Development, physicochemical characterization and in-vitro biocompatibility study of dromedary camel dentine derived hydroxyapatite for bone repair.

This study aimed to produce hydroxyapatite from the dentine portion of camel teeth using a defatting and deproteinizing procedure and characterize its physicochemical and biocompatibility properties. Biowaste such as waste camel teeth is a valuable source of hydroxyapatite, the main inorganic constituent of human bone and teeth which is frequently used as bone grafts in the biomedical field. Fourier Transform infrared (FTIR), and micro-Raman spectroscopy confirmed the functional groups as-sociated with hydroxyapatite. X-ray diffraction (XRD) studies showed camel dentine-derived hydroxyapatite (CDHA) corresponded with hydroxyapatite spectra. Scanning electron micros-copy (SEM) demonstrated the presence of dentinal tubules measuring from 1.69-2.91 µm. The inorganic phases of CDHA were primarily constituted of calcium and phosphorus, with trace levels of sodium, magnesium, potassium, and strontium, according to energy dispersive X-ray analysis (EDX) and inductively coupled plasma mass spectrometry (ICP-MS). After 28 days of incubation in simulated body fluid (SBF), the pH of the CDHA scaffold elevated to 9.2. in-vitro biocompatibility studies showed that the CDHA enabled Saos-2 cells to proliferate and express the bone marker osteonectin after 14 days of culture. For applications such as bone augmentation and filling bone gaps, CDHA offers a promising material. However, to evaluate the clinical feasibility of the CDHA, further in-vivo studies are required.

Extraction of Hydroxyapatite from Camel Bone for Bone Tissue Engineering Application.

Waste tissues such as mammalian bone are a valuable source from which to extract hydroxyapatite. Camel bone-based hydroxyapatite (CBHA) was extracted from the femur of camel bones using a defatting and deproteinization procedure. The extracted CBHA was mechanically, chemically, physically, morphologically and structurally characterized. Fourier-Transform Infra-Red (FTIR) spectra, Micro-Raman, and X-ray diffraction analysis confirmed successful extraction of hydroxyapatite. The mechanical properties of the CBHA scaffold were measured using a Universal Instron compression tester. Scanning electron microscopy showed the presence of a characteristic interconnected porous architecture with pore diameter ranging from 50-600 µm and micro-computer tomography (Micro-CT) analysis identified a mean porosity of 73.93. Thermogravimetric analysis showed that the CBHA was stable up to 1000 °C and lost only 1.435% of its weight. Inductively coupled plasma-mass spectrometry (ICP-MS) and Energy-dispersive-X-ray (EDX) analysis demonstrated the presence of significant amounts of calcium and phosphorus and trace ions of sodium, magnesium, zinc, lead and strontium. Following 21 days of incubation in simulated body fluid (SBF), the pH fluctuated between 10-10.45 and a gradual increase in weight loss was observed. In conclusion, the extracted CBHA is a promising material for future use in bone tissue regeneration applications.

Assessing the therapeutic potential of agomelatine, ramelteon, and melatonin against SARS-CoV-2.

BACKGROUND: The SARS-Cov-2(severe acute respiratory syndrome coronavirus 2) infection affecting human populations worldwide is now a very concerning issue considering the morbidity and mortality rates. Despite several measures followed by the medical fraternity and general public, there is no resolution. Therapeutic measures to tackle the infection have been based on researching new designer drug molecules that could prevent viral entry into the human host. Melatonin has been tried as an adjuvant in the management of COVID 19(coronavirus disease) illness but its specific antiviral role has not been investigated. Objectives: The objectives of the present study were to conduct an in-silico analysis to investigate if melatonin and related drugs namely ramelteon and agomelatine could be used as antiviral agents in SARS-CoV-2 infection based on their binding to the SARS-CoV-2 receptor binding site (RBD) and Angiotensin-converting enzyme 2 (ACE 2). METHODS: For docking studies (Pdb Id 1M0J), the SARS-CoV-2 spike protein receptor-binding domain (RBD) crystal structure which was ACE2 cell receptor bounded was employed. From the PubChem database, the three-dimensional configuration of the ligands melatonin, ramelteon, and agomelatine was retrieved, and conceptual density functional theory (CDFT) was performed to determine molecular descriptors. Charges were added and optimized with the universal force field to prepare the ligands for the process of docking. For facilitation of readability by the AutoDock software conversion to PDBQT(Protein Data Bank, Partial Charge (Q), & Atom Type (T)) format was performed. AutoDock version 4.2.6 docking program and AutoDock Tools (ADT) version 1.5.6 were used for molecular docking. Desmond, a Package of Schrödinger LLC was used to simulate molecular dynamics for hundred nanoseconds using. RESULTS: Data from the present study reveal that melatonin, ramelteon, and agomelatine demonstrate significant binding with SARS-CoV-2 RBD and ACE 2 demonstrating the fact that they can strongly prevent viral entry into the host cells through dual binding effects. However, Ramelteon was found to be the most superior amongst the 3 drugs analyzed in its antiviral properties against SARS-CoV-2. CONCLUSION: Results advocate further research in exploring the potential therapeutic applications of melatonin, ramelteon, and agomelatine for the management of SARS-CoV-2 infection.

Efficacy and Safety of Enoxaparin versus New Oral Anticoagulants to Prevent Venous Thromboembolism after Total Hip Replacement: A Systematic Review and Meta-Analysis.

Prophylactic anticoagulant therapy is recommended for reducing the risk of venous thromboembolism (VTE) after a total hip replacement (THR). However, it is not clear which anticoagulant is preferable. Hence, a systematic review and meta-analysis of randomized double-blind controlled trials (RDBCTs) were conducted to investigate the clinical efficacy and safety of enoxaparin in comparison with newer oral anticoagulants for the prevention of VTE after THR. The Cochrane Library, Scopus, Web of Science, Embase, and PubMed/Medline databases were used for PICO search strategy. Relative risks (RR) of symptomatic VTE, clinically relevant bleeding, mortality, and a net clinical endpoint were estimated employing a random effect meta-analysis. ITC and RevMan software were used for indirect and direct comparisons, respectively. Nine RDBCTs comprising 24,584 patients were included. As compared to enoxaparin, a reduced risk for symptomatic VTE was observed with rivaroxaban (confidence interval [CI]: 0.32-0.77; RR: 0.46%) and comparable with apixaban (0.12-1.26; 0.42%) and dabigatran (0.22-2.20; 0.70%). Contrarily to enoxaparin, a greater risk for clinically relevant bleeding was observed with rivaroxaban (1.03-1.48; 1.23%), comparable with dabigatran (0.96-1.33; 1.10%) and reduced with apixaban (0.19-5.66; 0.96%). In indirect or direct comparisons, the interventions did not differ on the net clinical endpoint. In conclusion, the findings of this meta-analysis revealed no significant difference in the efficacy and safety of new oral anticoagulants as compared to enoxaparin for the prevention of VTE after total hip replacement surgery.

Prevalence and Diversity of Haplotypes of Sickle Cell Disease in the Eastern Province of Saudi Arabia.

Hb F modulates sickle cell disease. Five major haplotypes of the ß-globin gene cluster are associated with sickle cell disease. In the Eastern Province of Saudi Arabia, the Arab-Indian (AI) is most common. Single nucleotide polymorphism (SNP) genotyping (rs3834466, rs28440105, rs10128556, and rs968857) was carried out by nuclease allelic discrimination assay with target-specific forward and reverse primers, TaqMan probes, labeled with VIC and FAM. In 778 patients with sickle cell disease from the Eastern Province, a haplotype was assigned to 90.9% of all samples; 9.1% were classified as compound heterozygotes for the AI and an atypical haplotype. The distribution of haplotypes for 746 Hb S (HBB: c.20A > T) homozygotes was: 614 AI/AI, nine SEN/SEN (Senegal), 42 SEN/AI, nine CAM/CAM (Cameroon), one CAR (Central African Republic)/BEN (Benin), 71 AI/atypical. In Hb S/ß-thalassemia (Hb S/ß-thal), the distribution of Hb S haplotypes was: 22 AI/AI, one CAM/CAM, four AI/SEN, five AI/atypical. Mean Hb F in the haplotypes was: AI/AI 16.6 ± 7.5%, CAM/CAM 8.0 ± 4.1%, SEN/SEN 11.0 ± 5.1%, SEN/AI 15.1 ± 4.6%, AI/atypical 16.2 ± 6.5%. The presence of the SEN and CAM haplotypes was unexpected due to the apparent homogeneity of the population of the Eastern Province. We have successfully classified sickle cell disease haplotypes using the relatively inexpensive TaqMan assay for the first time. In addition, we have previously shown that children with AI haplotype have Hb F of 30.0% and mild disease, while in our cohort of adult AI patients, which might be the largest yet reported, Hb F was about 16.6%.

TNFSF/TNFRSF cytokine gene expression in sickle cell anemia: Up-regulated TNF-like cytokine 1A (TL1A) and its decoy receptor (DcR3) in peripheral blood mononuclear cells and plasma.

BACKGROUND: Sickle cell anemia (SCA), a disorder with an important inflammatory component, where vasoocclusion is major contributor to the disease pathophysiology. Pro-inflammatory cytokines play an important regulatory role in the process of inflammation. We investigated the expression TL1A/DR3/DcR3 cytokine signaling pathway in peripheral blood mononuclear cells (PBMC) and their corresponding plasma levels in SCA subjects who presented with acute painful episodes. MATERIALS AND METHODS: PBMC were isolated from the blood of SCA subjects and normal healthy controls. RNA isolated from PBMC was used for real time gene expression of TL1A/DR3/DcR3. Gene expression was compared in subgroups within SCA subjects with co-inherited fetal hemoglobin (HbF) or alpha-globin gene deletions. Plasma prepared from blood was used for determination of TL1A/DR3/DcR3 proteins by ELISA assays. RESULTS: In the PBMC of SCA subjects, expression of TL1A and DcR3 is elevated, while DR3 expression is lowered in comparison to normal control PBMC. In SCA subjects with HbF > 10%, TL1A/DcR3 expression is lower, while HbF < 10% is associated with increased TL1A/DcR3 expression. Moreover, subjects with HbF > 10% appear to have significantly fewer pain episodes in comparison to those with HbF < 10%. Deletion of alpha-globin genes appears to have no significant effect on TL1A/DR3/DcR3 expression. Circulating levels of TL1A, DR3 and DcR3 in plasma were significantly elevated in SCA subjects. CONCLUSIONS: Elevated TL1A and DcR3 expression in PBMC of SCA subjects during painful vasoocclusive crisis, suggest an altered TL1A expression may contribute to the pathophysiology of vasoocclusive crisis in SCA. HbF > 10% appears to moderate TL1A elevation, while HbF < 10% exacerbates TL1A/DcR3 responses. Furthermore, subjects with HbF > 10% have significantly lower pain episodes reported as compared to subjects with HbF < 10%.