaste for the first three months, followed by the use of fluoride containing tooth paste for the next 3 month. Quantitative changes of white spot lesions were measured at baseline, three, six, nine, and twelve months using DIAGNOdent pen 2910 (KaVo, Biberach and der Riss, Germany). Data for quantitative changes of white spot lesions were recorded and analysed for each group. Results: No statistically significant difference was found in overall DIAGNOdent pen mean readings between pearl powder gel and GC Tooth-Mousse groups at P=0.145. On the other hand, the intragroup comparison within both groups showed statistically significant difference between baseline, three, and six months follow-up periods, while after nine and twelve months there was no statistically significant difference among both groups. Conclusions: Pearl powder gel seem to have a caries prevention efficacy similar to GC Tooth-Mousse and may be considered as promising natural and bioavailable material in reducing the progression of enamel WSLs.

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