Mesenchymal stromal cells (MSCs) as a therapeutic agent of inflammatory disease and infectious COVID-19 virus: live or dead mesenchymal?

The COVID-19 infection is a worldwide disease that causes numerous immune-inflammatory disorders, tissue damage, and lung dysfunction. COVID-19 vaccines, including those from Pfizer, AstraZeneca, and Sinopharm, are available globally as effective interventions for combating the disease. The severity of COVID-19 can be most effectively reduced by mesenchymal stromal cells (MSCs) because they possess anti-inflammatory activity and can reverse lung dysfunction. MSCs can be harvested from various sources, such as adipose tissue, bone marrow, peripheral blood, inner organs, and neonatal tissues. The regulation of inflammatory cytokines is crucial in inhibiting inflammatory diseases and promoting the presence of anti-inflammatory cytokines for infectious diseases. MSCs have been employed as therapeutic agents for tissue damage, diabetes, autoimmune diseases, and COVID-19 patients. Our research aimed to determine whether live or dead MSCs are more suitable for the treatment of COVID-19 patients. Our findings concluded that dead MSCs, when directly administered to the patient, offer advantages over viable MSCs due to their extended presence and higher levels of immune regulation, such as T-reg, B-reg, and IL-10, compared to live MSCs. Additionally, dead and apoptotic MSCs are likely to be more readily captured by monocytes and macrophages, prolonging their presence compared to live MSCs.

Identification of a novel Bax-Cdk1 signalling complex that links activation of the mitotic checkpoint to apoptosis.

In eukaryotes, entry into and exit from mitosis is regulated, respectively, by the transient activation and inactivation of Cdk1. Taxol, an anti-microtubule anti-cancer drug, prevents microtubule-kinetochore attachments to induce spindle assembly checkpoint (SAC; also known as the mitotic checkpoint)-activated mitotic arrest. SAC activation causes mitotic arrest by chronically activating Cdk1. One consequence of prolonged Cdk1 activation is cell death. However, the cytoplasmic signal(s) that link SAC activation to the initiation of cell death remain unknown. We show here that activated Cdk1 forms a complex with the pro-apoptotic proteins Bax and Bak (also known as BAK1) during SAC-induced apoptosis. Bax- and Bak-mediated delivery of activated Cdk1 to the mitochondrion is essential for the phosphorylation of the anti-apoptotic proteins Bcl-2 and Bcl-xL (encoded by BCL2L1) and the induction of cell death. The interactions between a key cell cycle control protein and key pro-apoptotic proteins identify the Cdk1-Bax and Cdk1-Bak complexes as the long-sought-after cytoplasmic signal that couples SAC activation to the induction of apoptotic cell death.

Molecular evidence for the involvement of alternative splicing in jejunum epithelial cells in broiler chickens fed dietary supplementation with olive mill wastewater.

There is no doubt that alternative splicing is conserved in chickens and mammals, but evaluating the effects of nutrition on alternative splicing in chickens is crucial in a wide range of fields. Although the olive diet has been extensively studied in human, mouse, and chicken systems, little is known about its impact on chicken alternative splicing systems. Hence, the current study aimed to assess the effect of feeding polyphenol-enriched olive mill wastewater to female broiler chickens via alternative splicing by analyzing high-throughput sequencing raw reads of RNA utilizing genomics and bioinformatics methodologies. It also aimed to look for differences in isoform expression and discover molecular functions and biological processes linked to differentially transcribed genes. The findings of our study revealed that 51 genes involved in isoform switching and alternative splicing events were not used evenly. This is due to the reduced use of ATSS in olive mill wastewater groups compared to control groups. Furthermore, the gene ontology analysis revealed that 25 GO terms were enriched in biological processes, 16 GO terms were enriched in molecular function, and 25 GO terms were enriched in cellular components. Kinase and adenylyltransferase activities were significantly enriched in terms. The molecular analysis presented herein provides valuable insight into the role of phenolics in alternative gene-splicing mechanisms in chickens, demonstrating how an industrial waste product can be repurposed as a feed supplement with a satisfactory outcome.

Are some COVID-19 vaccines better than others regarding the short-term side effects?

Controlling the pandemic is primarily achieved through vaccination against COVID-19. Although various COVID-19 vaccines are used worldwide, little is known about their safety and side effects. As a result, the objectives of this research are to identify the shortterm side effects of the different COVID-19 vaccines used in Iraq. Furthermore, exploring the association between experienced side effects and the brand of vaccine received. The current study evaluated the shortterm side effects of Pfizer, Sinopharm and AstraZeneca vaccines among healthcare workers in Iraq. The study used a questionnaire that consisted of dedicated sections to collect demographic data, the brand of COVID-19 vaccine received, the short-term side effects, and the willingness to receive a third booster dose. Regarding the post-vaccination side effects, the studied COVID-19 vaccines showed a comparable range of side effects, such as headaches, fever, muscle pain, joint pain, malaise, tenderness, redness, as well as pain at the site of vaccination. However, the Pfizer vaccine showed a higher incidence of pain and tenderness at the site of injection and fever compared to AstraZeneca and Sinopharm, respectively. On the other hand, the Sinopharm vaccine was associated with a higher occurrence of headaches, muscle pain, joint pain, and malaise in comparison to the Pfizer and AstraZeneca vaccines, respectively. In summary, the short-term side effects of the three vaccines were comparable; however, the AstraZeneca vaccine was associated with a lower risk of side effects.

Impact of COVID-19 pandemic on the utilization and quality of antibiotic use in the primary care setting in England, March 2019-March 2023: a segmented interrupted time series analysis of over 53 million individuals.

BACKGROUND: Amid the COVID-19 pandemic, we evaluated the short-term impact of COVID-19 on antibiotic use in primary care in England, focusing on both antibiotic quantity (overuse) and quality (misuse) of use. RESEARCH DESIGN AND METHODS: A population-based segmented interrupted analysis was applied on monthly dispensed antibiotics prescriptions using the Prescription Cost Analysis dataset (March/2019-March/2023). The quantity was assessed using number of items dispensed per 1000 inhabitants (NTI) and defined daily doses per 1000 inhabitants per day (DID), while quality was evaluated using WHO's Access Watch Reserve (AWaRe) classification, the proportion of '4C' antibiotics and the percentage of broad- to narrow-spectrum antibiotics. RESULTS: Findings indicate 8.6 (17.2%) and 0.4 (2.6%) increase in the NTI and DID, respectively, with a statistically significant uptick in trend noted after the second lockdown (ß5) for 'total antibiotics' for NTI only (ß5 = 1.6; 95% CI:0.17, 3.1). Quality assessment showed an increase in 'Access' antibiotics from 77% in March/2019 to 86% in March/2023; however, COVID-19 had no significant impact on WHO AWaRe classes. CONCLUSION: COVID-19's impact on antibiotic use quality and quantity appeared to be minimal, though an increase in utilization post-second lockdown coincided with healthcare system recovery. This suggests a nuanced impact of the pandemic, highlighting the importance of continued antimicrobial stewardship.

Examining the quaternary ammonium chitosan Schiff base-ZnO nanocomposite's potential as protective therapy for rats' cisplatin-induced hepatotoxicity.

BACKGROUND: Despite cisplatin's long history as a cornerstone in cancer therapy, both acquired chemoresistance and significant impacts on healthy tissues limit its use. Hepatotoxicity is one of its side effects. Adjunct therapies have shown promise in not only attenuating liver damage caused by cisplatin but also in enhancing the efficacy of chemotherapy. In this context, a new quaternary ammonium chitosan Schiff base (QACSB) was synthesized and applied as an encapsulating agent for the in-situ synthesis of QACSB-ZnO nanocomposite. MATERIAL AND METHODS: Thirty male albino rats were classified into Group 1 (control) distilled water, Group 2 (Cisplatin-treated) (12 mg/kg, i.p), and Group 3 (QACSB-ZnO NCs/cisplatin-treated) (150 mg/kg/day QACSB-ZnO NCs, i.p) for 14 days + a single dose of cisplatin. Liver functions, tissue TNF-α, MDA, and GSH were measured as well as histopathological and immunohistochemical studies were performed. RESULTS: The QACSB-ZnO NCs significantly restore liver functions, tissue TNF-α, MDA, and GSH levels (p < 0.001). Histopathological examination showed patchy necrosis in the cisplatin-treated group versus other groups. The QACSB-ZnO NCs showed a weak TGF-ß1 (score = 4) and a moderate Bcl-2 immunohistochemistry expression (score = 6) versus the CP group. CONCLUSIONS: QACSB-ZnO NCs have been shown to protect the liver from cisplatin-induced hepatotoxicity.

Assessment of COVID-19 vaccination among healthcare workers in Iraq; adverse effects and hesitancy.

Several messenger ribonucleic acid (mRNA) and inactivated COVID-19 vaccines are available to the global population as of 2022. The acceptance of the COVID-19 vaccine will play a key role in combating the worldwide pandemic. Public confidence in this vaccine is largely based on its safety and effectiveness. This study was designed to provide independent evidence of the adverse effects associated with COVID-19 vaccines among healthcare workers in Iraq and to identify the attitudes of healthcare workers who rejected the vaccination. We conducted a cross-sectional study to collect data on the adverse effects of the Pfizer, AstraZeneca, and Sinopharm vaccines. Data were collected between October 2021 and February 2022. A total of 2,202 participants were enrolled in the study: (89.97%) received injections of the COVID-19 vaccines and (10.03%) were hesitant to receive the vaccination. Participants received either the Pfizer vaccine (62.9%), AstraZeneca vaccine (23.5%) or Sinopharm vaccine (13.6%). Most adverse effects were significantly less prevalent in the second dose than in the first dose. Notably, the adverse effects associated with the Pfizer vaccine were significantly more prevalent in females than in males. Following the first dose, the participants experienced more adverse effects with the AstraZeneca vaccine. Following the second dose, more adverse effects were associated with the Pfizer vaccine. Interestingly, the prevalence of COVID-19 infection in participants who received two doses of the Pfizer vaccine was significantly reduced compared to those who received two doses of either the AstraZeneca or Sinopharm vaccines. According to vaccine-hesitated participants, insufficient knowledge (29.9%), expeditious development (27.6%) and lack of trust in the vaccines (27.1%) were the three major reasons for refusing the vaccines. The results of our study indicated that these adverse effects do not present a significant problem and should not prevent successful control of the COVID-19 pandemic.

Evaluation of the Pharmacologic Treatment of COVID-19 Pandemic in Iraq.

The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, or COVID-19) has been detrimental to human health, economy, and wellbeing. Little information is known on the epidemiology and outcome of the disease in a localized community within Iraq. We carried out an audit of confirmed cases of COVID-19 in the Kirkuk General Hospital. Data from the 20th of June to the 31st of July, 2020, were collected and analyzed. Suspected COVID-19 cases were confirmed by real-time polymerase chain reaction (RT-PCR). Data on clinical symptoms, age, and treatment protocols were analyzed concerning the outcome. Our study included a total of 200 individual confirmed COVID-19 patients. The majority of cases 55% (n = 110) displayed severe symptoms, while 32.5% (65 cases) and 12.5% (25 cases) of patients displayed moderate to mild symptoms, respectively. The rate of death in the referred patients was 5%. Most patients admitted to the hospital for treatment recovered and were discharged from the hospital within 5 to 30 days post-diagnosis. Statistical analysis revealed that patients treated with oseltamivir, hydroxychloroquine, and azithromycin in combination with vitamins C and D have shorter hospital stay compared to patients receiving the same therapeutic protocol in combination with steroids. Moreover, a higher mortality rate (4.5%) was observed in patients treated with oseltamivir, hydroxychloroquine, ceftriaxone, and steroids. This study highlights a significant relationship between age, secondary ailments, and the choice of medications as simple predictors of the outcome of COVID-19.