Allelic Discrimination of Vitamin D Receptor Polymorphisms and Risk of Type 2 Diabetes Mellitus: A Case-Controlled Study

(1) Background: Type 2 diabetes mellitus (T2DM) is one of the rapidly growing healthcare problems, and several vitamin D receptor (VDR) polymorphisms seem to modulate the risk of T2DM. Our research was designed to investigate the allelic discrimination of VDR polymorphisms and T2DM occurrence risk. (2) Methods: This case-control research included 156 patients with T2DM and 145 healthy control subjects. Most of the study population were males 56.6% vs. 62.8% in the case and control groups, respectively. Genotyping for VDR single nucleotide polymorphisms (SNPs), rs228570 (Fok1), rs7975232 (Apa1), and rs1544410 (Bsm1) was compared between both groups. (3) Results: There was a negative link between vitamin D levels and insulin sensitivity. A significant difference was noted in the allelic discrimination of VDR polymorphism rs228570 and rs1544410 between the study groups (p \u3c 0.001). No difference was observed in the allelic discrimination of VDR polymorphism rs7975232 between the groups (p = 0.063). Moreover, T2DM patients had significantly higher levels of fasting blood sugar (FBS), glycated hemoglobin HbA1c, 2-h post-prandial blood sugar (PP), serum glutamic oxaloacetic transaminase (SGOT), serum glutamic-pyruvic transaminase (SGPT), total cholesterol, and triglycerides (p \u3c 0.001), while High-Density Lipoprotein (HDL) Cholesterol (HDL-C) was significantly decreased (p = 0.006). (4) Conclusions: VDR polymorphisms had a positive association with T2DM risk among the Egyptian population. Further large-scale research using deep sequencing of samples is strongly urged to investigate different vitamin D gene variants and interactions, as well as the influence of vitamin D on T2DM

Clinical significance of altered nm23-H1, EGFR, RB and p53 expression in bilharzial bladder cancer

<p>Abstract</p> <p>Background</p> <p>Clinical characterization of bladder carcinomas is still inadequate using the standard clinico-pathological prognostic markers. We assessed the correlation between <it>nm23-H1</it>, <it>Rb, EGFR </it>and <it>p53 </it>in relation to the clinical outcome of patients with muscle invasive bilharzial bladder cancer (MI-BBC).</p> <p>Methods</p> <p><it>nm23-H1</it>, <it>Rb, EGFR and p53 </it>expression was assessed in 59 MI-BBC patients using immunohistochemistry and reverse transcription (RT-PCR) and was correlated to the standard clinico-pathological prognostic factors, patient's outcome and the overall survival (OS) rate.</p> <p>Results</p> <p>Overexpression of <it>EGFR </it>and <it>p53 </it>proteins was detected in 66.1% and 35.6%; respectively. Loss of <it>nm23-H1</it>and <it>Rb </it>proteins was detected in 42.4% and 57.6%; respectively. Increased <it>EGFR and </it>loss of <it>nm23-H1 </it>RNA were detected in 61.5% and 36.5%; respectively. There was a statistically significant correlation between <it>p53 </it>and <it>EGFR </it>overexpression (<it>p </it>< 0.0001), <it>nm23 </it>loss (protein and RNA), lymph node status (<it>p </it>< 0.0001); between the incidence of local recurrence and <it>EGFR </it>RNA overexpression (p= 0.003) as well as between the incidence of metastasis and altered <it>Rb </it>expression (<it>p </it>= 0.026), <it>p53 </it>overexpression (<it>p </it>< 0.0001) and mutation (<it>p </it>= 0.04). Advanced disease stage correlated significantly with increased <it>EGFR </it>(protein and RNA) (<it>p </it>= 0.003 & 0.01), reduced <it>nm23-H1 </it>RNA (<it>p </it>= 0.02), altered <it>Rb </it>(<it>p </it>= 0.023), and <it>p53 </it>overexpression (<it>p </it>= 0.004). OS rates correlated significantly, in univariate analysis, with <it>p53 </it>overexpression (<it>p </it>= 0.011), increased <it>EGFR </it>(protein and RNA, <it>p </it>= 0.034&0.031), <it>nm23-H1 RNA </it>loss (<it>p </it>= 0.021) and aberrations of ≥ 2 genes. However, multivariate analysis showed that only high <it>EGFR </it>overexpression, metastatic recurrence, high tumor grade and the combination of ≥ 2 affected markers were independent prognostic factors.</p> <p>Conclusion</p> <p><it>nm23-H1, EGFR </it>and <it>p53 </it>could be used as prognostic biomarkers in MI-BBC patients. In addition to the standard pathological prognostic factors, a combination of these markers (≥ 2) has synergistic effects in stratifying patients into variable risk groups. The higher is the number of altered biomarkers, the higher will be the risk of disease progression and death.</p

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Generalised and versatile connected health solution on the Zynq SoC

This chapter presents a generalized and versatile connected health solution for patient monitoring. It consists of a mobile system that can be used at home, an ambulance and a hospital. The system uses the Shimmer sensor device to collect three axes (x, y and z) accelerometer data as well as electrocardiogram signals. The accelerometer data is used to implement a fall detection system using the k-Nearest Neighbors classifier. The classification algorithm is implemented on various platforms including a PC and the Zynq system on chip platform where both programmable logic and processing system of the Zynq are explored. In addition, the electrocardiogram signals are used to extract vital information, the signals are also encrypted using the Advanced Encryption Standard and sent wirelessly using Wi-Fi for further processing. Implementation results have shown that the best overall accuracy reaches 90% for the fall detection while meeting real-time performances when implemented on the Zynq and while using only 48% of Look-up Tables and 22% of Flip-Flops available on chip.This paper was made possible by National Priorities Research Program (NPRP) grant No. 5-080-2-028 from the Qatar National Research Fund (a member of Qatar Foundation).Scopu

Tumor Anti-Initiation and Anti-Progression Properties of Sulphated-Extract of Colocasia esculenta

Colocasia esculenta (Taro) is an edible tuberous plant; however, corms are its most worldwide consumed part while the corm powder is widely used in food industries. In this work, a sulphated polysaccharide extract of C. esculenta corm (SCE) was prepared and its cancer chemopreventive properties was explored. The amending of carcinogen metabolism and radical scavenging affinity revealed that SCE is a strong tumor anti-initiation agent via suppressing cytochrome P450-1A and enhancing glutathione and the carcinogen detoxification enzyme; glutathione S-transferase. SCE exhibited a strong scavenging affinity towards critical radicals (hydroxyl and peroxyl). It induced lymphocyte growth and modulated the macrophage functions into an anti-inflammatory profile, via elevating macrophage proliferation and its binding affinity of fluorescein isothiocyanate-lipopolysaccharide (FITC-LPS) and inhibiting nitric oxide and tumor necrosis factor-α generation. Furthermore, SCE showed a potent cytotoxicity against human breast MCF-7 carcinoma cells (IC50 27.73 µg/mL), whereas SCE treatment inhibited the activity of histone deacetylase (HDAC IC50 37.70 µg/mL) and disturbed the pattern of cell cycle phases. An arrest in both S- and G2/M-phases was linked with shifted cell populations towards late apoptosis and necrosis, as detected by flow cytometry. SCE is a promising cancer chemopreventive agent to be used in healthy food industries and for high breast cancer-risk population

Altered Regulatory B Cell Subsets in Children with Type 1 Diabetes Mellitus

B regulatory cells (Breg) refer to characteristic subsets of B cells that generally exert anti-inflammatory functions and maintain peripheral tolerance mainly through their ability to secrete interleukin-10 (IL10). Dysregulation in the function of Breg cells was reported in several autoimmune diseases. However, the relation between Breg and children with type 1 diabetes (T1D) is poorly understood. Thus, this study is aimed at determining whether Breg cells play a role in T1D in children or not, so we hypothesized that an altered phenotype of B cell subsets is associated with T1D in children. Children with T1D (n=29) and control children with normal blood glucose levels (n=14) were recruited. The percentages of different circulating IL10-producing Breg subsets, including B10, immature transitional, and plasmablasts were determined using flow cytometry analysis. Furthermore, the association between different IL10-producing B cells and patient parameters was investigated. The percentage of circulating IL10+CD24hiCD27+ (B10) and IL10+CD24hiCD38hi (immature transitional) subsets of Breg cells was significantly lower in T1D patients than in healthy controls. Moreover, these cells were also negatively correlated with fasting blood glucose and HbA1c levels. Breg cells did not correlate with autoantibody levels in the serum. These findings suggest that certain Breg subsets are numerically deficient in children with T1D. This alteration in frequency is associated with deficient islet function and glycemia. These findings suggest that Breg cells may be involved in the loss of auto-tolerance and consequent destruction of pancreatic cells and could, therefore, be a potential target for immunotherapy

Polysaccharide extracts of the brown alga <i>Sargassum</i><i>asperifolium</i> possess <i>in vitro</i> cancer chemopreventive properties

<div><p>The cancer chemopreventive activity of the polysaccharide extracts (<b>E1</b>–<b>E4</b>) of <i>Sargassum asperifolium</i>, a brown alga in Red Sea shores in Egypt, was investigated. Tumour anti-initiation activity (the modulation of carcinogen metabolism) indicated that <b>E3</b> and <b>E4</b> were potent anti-initiators by inhibiting the carcinogen activator cytochrome P450-1A, and enhancing carcinogen detoxification enzymes glutathione-<i>S</i>-transferase. Only <b>E4</b> significantly enhanced quinone reductase activity. All polysaccharide extracts possessed anti-promotion property by their anti-inflammatory activity. <b>E3</b> and <b>E4</b> dramatically induced the growth of spleen macrophages. <b>E2</b>, <b>E3</b> and <b>E4</b> significantly inhibited nitric oxide generation from lipopolysaccharide (LPS)-stimulated spleen macrophages, while <b>E1</b>, <b>E3</b> and <b>E4</b> led to significant inhibition of LPS-induced tumour necrosis factor-α. The extracts <b>E1</b>, <b>E2</b> and <b>E4</b> showed cytotoxicity against HepG2 cells, where <b>E2</b> and <b>E4</b> induced cell death due to apoptosis. In conclusion, <b>E3</b> and <b>E4</b> are promising cancer chemopreventive extracts, since they had tumour anti-initiating activity via their protective modulation of carcinogen metabolism.</p></div

Exposure to <i>Brucella</i> Species, <i>Coxiella burnetii</i>, and <i>Trichinella</i> Species in Recently Imported Camels from Sudan to Egypt: Possible Threats to Animal and Human Health

Brucellosis and coxiellosis/Q fever are bacterial infections caused by Brucella species and Coxiella burnetii, respectively; camels are highly susceptible to both pathogens. Trichinellosis is a parasitic infection caused by various Trichinella nematode species. Reportedly, camels are susceptible to experimental infection with Trichinella spp., but information on this potential host species is scarce. All three infections are of zoonotic nature and thus of great public health concern. The current study aimed to determine antibodies against the three pathogens in recently imported camels (n = 491) from Sudan at the two main ports for the entrance of camels into southern Egypt using commercial indirect ELISAs. Samples were collected in two sampling periods. The seropositivity rates of Brucella spp., C. burnetii, and Trichinella spp. were 3.5%, 4.3%, and 2.4%, respectively. Mixed seropositivity was found in 1% for Brucella spp. and C. burnetii. Marked differences were found between the two study sites and the two sampling periods for Brucella. A higher rate of seropositivity was recorded in the Red Sea/older samples that were collected between 2015 and 2016 (4.3%, 17/391; odds ratio = 9.4; p C. burnetii, samples collected during November and December 2015 had a significantly higher positivity rate than the other samples (13%, 13/100; OD = 4.8; p Trichinella spp., with samples collected during November and December 2015 showing a higher positivity rate than the other samples (7%, 7/100; OD = 10.9; p Brucella spp. and additional novel information on C. burnetii and Trichinella spp. in recently imported camels kept in quarantine before delivery to other Egyptian regions. This knowledge can be utilized to reduce health hazards and financial burdens attributable to brucellosis, Q fever, and trichinellosis in animals and humans in Egypt