Glycation of biomolecules results in the formation of advanced glycation end products (AGEs). Imm... more Glycation of biomolecules results in the formation of advanced glycation end products (AGEs). Immunoglobulin G (IgG) has been implicated in the progression of various diseases, including diabetes and cancer. This study purified three IgG subclasses (IgG1, IgG2, and IgG3) from Camelus dromedarius colostrum using ammonium sulfate fractionation and chromatographic procedures. SDS‐PAGE was performed to confirm the purity and molecular weight of the IgG subclasses. Several biochemical and biophysical techniques were employed to study the effect of glycation on camel IgG using methylglyoxal (MGO), a dicarbonyl sugar. Early glycation measurement showed an increase in the fructosamine content by ~four‐fold in IgG2, ~two‐fold in IgG3, and a slight rise in IgG1. AGEs were observed in all classes of IgGs with maximum hyperchromicity (96.6%) in IgG2. Furthermore, glycation‐induced oxidation of IgGs led to an increase in carbonyl content and loss of ‐SH groups. Among subclass, IgG2 showed the hi...
Background: T cell mediated immune dysregulation is an important feature of MDS. The expansion of... more Background: T cell mediated immune dysregulation is an important feature of MDS. The expansion of regulatory T cells (Tregs) is one of the important factors in the progression of intermediate/high risk myelodysplastic syndrome (MDS) to acute myeloid leukemia. However, the exact mechanism for the expansion of Tregs in MDS is not known. Intracellular complements (particularly C3a and C5a) play a crucial role in the polarization of CD4+ T cells toward regulatory or effector phenotypes through Transforming growth factor-beta (TGF-β) pathway (C5aR2 mediated) or Mammalian Target of Rapamycin (mTOR)(C5aR mediated) respectively. The aim of this study was to investigate the potential role of mTOR and Akt as important proteins in complement related polarization of CD4+ T cells toward pro-inflammatory T helper cells in MDS. We have also studied the TGF-β signaling pathway related proteins, which are crucial for the expansion of Tregs. We investigated the level of TGF- β related proteins (phosphorylated (p) SMADs), as well as mTORc and Akt (Ser473) in high risk MDS and healthy donors (HD) before and after stimulation with CD3 and CD46 as a complement related co-stimulatory molecule. Methods: Peripheral blood mononuclear cell (PBMCs) from healthy controls and high-risk MDS patients were used for this study. Anti-CD3 (2.0 µg/mL), anti-CD28 (3.0 µg/mL) and/or anti-CD46 (2.0 µg/mL) antibodies were used to stimulate cells. The total protein was extracted by Bicinchoninic Acid (BCA) assay and quantified by nano-drop. The MILLIPLEX MAP Human TGF-β Signaling Magnetic Bead Panel 6-plex was used to detect the signaling changes in cell lysates using the Luminex® system following the manufacturer's instructions. Data were analysed using Microsoft Excel and expressed in means and standards deviation. The students T-test were used to assess the difference in means between groups. Results: TGF-β signaling pathway proteins pSMAD2, pSMAD3 and pSMAD4 as well as mTORc were evaluated. Unstimulated PBMCs from high-risk MDS patients showed a significantly lower level of m-TOR (p=0.01), pSMAD2 (p=0.01), pSMAD3 (p=0.02) and pSMAD4 (p=0.044) as compared to healthy donors. Following stimulation with anti-CD3±CD46 for 24 hours, there was no significant increase in protein levels of mTORc or Akt. However, in high-risk MDS patients the level of pSMAD2 (p=0.02) and pSMAD4 (p=0.006) remain significantly lower than healthy donors after 24 hours of stimulation with anti-CD3 and CD46. An aliquot of cells were used for flowcytometry following stimulation. Interestingly Tregs phenotype CD4+CD25highCD127lowexpressed higher level of intracellular C5aR2 in MDS (n=5) compared to HD (n=5). Conclusion: mTORc protein level in MDS is reduced and does not change in response to complement receptor stimulation neither does the level of Akt. This may prevent T cells to polarize toward pro-inflammatory T cells (Th1 or Th17) therefore avert an effective immune-surveillance against malignant clone. Lack of response to complement related co-stimulation and increase in C5aR2 expression suggest a potential mechanism for Treg expansion in MDS. These findings may lead to identification of new therapeutic targets in MDS, although need further studies on larger cohort of patients. Disclosures No relevant conflicts of interest to declare.
Leishmaniasis affects more than twelve million people globally and a further one billion people a... more Leishmaniasis affects more than twelve million people globally and a further one billion people are at risk in leishmaniasis endemic areas. The lack of a vaccine for leishmaniasis coupled with the limitations of existing anti-leishmanial therapies prompted this study. Computational techniques have profound applications in screening large libraries of compounds, studying protein-ligand interactions, analysing pharmacokinetic properties, and designing new drug entities with great speed, accuracy, and precision. This study was carried out to evaluate the multi-protein targeting potential of some diselenides by virtual docking screening using four Leishmania protein targets (2XOX, 3SPX, 5ZWY, and 6K91). Selected analogues were screened using Lipinski filter, and the resulting lead compounds were profiled by ADMET, density functional theory (DFT), and molecular dynamics (MD) simulation analyses. The overall average binding affinity of ligands to target proteins follow the order: 3SPX (-1...
COVID-19 is a highly contagious disease caused by SARS-CoV-2. Vaccination against the virus was f... more COVID-19 is a highly contagious disease caused by SARS-CoV-2. Vaccination against the virus was first approved in Saudi Arabia in December 2020. Vaccinated individuals are still at risk of getting infected with the virus and can transmit the disease. Therefore, the perception of vaccinated individuals regarding the disease can help limit the spread of the virus. Objectives: To measure the risk perception of COVID-19 following vaccination and factors that have an effect on risk perception; to identify the health protective behaviours of the vaccinated individuals. Methodology: This is a quantitative analytical cross-sectional, questionnaire-based study. The target population includes individuals aged 18 and above who live in the Riyadh region and have been vaccinated, during the period of June 2021 to December 2021. Results: The perception of 30.2% of participants did not change after vaccination, with many participants continuing to “always” take precautions even after vaccination. ...
The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused a highly challenging ... more The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused a highly challenging and threatening situation worldwide. SARS-CoV-2 patients develop various clinical symptoms. The olfactory and taste dysfunctions are potential neurological manifestations among SARS-CoV-2 patients; however, their relationship with blood groups has rarely been investigated. This study aimed to investigate the prevalence of chemosensitive neurological disorders of smell and taste and their association with blood groups in SARS-CoV-2 patients. The present cross-sectional study was performed in the Department of Pathology, and Physiology, College of Medicine, King Saud University, Riyadh, Saudi Arabia. A well-structured, self-administered questionnaire was designed and distributed through social media platforms. A total of 922 Saudi and non-Saudi adults aged 18 years or older participated in the study. Out of 922 participants, the number of people who had anosmia was 309 (33.5%), 211 (22.9%)...
Glycation of biomolecules results in the formation of advanced glycation end products (AGEs). Imm... more Glycation of biomolecules results in the formation of advanced glycation end products (AGEs). Immunoglobulin G (IgG) has been implicated in the progression of various diseases, including diabetes and cancer. This study purified three IgG subclasses (IgG1, IgG2, and IgG3) from Camelus dromedarius colostrum using ammonium sulfate fractionation and chromatographic procedures. SDS‐PAGE was performed to confirm the purity and molecular weight of the IgG subclasses. Several biochemical and biophysical techniques were employed to study the effect of glycation on camel IgG using methylglyoxal (MGO), a dicarbonyl sugar. Early glycation measurement showed an increase in the fructosamine content by ~four‐fold in IgG2, ~two‐fold in IgG3, and a slight rise in IgG1. AGEs were observed in all classes of IgGs with maximum hyperchromicity (96.6%) in IgG2. Furthermore, glycation‐induced oxidation of IgGs led to an increase in carbonyl content and loss of ‐SH groups. Among subclass, IgG2 showed the hi...
Background: T cell mediated immune dysregulation is an important feature of MDS. The expansion of... more Background: T cell mediated immune dysregulation is an important feature of MDS. The expansion of regulatory T cells (Tregs) is one of the important factors in the progression of intermediate/high risk myelodysplastic syndrome (MDS) to acute myeloid leukemia. However, the exact mechanism for the expansion of Tregs in MDS is not known. Intracellular complements (particularly C3a and C5a) play a crucial role in the polarization of CD4+ T cells toward regulatory or effector phenotypes through Transforming growth factor-beta (TGF-β) pathway (C5aR2 mediated) or Mammalian Target of Rapamycin (mTOR)(C5aR mediated) respectively. The aim of this study was to investigate the potential role of mTOR and Akt as important proteins in complement related polarization of CD4+ T cells toward pro-inflammatory T helper cells in MDS. We have also studied the TGF-β signaling pathway related proteins, which are crucial for the expansion of Tregs. We investigated the level of TGF- β related proteins (phosphorylated (p) SMADs), as well as mTORc and Akt (Ser473) in high risk MDS and healthy donors (HD) before and after stimulation with CD3 and CD46 as a complement related co-stimulatory molecule. Methods: Peripheral blood mononuclear cell (PBMCs) from healthy controls and high-risk MDS patients were used for this study. Anti-CD3 (2.0 µg/mL), anti-CD28 (3.0 µg/mL) and/or anti-CD46 (2.0 µg/mL) antibodies were used to stimulate cells. The total protein was extracted by Bicinchoninic Acid (BCA) assay and quantified by nano-drop. The MILLIPLEX MAP Human TGF-β Signaling Magnetic Bead Panel 6-plex was used to detect the signaling changes in cell lysates using the Luminex® system following the manufacturer's instructions. Data were analysed using Microsoft Excel and expressed in means and standards deviation. The students T-test were used to assess the difference in means between groups. Results: TGF-β signaling pathway proteins pSMAD2, pSMAD3 and pSMAD4 as well as mTORc were evaluated. Unstimulated PBMCs from high-risk MDS patients showed a significantly lower level of m-TOR (p=0.01), pSMAD2 (p=0.01), pSMAD3 (p=0.02) and pSMAD4 (p=0.044) as compared to healthy donors. Following stimulation with anti-CD3±CD46 for 24 hours, there was no significant increase in protein levels of mTORc or Akt. However, in high-risk MDS patients the level of pSMAD2 (p=0.02) and pSMAD4 (p=0.006) remain significantly lower than healthy donors after 24 hours of stimulation with anti-CD3 and CD46. An aliquot of cells were used for flowcytometry following stimulation. Interestingly Tregs phenotype CD4+CD25highCD127lowexpressed higher level of intracellular C5aR2 in MDS (n=5) compared to HD (n=5). Conclusion: mTORc protein level in MDS is reduced and does not change in response to complement receptor stimulation neither does the level of Akt. This may prevent T cells to polarize toward pro-inflammatory T cells (Th1 or Th17) therefore avert an effective immune-surveillance against malignant clone. Lack of response to complement related co-stimulation and increase in C5aR2 expression suggest a potential mechanism for Treg expansion in MDS. These findings may lead to identification of new therapeutic targets in MDS, although need further studies on larger cohort of patients. Disclosures No relevant conflicts of interest to declare.
Leishmaniasis affects more than twelve million people globally and a further one billion people a... more Leishmaniasis affects more than twelve million people globally and a further one billion people are at risk in leishmaniasis endemic areas. The lack of a vaccine for leishmaniasis coupled with the limitations of existing anti-leishmanial therapies prompted this study. Computational techniques have profound applications in screening large libraries of compounds, studying protein-ligand interactions, analysing pharmacokinetic properties, and designing new drug entities with great speed, accuracy, and precision. This study was carried out to evaluate the multi-protein targeting potential of some diselenides by virtual docking screening using four Leishmania protein targets (2XOX, 3SPX, 5ZWY, and 6K91). Selected analogues were screened using Lipinski filter, and the resulting lead compounds were profiled by ADMET, density functional theory (DFT), and molecular dynamics (MD) simulation analyses. The overall average binding affinity of ligands to target proteins follow the order: 3SPX (-1...
COVID-19 is a highly contagious disease caused by SARS-CoV-2. Vaccination against the virus was f... more COVID-19 is a highly contagious disease caused by SARS-CoV-2. Vaccination against the virus was first approved in Saudi Arabia in December 2020. Vaccinated individuals are still at risk of getting infected with the virus and can transmit the disease. Therefore, the perception of vaccinated individuals regarding the disease can help limit the spread of the virus. Objectives: To measure the risk perception of COVID-19 following vaccination and factors that have an effect on risk perception; to identify the health protective behaviours of the vaccinated individuals. Methodology: This is a quantitative analytical cross-sectional, questionnaire-based study. The target population includes individuals aged 18 and above who live in the Riyadh region and have been vaccinated, during the period of June 2021 to December 2021. Results: The perception of 30.2% of participants did not change after vaccination, with many participants continuing to “always” take precautions even after vaccination. ...
The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused a highly challenging ... more The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused a highly challenging and threatening situation worldwide. SARS-CoV-2 patients develop various clinical symptoms. The olfactory and taste dysfunctions are potential neurological manifestations among SARS-CoV-2 patients; however, their relationship with blood groups has rarely been investigated. This study aimed to investigate the prevalence of chemosensitive neurological disorders of smell and taste and their association with blood groups in SARS-CoV-2 patients. The present cross-sectional study was performed in the Department of Pathology, and Physiology, College of Medicine, King Saud University, Riyadh, Saudi Arabia. A well-structured, self-administered questionnaire was designed and distributed through social media platforms. A total of 922 Saudi and non-Saudi adults aged 18 years or older participated in the study. Out of 922 participants, the number of people who had anosmia was 309 (33.5%), 211 (22.9%)...
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