PLEIOTROPIC ROLE OF SIMVASTATIN AND ALENDRONATE ON MESENCHYMAL STEM CELLS

Objectives: Previously, our research group has investigated the effect of alendronate (ALN) and simvastatin (SV) in their minimum inhibitory dose (IC50) on oral squamous cell carcinoma cell line where inhibition of angiogenesis has been demonstrated. In the present study, we further investigate the effect of the previously calculated IC50 of SV and ALN and their combination on two different types of stem cells to show that the same drug may have different effects on different cells.Methods: Stem cells were isolated from rat adipose tissue and oral mucosa. After passaging, cells were subjected to Aln, Sv separately as well as combined in their half maximal inhibitory concentration (IC50). 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay was performed to evaluate cytotoxicity. After seven days, osteogenic differentiation was evaluated using alizarin stain. Real time polymerase chain reaction was used to evaluate Osteopontin gene expression.Results: Our results demonstrated that the proposed combination of Aln and Sv in their IC50 enhanced the osteogenic differentiation of both types of stem cells.Conclusion: The combined effect of Aln and Sv may represent a novel pharmacological approach in treating bone metastasis and at the same time treating the cancer itself

Evaluation of health-related quality of life and muscular strength in children with beta thalassemia major

Background: Thalassemia is an inherited blood disorder that requires repeated blood transfusions and chelation regimes. This may lead to restrictions in physical activities, social participation as well as decreased muscle strength.Aim: The aim of this study was to evaluate the health-related quality of life (HRQoL), muscular strength and pain in children with β-thalassemia major.Patients and method: One hundred and twenty children (60 with β-thalassemia major and 60 age-matched healthy) were participated in a cross-sectional study from both sexes (57 girls and 63 boys) with ages ranging from two to twelve years. HRQoL (physical, emotional, social and school functioning), muscular strength and pain were evaluated for all children by using the pediatric quality of life inventoryTM (PedsQLTM) 4.0 generic core scale, hand-held dynamometer and visual analogue scale (VAS) respectively.Results: Children with β-thalassemia major showed a significant decrease in all domains of health-related quality of life and handgrip strength with a significant increase in VAS score (p ≤ 0.0001).Conclusions: The study concluded that thalassemia as a chronic disease has a negative impact on HRQoL and muscle strength of children in different age group.Keywords: Beta thalassemia, Quality of life, Handgrip strength, childre

Preclinical Assessment of the Proliferation Capacity of Gingival and Periodontal Ligament Stem Cells from Diabetic Patients

BACKGROUND: Stem cells have recently received great interest as potential therapeutics alternative for a variety of diseases. The oral and maxillofacial region, in particular, encompasses a variety of distinctive mesenchymal (MSC) populations and is characterized by a potent multilineage differentiation capacity.AIM: In this report, we aimed to investigate the effect of diabetes on the proliferation potential of stem cells isolated from controlled diabetic patients (type 2) and healthy individuals.SUBJECTS & METHODS: The proliferation rate of gingival and periodontal derived stem cells isolated from diabetic & healthy individuals were compared using MTT Assay. Expression levels of Survivin in isolated stem cells from all groups were measured by qRt - PCR.RESULTS: There was a significantly positive correlation between proliferation rate and expression of Survivin in all groups which sheds light on the importance of Survivin as a reliable indicator of proliferation. The expression of Survivin further confirmed the proliferation results from MTT Assay where the expression of stem cells from non - diabetic individuals was higher than diabetic patients. Conclusion: Taking together all the results, it could be concluded that PDLSC and GSC are promising candidates for autologous regenerative therapy due to their ease of accessibility in addition to their high proliferative rates

A systematic review of deep learning microalgae classification and detection

Algae represent the majority of the diversity on Earth and are a large group of organisms that have photosynthetic properties that are important to life. The species of algae are estimated to be more than 1 million, they play an important role in many fields such as agriculture, industry, food, and medicine. It is important to determine the type of algae, to determine if it is harmful or useful, and to indicate the health of the ecosystem, water quality, health, and safety risks. The conventional process of classifying algae is difficult, tedious, and time-consuming. Recently various computer vision techniques have been used to classify algae to overcome challenges and automate the process of classification. This paper presents a review of research done on image classification for microorganism algae using machine learning and deep learning techniques. The paper focuses on three important research questions to highlight the challenges of classifying microalgae. A systematic literature review or SLR has been conducted to determine how deep learning and machine learning have improved and enhanced automatic microalgae classification rather than manual classification. 51 articles have been included from well-known databases. The outcome of this SLR is beneficial due to the detailed analysis and comprehensive overview of the algorithms and the architectures and information about the dataset used in each included article. The future work focuses on getting a large dataset with high resolution, trying different methods to manage imbalance problems, and giving more attention to the fusion of deep learning techniques and traditional machine learning techniques

Distinct molecular signatures of clinical clusters in people with type 2 diabetes:an IMI-RHAPSODY study

Type 2 diabetes is a multifactorial disease with multiple underlying aetiologies. To address this heterogeneity a previous study clustered people with diabetes into five diabetes subtypes. The aim of the current study is to investigate the aetiology of these clusters by comparing their molecular signatures. In three independent cohorts, in total 15,940 individuals were clustered based on five clinical characteristics. In a subset, genetic- (N=12828), metabolomic- (N=2945), lipidomic- (N=2593) and proteomic (N=1170) data were obtained in plasma. In each datatype each cluster was compared with the other four clusters as the reference. The insulin resistant cluster showed the most distinct molecular signature, with higher BCAAs, DAG and TAG levels and aberrant protein levels in plasma enriched for proteins in the intracellular PI3K/Akt pathway. The obese cluster showed higher cytokines. A subset of the mild diabetes cluster with high HDL showed the most beneficial molecular profile with opposite effects to those seen in the insulin resistant cluster. This study showed that clustering people with type 2 diabetes can identify underlying molecular mechanisms related to pancreatic islets, liver, and adipose tissue metabolism. This provides novel biological insights into the diverse aetiological processes that would not be evident when type 2 diabetes is viewed as a homogeneous diseas

Medical prospects of cryptosporidiosis in vivo control using biofabricated nanoparticles loaded with Cinnamomum camphora extracts by Ulva fasciata

Background and Aim: Global efforts are continuing to develop preparations against cryptosporidiosis. This study aimed to investigate the efficacy of biosynthesized Ulva fasciata loading Cinnamomum camphora oil extract on new zinc oxide nanoparticles (ZnONPs shorten to ZnNPs) and silver nanoparticles (AgNPs) as alternative treatments for Cryptosporidium parvum experimental infection in rats. Materials and Methods: Oil extract was characterized by gas chromatography-mass spectrometry, loaded by U. fasciata on ionic-based ZnO and NPs, and then characterized by transmission electron microscopy, scanning electron microscopy, and X-ray diffraction. Biosafety and toxicity were investigated by skin tests. A total of 105 C. parvum oocysts/rat were used (n = 81, 2–3 W, 80–120 g, 9 male rats/group). Oocysts shedding was counted for 21 d. Doses of each preparation in addition to reference drug were administered daily for 7 d, starting on post-infection (PI) day (3). Nitazoxanide (100 mg) was used as the reference drug. After 3 weeks, the rats were sacrificed for postmortem examination and histopathological examination. Two blood samples/rat/group were collected on the 21st day. Ethylenediaminetetraacetic acid blood samples were also used for analysis of biochemistry, hematology, immunology, micronucleus prevalence, and chromosomal abnormalities. Results: C. camphora leaves yielded 28.5 ± 0.3 g/kg oil and 20 phycocompounds were identified. Spherical and rod-shaped particles were detected at 10.47–30.98 nm and 18.83–38.39 nm, respectively. ZnNPs showed the earliest anti-cryptosporidiosis effect during 7–17 d PI. Other hematological, biochemical, immunological, histological, and genotoxicity parameters were significantly fruitful; hence, normalized pathological changes induced by infestation were observed in the NPs treatments groups against the infestation-free and Nitazoxanide treated group. Conclusion: C. camphora, U. fasciata, ZnNPs, and AgNPs have refluxed the pathological effects of infection as well as positively improved host physiological condition by its anticryptosporidial immunostimulant regenerative effects with sufficient ecofriendly properties to be proposed as an alternative to traditional drugs, especially in individuals with medical reactions against chemical commercial drugs

Four missense genetic variants in CUBN are associated with higher levels of eGFR in non-diabetes but not in diabetes mellitus or its subtypes: A genetic association study in Europeans.

AIM: Rare genetic variants in the CUBN gene encoding the main albumin-transporter in the proximal tubule of the kidneys have previously been associated with microalbuminuria and higher urine albumin levels, also in diabetes. Sequencing studies in isolated proteinuria suggest that these variants might not affect kidney function, despite proteinuria. However, the relation of these CUBN missense variants to the estimated glomerular filtration rate (eGFR) is largely unexplored. We hereby broadly examine the associations between four CUBN missense variants and eGFR creatinine in Europeans with Type 1 (T1D) and Type 2 Diabetes (T2D). Furthermore, we sought to deepen our understanding of these variants in a range of single- and aggregate- variant analyses of other kidney-related traits in individuals with and without diabetes mellitus. METHODS: We carried out a genetic association-based linear regression analysis between four CUBN missense variants ( rs141640975, rs144360241, rs45551835, rs1801239) and eGFR creatinine (ml/min/1.73 m 2, CKD-EPI creatinine(2012), natural log-transformed) in populations with T1D (n ~ 3,588) or T2D (n ~ 31,155) from multiple European studies and in individuals without diabetes from UK Biobank (UKBB, n ~ 370,061) with replication in deCODE (n = 127,090). Summary results of the diabetes-group were meta-analyzed using the fixed-effect inverse-variance method. RESULTS: Albeit we did not observe associations between eGFR creatinine and CUBN in the diabetes-group, we found significant positive associations between the minor alleles of all four variants and eGFR creatinine in the UKBB individuals without diabetes with rs141640975 being the strongest (Effect=0.02, P eGFR_creatinine=2.2 × 10 -9). We replicated the findings for rs141640975 in the Icelandic non-diabetes population (Effect=0.026, P eGFR_creatinine=7.7 × 10 -4). For rs141640975, the eGFR creatinine-association showed significant interaction with albuminuria levels (normo-, micro-, and macroalbuminuria; p = 0.03). An aggregated genetic risk score (GRS) was associated with higher urine albumin levels and eGFR creatinine. The rs141640975 variant was also associated with higher levels of eGFR creatinine-cystatin C (ml/min/1.73 m 2, CKD-EPI 2021, natural log-transformed) and lower circulating cystatin C levels. CONCLUSIONS: The positive associations between the four CUBN missense variants and eGFR in a large population without diabetes suggests a pleiotropic role of CUBN as a novel eGFR-locus in addition to it being a known albuminuria-locus. Additional associations with diverse renal function measures (lower cystatin C and higher eGFR creatinine-cystatin C levels) and a CUBN-focused GRS further suggests an important role of CUBN in the future personalization of chronic kidney disease management in people without diabetes

Genome-Wide Association Study and Functional Characterization Identifies Candidate Genes for Insulin-Stimulated Glucose Uptake

Distinct tissue-specific mechanisms mediate insulin action in fasting and postprandial states. Previous genetic studies have largely focused on insulin resistance in the fasting state, where hepatic insulin action dominates. Here we studied genetic variants influencing insulin levels measured 2 h after a glucose challenge in \u3e55,000 participants from three ancestry groups. We identified ten new loci (P \u3c 5 × 10-8) not previously associated with postchallenge insulin resistance, eight of which were shown to share their genetic architecture with type 2 diabetes in colocalization analyses. We investigated candidate genes at a subset of associated loci in cultured cells and identified nine candidate genes newly implicated in the expression or trafficking of GLUT4, the key glucose transporter in postprandial glucose uptake in muscle and fat. By focusing on postprandial insulin resistance, we highlighted the mechanisms of action at type 2 diabetes loci that are not adequately captured by studies of fasting glycemic traits

Mapping geographical inequalities in access to drinking water and sanitation facilities in low-income and middle-income countries, 2000-17

Background: Universal access to safe drinking water and sanitation facilities is an essential human right, recognised in the Sustainable Development Goals as crucial for preventing disease and improving human wellbeing. Comprehensive, high-resolution estimates are important to inform progress towards achieving this goal. We aimed to produce high-resolution geospatial estimates of access to drinking water and sanitation facilities. Methods: We used a Bayesian geostatistical model and data from 600 sources across more than 88 low-income and middle-income countries (LMICs) to estimate access to drinking water and sanitation facilities on continuous continent-wide surfaces from 2000 to 2017, and aggregated results to policy-relevant administrative units. We estimated mutually exclusive and collectively exhaustive subcategories of facilities for drinking water (piped water on or off premises, other improved facilities, unimproved, and surface water) and sanitation facilities (septic or sewer sanitation, other improved, unimproved, and open defecation) with use of ordinal regression. We also estimated the number of diarrhoeal deaths in children younger than 5 years attributed to unsafe facilities and estimated deaths that were averted by increased access to safe facilities in 2017, and analysed geographical inequality in access within LMICs. Findings: Across LMICs, access to both piped water and improved water overall increased between 2000 and 2017, with progress varying spatially. For piped water, the safest water facility type, access increased from 40·0% (95% uncertainty interval [UI] 39·4–40·7) to 50·3% (50·0–50·5), but was lowest in sub-Saharan Africa, where access to piped water was mostly concentrated in urban centres. Access to both sewer or septic sanitation and improved sanitation overall also increased across all LMICs during the study period. For sewer or septic sanitation, access was 46·3% (95% UI 46·1–46·5) in 2017, compared with 28·7% (28·5–29·0) in 2000. Although some units improved access to the safest drinking water or sanitation facilities since 2000, a large absolute number of people continued to not have access in several units with high access to such facilities (>80%) in 2017. More than 253 000 people did not have access to sewer or septic sanitation facilities in the city of Harare, Zimbabwe, despite 88·6% (95% UI 87·2–89·7) access overall. Many units were able to transition from the least safe facilities in 2000 to safe facilities by 2017; for units in which populations primarily practised open defecation in 2000, 686 (95% UI 664–711) of the 1830 (1797–1863) units transitioned to the use of improved sanitation. Geographical disparities in access to improved water across units decreased in 76·1% (95% UI 71·6–80·7) of countries from 2000 to 2017, and in 53·9% (50·6–59·6) of countries for access to improved sanitation, but remained evident subnationally in most countries in 2017. Interpretation: Our estimates, combined with geospatial trends in diarrhoeal burden, identify where efforts to increase access to safe drinking water and sanitation facilities are most needed. By highlighting areas with successful approaches or in need of targeted interventions, our estimates can enable precision public health to effectively progress towards universal access to safe water and sanitation