Protective potential of mesenchymal stem cells against COVID-19 during pregnancy.

SARS-CoV-2 causes COVID-19. COVID-19 has led to severe clinical illnesses and an unprecedented death toll. The virus induces immune inflammatory responses specifically cytokine storm in lungs. Several published reports indicated that pregnant females are less likely to develop severe symptoms compared with non-pregnant. Putative protective role of maternal blood circulating fetal mesenchymal stem cells (MSCs) has emerged and have been put forward as an explanation to alleviated symptoms. MSCs with immune-modulatory, anti-inflammatory and anti-viral roles, hold great potential for the treatment of COVID-19. MSCs could be an alternative to treat infections resulting from the SARS-CoV-2 and potential future outbreaks. This review focuses on the MSCs putative protective roles against COVID-19 in pregnant females.

The COVID-19 outbreak is still posing a global health concern. Despite the herd immunity provided by vaccination programs, no efficient treatments are yet available especially against the severe forms of the disease. According to published reports, pregnant females are less likely to develop the severe form of the disease due to the protective effect of specialized cells named mesenchymal stem cells (MSCs). These cells are present in the placenta and amniotic fluid. They can migrate from these tissues to the mother's blood stream and are believed to confer protection to the pregnant females against severe form of COVID-19. Further investigations are on the way to uncover the potential role of MSC as an alternative therapy for COVID-19 and other diseases.

The virus SARS-CoV-2 results in COVID-19 infection. Several reports indicated that pregnant females are less likely to develop severe symptoms. Circulating fetal Mesenchymal stem cells in pregnant females might protect them.

Transcriptomics Demonstrates Significant Biological Effect of Growing Stem Cells on RGD-Cotton Scaffold.

Stem cell therapy provides a viable alternative treatment for degenerated or damaged tissue. Stem cells have been used either alone or in conjunction with an artificial scaffold. The latter provides a structural advantage by enabling the cells to thrive in three-dimensional (3D) settings, closely resembling the natural in vivo environments. Previously, we disclosed the development of a 3D scaffold made from cotton, which was conjugated with arginyl-glycyl-aspartic acid (RGD), to facilitate the growth and proliferation of mesenchymal stem cells (MSCs). This scaffold allowed the MSCs to adhere and proliferate without compromising their viability or their stem cell markers. A comprehensive analysis investigation of the molecular changes occurring in MSCs adhering to the cotton fibers will contribute to the advancement of therapy. The objective of this study is to analyze the molecular processes occurring in the growth of MSCs on a cotton-RGD conjugated-based scaffold by examining their gene expression profiles. To achieve this, we conducted an experiment where MSCs were seeded with and without the scaffold for a duration of 48 h. Subsequently, cells were collected for RNA extraction, cDNA synthesis, and whole-transcriptomic analysis performed on both populations. Our analysis revealed several upregulated and downregulated differently expressed genes in the MSCs adhering to the scaffold compared with the control cells. Through gene ontology analysis, we were able to identify enriched biological processes, molecular functions, pathways, and protein-protein interactions in these differentially expressed genes. Our data suggest that the scaffold may have the potential to enhance osteogenesis in the MSCs. Furthermore, our results indicate that the scaffold does not induce oxidative stress, inflammation, or aging in the MSCs. These findings provide valuable insights for the application of MSCs in tissue engineering and regenerative medicine.

Public awareness and understanding of stem cell treatments available in Saudi Arabia and their trust in hospitals and research centers involved in stem cell research-a cross sectional study.

Introduction: Although stem cell research and therapeutic applications hold great promise for medical advancements, and have rapidly progressed globally, there remains a lack of genuine public awareness of the status of this subject in Saudi Arabia. Successful integration of stem cell therapy into healthcare relies on public awareness, understanding, and trust. Therefore, we aimed in this cross-sectional study to assess the public's knowledge, awareness, trust, support, participation, and confidence in stem cell treatments and centers involved in it. Materials and methods: A voluntary questionnaire of 20 questions was distributed randomly via social media outlets. Results: Three thousand five hundred eighty four individuals participated in the survey, with approximately half of them falling within the age range of 35-50 years (46.71%). Majority of the participants, 90.71%, would like to know more about stem cell therapy and more than half of the participants (56.94%) were unfamiliar with the idea, and a comparable proportion (50.41%) expressed concerns about the safety of stem cell therapy. A lower level of awareness, indicated by a score of 5, was evenly distributed across all age groups and genders. However, regardless of gender, older participants-especially those 50 years of age or older-tended to report higher levels of confidence, trust, and support than participants in other age groups. Moreover, trust, support, participation, and confidence score for those attained high school or less was statistically significantly lower than those attained master's or PhD degree. Of the participants, 33.57% had either received stem cell therapy themselves or known someone who had; about 24.07% of them reported that it was a cosmetic type of treatment. Conclusion: The study emphasizes the persistent need for awareness and educational initiatives to minimize the lack of public awareness and understanding of approved stem cell treatments in Saudi Arabia. It advocates for increased education, transparency, and communication to bridge knowledge gaps and enhance public trust to ensure the understanding of successful treatment.

Disease burden and projection of total and early-onset colorectal cancer in Gulf cooperation council countries from 1990 to 2019.

BACKGROUND: Early-onset colorectal cancer (EO-CRC) incidence and prevalence trends in the rise in high income countries, such as the Gulf Cooperation Council (GCC) countries. The study aimed to offer an up-to-date assessment of the overall burden of CRC, and EO-CRC in GCC countries and project its incidence and mortality in 2030. METHOD: The prevalence, incidence, mortality, years of life lived with disability (YLDs), and disability-adjusted life years (DALYs) of CRC were obtained from the Global Burden of Disease (GBD) Study 2019. The incidence and mortality of CRC, and EO-CRC up to 2030 were predicted. RESULTS: All GCC countries showed a higher annual average percentage changes (AAPC) AAPC incidence rate for EO-CRC compared to CRC. In Saudi Arabia the number of CRC cases has increased from 1990 1484.57; (95 % UI 1987.98,1083.86) 11.4-fold-increase to 16991.83; (95 % UI 21754.79,12892.12) in 2019. In 2030, the total incidence cases of CRC for the six Gulf countries are expected to reach 13,339 thousand, primarily driven by Saudi Arabia with 7,910.19 cases. In 2030, the CRC mortality rate is projected to be 7,647 cases, with nearly 57 % of CRC mortality cases anticipated in Saudi Arabia. CONCLUSION: This study sheds light on the alarming rise in CRC and EO-CRC across Gulf countries from 1990 to 2019, emphasizing Saudi Arabia's significant burden. It projects a concerning increase in CRC incidence and mortality by 2030, primarily in Saudi Arabia, and highlights the need for immediate public health interventions.

Mortality-to-incidence ratio of early-onset colorectal cancer in high-income Asian and Middle Eastern countries: A systemic analysis of the Global Burden of Diseases Study 2019.

BACKGROUND: The incidence of early-onset colorectal cancer (EO-CRC) has been consistently rising leading to a significant cancer burden among younger adults in Asian and Middle Eastern high-income countries. The study aims to investigate the survival outcomes of EO-CRC among high-income Asian and Middle Eastern populations from 1990 to 2019 using the mortality-to-incidence ratio, with a focus on examining the differences in gender. METHODS: This is a systematic analysis of the Global Burden of Disease (GBD) 2019 study. We include individuals aged 15 to 49 years old in high-income Asian and the Middle Eastern countries. The colorectal cancer mortality-to-incidence ratio (MIR) was calculated for both genders by dividing the age-specific mortality rate per 100,000 for colorectal cancer by the age-specific incidence rate per 100,000 for each nation in the sample for a given year. RESULTS: An overall decline in male and female MIR was observed from 1990 to 2019 in Asian and Middle Eastern countries. Ten out of thirteen Asian and Middle Eastern countries had a higher female MIR compared to their male counterparts. The global male MIR was found to be significantly higher than that of female (p-value 0.008, coefficient estimate: 1.51). In Middle Eastern countries, Saudi Arabia had a significantly higher female MIR compared to their male counterparts (p < 0.0001, coefficient estimate: 12.65). CONCLUSION: This research addresses the knowledge gap concerning gender-based differences in EO-CRC survival outcomes in high-income Asian and Middle Eastern countries, providing insights into the factors influencing these disparities in these regions. Policymakers should focus on developing targeted prevention and treatment programs for women, and addressing cultural and social barriers that may prevent women from seeking timely medical care.

Early-Onset Colorectal Cancer Survival among Unscreened Population -Multicenter Cohort Retrospective Analysis.

BACKGROUND: In Saudi Arabia and across the world, the incidence of early-onset colorectal cancer (< 50 years) has increased. The diagnosis of EOCRC, on the other hand, is frequently delayed. It is critical to implement a national screening program to identify those group of patients who might benefit from early diagnosis. METHOD: A retrospective search was conducted using data from the Ministry of National Guard Health Affairs' (MNG-HA) Cancer Registry. The population of 1440 CRC patients were eligible for the analyses. Patients' demographics including age at diagnosis, gender, and marital status, were all reported. The demographic and clinical characteristics were assessed across early-onset and late-onset groups using Chi-square and Fisher exact test where appropriate. RESULTS: CRC patients, early-onset CRC (18-50 years) was reported in 23.26%, mainly with advance disease. Late-onset (>50 years) CRC individuals have worse survival rate and higher probability of dying compared to early-onset CRC individuals. After age at diagnosis classification into three categories (18-40 years), (41-50 years), and (>50 years) the Kaplan-Meier Survival curve show that early-onset (18-40 years) CRC individuals had significantly better survival than (41-50 years), and (>50 years) CRC patients. CONCLUSIONS: Comparing our data to another screened population using US SEER datasets, we discovered a substantial difference in survival rates, with the SEER population having a considerably greater chance of survival. There is very little research on the significance of screening for Saudi CRC patients, and this is an issue that needs to be looked into more. LIMITATIONS: A study's drawback is the lack of data for a variety of risk variables linked to colorectal cancer incidence, such as the KRAS mutation and environmental risk factors including BMI and smoking. More research with a nationally representative sample and comprehensive demographic and clinical data accessible is needed.

The emerging role of MCPH1/BRIT1 in carcinogenesis.

The MCPH1 gene, also known as BRCT-repeat inhibitor of hTERT expression (BRIT1), has three BRCA1 carboxyl-terminal domains which is an important regulator of DNA repair, cell cycle checkpoints and chromosome condensation. MCPH1/BRIT1 is also known as a tumour suppressor in different types of human cancer. The expression level of the MCPH1/BRIT1 gene is decreased at the DNA, RNA or protein level in a number of types of cancers including breast cancer, lung cancer, cervical cancer, prostate cancer and ovarian cancer compared to normal tissue. This review also showed that deregulation of MCPH1/BRIT1 is significantly associated with reduced overall survival in 57% (12/21) and relapsed free survival in 33% (7/21) of cancer types especially in oesophageal squamous cell carcinoma and renal clear cell carcinoma. A common finding of this study is that the loss of MCPH1/BRIT1 gene expression plays a key role in promoting genome instability and mutations supporting its function as a tumour suppressor gene.

An Update on Alopecia and its Association With Thyroid Autoimmune Diseases.

Alopecia is comorbid with several illnesses, including various autoimmune conditions such as thyroid disease. Leukocyte-mediated inflammation of hair follicles in alopecia was first described over a century ago. However, the high prevalence of the role of thyroid autoimmune disease in the pathogenesis of alopecia has only recently come to light, together with a strong association between the two. Therefore, this review focuses on articles published between 2011 and 2022 on alopecia's association with thyroid autoimmune disease, and the mechanism behind it. In addition, it highlights the link between alopecia and thyroid cancer, as patients with alopecia have increased risk of thyroid cancer. In conclusion, this comprehensive, focused, scoping review will serve as a reference highlighting recent information on alopecia, exploring its association with thyroid autoimmune diseases.

An Infodemic of Misinformation on Stem Cell Therapy Among the Population of Saudi Arabia: A Cross-Sectional Study.

In recent years, the industry of unproven stem cell-based therapies has been on the rise around the globe, putting patients at great risk of potential harm. In this cross-sectional study, we aimed to assess the level of knowledge and awareness of the general public, including patients and/or their relatives, in Saudi Arabia on stem cell therapy and to assess the degree of willingness to try stem cell-based treatment options, should it be offered to them. Methods: A voluntary questionnaire of 16 questions was distributed randomly through social media outlets. Results: In the survey of this study, 2,030 individuals participated. A total of 1,292 (63.6%) stated that they would accept stem cell therapy or would recommend it to their friends and relatives. Alarmingly, 72.1% of participants were unaware that using unapproved stem cell-based treatments may lead to serious health complications including cancer. More than 20% believed that stem cell therapy is already approved for organ/tissue regeneration. Worryingly, 60.6% of the physicians and 56.4% of the medical students stated that they would recommend stem cell treatment for their patients. Conclusions: There is a concerning spread of misinformation among the Saudi population, including physicians, regarding stem cell therapy. This calls for a targeted effort to raise awareness about the current status of stem cell treatment in the general public and among health care practitioners.

Living with the enemy: from protein-misfolding pathologies we know, to those we want to know.

Conformational diseases are caused by the aggregation of misfolded proteins. The risk for such pathologies develops years before clinical symptoms appear, and is higher in people with alpha-1 antitrypsin (AAT) polymorphisms. Thousands of people with alpha-1 antitrypsin deficiency (AATD) are underdiagnosed. Enemy-aggregating proteins may reside in these underdiagnosed AATD patients for many years before a pathology for AATD fully develops. In this perspective review, we hypothesize that the AAT protein could exert a new and previously unconsidered biological effect as an endogenous metal ion chelator that plays a significant role in essential metal ion homeostasis. In this respect, AAT polymorphism may cause an imbalance of metal ions, which could be correlated with the aggregation of amylin, tau, amyloid beta, and alpha synuclein proteins in type 2 diabetes mellitus (T2DM), Alzheimer's and Parkinson's diseases, respectively.

Using NMR spectroscopy to investigate the role played by copper in prion diseases.

Prion diseases are a group of rare neurodegenerative disorders that develop as a result of the conformational conversion of normal prion protein (PrPC) to the disease-associated isoform (PrPSc). The mechanism that actually causes disease remains unclear. However, the mechanism underlying the conformational transformation of prion protein is partially understood-in particular, there is strong evidence that copper ions play a significant functional role in prion proteins and in their conformational conversion. Various models of the interaction of copper ions with prion proteins have been proposed for the Cu (II)-binding, cell-surface glycoprotein known as prion protein (PrP). Changes in the concentration of copper ions in the brain have been associated with prion diseases and there is strong evidence that copper plays a significant functional role in the conformational conversion of PrP. Nevertheless, because copper ions have been shown to have both a positive and negative effect on prion disease onset, the role played by Cu (II) ions in these diseases remains a topic of debate. Because of the unique properties of paramagnetic Cu (II) ions in the magnetic field, their interactions with PrP can be tracked even at single atom resolution using nuclear magnetic resonance (NMR) spectroscopy. Various NMR approaches have been utilized to study the kinetic, thermodynamic, and structural properties of Cu (II)-PrP interactions. Here, we highlight the different models of copper interactions with PrP with particular focus on studies that use NMR spectroscopy to investigate the role played by copper ions in prion diseases.

Molecular characterisation in tongue squamous cell carcinoma reveals key variants potentially linked to clinical outcomes.

BACKGROUND: Oral tongue squamous cell carcinoma (OTSCC) is a highly aggressive malignancy characterized by frequent recurrence, poor survival with relatively few therapeutic options due to the late diagnosis in many cases. OBJECTIVES: Understanding the molecular pathways underlying OTSCC tumourigenesis and the discovery of diagnostic and/or prognostic biomarkers. METHODS: We performed high-throughput mutational analysis of 44 OTSCC formalin-fixed paraffin-embedded (FFPE) cases using the Cancer Hotspots Panel (CHP) v2 on the Ion Torrent™platform. We determined the frequency of human papilloma virus (HPV) using PCR and Epstein bar virus (EBV) positivity using immunohistochemistry. As a control for EBV infection we screened matched non-tumourous tissues. RESULTS: Sequencing analysis identified missense, nonsense and frameshift mutations in TP53 (66%), PIK3CA (27%), CDKN2A (25%), EGFR (18%), and PTEN (14%). Interestingly, no significant associations were found between damaging mutations and clinicopathological data. A total of 10/44 of the OTSCC samples (23%) tested was positive for HPV18 DNA. OTSCC patients with positive HPV infection had worse overall survival compared to HPV-negative cases as determined by Kaplan-Meier survival (p= 0.023). Furthermore, EBNA1 expression showed a strong tumour-enriched expression pattern in 20 out of 21 samples (95%) in the epithelial compartments of the tissues analysed. CONCLUSIONS: Taken together, this study highlights that the two most common events in OTSCC are TP53 mutations and EBV positivity. Helping to understand the contribution of TP53 mutations and EBV infection events could serve as useful biomarkers for OTSCC.

Expression analysis of the MCPH1/BRIT1 and BRCA1 tumor suppressor genes and telomerase splice variants in epithelial ovarian cancer.

AIMS: The aim of this study was to explore the correlation of hTERT splice variant expression with MCPH1/BRIT1 and BRCA1 expression in epithelial ovarian cancer (EOC) samples. BACKGROUND: Telomerase activation can contribute to the progression of tumors and the development of cancer. However, the regulation of telomerase activity remains unclear. MCPH1 (also known as BRIT1, BRCT-repeat inhibitor of hTERT expression) and BRCA1 are tumor suppressor genes that have been linked to telomerase expression. METHODS: qPCR was used to investigate telomerase splice variants, MCPH1/BRIT1 and BRCA1 expression in EOC tissue and primary cultures. RESULTS: The wild type α+/ß+ hTERT variant was the most common splice variant in the EOC samples, followed by α+/ß- hTERT, a dominant negative regulator of telomerase activity. EOC samples expressing high total hTERT demonstrated significantly lower MCPH1/BRIT1 expression in both tissue (p = 0.05) and primary cultures (p = 0.03). We identified a negative correlation between MCPH1/BRIT1 and α+/ß+ hTERT (p = 0.04), and a strong positive association between MCPH1/BRIT1 and both α-/ß+ hTERT and α-/ß- hTERT (both p = 0.02). A positive association was observed between BRCA1 and α-/ß+ hTERT and α-/ß- hTERT expression (p = 0.003 and p = 0.04, respectively). CONCLUSIONS: These findings support a regulatory effect of MCPH1/BRIT1 and BRCA1 on telomerase activity, particularly the negative association between MCPH1/BRIT1 and the functional form of hTERT (α+/ß+).

Prognostic potential of KLOTHO and SFRP1 promoter methylation in head and neck squamous cell carcinoma.

Hypermethylation in the CpG island promoter regions of tumor suppressors is known to play a significant role in the development of HNSCC and the detection of which can aid the classification and prognosis of HNSCC. This study aims to profile the methylation patterns in a panel of key genes including CDKN2A, CDKN2B, KLOTHO (KL), RASSF1A, RARB, SLIT2, and SFRP1, in a group of HNSCC samples from Saudi Arabia. The extent of methylation in these genes is determined using the MethyLight assay and correlated with known clinicopathological parameters in our samples of 156 formalin-fixed and paraffin-embedded HNSCC tissues. SLIT2 methylation had the highest frequency (64.6%), followed by RASSF1A (41.3%), RARB (40.7%), SFRP1 (34.9), KL (30.7%), CKDN2B (29.6%), and CKDN2A (29.1%). KL and SFRP1 methylation were more predominant in nasopharyngeal tumors (P = 0.001 and P = 0.031 respectively). Kaplan Meier analysis showed that patients with moderately differentiated tumors who display SFRP1 methylation have significantly worse overall survival in comparison with other samples. In contrast, better clinical outcomes were seen in patients with KL methylation. In conclusion, our findings suggest that the detection of frequent methylation in SFRP1 and KL genes' promoters could serve as prognostic biomarkers for HNSCC.

Deregulation of microcephalin and ASPM expression are correlated with epithelial ovarian cancer progression.

Mutations in the MCPH1 (Microcephalin) and ASPM (abnormal spindle-like microcephaly associated) genes cause primary microcephaly. Both are centrosomal associated proteins involved in mitosis. Microcephalin plays an important role in DNA damage response and ASPM is required for correct division of proliferative neuro-epithelial cells of the developing brain. Reduced MCPH1 mRNA expression and ASPM mRNA over-expression have been implicated in the development of human carcinomas. Epithelial ovarian cancer (EOC) is characterised by highly aneuploid tumours. Previously we have reported low Microcephalin and high ASPM protein levels and associations with clinico-pathological parameters in malignant cells from ascitic fluids. To confirm these previous findings on a larger scale Microcephalin and ASPM expression levels and localisations were evaluated by immunohistochemistry in two cohorts; a training set of 25 samples and a validation set of 322 EOC tissue samples. Results were correlated to the associated histopathological data. In normal ovarian tissues the Microcephalin nuclear staining pattern was consistently strong. In the cancer tissues, we identified low nuclear Microcephalin expression in high grade and advanced stage tumours (p<0.0001 and p = 0.0438 respectively). ASPM had moderate to high nuclear and low to moderate cytoplasmic expression in normal tissue. Cytoplasmic ASPM expression decreased with tumour grade and stage in the serous subtype of EOC (p = 0.023 and p = 0.011 respectively). Cytoplasmic ASPM increased with tumour stage in the endometrioid subtype (p = 0.023). Increasing tumour invasiveness (T3) and lymph node involvement (N1) also correlated with a decrease in cytoplasmic ASPM in EOC (p = 0.02 and p = 0.04 respectively). We have validated previous findings of deregulated expression of Microcephalin and ASPM in EOC by confirming associations for low nuclear Microcephalin levels and high cytoplasmic ASPM levels in a larger scale tumour tissue study. Microcephalin and ASPM may prove useful biomarkers in EOC.

NuMA overexpression in epithelial ovarian cancer.

Highly aneuploid tumours are common in epithelial ovarian cancers (EOC). We investigated whether NuMA expression was associated with this phenomenon.NuMA protein levels in normal and tumour tissues, ovarian cell lines and primary cultures of malignant cells derived from ovarian ascitic fluids were analysed by Affymetrix microarray analysis, immunoblotting, immunohistochemistry (IHC) and immunofluorescence (IF), with results correlated to associated clinical data. Aneuploidy status in primary cultures was determined by FACS analysis.Affymetrix microarray data indicated that NuMA was overexpressed in tumour tissue, primary cultures and cell lines compared to normal ovarian tissue. IHC revealed low to weak NuMA expression in normal tissues. Expression was upregulated in tumours, with a significant association with disease stage in mucinous EOC subtypes (p = 0.009), lymph node involvement (p = 0.03) and patient age (p = 0.04). Additional discontinuous data analysis revealed that high NuMA levels in tumours decreased with grade (p = 0.02) but increased with disease stage (p = 0.04) in serous EOC. NuMA expression decreased in late disease stage 4 endometrioid EOCs. High NuMA levels decreased with increased tumour invasion in all subtypes (p = 0.03). IF of primary cultures revealed that high NuMA levels at mitotic spindle poles were significantly associated with a decreased proportion of cells in cytokinesis (p = 0.05), increased binucleation (p = 0.021) and multinucleation (p = 0.007), and aneuploidy (p = 0.008).NuMA is highly expressed in EOC tumours and high NuMA levels correlate with increases in mitotic defects and aneuploidy in primary cultures.