Publications
Kaimala, Suneesh; Lootah, Shareena Saeed; Mehra, Neha; Kumar, Challagandla Anil; Marzooqi, Saeeda Al; Sampath, Prabha; Ansari, Suraiya Anjum; Emerald, Bright Starling
The Long Non-Coding RNA Obesity-Related (Obr) Contributes To Lipid Metabolism Through Epigenetic Regulation Journal Article
In: Advanced Science, vol. n/a, no. n/a, pp. 2401939, 2024.
@article{https://doi.org/10.1002/advs.202401939,
title = {The Long Non-Coding RNA Obesity-Related (Obr) Contributes To Lipid Metabolism Through Epigenetic Regulation},
author = {Suneesh Kaimala and Shareena Saeed Lootah and Neha Mehra and Challagandla Anil Kumar and Saeeda Al Marzooqi and Prabha Sampath and Suraiya Anjum Ansari and Bright Starling Emerald},
url = {https://onlinelibrary.wiley.com/doi/abs/10.1002/advs.202401939},
doi = {https://doi.org/10.1002/advs.202401939},
year = {2024},
date = {2024-05-05},
journal = {Advanced Science},
volume = {n/a},
number = {n/a},
pages = {2401939},
abstract = {Abstract Obesity is a multifactorial disease that is part of today's epidemic and also increases the risk of other metabolic diseases. Long noncoding RNAs (lncRNAs) provide one tier of regulatory mechanisms to maintain metabolic homeostasis. Although lncRNAs are a significant constituent of the mammalian genome, studies aimed at their metabolic significance, including obesity, are only beginning to be addressed. Here, a developmentally regulated lncRNA, termed as obesity related (Obr), whose expression in metabolically relevant tissues such as skeletal muscle, liver, and pancreas is altered in diet-induced obesity, is identified. The Clone 9 cell line and high-fat diet-induced obese Wistar rats are used as a model system to verify the function of Obr. By using stable expression and antisense oligonucleotide-mediated downregulation of the expression of Obr followed by different molecular biology experiments, its role in lipid metabolism is verified. It is shown that Obr associates with the cAMP response element-binding protein (Creb) and activates different transcription factors involved in lipid metabolism. Its association with the Creb histone acetyltransferase complex, which includes the cAMP response element-binding protein (CBP) and p300, positively regulates the transcription of genes involved in lipid metabolism. In addition, Obr is regulated by Pparγ in response to lipid accumulation.},
keywords = {},
pubstate = {published},
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}
Khasawneh, Lubna Q.; Alsafar, Habiba; Alblooshi, Hiba; Allam, Mushal; Patrinos, George P.; Ali, Bassam R.
The diversity and clinical implications of genetic variants influencing clopidogrel bioactivation and response in the Emirati population Journal Article
In: Human Genomics, vol. 18, no. 1, pp. 2, 2024, ISSN: 1479-7364.
@article{Khasawneh2024,
title = {The diversity and clinical implications of genetic variants influencing clopidogrel bioactivation and response in the Emirati population},
author = {Lubna Q. Khasawneh and Habiba Alsafar and Hiba Alblooshi and Mushal Allam and George P. Patrinos and Bassam R. Ali},
url = {https://doi.org/10.1186/s40246-023-00568-3},
doi = {10.1186/s40246-023-00568-3},
issn = {1479-7364},
year = {2024},
date = {2024-01-03},
journal = {Human Genomics},
volume = {18},
number = {1},
pages = {2},
abstract = {Clopidogrel is a widely prescribed prodrug that requires activation via specific pharmacogenes to exert its anti-platelet function. Genetic variations in the genes encoding its transporter, metabolizing enzymes, and target receptor lead to variability in its activation and platelet inhibition and, consequently, its efficacy. This variability increases the risk of secondary cardiovascular events, and therefore, some variations have been utilized as genetic biomarkers when prescribing clopidogrel.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Mohamed, Feda E.; Al-Jasmi, Fatma
Exploring the efficacy and safety of Ambroxol in Gaucher disease: an overview of clinical studies Journal Article
In: Frontiers in Pharmacology, vol. 15, 2024, ISSN: 1663-9812.
@article{10.3389/fphar.2024.1335058,
title = {Exploring the efficacy and safety of Ambroxol in Gaucher disease: an overview of clinical studies},
author = {Feda E. Mohamed and Fatma Al-Jasmi},
url = {https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1335058},
doi = {10.3389/fphar.2024.1335058},
issn = {1663-9812},
year = {2024},
date = {2024-01-01},
journal = {Frontiers in Pharmacology},
volume = {15},
abstract = {Gaucher disease (GD) is mainly caused by glucocerebrosidase (GCase) enzyme deficiency due to genetic variations in the
},GBA1 gene leading to the toxic accumulation of sphingolipids in various organs, which causes symptoms such as anemia, thrombocytopenia, hepatosplenomegaly, and neurological manifestations. GD is clinically classified into the non-neuronopathic type 1, and the acute and chronic neuronopathic forms, types 2 and 3, respectively. In addition to the current approved GD medications, the repurposing of Ambroxol (ABX) has emerged as a prospective enzyme enhancement therapy option showing its potential to enhance mutated GCase activity and reduce glucosylceramide accumulation in GD-affected tissues of differentGBA1 genotypes. The variability in response to ABX varies across different variants, highlighting the diversity in patients’ therapeutic outcomes. Its oral availability and safety profile make it an attractive option, particularly for patients with neurological manifestations. Clinical trials are essential to explore further ABX’s potential as a therapeutic medication for GD to encourage pharmaceutical companies’ investment in its development. This review highlights the potential of ABX as a pharmacological chaperone therapy for GD and stresses the importance of addressing response variability in clinical studies to improve the management of this rare and complex disorder.
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Gariballa, Nesrin; Badawi, Sally; Ali, Bassam R.
In: Traffic, vol. 25, no. 1, pp. e12928, 2024.
@article{https://doi.org/10.1111/tra.12928,
title = {Endoglin mutants retained in the endoplasmic reticulum exacerbate loss of function in hereditary hemorrhagic telangiectasia type 1 (HHT1) by exerting dominant negative effects on the wild type allele},
author = {Nesrin Gariballa and Sally Badawi and Bassam R. Ali},
url = {https://onlinelibrary.wiley.com/doi/abs/10.1111/tra.12928},
doi = {https://doi.org/10.1111/tra.12928},
year = {2024},
date = {2024-01-01},
journal = {Traffic},
volume = {25},
number = {1},
pages = {e12928},
abstract = {Abstract Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder affecting 1 in 5000–8000 individuals. Hereditary hemorrhagic telangiectasia type 1 (HHT1) is the most common HHT and manifests as diverse vascular malformations ranging from mild symptoms such as epistaxis and mucosal and cutaneous telangiectases to severe arteriovenous malformations (AVMs) in the lungs, brain or liver. HHT1 is caused by heterozygous mutations in the ENG gene, which encodes endoglin, the TGFβ homodimeric co-receptor. It was previously shown that some endoglin HHT1-causing variants failed to traffic to the plasma membrane due to their retention in the endoplasmic reticulum (ER) and consequent degradation by ER-associated degradation (ERAD). Endoglin is a homodimer formed in the ER, and we therefore hypothesized that mixed heterodimers might form between ER-retained variants and WT protein, thus hampering its maturation and trafficking to the plasma membrane causing dominant negative effects. Indeed, HA-tagged ER-retained mutants formed heterodimers with Myc-tagged WT endoglin. Moreover, variants L32R, V105D, P165L, I271N and C363Y adversely affected the trafficking of WT endoglin by reducing its maturation and plasma membrane localization. These results strongly suggest dominant negative effects exerted by these ER-retained variants aggravating endoglin loss of function in patients expressing them in the heterozygous state with the WT allele. Moreover, this study may help explain some of the variability observed among HHT1 patients due to the additional loss of function exerted by the dominant negative effects in addition to that due to haploinsufficiency. These findings might also have implications for some of the many conditions impacted by ERAD.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Krishnan, Anjana; Ali, Lizna M; Prabhu, Suresha G; Pillai, Vineeta N; Chameettachal, Akhil; Vivet-Boudou, Valerie; Bernacchi, Serena; Mustafa, Farah; Marquet, Roland; Rizvi, Tahir A
Identification of a Gag binding site critical for feline immunodeficiency virus (FIV) genomic RNA packaging Journal Article
In: RNA, vol. 30, no. 1, pp. 68-88, 2024.
@article{PMID:37914398,
title = {Identification of a Gag binding site critical for feline immunodeficiency virus (FIV) genomic RNA packaging},
author = {Anjana Krishnan and Lizna M Ali and Suresha G Prabhu and Vineeta N Pillai and Akhil Chameettachal and Valerie Vivet-Boudou and Serena Bernacchi and Farah Mustafa and Roland Marquet and Tahir A Rizvi},
doi = {10.1261/rna.079840.123},
year = {2024},
date = {2024-01-01},
urldate = {2024-01-01},
journal = {RNA},
volume = {30},
number = {1},
pages = {68-88},
abstract = {The retroviral Gag precursor plays a central role in the selection and packaging of viral genomic RNA (gRNA) by binding to virus-specific packaging signal(s) (psi or ψ). Previously, we have mapped the FIV ψ to two discontinuous regions within the 5' end of the gRNA that assumes a higher order structure harboring several structural motifs. To better define the region and structural elements important for gRNA packaging, we methodically investigated these FIV ψ sequences employing genetic, biochemical, and structure-function relationship approaches. Our mutational analysis revealed that the unpaired U85CUG88 stretch within FIV ψ is crucial for gRNA encapsidation into nascent virions. High-throughput Selective 2' Hydroxyl Acylation analyzed by Primer Extension (hSHAPE) performed on wild type and mutant FIV ψ sequences with substitutions in the U85CUG88 stretch revealed that these mutations had limited structural impact and maintained nucleotides 80 to 92 unpaired, as in the wild type structure. Since these mutations dramatically affected packaging, our data suggests that the single-stranded U85CUG88 sequence is important during FIV RNA packaging. Filter binding assays performed using purified FIV Pr50Gag on wild type and mutant U85CUG88 ψ RNAs led to reduced levels of Pr50Gag binding to mutant U85CUG88 ψ RNAs, indicating that the U85CUG88 stretch is crucial for ψ RNA-Pr50Gag interactions. Delineating sequences important for FIV gRNA encapsidation should enhance our understanding of both gRNA packaging and virion assembly, making them potential targets for novel retroviral therapeutic interventions, as well as development of FIV-based vectors for human gene therapy.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Khan, Wasif; Zaki, Nazar; Ahmad, Amir; Masud, Mohammad M; Govender, Romana; Rojas-Perilla, Natalia; Ali, Luqman; Ghenimi, Nadirah; Ahmed, Luai A
Node embedding-based graph autoencoder outlier detection for adverse pregnancy outcomes Journal Article
In: Scientific reports, vol. 13, no. 1, pp. 19817, 2023, ISSN: 2045-2322.
@article{PMID:37963898,
title = {Node embedding-based graph autoencoder outlier detection for adverse pregnancy outcomes},
author = {Wasif Khan and Nazar Zaki and Amir Ahmad and Mohammad M Masud and Romana Govender and Natalia Rojas-Perilla and Luqman Ali and Nadirah Ghenimi and Luai A Ahmed},
url = {https://europepmc.org/articles/PMC10645849},
doi = {10.1038/s41598-023-46726-4},
issn = {2045-2322},
year = {2023},
date = {2023-11-01},
journal = {Scientific reports},
volume = {13},
number = {1},
pages = {19817},
abstract = {Adverse pregnancy outcomes, such as low birth weight (LBW) and preterm birth (PTB), can have serious consequences for both the mother and infant. Early prediction of such outcomes is important for their prevention. Previous studies using traditional machine learning (ML) models for predicting PTB and LBW have encountered two important limitations: extreme class imbalance in medical datasets and the inability to account for complex relational structures between entities. To address these limitations, we propose a node embedding-based graph outlier detection algorithm to predict adverse pregnancy outcomes. We developed a knowledge graph using a well-curated representative dataset of the Emirati population and two node embedding algorithms. The graph autoencoder (GAE) was trained by applying a combination of original risk factors and node embedding features. Samples that were difficult to reconstruct at the output of GAE were identified as outliers considered representing PTB and LBW samples. Our experiments using LBW, PTB, and very PTB datasets demonstrated that incorporating node embedding considerably improved performance, achieving a 12% higher AUC-ROC compared to traditional GAE. Our study demonstrates the effectiveness of node embedding and graph outlier detection in improving the prediction performance of adverse pregnancy outcomes in well-curated population datasets.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Busaidi, Marwa Al; Mohamed, Feda E; Al-Ajmi, Eiman; Hashmi, Nadia Al; Al-Thihli, Khalid; Futaisi, Amna Al; Mamari, Watfa Al; Al-Murshedi, Fathiya; Al-Jasmi, Fatma
Expanding the clinical spectrum of cytosolic phosphoenolpyruvate carboxykinase deficiency: novel PCK1 variants in four Arabian Gulf families Journal Article
In: Orphanet journal of rare diseases, vol. 18, no. 1, pp. 344, 2023, ISSN: 1750-1172.
@article{PMID:37924129,
title = {Expanding the clinical spectrum of cytosolic phosphoenolpyruvate carboxykinase deficiency: novel PCK1 variants in four Arabian Gulf families},
author = {Marwa Al Busaidi and Feda E Mohamed and Eiman Al-Ajmi and Nadia Al Hashmi and Khalid Al-Thihli and Amna Al Futaisi and Watfa Al Mamari and Fathiya Al-Murshedi and Fatma Al-Jasmi},
url = {https://europepmc.org/articles/PMC10625263},
doi = {10.1186/s13023-023-02946-5},
issn = {1750-1172},
year = {2023},
date = {2023-11-01},
journal = {Orphanet journal of rare diseases},
volume = {18},
number = {1},
pages = {344},
abstract = {Background
In metabolic stress, the cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C) enzyme is involved in energy production through the gluconeogenesis pathway. PEPCK-C deficiency is a rare childhood-onset autosomal recessive metabolic disease caused by PCK1 genetic defects. Previous studies showed a broad clinical spectrum ranging from asymptomatic to recurrent hypoglycemia with/without lactic acidosis, encephalopathy, seizures, and liver failure.Results
In this article, we discuss the occurrence of PEPCK-C deficiency in four families from the United Arab Emirates and Oman. All patients presented with unexplained hypoglycemia as a common feature. Two out of the seven patients presented with episodes of encephalopathy that resulted in seizures and neuroregression leading to global developmental delay and one patient had a neonatal presentation. Observed biochemical abnormalities include elevated lactate, transaminases, and tricarboxylic acid cycle metabolites in most patients. Elevated creatine kinase was documented in two patients. Whole exome sequencing revealed two novel (c.574T > C, and c.1268 C > T) and a previously reported splice site (c.961 + 1G > A) PCK1 variant in the affected families.Conclusion
Patients become vulnerable during intercurrent illness; thus, prevention and prompt reversal of a catabolic state are crucial to avoid irreversible brain damage. This report will help to expand the clinical understanding of this rare disease and recommends screening for PEPCK-C deficiency in unexplained hypoglycemia.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Chameettachal, Akhil; Mustafa, Farah; Rizvi, Tahir A.
Understanding Retroviral Life Cycle and its Genomic RNA Packaging Journal Article
In: Journal of Molecular Biology, vol. 435, no. 3, pp. 167924, 2023, ISSN: 0022-2836.
@article{CHAMEETTACHAL2023167924,
title = {Understanding Retroviral Life Cycle and its Genomic RNA Packaging},
author = {Akhil Chameettachal and Farah Mustafa and Tahir A. Rizvi},
url = {https://www.sciencedirect.com/science/article/pii/S0022283622005514},
doi = {https://doi.org/10.1016/j.jmb.2022.167924},
issn = {0022-2836},
year = {2023},
date = {2023-01-01},
journal = {Journal of Molecular Biology},
volume = {435},
number = {3},
pages = {167924},
abstract = {Members of the family Retroviridae are important animal and human pathogens. Being obligate parasites, their replication involves a series of steps during which the virus hijacks the cellular machinery. Additionally, many of the steps of retrovirus replication are unique among viruses, including reverse transcription, integration, and specific packaging of their genomic RNA (gRNA) as a dimer. Progress in retrovirology has helped identify several molecular mechanisms involved in each of these steps, but many are still unknown or remain controversial. This review summarizes our present understanding of the molecular mechanisms involved in various stages of retrovirus replication. Furthermore, it provides a comprehensive analysis of our current understanding of how different retroviruses package their gRNA into the assembling virions. RNA packaging in retroviruses holds a special interest because of the uniqueness of packaging a dimeric genome. Dimerization and packaging are highly regulated and interlinked events, critical for the virus to decide whether its unspliced RNA will be packaged as a “genome” or translated into proteins. Finally, some of the outstanding areas of exploration in the field of RNA packaging are highlighted, such as the role of epitranscriptomics, heterogeneity of transcript start sites, and the necessity of functional polyA sequences. An in-depth knowledge of mechanisms that interplay between viral and cellular factors during virus replication is critical in understanding not only the virus life cycle, but also its pathogenesis, and development of new antiretroviral compounds, vaccines, as well as retroviral-based vectors for human gene therapy.},
keywords = {},
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tppubtype = {article}
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Elmoselhi, Adel B.; Bouzid, Amal; Allah, Mohamed Seif; Ibrahim, Zeinab; Bajbouj, Khuloud; Assaleh, Rebal S. Abou; Venkatachalam, Thenmozhi; Madkour, Mohamed; Siddiqui, Ruqaiyyah; Khan, Naveed Ahmed; Hamoudi, Rifat A.
Unveiling the molecular Culprit of arterial stiffness in vitamin D deficiency and obesity: Potential for novel therapeutic targets Journal Article
In: Heliyon, vol. 9, no. 11, pp. e22067, 2023, ISSN: 2405-8440.
@article{ELMOSELHI2023e22067,
title = {Unveiling the molecular Culprit of arterial stiffness in vitamin D deficiency and obesity: Potential for novel therapeutic targets},
author = {Adel B. Elmoselhi and Amal Bouzid and Mohamed Seif Allah and Zeinab Ibrahim and Khuloud Bajbouj and Rebal S. Abou Assaleh and Thenmozhi Venkatachalam and Mohamed Madkour and Ruqaiyyah Siddiqui and Naveed Ahmed Khan and Rifat A. Hamoudi},
url = {https://www.sciencedirect.com/science/article/pii/S2405844023092757},
doi = {https://doi.org/10.1016/j.heliyon.2023.e22067},
issn = {2405-8440},
year = {2023},
date = {2023-01-01},
journal = {Heliyon},
volume = {9},
number = {11},
pages = {e22067},
abstract = {Cardiovascular diseases (CVDs) are highly associated with both vitamin D deficiency and obesity, two prevalent health conditions worldwide. Arterial stiffness, an independent predictor of CVDs, is particularly elevated in both conditions, yet the molecular mechanisms underlying this phenomenon remain elusive, hindering effective management of CVDs in this population. We recruited 20 middle-aged Emiratis, including 9 individuals with vitamin D deficiency (Vit D level ≤20 ng) and obesity (BMI ≥30) and 11 individuals as control with Vit D level >20 ng and BMI <30. We measured arterial stiffness using pulse wave velocity (PWV) and performed whole transcriptome sequencing to identify differentially expressed genes (DEGs) and enriched pathways. We validated these findings using qRT-PCR, Western blot, and multiplex analysis. PWV was significantly higher in the vitamin D deficient and obese group relative to controls (p ≤ 0.05). The DEG analysis revealed that pathways related to interleukin 1 (IL-1), nitrogen metabolism, HIF-1 signaling, and MAPK signaling were over-activated in the vitamin D deficient and obese group. We found that HIF-1alpha, NOX-I, NOX-II, IL-1b, IL-8, IL-10, and VEGF were significantly upregulated in the vitamin D deficient and obese group (p < 0.05). Our study provides new insights into the molecular mechanisms of arterial stiffness in vitamin D deficiency and obesity, demonstrating the role of oxidative stress and inflammation in this process. Our findings suggest that these biomarkers may serve as potential therapeutic targets for early prevention of CVDs. Further studies are needed to investigate these pathways and biomarkers with larger cohort.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Badawi, Sally; Varghese, Divya Saro; Raj, Anjana; John, Anne; Al-Musafir, Hamda S.; Al-Ghamari, Ahmed J.; Alshamsi, Alreem R.; Ouda, Sara H.; Al-Dirbashi, Ghayth; Ali, Bassam R.
In: Frontiers in Cell and Developmental Biology, vol. 11, 2023, ISSN: 2296-634X.
@article{10.3389/fcell.2023.1294748,
title = {Unveiling the pathogenic mechanisms of NPR2 missense variants: insights into the genotype-associated severity in acromesomelic dysplasia and short stature},
author = {Sally Badawi and Divya Saro Varghese and Anjana Raj and Anne John and Hamda S. Al-Musafir and Ahmed J. Al-Ghamari and Alreem R. Alshamsi and Sara H. Ouda and Ghayth Al-Dirbashi and Bassam R. Ali},
url = {https://www.frontiersin.org/articles/10.3389/fcell.2023.1294748},
doi = {10.3389/fcell.2023.1294748},
issn = {2296-634X},
year = {2023},
date = {2023-01-01},
journal = {Frontiers in Cell and Developmental Biology},
volume = {11},
abstract = {Introduction: Natriuretic peptide receptor 2 (NPR2 or NPR-B) plays a central role in growth development and bone morphogenesis and therefore loss-of-function variations in NPR2 gene have been reported to cause Acromesomelic Dysplasia, Maroteaux type 1 and short stature. While several hypotheses have been proposed to underlie the pathogenic mechanisms responsible for these conditions, the exact mechanisms, and functional characteristics of many of those variants and their correlations with the clinical manifestations have not been fully established.Methods: In this study, we examined eight NPR2 genetic missense variants (p.Leu51Pro, p.Gly123Val, p.Leu314Arg, p.Arg318Gly, p.Arg388Gln, p.Arg495Cys, p.Arg557His, and p.Arg932Cys) Acromesomelic Dysplasia, Maroteaux type 1 and short stature located on diverse domains and broadly classified as variants of uncertain significance. The evaluated variants are either reported in patients with acromesomelic dysplasia in the homozygous state or short stature in the heterozygous state. Our investigation included the evaluation of their expression, subcellular trafficking and localization, N-glycosylation profiles, and cyclic guanosine monophosphate (cGMP) production activity.Results and Discussion: Our results indicate that variants p.Leu51Pro, p.Gly123Val, p.Leu314Arg, p.Arg388Gln have defective cellular trafficking, being sequestered within the endoplasmic reticulum (ER), and consequently impaired cGMP production ability. Conversely, variants p.Arg318Gly, p.Arg495Cys, and p.Arg557His seem to display a non-statistically significant behavior that is slightly comparable to WT-NPR2. On the other hand, p.Arg932Cys which is located within the guanylyl cyclase active site displayed normal cellular trafficking profile albeit with defective cGMP. Collectively, our data highlights the genotype-phenotype relationship that might be responsible for the milder symptoms observed in short stature compared to acromesomelic dysplasia. This study enhances our understanding of the functional consequences of several NPR2 variants, shedding light on their mechanisms and roles in related genetic disorders which might also help in their pathogenicity re-classification.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Masad, Ashraf Al-Sbiei Ghada Bashir Razan J.
In: 2023.
@article{masad2023oral,
title = {Oral administration of Manuka honey modulates gut microbiota composition and enhances anti-tumor immunity in a preclinical model of colorectal cancer},
author = {Ashraf Al-Sbiei Ghada Bashir Razan J. Masad},
url = {https://www.researchsquare.com/article/rs-3273451/v2.pdf?c=1692853595000},
doi = {10.21203/rs.3.rs-3273451/v2},
year = {2023},
date = {2023-01-01},
abstract = {Conclusions: Our findings demonstrate that oral administration of MH induces specific alterations in the gut microbiota and triggers innate and adaptive mucosal immune responses through the activation of type I/II IFN signaling pathways. This culminates in rendering the tumors more immunogenically responsive. Our data highlight the immunostimulatory properties of MH and demonstrate its potential utilization in cancer prevention.
Background: There is increasing interest in exploring alternative natural products for cancer prevention and treatment. Among these, we recently highlighted the potential utilization of Manuka honey (MH) as an immunomodulatory agent. In the present study, we characterized mechanistically the immunomodulatory properties of MH in a preclinical model of colorectal cancer (CRC).
Methods: MH was administered orally over a 4 week-period. A solution containing equivalent concentrations of the main sugars in MH was used as a control (SC). Mucosal and systemic lymphoid tissues were examined for alterations in cellular composition and activation status by multi-color flow cytometry (FACS). Fecal pellets were collected before and after treatment and used for bacterial 16S rRNA sequencing. Pretreated mice were implanted with CRC cells and followed for tumor growth. Tumors, lymph nodes, and spleens were analyzed by FACS, immunohistochemistry, and qRT-PCR 3-weeks post-implantation.
Results: Pretreatment with MH, but not SC solution, induced type I/II IFN response in mucosal and systemic lymphoid tissues, resulting in enhanced expression of IFN-inducible stem cell antigen-1 (Sca-1) and MHC class II proteins. In an implantable model of CRC, tumor growth was significantly retarded in MH-pretreated mice. These tumors had increased infiltration of immune cells, ~2.0-fold increase in the percentage of intratumoral CD4+ and CD8+ T cells, and a 50% decrease in the percentage of Ly6G+ myeloid cells. Immunohistochemical analysis of tumor tissues revealed an increase in CD4+ and CD8+ T cells and granzyme-B-expressing cells following MH treatment. Moreover, FACS analysis showed significantly elevated expression of MHC class I on tumors of MH-treated mice. qRT-PCR analysis of purified tumor-infiltrating leucocytes highlighted changes in the expression of various chemokines and inflammatory cytokines that underlie the increased tumor immunogenicity. Finally, bacterial 16S rRNA sequencing revealed unique enrichment of >20 bacterial genera in MH-treated mice.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background: There is increasing interest in exploring alternative natural products for cancer prevention and treatment. Among these, we recently highlighted the potential utilization of Manuka honey (MH) as an immunomodulatory agent. In the present study, we characterized mechanistically the immunomodulatory properties of MH in a preclinical model of colorectal cancer (CRC).
Methods: MH was administered orally over a 4 week-period. A solution containing equivalent concentrations of the main sugars in MH was used as a control (SC). Mucosal and systemic lymphoid tissues were examined for alterations in cellular composition and activation status by multi-color flow cytometry (FACS). Fecal pellets were collected before and after treatment and used for bacterial 16S rRNA sequencing. Pretreated mice were implanted with CRC cells and followed for tumor growth. Tumors, lymph nodes, and spleens were analyzed by FACS, immunohistochemistry, and qRT-PCR 3-weeks post-implantation.
Results: Pretreatment with MH, but not SC solution, induced type I/II IFN response in mucosal and systemic lymphoid tissues, resulting in enhanced expression of IFN-inducible stem cell antigen-1 (Sca-1) and MHC class II proteins. In an implantable model of CRC, tumor growth was significantly retarded in MH-pretreated mice. These tumors had increased infiltration of immune cells, ~2.0-fold increase in the percentage of intratumoral CD4+ and CD8+ T cells, and a 50% decrease in the percentage of Ly6G+ myeloid cells. Immunohistochemical analysis of tumor tissues revealed an increase in CD4+ and CD8+ T cells and granzyme-B-expressing cells following MH treatment. Moreover, FACS analysis showed significantly elevated expression of MHC class I on tumors of MH-treated mice. qRT-PCR analysis of purified tumor-infiltrating leucocytes highlighted changes in the expression of various chemokines and inflammatory cytokines that underlie the increased tumor immunogenicity. Finally, bacterial 16S rRNA sequencing revealed unique enrichment of >20 bacterial genera in MH-treated mice.
Arafat, Kholoud; Al-Azawi, Aya Mudhafar; Sulaiman, Shahrazad; Attoub, Samir
Exploring the Anticancer Potential of Origanum majorana Essential Oil Monoterpenes Alone and in Combination against Non-Small Cell Lung Cancer Journal Article
In: Nutrients, vol. 15, no. 23, 2023, ISSN: 2072-6643.
@article{nu15235010,
title = {Exploring the Anticancer Potential of Origanum majorana Essential Oil Monoterpenes Alone and in Combination against Non-Small Cell Lung Cancer},
author = {Kholoud Arafat and Aya Mudhafar Al-Azawi and Shahrazad Sulaiman and Samir Attoub},
url = {https://www.mdpi.com/2072-6643/15/23/5010},
doi = {10.3390/nu15235010},
issn = {2072-6643},
year = {2023},
date = {2023-01-01},
journal = {Nutrients},
volume = {15},
number = {23},
abstract = {Lung cancer is the second most commonly diagnosed cancer and has the highest mortality rate worldwide despite the remarkable advances in its treatment. Origanum majorana Essential Oil (OMEO) has been shown to be effective against non-small cell lung cancer (NSCLC) cells, decreasing their viability and colony growth in vitro, as well as inhibiting tumor growth in chick embryo chorioallantoic membranes (CAM) and nude mice in vivo. OMEO is mainly composed of four monoterpenes, namely terpinen-4-ol, sabinene hydrate, α-terpinene, and γ-terpinene. In this study, we aimed to investigate the potential anticancer effects of these monoterpenes, either alone or in combination, on NSCLC. Our findings indicate that these four monoterpenes significantly decreased NSCLC cell viability in a concentration-dependent manner, reduced their colony growth in vitro, and also downregulated survivin expression in these cells. Moreover, different combined mixtures of these monoterpenes further enhanced their anticancer effects on cellular viability, with a terpinen-4-ol and sabinene hydrate combination being the most potent. We also found that terpinen-4-ol, in combination with sabinene hydrate, markedly enhanced the anticancer effect of the individual monoterpenes on NSCLC viability within a shorter treatment duration through, at least in part, survivin downregulation. Furthermore, this combination enhanced the inhibition of colony growth in vitro and the tumor growth of NSCLC cells xenografted onto chick embryo CAM in vivo. Altogether, our study highlights the potential of these monoterpenes for use in further pre-clinical investigations against various cancer hallmarks.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Statsenko, Yauhen; Kuznetsov, Nik V.; Morozova, Daria; Liaonchyk, Katsiaryna; Simiyu, Gillian Lylian; Smetanina, Darya; Kashapov, Aidar; Meribout, Sarah; Gorkom, Klaus Neidl-Van; Hamoudi, Rifat; Ismail, Fatima; Ansari, Suraiya Anjum; Emerald, Bright Starling; Ljubisavljevic, Milos
Reappraisal of the Concept of Accelerated Aging in Neurodegeneration and Beyond Journal Article
In: Cells, vol. 12, no. 20, 2023, ISSN: 2073-4409.
@article{cells12202451,
title = {Reappraisal of the Concept of Accelerated Aging in Neurodegeneration and Beyond},
author = {Yauhen Statsenko and Nik V. Kuznetsov and Daria Morozova and Katsiaryna Liaonchyk and Gillian Lylian Simiyu and Darya Smetanina and Aidar Kashapov and Sarah Meribout and Klaus Neidl-Van Gorkom and Rifat Hamoudi and Fatima Ismail and Suraiya Anjum Ansari and Bright Starling Emerald and Milos Ljubisavljevic},
url = {https://www.mdpi.com/2073-4409/12/20/2451},
doi = {10.3390/cells12202451},
issn = {2073-4409},
year = {2023},
date = {2023-01-01},
journal = {Cells},
volume = {12},
number = {20},
abstract = {Background: Genetic and epigenetic changes, oxidative stress and inflammation influence the rate of aging, which diseases, lifestyle and environmental factors can further accelerate. In accelerated aging (AA), the biological age exceeds the chronological age. Objective: The objective of this study is to reappraise the AA concept critically, considering its weaknesses and limitations. Methods: We reviewed more than 300 recent articles dealing with the physiology of brain aging and neurodegeneration pathophysiology. Results: (1) Application of the AA concept to individual organs outside the brain is challenging as organs of different systems age at different rates. (2) There is a need to consider the deceleration of aging due to the potential use of the individual structure-functional reserves. The latter can be restored by pharmacological and/or cognitive therapy, environment, etc. (3) The AA concept lacks both standardised terminology and methodology. (4) Changes in specific molecular biomarkers (MBM) reflect aging-related processes; however, numerous MBM candidates should be validated to consolidate the AA theory. (5) The exact nature of many potential causal factors, biological outcomes and interactions between the former and the latter remain largely unclear. Conclusions: Although AA is commonly recognised as a perspective theory, it still suffers from a number of gaps and limitations that assume the necessity for an updated AA concept.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Shihab, I; Bouzid, A; Yener, B; Altaie, A; Bhamidimarri, P Manasa; Ameri, M Al; Bendardaf, R; Hamad, M; Hamoudi, R
In: F1000Research, vol. 12, no. 1117, 2023.
@article{10.12688/f1000research.130316.1,
title = {Impact of estrogen and progesterone hormone receptors on the progression of interferon-? sensitized breast cancer cells [version 1; peer review: 1 approved]},
author = {I Shihab and A Bouzid and B Yener and A Altaie and P Manasa Bhamidimarri and M Al Ameri and R Bendardaf and M Hamad and R Hamoudi},
doi = {10.12688/f1000research.130316.1},
year = {2023},
date = {2023-01-01},
journal = {F1000Research},
volume = {12},
number = {1117},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Marzook, Hezlin; Gupta, Anamika; Tomar, Dhanendra; Saleh, Mohamed A.; Patil, Kiran; Semreen, Mohammad H.; Hamoudi, Rifat; Soares, Nelson C.; Qaisar, Rizwan; Ahmad, Firdos
Nicotinamide riboside kinase-2 regulates metabolic adaptation in the ischemic heart Journal Article
In: Journal of Molecular Medicine, vol. 101, no. 3, pp. 311–326, 2023, ISSN: 1432-1440.
@article{marzook2023nicotinamide,
title = {Nicotinamide riboside kinase-2 regulates metabolic adaptation in the ischemic heart},
author = {Hezlin Marzook and Anamika Gupta and Dhanendra Tomar and Mohamed A. Saleh and Kiran Patil and Mohammad H. Semreen and Rifat Hamoudi and Nelson C. Soares and Rizwan Qaisar and Firdos Ahmad},
url = {https://doi.org/10.1007/s00109-023-02296-6},
doi = {10.1007/s00109-023-02296-6},
issn = {1432-1440},
year = {2023},
date = {2023-01-01},
journal = {Journal of Molecular Medicine},
volume = {101},
number = {3},
pages = {311–326},
abstract = {Ischemia-induced metabolic remodeling plays a critical role in the pathogenesis of adverse cardiac remodeling and heart failure. However, the underlying molecular mechanism is largely unknown. Here, we assess the potential roles of nicotinamide riboside kinase-2 (NRK-2), a muscle-specific protein, in ischemia-induced metabolic switch and heart failure through employing transcriptomic and metabolomic approaches in ischemic NRK-2 knockout mice. The investigations revealed NRK-2 as a novel regulator of several metabolic processes in the ischemic heart. Cardiac metabolism and mitochondrial function and fibrosis were identified as top dysregulated cellular processes in the KO hearts post-MI. Several genes linked to mitochondrial function, metabolism, and cardiomyocyte structural proteins were severely downregulated in the ischemic NRK-2 KO hearts. Analysis revealed significantly upregulated ECM-related pathways which was accompanied by the upregulation of several key cell signaling pathways including SMAD, MAPK, cGMP, integrin, and Akt in the KO heart post-MI. Metabolomic studies identified profound upregulation of metabolites mevalonic acid, 3,4-dihydroxyphenylglycol, 2-penylbutyric acid, and uridine. However, other metabolites stearic acid, 8,11,14-eicosatrienoic acid, and 2-pyrrolidinone were significantly downregulated in the ischemic KO hearts. Taken together, these findings suggest that NRK-2 promotes metabolic adaptation in the ischemic heart. The aberrant metabolism in the ischemic NRK-2 KO heart is largely driven by dysregulated cGMP and Akt and mitochondrial pathways.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Pedersini, Caterina A.; Miller, Nathaniel P.; Gandhi, Tapan K.; Gilad-Gutnick, Sharon; Mahajan, Vidur; Sinha, Pawan; Rokers, Bas
White matter plasticity following cataract surgery in congenitally blind patients Journal Article
In: Proceedings of the National Academy of Sciences, vol. 120, no. 19, pp. e2207025120, 2023.
@article{doi:10.1073/pnas.2207025120,
title = {White matter plasticity following cataract surgery in congenitally blind patients},
author = {Caterina A. Pedersini and Nathaniel P. Miller and Tapan K. Gandhi and Sharon Gilad-Gutnick and Vidur Mahajan and Pawan Sinha and Bas Rokers},
url = {https://www.pnas.org/doi/abs/10.1073/pnas.2207025120},
doi = {10.1073/pnas.2207025120},
year = {2023},
date = {2023-01-01},
journal = {Proceedings of the National Academy of Sciences},
volume = {120},
number = {19},
pages = {e2207025120},
abstract = {The visual system develops abnormally when visual input is absent or degraded during a critical period early in life. Restoration of the visual input later in life is generally thought to have limited benefit because the visual system will lack sufficient plasticity to adapt to and utilize the information from the eyes. Recent evidence, however, shows that congenitally blind adolescents can recover both low-level and higher-level visual function following surgery. In this study, we assessed behavioral performance in both a visual acuity and a face perception task alongside longitudinal structural white matter changes in terms of fractional anisotropy (FA) and mean diffusivity (MD). We studied congenitally blind patients with dense bilateral cataracts, who received cataract surgery at different stages of adolescence. Our goal was to differentiate between age- and surgery-related changes in both behavioral performance and structural measures to identify neural correlates which might contribute to recovery of visual function. We observed surgery-related long-term increases of structural integrity of late-visual pathways connecting the occipital regions with ipsilateral fronto-parieto-temporal regions or homotopic contralateral areas. Comparison to a group of age-matched healthy participants indicated that these improvements went beyond the expected changes in FA and MD based on maturation alone. Finally, we found that the extent of behavioral improvement in face perception was mediated by changes in structural integrity in late visual pathways. Our results suggest that sufficient plasticity remains in adolescence to partially overcome abnormal visual development and help localize the sites of neural change underlying sight recovery.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Badawi, Sally; Mohamed, Feda E.; Varghese, Divya Saro; Ali, Bassam R.
Genetic disruption of mammalian endoplasmic reticulum-associated protein degradation: Human phenotypes and animal and cellular disease models Journal Article
In: Traffic, vol. 24, no. 8, pp. 312-333, 2023.
@article{https://doi.org/10.1111/tra.12902,
title = {Genetic disruption of mammalian endoplasmic reticulum-associated protein degradation: Human phenotypes and animal and cellular disease models},
author = {Sally Badawi and Feda E. Mohamed and Divya Saro Varghese and Bassam R. Ali},
url = {https://onlinelibrary.wiley.com/doi/abs/10.1111/tra.12902},
doi = {https://doi.org/10.1111/tra.12902},
year = {2023},
date = {2023-01-01},
journal = {Traffic},
volume = {24},
number = {8},
pages = {312-333},
abstract = {Abstract Endoplasmic reticulum-associated protein degradation (ERAD) is a stringent quality control mechanism through which misfolded, unassembled and some native proteins are targeted for degradation to maintain appropriate cellular and organelle homeostasis. Several in vitro and in vivo ERAD-related studies have provided mechanistic insights into ERAD pathway activation and its consequent events; however, a majority of these have investigated the effect of ERAD substrates and their consequent diseases affecting the degradation process. In this review, we present all reported human single-gene disorders caused by genetic variation in genes that encode ERAD components rather than their substrates. Additionally, after extensive literature survey, we present various genetically manipulated higher cellular and mammalian animal models that lack specific components involved in various stages of the ERAD pathway.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Ahmad, Waqar; Gull, Bushra; Baby, Jasmin; Panicker, Neena G.; Khader, Thanumol A.; Akhlaq, Shaima; Rizvi, Tahir A.; Mustafa, Farah
Differentially-regulated miRNAs in COVID-19: A systematic review Journal Article
In: Reviews in Medical Virology, vol. 33, no. 4, pp. e2449, 2023.
@article{https://doi.org/10.1002/rmv.2449,
title = {Differentially-regulated miRNAs in COVID-19: A systematic review},
author = {Waqar Ahmad and Bushra Gull and Jasmin Baby and Neena G. Panicker and Thanumol A. Khader and Shaima Akhlaq and Tahir A. Rizvi and Farah Mustafa},
url = {https://onlinelibrary.wiley.com/doi/abs/10.1002/rmv.2449},
doi = {https://doi.org/10.1002/rmv.2449},
year = {2023},
date = {2023-01-01},
journal = {Reviews in Medical Virology},
volume = {33},
number = {4},
pages = {e2449},
abstract = {Abstract Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for coronavirus disease of 2019 (COVID-19) that infected more than 760 million people worldwide with over 6.8 million deaths to date. COVID-19 is one of the most challenging diseases of our times due to the nature of its spread, its effect on multiple organs, and an inability to predict disease prognosis, ranging from being completely asymptomatic to death. Upon infection, SARS-CoV-2 alters the host immune response by changing host-transcriptional machinery. MicroRNAs (miRNAs) are regarded as post-transcriptional regulators of gene expression that can be perturbed by invading viruses. Several in vitro and in vivo studies have reported such dysregulation of host miRNA expression upon SARS-CoV-2 infection. Some of this could occur as an anti-viral response of the host to the viral infection. Viruses themselves can counteract that response by mounting their own pro-viral response that facilitates virus infection, an aspect which may cause pathogenesis. Thus, miRNAs could serve as possible disease biomarkers in infected people. In the current review, we have summarised and analysed the existing data about miRNA dysregulation in patients infected with SARS-CoV-2 to determine their concordance between studies, and identified those that could serve as potential biomarkers during infection, disease progression, and death, even in people with other co-morbidities. Having such biomarkers can be vital in not only predicting COVID-19 prognosis, but also the development of novel miRNA-based anti-virals and therapeutics which can become invaluable in case of the emergence of new viral variants with pandemic potential in the future.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Salameh, Laila; Mahmood, Walid; Hamoudi, Rifat; Almazrouei, Khulood; Lochanan, Mahesh; Seyhoglu, Suheyl; Mahboub, Bassam
The Role of Vitamin D Supplementation on Airway Remodeling in Asthma: A Systematic Review Journal Article
In: Nutrients, vol. 15, no. 11, 2023, ISSN: 2072-6643.
@article{nu15112477,
title = {The Role of Vitamin D Supplementation on Airway Remodeling in Asthma: A Systematic Review},
author = {Laila Salameh and Walid Mahmood and Rifat Hamoudi and Khulood Almazrouei and Mahesh Lochanan and Suheyl Seyhoglu and Bassam Mahboub},
url = {https://www.mdpi.com/2072-6643/15/11/2477},
doi = {10.3390/nu15112477},
issn = {2072-6643},
year = {2023},
date = {2023-01-01},
journal = {Nutrients},
volume = {15},
number = {11},
abstract = {Asthma is a common chronic respiratory disease that affects millions of people worldwide, and its prevalence continues to increase. Vitamin D has been proposed as a potential environmental factor in asthma pathogenesis, due to its immunomodulatory effects. This systematic review aimed to evaluate the effect of vitamin D supplementation in order to prevent airway remodeling in asthmatic patients. Four electronic databases, namely PubMed, Embase, Clinical trails.gov, and CINAHL, were thoroughly searched to conduct a comprehensive literature review. The International Prospective Register of Systematic Reviews (CRD42023413798) contains a record of the registered protocol. We identified 9447 studies during the initial search; 9 studies (0.1%) met the inclusion criteria and were included in the systematic review. All included studies were experimental studies that investigated the impact of vitamin D supplementation on airway remodeling in asthma. The studies included in this review suggest that vitamin D inhibits airway smooth muscle cell contraction and remodeling, reduces inflammation, regulates collagen synthesis in the airways, and modulates the action of bronchial fibroblasts. However, one study suggests that TGF-β1 can impair vitamin D-induced and constitutive airway epithelial host defense mechanisms. Overall, vitamin D appears to have a potential role in the prevention and management of asthma.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Statsenko, Yauhen; Smetanina, Darya; Arora, Teresa; Östlundh, Linda; Habuza, Tetiana; Simiyu, Gillian Lylian; Meribout, Sarah; Talako, Tatsiana; King, Fransina Christina; Makhnevych, Iryna; Gelovani, Juri George; Das, Karuna M; Gorkom, Klaus Neidl-Van; Almansoori, Taleb M; Zahmi, Fatmah Al; Sz'olics, Mikl'os; Ismail, Fatima; Ljubisavljevic, Milos
In: BMJ Open, vol. 13, no. 7, 2023, ISSN: 2044-6055.
@article{Statsenkoe068608,
title = {Multimodal diagnostics in multiple sclerosis: predicting disability and conversion from relapsing-remitting to secondary progressive disease course – protocol for systematic review and meta-analysis},
author = {Yauhen Statsenko and Darya Smetanina and Teresa Arora and Linda Östlundh and Tetiana Habuza and Gillian Lylian Simiyu and Sarah Meribout and Tatsiana Talako and Fransina Christina King and Iryna Makhnevych and Juri George Gelovani and Karuna M Das and Klaus Neidl-Van Gorkom and Taleb M Almansoori and Fatmah Al Zahmi and Mikl'os Sz'olics and Fatima Ismail and Milos Ljubisavljevic},
url = {https://bmjopen.bmj.com/content/13/7/e068608},
doi = {10.1136/bmjopen-2022-068608},
issn = {2044-6055},
year = {2023},
date = {2023-01-01},
journal = {BMJ Open},
volume = {13},
number = {7},
publisher = {British Medical Journal Publishing Group},
abstract = {Background The number of patients diagnosed with multiple sclerosis (MS) has increased significantly over the last decade. The challenge is to identify the transition from relapsing-remitting to secondary progressive MS. Since available methods to examine patients with MS are limited, both the diagnostics and prognostication of disease progression would benefit from the multimodal approach. The latter combines the evidence obtained from disparate radiologic modalities, neurophysiological evaluation, cognitive assessment and molecular diagnostics. In this systematic review we will analyse the advantages of multimodal studies in predicting the risk of conversion to secondary progressive MS.Methods and analysis We will use peer-reviewed publications available in Web of Science, Medline/PubMed, Scopus, Embase and CINAHL databases. In vivo studies reporting the predictive value of diagnostic methods will be considered. Selected publications will be processed through Covidence software for automatic deduplication and blind screening. Two reviewers will use a predefined template to extract the data from eligible studies. We will analyse the performance metrics (1) for the classification models reflecting the risk of secondary progression: sensitivity, specificity, accuracy, area under the receiver operating characteristic curve, positive and negative predictive values; (2) for the regression models forecasting disability scores: the ratio of mean absolute error to the range of values. Then, we will create ranking charts representing performance of the algorithms for calculating disability level and MS progression. Finally, we will compare the predictive power of radiological and radiomical correlates of clinical disability and cognitive impairment in patients with MS.Ethics and dissemination The study does not require ethical approval because we will analyse publicly available literature. The project results will be published in a peer-review journal and presented at scientific conferences.PROSPERO registration number CRD42022354179.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}