Bone marrow stromal cells (BMSCs, also known as bone marrow-derived mesenchymal stem cells) and their progenitors have been identified based on retrospective functional criteria. CD markers are employed to define cell populations with distinct functional characteristics. However, defining and prospective isolation of BMSCs and committed progenitors are lacking. Here, we compared the transcriptome profile of CD markers expressed at baseline and during the course of osteoblast and adipocyte differentiation of two well-characterized osteogenic-committed murine BMSCs (mBMSC(Bone)) and adipogenic-committed mBMSCs (mBMSC(Adipo)), respectively. Bioinformatic analysis revealed the presence of a core set of canonical mBMSC CD markers with comparable expression levels in mBMSC(Bone) and mBMSC(Adipo) at baseline and during their differentiation. We identified 11 CD markers that are differentially expressed between mBMSC(Adipo) and mBMSC(Bone). Among these, we identified osteoprogenitor-associated CD markers expressed only in mBMSC(Bone): CD34, CD54, CD73, CD132, CD200, CD227 and adipoprogenitor-associated CD markers expressed only in mBMSC(Adipo): CD53, CD80, CD134, CD141 and CD212. FACS analysis confirmed these results. We selected CD34 for further analysis. CD34 was expressed at baseline of mouse stromal cell line ST2, primary mBMSCs, mBMSC(Bone) and its expression decreased during osteoblast differentiation. FACS-sorted CD34(+) primary mBMSCs exhibited higher expression of 70% osteoblast-associated genes, and formed significantly higher heterotopic bone in vivo when implanted subcutaneously in immune-deficient mice compared with CD34(-) primary mBMSCs. Our results demonstrate that a set of CD markers can distinguish osteoprogenitor versus adipoprogenitor populations of mBMSCs. CD34 is suitable for prospective isolation of mouse bone marrow osteoprogenitors.

Background: The expected second wave of the COVID-19 pandemic has started in various regions of the world. Public health experts warned that it could be as lethal as the first wave if people did not comply with self-protective measures. Currently, there is a gap in the literature on the relationship between peoples’ assessment of the effectiveness of community-based measures regarding adherence to self-protective behaviors for COVID-19 prevention and control. This study aimed to assess the role of the perceived effectiveness of community-based measures in adherence to self-protective behaviors during the COVID-19 pandemic. Methods: The cross-sectional online survey conducted from March 24 to June 22, 2020. The study sample Included 400 participants (49% male and 51% female) from the Kingdom of Saudi Arabia (KSA). The outcome measure was compliance to four self-protective behaviors i.e., "social distancing;" "wearing facemask;" "washing hands more frequently;" and "disinfecting surfaces in homes." We computed Chi-square statistics and odds ratios (ORs) using 95% confidence intervals (CIs). Results: The findings demonstrated that participants aged 25–34 years old were 25% less likely to comply with hand hygiene (OR = 0.75; 95% CI: 0.33–0.95) and social distancing (OR = 0.76; 95% CI: 0.34–0.98). Misconceptions related to COVID-19 significantly decreased compliance with self-protective behaviors by up to 27%. Participants who rated government decisions as useful were approximately 1.7 times more likely to comply with self-protective behaviors. Conclusion: Community-based measures should focus on engaging segments of the population That are currently less compliant. Health education policies should also focus on enhancing the perceived sense of control and personal responsibility and reduce anxiety levels. A continuous commitment to the implementation of preventive interventions and the clarification of misconceptions are required to combat the expected second wave.

Diabetic peripheral neuropathy (DPN) is a common diabetes complication (DM). Aldose reductase -2 (ALR-2) is an oxidoreductase enzyme that is most extensively studied therapeutic target for diabetes-related complications that can be inhibited by epalrestat, which has severe adverse effects; hence the discovery of potent natural inhibitors is desired. In response, a pharmacophore model based on the properties of eplarestat was generated. The specified pharmacophore model searched the NuBBE_DB database of natural compounds for prospective lead candidates. To assess the drug-likeness and ADMET profile of the compounds, a series of in silico filtering procedures were applied. The compounds were then put through molecular docking and interaction analysis. In comparison to the reference drug, four compounds showed increased binding affinity and demonstrated critical residue interactions with greater stability and specificity. As a result, we have identified four potent inhibitors: ZINC000002895847, ZINC000002566593, ZINC000012447255, and ZINC000065074786, that could be used as pharmacological niches to develop novel ALR-2 inhibitors.

The collection and storage of umbilical cord stem cells (UCSCs) have a crucial role in improving and expanding stem cell-based therapies, which are becoming popular in Saudi Arabia and other Middle East countries. Many patients and families in Saudi Arabia depend on private cord banks in foreign countries to purchase stem cells, which has financial and medical implications. The current study aims at determining the predictors of current registration status and willingness to donate cord blood stem cells among expectant mothers in Saudi Arabia. A cross-sectional study collected data from 714 expectant mothers from all thirteen regions of Saudi Arabia in December 2022. The online survey questionnaire assessed women’s awareness, direct and indirect exposure to stem-cell therapy, sources of knowledge, willingness, reluctance, and current registration status to donate cord blood. Although women demonstrated higher acceptance and lower rejection towards the donation of UCSCs, just one percent (n = 7; 1%) of expectant mothers in this sample are registered with the Saudi Stem Cell Registry. Overall, 48% indicated their willingness to register in the future. Both correlational analysis and multiple regression analysis demonstrated that awareness significantly predicted willingness to donate (p < 0.01), and rejection attitudes were negatively related to willingness to donate (p < 0.001). Although the mean scores on acceptance were high, they were not found to be significantly associated with willingness to donate. Prior direct and indirect exposure to stem cell therapy appeared to be the strongest predictor of pregnant women’s willingness to register (p < 0.001). Findings suggest that acceptance attitudes do not have a symmetrical relationship with intention. Women’s prior exposure to stem cell therapy was the most significant factor; therefore, findings demonstrate that currently women are relying on their firsthand experience to decide about cord blood donation rather than the information obtained from other sources, such as social media and the internet. Though attitudes were not identified as significant predictors in the statistical models, awareness was a relevant factor, and the findings signify increasing awareness in various target populations to enhance the probability of intention to donate cord stem cells.

Protein tyrosine phosphatase-1B (PTP-1B) is a well-known therapeutic target for diabetes and obesity as it suppresses insulin and leptin signaling. PTP-1B deletion or pharmacological suppression boosted glucose homeostasis and insulin signaling without altering hepatic fat storage. Inhibitors of PTP-1B may be useful in the treatment of type 2 diabetes, and shikonin, a naturally occurring naphthoquinone dye pigment, is reported to inhibit PTP-1B and possess antidiabetic properties. Since the cell contains a large number of phosphatases, PTP-1B inhibitors must be effective and selective. To explore more about the mechanism underlying the inhibitors efficacy and selectivity, we investigated its top four pharmacophores and used site-directed mutagenesis to insert amino acid mutations into PTP-1B as an extension of our previous study where we identified 4 pharmacophores of shikonin. The study aimed to examine the site-directed mutations like R24Y, S215E, and S216C influence the binding of shikonin pharmacophores, which act as selective inhibitors of PTP-1B. To achieve this purpose, docking and molecular dynamics simulations of wild-type (WT) and mutant PTP-1B with antidiabetic compounds were undertaken. The simulation results revealed that site-directed mutations can change the hydrogen bond and hydrophobic interactions between shikonin pharmacophores and many residues in PTP-1Bs active site, influencing the drugs binding affinity. These findings could aid researchers in better understanding PTP-1B inhibitors selective binding mechanism and pave the path for the creation of effective PTP-1B inhibitors.

Background: Knowledge, sensitivity, and acceptance attitudes towards social, moral and ethical aspects of stem-cell donation and treatment are important factors in preventing professional negligence and improving healthcare risk management and health justice in this specialized area of health services. Objective: To assess knowledge, sensitivity, acceptance and rejection attitudes towards stem-cell transplantation and research and its associated factors among medical professionals in Saudi Arabia. Methods: A quantitative and cross-sectional study was conducted in December 2022. Data were collected from 260 medical workers from various regions in Saudi Arabia. T-tests, ANOVA, and multiple linear regression were applied to find variations and associations of gender, age, profession, nationality, religious orientation, and work experiences of professionals with knowledge, sensitivity, acceptance and rejection attitude towards stem-cell donation, therapy, and research. A confidence interval (CI) of 95% and a significance level of p≤ 0.05 was chosen for testing statistical models. Results: A total of (n=260) medical professionals, among which clinicians (n=98;38%), pharmacists (n=78;30%), and nurses (n=84;32%) completed the survey questionnaire. Findings show that (n=27; 10%) participants have work experience in stem-cell donation, (n=67; 26%) in stem-cell therapy, and (n=124; 48%) in stem-cell research. Clinicians and pharmacists, in comparison to nurses, had better knowledge (p< 0.01 and p< 0.05); pharmacists had higher sensitivity (p< 0.05) than nurses. Compared to those who do not have work experience in stem-cell research, those who had work experience had higher levels of knowledge, sensitivity, and acceptance attitudes at (p< 0.001) and (p< 0.01). Acceptance attitudes are considerably higher among male participants than females and similarly higher among older participants than younger participants (p< 0.05). Compared to non-Saudi nationals, Saudi nationals scored higher on rejection attitudes (p< 0.01). Compared to those having work experience in stem-cell donation and research, those without work experience are more likely to hold rejection attitudes (p< 0.01). Conclusion: Findings suggest female professionals, Saudi nationals and those who do not have prior work experience in stem-cell donation, therapy, or research had low levels of knowledge, less sensitivity, and less acceptance attitude and are more likely to hold rejection attitude, signifying the need to address them to improve healthcare risk management.