Can COVID-19 Vaccines Induce Premature Non-Communicable Diseases: Where Are We Heading to?

According to the WHO, as of January 2023, more than 850 million cases and over 6.6 million deaths from COVID-19 have been reported worldwide. Currently, the death rate has been reduced due to the decreased pathogenicity of new SARS-CoV-2 variants, but the major factor in the reduced death rates is the administration of more than 12.8 billion vaccine doses globally. While the COVID-19 vaccines are saving lives, serious side effects have been reported after vaccinations for several premature non-communicable diseases (NCDs). However, the reported adverse events are low in number. The scientific community must investigate the entire spectrum of COVID-19-vaccine-induced complications so that necessary safety measures can be taken, and current vaccines can be re-engineered to avoid or minimize their side effects. We describe in depth severe adverse events for premature metabolic, mental, and neurological disorders; cardiovascular, renal, and autoimmune diseases, and reproductive health issues detected after COVID-19 vaccinations and whether these are causal or incidental. In any case, it has become clear that the benefits of vaccinations outweigh the risks by a large margin. However, pre-existing conditions in vaccinated individuals need to be taken into account in the prevention and treatment of adverse events

Leveraging technology-driven strategies to untangle omics big data: circumventing roadblocks in clinical facets of oral cancer

Oral cancer is one of the 19most rapidly progressing cancers associated with significant mortality, owing to its extreme degree of invasiveness and aggressive inclination. The early occurrences of this cancer can be clinically deceiving leading to a poor overall survival rate. The primary concerns from a clinical perspective include delayed diagnosis, rapid disease progression, resistance to various chemotherapeutic regimens, and aggressive metastasis, which collectively pose a substantial threat to prognosis. Conventional clinical practices observed since antiquity no longer offer the best possible options to circumvent these roadblocks. The world of current cancer research has been revolutionized with the advent of state-of-the-art technology-driven strategies that offer a ray of hope in confronting said challenges by highlighting the crucial underlying molecular mechanisms and drivers. In recent years, bioinformatics and Machine Learning (ML) techniques have enhanced the possibility of early detection, evaluation of prognosis, and individualization of therapy. This review elaborates on the application of the aforesaid techniques in unraveling potential hints from omics big data to address the complexities existing in various clinical facets of oral cancer. The first section demonstrates the utilization of omics data and ML to disentangle the impediments related to diagnosis. This includes the application of technology-based strategies to optimize early detection, classification, and staging via uncovering biomarkers and molecular signatures. Furthermore, breakthrough concepts such as salivaomics-driven non-invasive biomarker discovery and omics-complemented surgical interventions are articulated in detail. In the following part, the identification of novel disease-specific targets alongside potential therapeutic agents to confront oral cancer via omics-based methodologies is presented. Additionally, a special emphasis is placed on drug resistance, precision medicine, and drug repurposing. In the final section, we discuss the research approaches oriented toward unveiling the prognostic biomarkers and constructing prediction models to capture the metastatic potential of the tumors. Overall, we intend to provide a bird’s eye view of the various omics, bioinformatics, and ML approaches currently being used in oral cancer research through relevant case studies

The International Natural Product Sciences Taskforce (INPST) and the power of Twitter networking exemplified through #INPST hashtag analysis

Background: The development of digital technologies and the evolution of open innovation approaches have enabled the creation of diverse virtual organizations and enterprises coordinating their activities primarily online. The open innovation platform titled "International Natural Product Sciences Taskforce" (INPST) was established in 2018, to bring together in collaborative environment individuals and organizations interested in natural product scientific research, and to empower their interactions by using digital communication tools. Methods: In this work, we present a general overview of INPST activities and showcase the specific use of Twitter as a powerful networking tool that was used to host a one-week "2021 INPST Twitter Networking Event" (spanning from 31st May 2021 to 6th June 2021) based on the application of the Twitter hashtag #INPST. Results and Conclusion: The use of this hashtag during the networking event period was analyzed with Symplur Signals (https://www.symplur.com/), revealing a total of 6,036 tweets, shared by 686 users, which generated a total of 65,004,773 impressions (views of the respective tweets). This networking event's achieved high visibility and participation rate showcases a convincing example of how this social media platform can be used as a highly effective tool to host virtual Twitter-based international biomedical research events

<i>Staphylococcus epidermidis</i> Pathogenesis: Interplay of <i>icaADBC</i> Operon and MSCRAMMs in Biofilm Formation of Isolates from Pediatric Bacteremia in Peshawar, Pakistan

Background and Objective: Staphylococcus epidermidis is an opportunistic pathogen from pediatric bacteremia that is commonly isolated. Biofilm is the major virulence factor of S. epidermidis; however, the role of biofilm determinants in biofilm formation is highly contradictory and diverse. The current study aimed to investigate the role of polysaccharide-dependent and polysaccharide-independent pathogenic determinants in biofilm formation under physiological stress conditions. Materials and Methods: The isolates (n = 75) were identified and screened for the icaADBC operon, IS256, and an array of MSCRAMMs (Microbial Surface Component Recognizing Adhesive Matrix Molecules) through PCR analysis. The activity of the icaADBC operon was detected by Congo red assay, and the biofilm formation was analyzed through microtiter plate assay. Results: S. epidermidis isolates produced biofilm (n = 65; 86.6%) frequently. The icaA was the major representative module of the actively expressing icaADBC operon (n = 21; 80.7% sensitivity). The MSCRAMMs, including fbe (n = 59; 90.7%; p = 0.007), and embp (n = 57; 87.6%; p = 0.026), were highly prevalent and associated with biofilm positive S. epidermidis. The prevalence of icaADBC operon in biofilm positive and negative S. epidermidis was not significant (n = 41; 63%; p = 0.429). No significant association was found between IS256 and actively complete icaADBC operon (n = 10; 47.6%; p = 0.294). In the presence of 5% human plasma and glucose stress, S. epidermidis produced a strong biofilm (n = 55; 84.6%). Conclusion: The polysaccharide-dependent biofilm formation is significantly replaced (n = 21; 28%; p = 0.149) by a polysaccharide-independent mechanism (n = 59; 90.7%; p = 0.007), in which the MSCRAMMs might actively play their role. The fibrinogen-binding protein and extracellular matrix-binding protein might be potential anti-biofilm drug targets, markers of rapid diagnosis, and potential vaccine candidates of S. epidermidis involved in pediatric bacteremia

Exploring the multi-gene regulatory molecular mechanism of Saudi Arabian flora against epilepsy based on data mining, network pharmacology and docking analysis

Epilepsy is a chronic neurological disorder marked by recurrent seizures, significantly affecting the population in Saudi Arabia across all age demographics. The global prevalence of active epilepsy is around 6.38/1,000 persons and in the Arabian region, the median prevalence of active epilepsy is 4.4/1,000 persons. However, over 75% of individuals are untreated. Consequently, the development of therapeutic strategies with increased efficacy and safety profiles is essential to improve the survival rate among epilepsy patients. The current study integrates network pharmacology along with Bioinformatics approaches to explore the potential molecular mechanisms of local flora of Saudi Arabia including Solanum incanum, Abrus precatorius, Withania somnifera, and Azadirachta indica in epilepsy treatment. In the preliminary phase, data related to the bioactive components of the local plants and the associated target genes of both these plants and epilepsy were gathered from scientific literature and open-source databases. This data was then analyzed to identify common targets between the plants and ovarian cancer. Based on these common targets, a protein–protein interaction (PPI) network was constructed utilizing the STRING database, which was subsequently incorporated into the Cytoscape software for identification of hub genes based on their degree of connectivity. Lastly, an interplay network depicting the associations between the compounds and the overlapping genes was formulated via Cytoscape, to study the potential network pharmacology implications of these active compounds in relation to ovarian cancer. Following that, a compound-target protein-pathway network was constructed which uncovered that namely abrectorin, genistin, (+)-catechin, precatorine, (+)-ascorbic acid, licoflavanone, skrofulein, stigmasterone, 5,7-Dihydroxy-4′-methoxy-8,3′-di-C-prenylflavanone could potentially be used as antagonists for the therapeutic management of epilepsy by targeting TNF and TP53 proteins. Furthermore, the implementation of molecular docking reinforces the binding affinity of the compound, indicating a robust stability of the forecasted compounds at the docked site. This research lays both a theoretical and experimental groundwork for more profound investigations and establishes a practical method for the strategic employment of active compounds in the development of anti-epileptic therapeutics

Inhibitory effect of lupeol, quercetin, and solasodine on Rhizopus oryzae: A molecular docking and dynamic simulation study

Background: Mucormycosis is an infection caused by fungi belonging to the order Mucorales. Rhizopus oryzae is one of the most prevalent organisms identified in mucormycosis patients. Because it spreads quickly through the blood vessels, this opportunistic illness has an exceptionally high fatality rate, even when vigorous treatment is administered. Nonetheless, it has a high tolerance to antifungal medicines, limiting treatment options. As a result, improved methods for preventing and treating mucormycosis are desperately needed. Hence, this study was aimed at assessing the effect of lupeol, quercetin, and solasodine against mucormycosis based on computational approaches. Methods: The Rhizopus oryzae RNA-dependent RNA polymerase (RdRp) was the target for the design of drugs against the deadly mucormycosis. The three-dimensional structure of the RdRp was modelled with a Swiss model and validated using PROCHECK, VERIFY 3D, and QMEAN. Using the Schrodinger maestro module, a molecular docking study was performed between RdRp and the antimicrobial phytochemicals lupeol, quercetin, and solasodine. A molecular dynamics (MD) simulation study was used to assess the stability and interaction of the RdRp with these phytochemicals. Results: The RdRp protein binds strongly to lupeol (−7.2 kcal/mol), quercetin (−9.1 kcal/mol), and solasodine (−9.6 kcal/mol), according to molecular docking assessment based on the lowest binding energy, confirmation, and bond interaction. Simulations suggest that lupeol, quercetin, and solasodine complexes with RdRp and showed stable confirmation with minimal fluctuation throughout the 200 nanoseconds based on the RMSD and RMSF trajectory assessments. Conclusion: The molecular docking and MD simulation investigation improved our understanding of phytochemical-RdRp interactions. Due to its high affinity for RdRp, solasodine may be a better treatment option for mucormycosis

Dose-Dependent Effects of Melatonin on the Viability, Proliferation, and Differentiation of Dental Pulp Stem Cells (DPSCs)

(1) Background: Dental pulp stem cells (DPSCs) are derived from pulp tissue lodged within human teeth and are mesenchymal in origin. These DPSCs have been demonstrated to dissociate into clusters of various cell lineages and are very easy to isolate, culture, and expand. Melatonin, a multifaceted molecule with a spectrum of effects in the human body, is known to influence stem cell viability, proliferation, and differentiation, but little is known about the impact melatonin has on the capacity of DPSCs to differentiate into adipocytes, osteocytes, and chondrocytes. The primary objective of this research was to explore the impact that melatonin has on proliferation, and the capacity of DPSCs to differentiate into adipocytes, osteocytes, and chondrocytes. (2) Methodology: DPSCs were extracted from 12 healthy human teeth, cultured, and expanded. Flow cytometry was performed to examine the surface stem cell markers. Further, melatonin was added to the cultured DPSCs in various concentrations, to assess cytotoxicity using an MTT assay. Following this, the DPSCs were tested for their proliferative ability, as well as adipogenic, osteogenic, and chondrogenic differentiation capabilities under the influence of variable concentrations of melatonin. (3) Results: DPSCs obtained from human teeth demonstrated surface characteristics of mesenchymal stem cells, as shown by the positive expression of CD105, CD90, and CD73 markers. An MTT cytotoxicity assay revealed that melatonin was well tolerated by the cells at low (1 &micro;M) and high (25 &micro;M) concentrations. Assessment of DPSC cell differentiation elucidated that melatonin at 1 &micro;M and 25 &micro;M concentrations with the induction media stimulated DPSCs to differentiate into osteocytes, but did not have much influence on adipogenic and chondrogenic differentiation. (4) Conclusions: Melatonin could be used in stem cell and tissue engineering applications for osteogenic differentiation of DPSCs and could protect these cells due to its cytoprotective, immunomodulatory, and antioxidant roles, in addition to being an osteopromoter molecule

COVID-19 Vaccination in Pediatrics: Was It Valuable and Successful?

Background: The mass vaccination of children against coronavirus 2019 disease (COVID-19) has been frequently debated. The risk–benefit assessment of COVID-19 vaccination versus infection in children has also been debated. Aim: This systematic review looked for answers to the question “was the vaccination of our children valuable and successful?”. Methods: The search strategy of different articles in the literature was based on medical subject headings. Screening and selection were based on inclusion/exclusion criteria. Results and Discussion: The search results revealed that the majority of the reported adverse events after COVID-19 vaccination in pediatrics were mild to moderate, with few being severe. Injection site discomfort, fever, headache, cough, lethargy, and muscular aches and pains were the most prevalent side effects. Few clinical studies recorded significant side effects, although the majority of these adverse events had nothing to do with vaccination. In terms of efficacy, COVID-19 disease protection was achieved in 90–95% of cases for mRNA vaccines, in 50–80% of cases for inactivated vaccines, and in 58–92% of cases for adenoviral-based vaccines in children and adolescents. Conclusions: Based on available data, COVID-19 immunizations appear to be safe for children and adolescents. Furthermore, multiple studies have proven that different types of vaccines can provide excellent protection against COVID-19 in pediatric populations. The efficacy of vaccines against new SARS-CoV-2 variants and the reduction in vaccine-related long-term adverse events are crucial for risk–benefit and cost-effectiveness assessments; therefore, additional safety studies are required to confirm the long-term safety and effectiveness of vaccinations in children