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Mona A El-Zamkan,1 Bassma A Hendy,2 Hassan Mahmoud Diab,3 Najat Marraiki,4 Gaber El-Saber Batiha,5 Hani Saber,6 Waleed Younis,7 Shankar Thangamani,8 Khalid J Alzahrani,9 Ahmed Shaban Ahmed1 1Department of Food Hygiene and Control (Milk Hygiene), Faculty of Veterinary Medicine, South Valley University, Qena, 83523, Egypt; 2Reference Lab for Food Safety, Animal Health Research Institute (AHRI), Agriculture Research Center (ARC), Dokki, Giza, 12622, Egypt; 3Department of Animal and Poultry Health and Environment, Faculty of Veterinary Medicine, South Valley University, Qena, 83523, Egypt; 4Department of Botany and Microbiology, College of Science, King Saud University, Riyadh, 11451, Saudi Arabia; 5Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour, Al-Beheira 22511, Egypt; 6Department of Botany and Microbiology, Faculty of Science, South Valley University, Qena, 83523, Egypt; 7Department of Microbiology, Faculty of Veterinary Medicine, South Valley University, Qena, 83523, Egypt; 8Department of Pathology and Population Medicine, College of Veterinary Medicine, Midwestern University, Glendale, AZ, USA; 9Department of Clinical Laboratories Sciences, College of Applied Medical Sciences, Taif University, Taif, 21944, Saudi ArabiaCorrespondence: Mona A El-ZamkanDepartment of Food Hygiene and Control (Milk Hygiene), Faculty of Veterinary Medicine, South Valley University, Qena, 83523, EgyptEmail m_zam@vet.svu.edu.egShankar ThangamaniDepartment of Pathology and Population Medicine, College of Veterinary Medicine, Midwestern University, Glendale, AZ, USAEmail sthang@midwestern.eduIntroduction: Listeria monocytogenes is an important foodborne pathogen of public- and animal-health concern globally. The persistence of L. monocytogenes in the dairy-processing environment has multifactorial causes, including lack of hygiene, inefficient cleaning, and improper disinfection practices.Materials and Methods: A total of 300 dairy-product and environmental samples were collected from dairy-cattle facilities and local dairy shops and vendors in Qena, Egypt. Samples were screened for the incidence of Listeria spp. and to detect virulence determinants and disinfectant-resistance genes. Three marine algal species — Caulerpa racemosa, Jania rubens, and Padina pavonica — were collected from Hurghada on the Red Sea coast. Algal extracts were screened using gas chromatography–mass spectrometry. The antimicrobial activity of some marine algal extracts, nanoparticles derived therefrom, and some disinfectants against L. monocytogenes strains were assessed in vitro using agar-well diffusion and liquid-broth methods. The impact of P. pavonica extract on the growth and survival of virulent L. monocytogenes in cheese and whey were clarified.Results and Discussion: The incidence of L. monocytogenes in dairy products and environmental samples was 15.5% and 19%, respectively. The most common toxigenic gene profile found among the isolates was hlyA+–inlA+–prfA+. The sensitivity pattern of L. monocytogenes strains to disinfectant containing alkyl (C12– 16) dimethyl BAC was high compared to other tested quaternary ammonium compounds (QAC) disinfectants tested, which showed lower log reductions against resistant strains. The QAC disinfectant–resistance gene qacH was detected in 40% of the isolates. Potent bactericidal activity of a petroleum ether extract of P. pavonica and silver nanoparticles of P. pavonica were obtained against the virulent L. monocytogenes strain. The population of L. monocytogenes in cheese curd and whey after 14 days was reduced at a rate of 9 log CFU/g and 8 log CFU/mL, respectively due to the effect of P. pavonica extract. After 28 days of storage, L. monocytogenes was completely inactivated in those dairy products.Conclusion: P. pavonica extract showed promising antimicrobial properties, calling for further comprehensive studies prior to it being applied in the food industry to enhance the safety, quality, and shelf life of products and protect public health.Keywords: Listeria monocytogenes, virulence genes, cheese, qacH gene, disinfectants, algae, antimicrobial activity

Matrix metalloproteinases (MMPs) are a diverse group of proteases involved in various physiological and pathological processes through modulation of extracellular matrix (ECM) components, cytokines, and growth factors. In the central nervous system (CNS), MMPs play a major role in CNS development, plasticity, repair, and reorganisation contributing to learning, memory, and neuroimmune response to injury. MMPs are also linked to various neurological disorders such as Alzheimer's disease, Parkinson's disease, cerebral aneurysm, stroke, epilepsy, multiple sclerosis, and brain cancer suggesting these proteases as key regulatory factors in the nervous system. Moreover, MMPs have been involved in the pathogenesis of neurotropic viral infections via dysregulation of various cellular processes, which may highlight these factors as potential targets for the treatment and control of neurological complications associated with viral pathogens. This review provides an overview of the roles of MMPs in various physiological processes of the CNS and their interactions with neurotropic viral pathogens., (© 2024 John Wiley & Sons Ltd.)

Background: The 2023 dengue outbreak has proven that dengue is not only an endemic disease but also an emerging health threat in Bangladesh. Integrated studies on the epidemiology, clinical characteristics, seasonality, and genotype of dengue are limited. This study was conducted to determine recent trends in the molecular epidemiology, clinical features, and seasonality of dengue outbreaks., Methods: We analyzed data from 41 original studies, extracting epidemiological information from all 41 articles, clinical symptoms from 30 articles, and genotypic diversity from 11 articles. The study adhered to the standards of the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) Statement and Cochrane Collaboration guidelines., Results: A total of 565,438 dengue cases and 2,587 fatalities were documented from January 2000 to March 2024. Notably, 60% of cases during the 2019 and 2023 outbreaks were reported in regions previously considered non-endemic. Fatalities were more frequent among women (70%). The majority of the studies (95-100%) used the NS1Ag test, followed by IgG or IgM and RT-PCR tests. New hotspots of dengue transmission were identified in the southern (Khulna, 10.8% and Barishal, 11.8%) and southeastern (Chattogram, 13.8%) regions of Bangladesh. Serotyping was conducted on 92.4% (1,456 of 1,575) of isolates between 2012 and 2023. Of the four serotypes, DENV3 was the most prevalent (57%), followed by DENV2 (30%), DENV1 (11%), and DENV4 (<1%). Genotype DENV3-I (43 of 59 isolates) was the most prevalent, followed by DENV3-II (8 of 59). The highest frequency of dengue cases was observed in August (26.3%), followed by September (22.5%), October (20.2%), and November (13.08%). Fever (90.51, 95% CI 85-100%) was the most prevalent symptom, followed by headache (57.98, 95% CI 12-100%), vomiting (51.16, 95% CI 23-91%), abdominal pain (34.12, 95% CI 12-85%), and myalgia (25.53, 95% CI 13-85%), respectively., Conclusion: This study provides integrated insights into the molecular epidemiology, clinical features, seasonality, and transmission of dengue in Bangladesh and highlights research gaps for future studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Sharif, Opu, Saha, Masud, Naim, Alsharif, Alzahrani, Alvarado, Noya, De la Torre Díez and Dey.)

Assessment of side effects associated with COVID-19 vaccination is required to monitor safety issues and acceptance of vaccines in the long term. We found a significant knowledge gap in the safety profile of COVID-19 vaccines in Bangladesh. We enrolled 1805 vaccine recipients from May 5, 2021, to April 4, 2023. Kruskal-Wallis test and χ2 test were performed. Multivariable logistic regression was also performed. First, second and third doses were administered among 1805, 1341, and 923 participants, respectively. Oxford-AstraZeneca (2946 doses) was the highest administered followed by Sinopharm BIBP (551 doses), Sinovac (214 doses), Pfizer-BioNTech (198 doses), and Moderna (160 doses), respectively. Pain at the injection site (80-90%, 3200-3600), swelling (85%, 3458), redness (78%, 3168), and heaviness in hand (65%, 2645) were the most common local effects, and fever (85%, 3458), headache (82%, 3336), myalgia (70%, 2848), chills (67%, 2726), muscle pain (60%, 2441) were the most prevalent systemic side effects reported within 48 h of vaccination. Thrombosis was only reported among the Oxford-AstraZeneca recipients (3.5-5.7%). Both local and systemic effects were significantly associated with the Oxford-AstraZeneca (p-value < 0.05), Pfizer-BioNTech (p-value < 0.05), and Moderna (p-value < 0.05) vaccination. Chronic urticaria and psoriasis were reported by 55-60% of the recipients after six months or later. The highest percentage of local and systemic effects after 2nd and 3rd dose were found among recipients of Moderna followed by Pfizer-BioNTech and Oxford-AstraZeneca. Homogenous doses of Oxford-AstraZeneca and heterogenous doses of Moderna and Pfizer-BioNTech were significantly associated with elevated adverse effects. Females, aged above 60 years with preexisting health conditions had higher risks. Vaccination with Pfizer-BioNTech (OR 4.34, 95% CI 3.95-4.58) had the highest odds of severe and long-term effects followed by Moderna (OR 4.15, 95% CI 3.92-4.69) and Oxford-AstraZeneca (OR 3.89, 95% CI 3.45-4.06), respectively. This study will provide an integrated insight into the safety profile of COVID-19 vaccines., (© 2024. The Author(s).)

Poxviridae is a diverse family of double-stranded DNA viruses, historically significant for diseases like smallpox caused by variola virus (VARV). These viruses exhibit unique cytoplasmic replication strategies, large genomes encoding numerous proteins, and the ability to cause severe cutaneous and systemic diseases. Recent attention has focused on their neurotropic potential, including mechanisms of CNS invasion, immune-mediated damage, and clinical manifestations such as encephalitis and myelitis. This review synthesises current knowledge on poxvirus neurotropism, highlighting pathophysiological mechanisms and clinical implications., (© 2024 John Wiley & Sons Ltd.)

Background and Objectives : In the undertaken study, proteomics alterations of blood-borne XDR S. Typhi isolated from Pakistan were investigated using mass spectrometry. Materials and Methods : MDR and XDR S. Typhi total protein lysates were fractionated, digested, and processed for nanoflow LC-LTQ- Orbitrap MS analysis. Results : Among the 1267 identified proteins, 37 were differentially regulated, of which 28 were up-regulated, and 9 were down-regulated in XDR S. Typhi as compared to MDR S. Typhi. Based on the functional annotation, proteins found up-regulated are involved mainly in metabolic pathways (ManA, FadB, DacC, GpmA, AphA, PfkB, TalA, FbaB, OtsA, 16504242), the biosynthesis of secondary metabolites (ManA, FadB, GlpB, GpmA, PfkB, TalA, FbaB, OtsA), microbial metabolism in diverse environments (FadB, GpmA, PfkB, NfnB, TalA, FbaB), and ABC transporters (PstS, YbeJ, MglB, RbsB, ArtJ). Proteins found down-regulated are involved mainly in carbon metabolism (FadB, GpmA, PfkB, FalA, FbaB) and the biosynthesis of amino acids (GpmA, PfkB, TalA, FbaB). Most of the identified differential proteins were predicted to be antigenic, and matched with resistome data. Conclusions : A total of 28 proteins were up-regulated, and 9 were down-regulated in XDR S. Typhi. Further characterization of the identified proteins will help in understanding the molecular signaling involved in the emergence of XDR S . Typhi.

Extracellular vesicles (EVs) have emerged as key intercellular communication and pathogenesis mediators. Parasitic organisms' helminths, cause widespread infections with significant health impacts worldwide. Recent research has shed light on the role of EVs in the lifecycle, immune evasion, and disease progression of these parasitic organisms. These tiny membrane-bound organelles including microvesicles and exosomes, facilitate the transfer of proteins, lipids, mRNAs, and microRNAs between cells. EVs have been isolated from various bodily fluids, offering a potential diagnostic and therapeutic avenue for combating infectious agents. According to recent research, EVs from helminths hold great promise in the diagnosis of parasitic infections due to their specificity, early detection capabilities, accessibility, and the potential for staging and monitoring infections, promote intercellular communication, and are a viable therapeutic tool for the treatment of infectious agents. Exploring host-parasite interactions has identified promising new targets for diagnostic, therapy, and vaccine development against helminths. This literature review delves into EVS's origin, nature, biogenesis, and composition in these parasitic organisms. It also highlights the proteins and miRNAs involved in EV release, providing a comprehensive summary of the latest findings on the significance of EVs in the biology of helminths, promising targets for therapeutic and diagnostic biomarkers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Qadeer, Wajid, Rafey, Nawaz, Khan, Rahman, Alzahrani, Khan, Alsabi, Ullah, Safi, Xia and Zahoor.)

Background: The COVID-19 pandemic caused by SARS-CoV-2 is an unparalleled health risk, needing fast antiviral medication development. One of the most effective strategies for developing therapies against novel and emerging viruses is drug repurposing. Recently, systems biology approaches toward the discovery of repurposing medications are gaining prominence., Aim: This study aimed to implement a systems biology approach to identify crucial drug targets as well as potential drug candidates against COVID infection., Methods: Our approach utilizes differential gene expression in COVID conditions that enable the construction of a protein-protein interaction (PPI) network. Core clusters were extracted from this network, followed by molecular enrichment analysis. This process identified critical drug targets and potential drug candidates targeting various stages of COVID-19 infection., Results: The network was built using the top 200 differently expressed genes in mild, moderate, and severe COVID-19 infections. Top 3 clusters for each disease condition were identified, representing the core mechanism of the network. Molecular enrichment revealed the majority of the pathways in the mild state were associated with transcription regulation, protein folding, angiogenesis, and cytokine-signaling pathways. Whereas, the enriched pathways in moderate and severe disease states were predominately linked with the immune system and apoptotic processes, which include NF-kappaB signaling, cytokine signaling, TNF-mediated signaling, and oxidative stress-induced cell death. Further analysis identifies 28 potential drugs that can be repurposed to treat moderate and severe COVID-19, most of which are currently used in cancer treatment., Conclusion: Interestingly, some of the proposed drugs have demonstrated inhibitory effects against SARS-CoV-2, as supported by literature evidence. Overall, the drug repurposing method described here will help develop potential antiviral medications to treat emerging COVID strains., (Copyright © 2024 Copyright: © 2024 Nigerian Journal of Clinical Practice.)

Cardiovascular diseases (CVDs) are the leading cause of death worldwide and are associated with increasing financial health burden that requires research into novel therapeutic approaches. Since the early 2000s, the availability of next-generation sequencing techniques such as microRNAs, circular RNAs, and long non-coding RNAs have been proven as potential therapeutic targets for treating various CVDs. Therapeutics based on RNAs have become a viable option for addressing the intricate molecular pathways that underlie the pathophysiology of CVDs. We provide an in-depth analysis of the state of RNA therapies in the context of CVDs, emphasizing various approaches that target the various stages of the basic dogma of molecular biology to effect temporary or long-term changes. In this review, we summarize recent methodologies used to screen for novel coding and non-coding RNA candidates with diagnostic and treatment possibilities in cardiovascular diseases. These methods include single-cell sequencing techniques, functional RNA screening, and next-generation sequencing.Lastly, we highlighted the potential of using oligonucleotide-based chemical products such as modified RNA and RNA mimics/inhibitors for the treatment of CVDs. Moreover, there will be an increasing number of potential RNA diagnostic and therapeutic for CVDs that will progress to expand for years to come., Competing Interests: Declaration of competing interest The author declared that they have no competing interests’ among them., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Transient receptor potential vanilloid 1 protein (TRPV1) is expressed widely in skin and sensory neurons that contribute to pain/heat sensation in the human system. TRPV1 gene polymorphisms are susceptible to multiple diseases and it is considered a therapeutic target for various inflammatory conditions. Among the TRPV1 variants, rs8065080 (1911 A > G) plays a vital role in painful osteoarthritis and migraine. The presence of rs8065080 polymorphism may render drug efficacy. This study aimed to identify better antagonists against wild-type and variant TRPV1 that may help in the relief of pain/inflammation. We constructed suitable TRPV1 protein structures for wild-type and rs8065080 variant through a homology modelling approach. A total of 3363 anti-inflammatory compounds with high chemical diversity and good drug-like properties were collected and screened against the generated structures. Molecular docking showed that nobilamide B had the highest binding affinity (-5.83 kcal/mol) towards the wild-type. Whereas, isoquinoline analogue displayed highest binding potency with the variant TRPV1 (-11.65 kcal/mol). Besides those, C18H15F3N4O showed affinity towards both wild-type (-5.53 kcal/mol) and variant TRPV1 (-9.75 kcal/mol). Then, molecular dynamic simulation revealed stable conformation in wild-type and variant TRPV1 upon binding of nobilmaide B, isoquinoline analogue and C18H15F3N4O. Additionally, density functional theory (DFT) using B3LYP hybrid function showed high chemical reactiveness of nobilamie B, isoquinoline analogue and C18H15F3N4O. Overall, our systematic investigations provide, C18H15F3N4O could be a potential analgesic inhibiting both wild-type and variant TRPV1 against inflammatory conditions.

Vector-borne viruses pose a significant health problem worldwide, as they are transmitted to humans through the bite of infected arthropods such as mosquitoes and ticks. In recent years, emerging and re-emerging vector-borne diseases have gained attention as they can cause a wide spectrum of neurological manifestations. The neurological manifestations of vector-borne viruses encompass a board spectrum of clinical manifestations, ranging from mild and self-limiting symptoms to severe and life-threatening conditions. Common neurological complications include viral encephalitis, acute flaccid paralysis, aseptic meningitis, and various neuromuscular disorders. The specific viruses responsible for these neurological sequelae vary by geographic region and include Orthoflavivirus nilense, Zika virus, dengue virus, chikungunya virus, Japanese encephalitis virus, and tick-borne encephalitis virus. This review focuses on the pathogenesis of these neurologic complications and highlights the mechanisms by which vector-borne viruses invade the central nervous system and trigger neuroinflammatory responses. Diagnostic challenges and strategies for early detection of neurological manifestations are discussed, emphasising the importance of clinical suspicion and advanced laboratory testing., (© 2024 John Wiley & Sons Ltd.)

Asiatic acid (AA) is a polyphenolic compound with potent antioxidative and anti-inflammatory activities that make it a potential choice to attenuate inflammation and oxidative insults associated with ulcerative colitis (UC). Hence, the present study aimed to evaluate if AA can attenuate molecular, biochemical, and histological alterations in the acetic acid-induced UC model in rats. To perform the study, five groups were applied, including the control, acetic acid-induced UC, UC-treated with 40 mg/kg aminosalicylate (5-ASA), UC-treated with 20 mg/kg AA, and UC-treated with 40 mg/kg AA. Levels of different markers of inflammation, oxidative stress, and apoptosis were studied along with histological approaches. The induction of UC increased the levels of lipid peroxidation (LPO) and nitric oxide (NO). Additionally, the nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream antioxidant proteins [catalase (CAT), superoxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxidase (GPx), and glutathione reductase (GR)] were down-regulated in the colon tissue. Moreover, the inflammatory mediators [myeloperoxidase (MPO), monocyte chemotactic protein 1 (MCP1), prostaglandin E2 (PGE2), nuclear factor-kappa B (NF-κB), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β)] were increased in the colon tissue after the induction of UC. Notably, an apoptotic response was developed, as demonstrated by the increased caspase-3 and Bax and decreased Bcl2. Interestingly, AA administration at both doses lessened the molecular, biochemical, and histopathological changes following the induction in the colon tissue of UC. In conclusion, AA could improve the antioxidative status and attenuate the inflammatory and apoptotic challenges associated with UC., (© 2024 The Author(s).)

Aim: To investigate different approaches to RA treatment that might lead to greater efficacy and better safety profiles. Methods: The Search strategy was based on medical subject headings, and screening and selection were based on inclusion/exclusion criteria. Results & discussion: Early therapy is critical for disease control and loss of bodily function. The most promising outcomes came from the development of disease-modifying anti-rheumatic drugs. Different foods have anti-inflammatory and antioxidant qualities that protect against the development of rheumatoid arthritis (RA). Some dietary patterns and supplements have been shown to have potential protective benefits against RA. Conclusion: Improvement in the quality of life of RA patients requires a tailored management approach based on the current patient medical data., Competing Interests: The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties., (© 2024 The Authors.)

Researchers are consistently investigating novel and distinctive methods and materials that are compatible for human life and environmental conditions This study aimed to synthesize gold nanoparticles (ALPs-AuNPs) using for the first time an alkaline protease (ALPs) derived from Phalaris minor seed extract. A series of physicochemical techniques were used to inquire the formation, size, shape and crystalline nature of ALPs-AuNPs. The nanoparticles' ability to degrade methylene blue (MB) through photocatalysis under visible light irradiation was assessed. The findings demonstrated that ALPs-AuNPs exhibited remarkable efficacy by destroying 100 % of MB within a mere 30-minute irradiation period. In addition, the ALPs-AuNPs demonstrated remarkable effectiveness in inhibiting the growth of gram-positive (S. aureus) and gram-negative (E. coli) bacteria. The inhibition zones examined against the two bacterial strains were 23(±0.3) mm and 19(±0.4); 13(±0.3) mm and 11(±0.5) mm under light and dark conditions respectively. The ALPs-AuNPs exhibited significant antioxidant activity by effectively scavenging 88 % of stable and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals. As a result, the findings demonstrated that the environmentally friendly ALPs-AuNPs showed a strong potential for MB degradation and bacterial pathogen treatment., Competing Interests: Declaration of competing interest The author has no conflict of interest exits in the submission of this manuscript and the authors have complied with journal ethical requirements. Moreover, manuscript is approved by all authors as well as all the authorities acknowledged for publication., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Open reduction and internal fixation represent prevalent orthopedic procedures, sparking ongoing discourse over whether to retain or remove asymptomatic implants. Achieving consensus on this matter is paramount for orthopedic surgeons. This study aims to quantify the impact of routine implant removal on patients and healthcare facilities. A retrospective analysis of implant removal cases from 2016 to 2022 at King Fahad Hospital of the University (KFHU) was conducted and subjected to statistical scrutiny. Among these cases, 44% necessitated hospitalization exceeding one day, while 56% required only a single day. Adults exhibited a 55% need for extended hospital stays, contrasting with 22.8% among the pediatric cohort. The complication rate was 6%, with all patients experiencing at least one complication. Notably, 34.1% required sick leave and 4.8% exceeded 14 d. General anesthesia was predominant (88%). Routine implant removal introduces unwarranted complications, particularly in adults, potentially prolonging hospitalization. This procedure strains hospital resources, tying up the operating room that could otherwise accommodate critical surgeries. Clearly defined institutional guidelines are imperative to regulate this practice., Aim: To measure the burden of routine implant removal on the patients and hospital., Methods: This is a retrospective analysis study of 167 routine implant removal cases treated at KFHU, a tertiary hospital in Saudi Arabia. Data were collected in the orthopedic department at KFHU from February 2016 to August 2022, which includes routine asymptomatic implant removal cases across all age categories. Nonroutine indications such as infection, pain, implant failure, malunion, nonunion, restricted range of motion, and prominent hardware were excluded. Patients who had external fixators removed or joints replaced were also excluded., Results: Between February 2016 and August 2022, 360 implants were retrieved; however, only 167 of those who met the inclusion criteria were included in this study. The remaining implants were rejected due to exclusion criteria. Among the cases, 44% required more than one day in the hospital, whereas 56% required only one day. 55% of adults required more than one day of hospitalization, while 22.8% of pediatric patients required more than one day of inpatient care. The complication rate was 6%, with each patient experiencing at least one complication. Sick leave was required in 34.1% of cases, with 4.8% requiring more than 14 d. The most common type of anesthesia used in the surgeries was general anesthesia (88%), and the mean (SD) surgery duration was 77.1 (54.7) min., Conclusion: Routine implant removal causes unnecessary complications, prolongs hospital stays, depletes resources and monopolizing operating rooms that could serve more critical procedures., Competing Interests: Conflict-of-interest statement: All authors have no conflict of interests., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Satish, Saravanan, Augustine, Saraswathy, V, Khan, H, Chakraborty, Dsouza, N, Halawani, Alzahrani, Alzahrani and Patil.)

The clinical management of oral cancer is often frequented with challenges that arise from relapse, recurrence, invasion and resistance towards the cornerstone chemo and radiation therapies. The recent conceptual advancement in oncology has substantiated the role of cancer stem cells (CSC) as a predominant player of these intricacies. CSC are a sub-group of tumor population with inherent adroitness to self-renew with high plasticity. During tumor evolution, the structural and functional reprogramming persuades the cancer cells to acquire stem-cell like properties, thus presenting them with higher survival abilities and treatment resistance. An appraisal on key features that govern the stemness is of prime importance to confront the current challenges encountered in oral cancer. The nurturing niche of CSC for maintaining its stemness characteristics is thought to be modulated by complex multi-layered components encompassing neoplastic cells, extracellular matrix, acellular components, circulatory vessels, various cascading signaling molecules and stromal cells. This review focuses on recapitulating both intrinsic and extrinsic mechanisms that impart the stemness. There are contemplating evidences that demonstrate the role of transcription factors (TF) in sustaining the neoplastic stem cell's pluripotency and plasticity alongside the miRNA in regulation of crucial genes involved in the transformation of normal oral mucosa to malignancy. This review illustrates the interplay between miRNA and various known TF of oral cancer such as c-Myc, SOX, STAT, NANOG and OCT in orchestrating the stemness and resistance features. Further, the cross-talks involved in tumor micro-environment inclusive of cytokines, macrophages, extra cellular matrix, angiogenesis leading pathways and influential factors of hypoxia on tumorigenesis and CSC survival have been elucidated. Finally, external factorial influence of oral microbiome gained due to the dysbiosis is also emphasized. There are growing confirmations of the possible roles of microbiomes in the progression of oral cancer. Given this, an attempt has been made to explore the potential links including EMT and signaling pathways towards resistance and stemness. This review provides a spectrum of understanding on stemness and progression of oral cancers at various regulatory levels along with their current therapeutic knowledge. These mechanisms could be exploited for future research to expand potential treatment strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Vastrad, Ritesh, V, Saraswathy, Augustine, Alzahrani, Alzahrani, Halawani, Ashi, Alshahrani, Hassan, Baeshen, Saravanan, Satish, Vutukuru and Patil.)

Background: Extraoral and intraoral dental photographs serve as preoperative records and document the entire treatment. Correctly composed orthodontic photographs are crucial for remote diagnosis and may serve as a bulwark against medicolegal challenges., Materials and Methods: In this prospective study, intraoral frontal photographs of patients with ideal occlusion were taken using two types of lenses (EF-S 18-55 mm f/3.5-5.6 IS STM lens (Canon, Tokyo, JP), SP 90 mm F/2.8 MACRO VC lens (Model F017 Tamron, NY, USA)) and two different ring flash systems (Meike FC-100 Macro Ring LED Light (Meike, China), Macro Ring flash Lite YN-14EX (Yongnuo digital, China)). The combination of lens and flash used was grouped into four groups. Twenty-eight intraoral photographs of patients were taken. An image quality assessment survey was distributed among two groups - 50 orthodontists and 50 other dental specialists., Results: The participants were asked to assess all the intraoral images and subjectively score them on a scale of one to ten, with one being very poor and ten being excellent, considering the sharpness, color, brightness, contrast, and overall quality of the image. The general dentists rated the images taken with a 90-mm macro lens and ring flash as the best quality photographs. Images obtained using an 18-55 mm lens and ring LED received significantly lesser scores and were graded good by dentists., Conclusion: This combination of lens and flash may prove a valuable investment in the long-term aiding in excellent dental images for diagnosis and treatment monitoring., (Copyright © 2023 Copyright: © 2023 Nigerian Journal of Clinical Practice.)

Background: Serum urea levels are essential for the diagnosis of chronic kidney disease (CKD), as they are a measure of renal function. Salivary urea has been used as an alternative to serum urea in patients with CKD., Aim: To estimate serum urea levels and their correlation with salivary urea levels in order to validate the use of saliva as an alternative diagnostic tool for renal dysfunction., Patients and Methods: Thirty healthy individuals and 150 patients with CKD (30 from each CKD stage) were recruited for the study. Serum and salivary samples were collected to estimate the urea levels, and statistical analyses were performed., Results: Statistically significant (P < 0.05) differences in the mean serum and salivary urea levels were observed between the healthy and each stage of the CKD group; significance at P < 0.05 was observed within the stages of CKD as well. Correlation analysis also showed significant differences between the serum and salivary urea levels at each stage of the disease. Receiver operating characteristic analysis revealed a higher area under the curve of 0.917 at a 95% confidence interval with a salivary urea cut-off of 28.25 mg/dl (sensitivity and specificity: 88% and 84%, respectively)., Conclusion: The variability in salivary urea levels in the early and late stages suggests the use of salivary urea in the late stages of CKD. It is suggested that salivary urea levels may be used as an alternative to serum to assess and monitor the progression of renal impairment along with other standard renal function markers., (Copyright © 2023 Copyright: © 2023 Nigerian Journal of Clinical Practice.)

Intussusception (ISN) is a dangerous condition where a portion of the intestine slides into an adjacent area of the intestine. This telescoping motion frequently prevents liquids or food from flowing through. Developing management guidelines for ileocolic (IC) intussusception was the aim of this systematic study. Data sources were PubMed/Medical Literature Analysis and Retrieval System Online (MEDLINE), Scopus, and Embase databases. Our review investigated English-language articles (from 2010 to 2023) according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Overall, there were 15 articles. Surveys and analyses of national databases were the most widely used methods (n=15). The search identified 561 studies; 15 were eligible for inclusion in the analysis. Further understanding of the management of intussusception may help improve evaluation and management in the future. The use of preventive antibiotics does not reduce problems following radiologic reduction. When clinically appropriate, repeated attempts at enema reduction may be made. After the enema reduction of ileocolic intussusception, patients can be safely watched in the emergency room (ER), thereby avoiding hospitalization. Success rates for laparoscopic reduction are high. When it comes to intussusception in children who are hemodynamically stable and do not have a serious illness, there is no need for pre-reduction antibiotics. Prioritizing nonoperative outpatient (OP) therapy is recommended as the primary approach, with the utilization of minimally invasive procedures to avoid the necessity for laparotomy. The management of colonic intussusception involves complete removal in one piece, while enteric intussusception can be addressed through reduction followed by resection. A targeted approach is recommended, recognizing the intermediate forms of intussusception that may exist between the colonic and enteric types. It is essential to note that the prevailing treatment for adult intussusception remains to be surgical intervention., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Attoun et al.)

Diabetes mellitus is a complex metabolic syndrome that involves dysfunction of spleen and other lymphoid organs. Medicinal plants, including okra ( Abelmoschus esculentus (L.) Moench), were used widely for diabetes treatment. Scarce data are available about the potential anti-diabetic effects of okra, the histopathological alterations in splenic tissues and the mechanistic pathways underlying this association. The current research investigated the effects of okra pod extract on the biochemical parameters and expression of CD8 + T cells and nuclear factor kappa (NF-k) B and releasing proinflammatory cytokines in spleen in streptozotocin (STZ)-induced diabetic rat models. A total of 50 mature male Wister albino rats were divided into five isolated groups; the first served as control (untreated) animals, the second (DM group) diabetes induced by STZ (at a dose of 45 mg/kg body weight, administered intraperitoneally), the third group (DM + Insulin): diabetic rats administered insulin subcutaneously (10 units/kg bw/day) daily for 4 weeks, the fourth group was administrated 400 mg/kg okra extract daily for 4 weeks, and diabetic induced rats in the fifth group were administrated 400 mg/kg okra extract daily for 4 weeks. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity in Abelmoschus esculentus (L.) Moench was studied, and the content of phenolic compounds in okra pods was estimated using high-performance liquid chromatography. Diabetes induction led to decreased body weight, increased blood glucose levels. Capsular thickness was significantly increased, white pulp was widely dispersed, and mature lymphocytes in the periphery were also drastically decreased, with thick follicular arteries, necrosis, and depletion of lymphocytes in the germinal center. Red pulp revealed severe congestion and degenerative changes, deposition of hemosiderin granules and lymphocytic depletion. In addition, collagen fiber deposition was increased also in this group. The induction of diabetes exaggerated NF-kβ expression and mediated downregulation of the expression of CD8 + T cells in spleen tissue. Interestingly, oral administration of okra extracts post diabetes induction could mitigate and reverse such adverse effects. Altogether, our study points out the potential benefits of okra in improving blood glucose levels and restoring histopathological alterations in splenic tissues through CD8 + T cells and NF-kβ expression in a diabetic rat model., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Alblihd, Alsharif, Hamad, Ali, Hussein, Alhegaili, Hassan, Al-Amer, Albezrah, Almalki, Albarakati, Alghamdi, Alzahrani, Albrakati, Alrubai, ElAshmouny and Elmahallawy.)

Background: The oral cavity has been referred to as "the gateway to overall health." It is also said to be the meeting point of medicine and dentistry., Aims: Our study sought to determine the extent to which the public was aware of the connection between oral/periodontal conditions and general health., Settings and Design: The observational cross-sectional study's questionnaire was sectioned into oral health awareness, systemic influence on oral health, and personal oral health assessment., Materials and Methods: A total of 994 responses were recorded and a Chi-square test was performed to uncover the relationships using SPSS version 22.0. According to responses, 70% of the population on average comprehended the responses to the majority of the oral health awareness-related questions., Results: It has been noticed that only 30% of the general public was aware of the prevalent health issues like diabetes, hypertension, and malnutrition's impact on dental health. However, more than 60% had confidence in their oral health and gave a rating of at least 5., Conclusion: The study indicates that a good number of the population was prioritizing their oral health. However, there exists a definitive need to improve oral health awareness thereby ameliorating the overall health of an individual., (Copyright © 2023 Copyright: © 2023 Nigerian Journal of Clinical Practice.)

Introduction: Co-prevalence of long-COVID-19, cardiovascular diseases and diabetes is one of the major health challenges of the pandemic worldwide. Studies on long-COVID-19 and associated health outcomes are absent in Bangladesh. The main aim of this study was to determine the prevalence and impact of long-COVID-19 on preexisting diabetes and cardiovascular diseases (CVD) on health outcomes among patients in Bangladesh., Methods: We collected data from 3,250 participants in Bangladesh, retrospectively. Multivariable logistic regression model was used to determine the odds ratio between independent and dependent variables. Kaplan-Meier survival curve was used to determine the cumulative survival., Results: COVID-19 was detected among 73.4% (2,385 of 3,250) participants. Acute long-COVID-19 was detected among 28.4% (678 of 2,385) and chronic long-COVID-19 among 71.6% (1,707 of 2,385) patients. CVD and diabetes were found among 32%, and 24% patients, respectively. Mortality rate was 18% (585 of 3,250) among the participants. Co-prevalence of CVD, diabetes and COVID-19 was involved in majority of fatality (95%). Fever (97%), dry cough (87%) and loss of taste and smell (85%) were the most prevalent symptoms. Patients with co-prevalence of CVD, diabetes and COVID-19 had higher risk of fatality (OR: 3.65, 95% CI, 2.79-4.24). Co-prevalence of CVD, diabetes and chronic long-COVID-19 were detected among 11.9% patients., Discussion: Risk of hospitalization and fatality reduced significantly among the vaccinated. This is one of the early studies on long-COVID-19 in Bangladesh., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Sharif, Sharif, Khan, Halawani, Alzahrani, Alzahrani, Díez, Vargas, Castilla, Parvez and Dey.)

Background: Tobacco use by youth is ever-demanding, and it is increasingly distributed not only in India but also globally. Saliva is a complex oral bio-fluid, freely available, performing absolute tasks for maintaining oral health and homeostasis. It contains a plethora of significant constituents such as proline-rich proteins (PRPs), immunoglobulins, IgA, enzymes lysozyme, lactoferrin, peroxidases, amylase, etc. The basic ecological balance of the oral cavity is stabilized via salivary clearance by reduced aggregation and adherence of microorganisms by direct microbial activity. This balance of oral activity is also done by indirect mechanisms by immunological as well as non-immunological means and also by effectively regulating salivary pH flow rate. This institutional observational study was planned to assess and compare salivary parameters (pH, salivary flow rate), total proteins, α-amylase, calcium, phosphate, and IgA, of unstimulated whole saliva of both tobacco abusers and tobacco non-users., Methods: The Study consisted of 270 participants (Tobacco habit) group, n = 135 and Control (Healthy) group, n = 135 and were in the age range of 20-50 years. They were assessed for oral health status, followed by the analysis of salivary pH, flow rate, total proteins, amylase, calcium, phosphates, and IgA of unstimulated whole saliva., Results: Comparative evaluation of salivary parameters among groups found that varying tobacco abusers had increased salivary amylase, protein levels, and phosphate whereas decreased salivary pH, flow rate, IgA, and in the whole unstimulated saliva samples than those of non-tobacco users. This difference among groups was statistically significant. ( p < 0.05), and calcium levels were not altered significantly., Conclusions: This study concludes that salivary parameters are altered in tobacco abusers when compared to those of non-abusers, and it was more significant in smokeless tobacco abusers than in any other form of tobacco abuse., Competing Interests: Given Rodolfo Reda’s role as Guest Editor and Luca Testarelli’s role as Guest Editor and Editorial Board member of the journal, they had no involvement in the peer-review of this article and has no access to information regarding its peer-review. Full responsibility for the editorial process for this article was delegated to Ru Chen. The authors declare no conflict of interest., (© 2023 The Author(s). Published by IMR Press.)

Background and Aims: The 2022-mpox outbreak has spread worldwide in a short time. Integrated knowledge of the epidemiology, clinical characteristics, and transmission of mpox are limited. This systematic review of peer-reviewed articles and gray literature was conducted to shed light on the epidemiology, clinical features, and transmission of 2022-mpox outbreak., Methods: We identified 45 peer-reviewed manuscripts for data analysis. The standards of the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) Statement and Cochrane Collaboration were followed for conducting the study., Results: The case number of mpox has increased about 100 times worldwide. About 99% of the cases in 2022 outbreak was from non-endemic regions. Men (70%-98% cases) were mostly infected with homosexual and bisexual behavior (30%-60%). The ages of the infected people ranged between 30 and 40 years. The presence of HIV and sexually transmitted infections among 30%-60% of cases were reported. Human-to-human transmission via direct contact and different body fluids were involved in the majority of the cases (90%-100%). Lesions in genitals, perianal, and anogenital areas were more prevalent. Unusually, pharyngitis (15%-40%) and proctitis (20%-40%) were more common during 2022 outbreak than pre-2022 outbreaks. Brincidofovir is approved for the treatment of smallpox by FDA (USA). Two vaccines, including JYNNEOSTM and ACAM2000®, are approved and used for pre- and post-prophylaxis in cases. About 100% of the cases in non-endemic regions were associated with isolates of IIb clade with a divergence of 0.0018-0.0035. Isolates from B.1 lineage were the most predominant followed by B.1.2 and B.1.10., Conclusion: This study will add integrated knowledge of the epidemiology, clinical features, and transmission of mpox., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. Health Science Reports published by Wiley Periodicals LLC.)

BACKGROUND Dental root coverage, crucial in managing gingival recessions, traditionally utilizes subepithelial connective tissue grafts. However, this approach has limitations such as donor site morbidity and graft availability. Recent studies have introduced platelet-rich fibrin (PRF) as an alternative, leveraging its regenerative potential and growth factors. Despite the promise, comparative assessments between PRF and conventional grafts remain limited. This research probes whether PRF, when used beneath a modified Ruben's mixed flap, could provide comparable or superior dental root coverage than a subepithelial connective tissue graft. MATERIAL AND METHODS We enrolled 30 patients exhibiting Miller's class I and II recession in this comparative case series. Patients were randomly assigned to receive either a connective tissue graft (15 patients) or a PRF matrix (15 patients), both covered by a modified Ruben's mixed flap. RESULTS Clinical parameters, including full mouth plaque scores, bleeding scores, probing sulcus depth, clinical attachment level, gingival position assessment, width, and thickness of attached gingiva, were assessed in both the control and test groups at baseline, 6 months, and 12 months post-surgery. Significant differences were observed at all intervals.At the 12-month mark, the control group (connective tissue graft) achieved 91% complete root coverage, while the test group (PRF matrix) achieved 86%. However, this difference was not statistically significant. CONCLUSIONS The study outcomes suggest comparable gains in root coverage and attached gingiva between the connective tissue graft and PRF matrix groups. Thus, the results support our hypothesis that a subepithelial PRF matrix can serve as a viable alternative to a subepithelial connective tissue graft for treating dental root coverage.

Despite their high success rates, peri-implantitis can affect the stability and function of dental implants. Various treatment modalities have been investigated for the treatment of peri-implantitis to achieve re-osseointegration. An electronic literature search was performed supplemented by a manual search to identify studies published until January 2022. Articles that evaluated re-osseointegration in peri-implantitis sites in animal models following laser therapy or antimicrobial photodynamic therapy (aPDT) were included. Case reports, case series, systematic reviews, and letters to the editor were excluded. Risk of bias and GRADE assessment were followed to evaluate the quality of the evidence. Six studies out of 26 articles identified on electronic search were included in this review. The studies included animal studies conducted on canine models. Four out of six studies reported a higher degree of re-osseointegration following treatment of implants with laser therapy. The findings suggest that laser decontamination shows potential in enhancing re-osseointegration, particularly with the Er: YAG laser, which effectively decontaminated implant surfaces. However, conflicting outcomes and limitations in the evidence quality warrant caution in drawing definitive conclusions. Based on the limited available evidence, laser therapy may show a higher degree of re-osseointegration of implants than mechanical debridement., (© 2023. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Objective: The aim of this study was to compare the scanning accuracy of two different intra-oral scanners- MEDIT i500 and TRIOS 3 shape in reproducing orthodontic bracket dimensions., Materials and Methods: This in vivo cross-sectional study comprised seven subjects with a full complement of permanent dentition without third molars. Complete arch scanning was carried out with two intraoral scanners, such as MEDIT i500, TRIOS 3 shape, after bonding with brackets. The control group consisted of bracket dimensions measured directly by using Vernier calipers before bonding. Bracket dimensions of three-dimensional (3D) images were measured by using OrthoAnalyzer software. The accuracy of intraoral scanning was investigated by comparing bracket dimensions among the three groups using One-way ANOVA and Post-Hoc Tukey HSD test, and by evaluating outcomes for each quadrant and an individual tooth in complete-arch scans., Results: When comparing bracket dimensions of 3D images with manual measurements using a traditional Vernier caliper, MEDIT i500 showed no significant difference when compared to the control group (p>0.05) in full arch scanning as well as the quadrant and single tooth scans in complete arch scanning. TRIOS 3 shape showed a significant difference when compared to the control and MEDIT i500 group (p<0.05) for all parameters., Conclusions: MEDIT i500 showed higher accuracy and better reproduction of orthodontic bracket dimensions than TRIOS 3 shape.

Objective: The oral cavity is a colossal reservoir for the bacteria. The healing of tissues is compromised after flap surgery, particularly in the presence of sutures, as they can act as repositories for bacteria, ultimately leading to surgical site infections. Hence, antibacterial-coated sutures have been considered as an alternative to reduce the risk of these infections and further improve the wound healing of the tissues after flap surgery. Since minimal information is available on the effect of antibacterial-coated sutures on periodontal tissues, this study aims to clinically and microbiologically assess the antibacterial efficacy of Triclosan (TCS) and Chlorhexidine-coated sutures (CCS) on periodontal tissues compared to non-coated sutures (NCS)., Patients and Methods: A total of 75 subjects with moderate to severe periodontitis were included in the study and randomly allocated to one of the three groups, (TCS, CCS, and NCS groups) equally. Suture removal was performed on postoperative day 8, and parameters such as wound healing and post-operative pain were evaluated. The retrieved suture samples were subjected to microbiological analysis and the bacteria were identified quantitatively and qualitatively., Results: Intragroup analysis of the wound healing index and post-operative pain for all the groups showed a significant improvement (p<0.01), from day 8 to day 30. Intergroup analysis of the wound healing index revealed significant wound healing (p<0.05) on day 15 and day 30. For post-operative pain, intergroup analyses showed significantly low pain scores (p<0.01) for the TCS group. Microbiologic analysis of aerobic colony counts in both anterior and posterior regions revealed significantly (p<0.01) least colony counts in TCS and highest colony counts in NCS groups, respectively. Although anaerobic colony counts were not statistically significant, relatively fewer colony counts were identified in the TCS group. Whereas, relatively higher anaerobic colony counts were seen in the CCS group in the anterior region and in the NCS group in the posterior region. Qualitative assessment revealed higher amounts of Streptococcus and Staphylococcus species in all the three groups (TCS, CCS, and NCS groups)., Conclusions: Antibacterial-coated sutures, particularly Triclosan-coated sutures, are effective in reducing bacterial accumulation compared to non-coated sutures. Therefore, these sutures can be effectively utilized in periodontal flap surgery.

Background: Diabetes mellitus (DM) is a chronic metabolic disorder. Hepatopathy is one of the serious effects of DM Melatonin (MT) is a potent endogenous antioxidant that can control insulin output. However, little information is available about the potential association between melatonin and hepatic alpha-fetoprotein expression in diabetes., Objective: This study was conducted to assess the influence of MT on diabetes-related hepatic injuries and to determine how β-cells of the pancreas in diabetic rats respond to MT administration., Materials and Methods: Forty rats were assigned to four groups at random (ten animals per group). Group I served as a normal control group. Group II was induced with DM, and a single dose of freshly prepared streptozotocin (45 mg/kg body weight) was intraperitoneally injected. In Group III, rats received 10 mg/kg/day of intraperitoneal melatonin (IP MT) intraperitoneally over a period of 4 weeks. In Group IV (DM + MT), following the induction of diabetes, rats received MT (the same as in Group III). Fasting blood sugar, glycosylated hemoglobin (HbA1c), and serum insulin levels were assessed at the end of the experimental period. Serum liver function tests were performed. The pancreas and liver were examined histopathologically and immunohistochemically for insulin and alpha-fetoprotein (AFP) antibodies, respectively., Results: MT was found to significantly modulate the raised blood glucose, HbA1c, and insulin levels induced by diabetes, as well as the decreased alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Furthermore, MT attenuated diabetic degenerative changes in the pancreas and the hepatic histological structure, increased the β-cell percentage area, and decreased AFP expression in the liver tissue. It attenuated diabetes-induced hepatic injury by restoring pancreatic β-cells; its antioxidant effect also reduced hepatocyte injury., Conclusion: Collectively, the present study confirmed the potential benefits of MT in downregulating the increased hepatic alpha-fetoprotein expression and in restoring pancreatic β-cells in a streptozotocin-induced diabetic rat model, suggesting its promising role in the treatment of diabetes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Alsharif, Hamad, Alblihd, Ali, Mohammed, Theyab, Al-Amer, Almuqati, Almalki, Albarakati, Alzahrani, Albrakati, Albarakati, Abass, Lokman and Elmahallawy.)

Porphyromonas gingivalis is associated with endodontic pulpitis, causing damage to the dental pulp, leading to severe pain and a decline in quality of life. Regenerative pulp treatments using dental pulp stem cells (DPSCs) can be hindered by interactions between DPSCs and the infecting bacteria. The protein WNT family member 4 (Wnt4) plays a critical role in the differentiation of DPSCs and the regeneration of odontogenic tissue. However, the specific influence of P. gingivalis on Wnt4 remains unclear. In this study, we employed a computational approach to investigate the underlying mechanisms through which P. gingivalis -produced metabolites inhibit the Wnt4 protein, thereby diminishing the regenerative potential and therapeutic efficacy of odontogenic tissue. Among the metabolites examined, C 29 H 46 N 7 O 18 P 3 S -4 exhibited the strongest inhibitory effect on the Wnt4 protein, as evidenced by the lowest binding energy score of -6782 kcal/mol. Molecular dynamic simulation trajectories revealed that the binding of C 29 H 46 N 7 O 18 P 3 S -4 significantly altered the structural dynamics and stability of the Wnt4 protein. These alterations in protein trajectories may have implications for the molecular function of Wnt4 and its associated pathways. Overall, our findings shed light on the inhibitory impact of P. gingivalis -produced metabolites on the Wnt4 protein. Further in vitro, in vivo, and clinical studies are necessary to validate and expand upon our findings.

Background: Active molecular surveillance and rapid diagnosis method to track an outbreak of norovirus in Bangladesh is lacking. This study aims to determine the genotypic diversity, molecular epidemiology and evaluate a rapid diagnosis method., Methods: A total of 404 fecal specimens were collected from children aged below 60 months from January 2018 to December 2021. All samples were analyzed by reverse transcriptase polymerase chain reaction molecular sequencing of partial VP1 nucleotide. Immunochromatography kit (IC, IP Rota/Noro) was evaluated against reference test method., Results: We found norovirus in 6.7 % (27 of 404) fecal specimens. A wide diversity of norovirus genotype including GII.3, GII.4, GII.5, GII.6, GII.7, and GII.9 were detected. Norovirus strain GII.4 Sydney-2012 was the most predominant (74 %, 20 of 27) followed by GII.7 (7.4 %), GII.9 (7.4 %), GII.3 (3.7 %), GII.5 (3.7 %) and GII.6 (3.7 %), respectively. Co-infection of rotavirus and norovirus (19 [4.7 %] of 404) was the most prevalent. We found higher odds of prolonged health impact [OR 1.93 (95 % CI 0.87-3.12) (p = .001)] among patients with co-infection. The incidence of norovirus was significant among the children below 24 months (p = 0.001). Significant relation of temperature with the cases of norovirus was detected (p = 0.001). The IC kit provided high specificity (99.3 %) and sensitivity (100 %) for the detection of norovirus., Conclusions: This study will provide an integrated insight on the genotypic diversity and rapid identification method of norovirus in Bangladesh., Competing Interests: Declaration of Competing Interest We have no conflict of interest to declare., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Pesticides kill neurons, but the mechanism leading to selective dopaminergic loss in Parkinson's disease (PD) is unknown. Understanding the pesticide's effect on dopaminergic neurons (DA) can help to screen and treat PD. The critical uptake of pesticides by the membrane receptors at DA is hypothesized to activate a signaling cascade and accelerate degeneration. Using MPTP as a reference, we demonstrate the mechanisms of eleven crucial pesticides through molecular docking, protein networks, regulatory pathways, and prioritization of key pesticide-regulating proteins. Participants were recruited and grouped into control and PD based on clinical characteristics as well as pesticide traces in their blood plasma. Then, qPCR was used to measure pesticide-associated gene expression in peripheral blood mononuclear cells between groups. As a result of molecular docking, all eleven pesticides and the MPTP showed high binding efficiency against 274 membrane receptor proteins of DA. Further, the protein interaction networks showed activation of multiple signaling cascades through these receptors. Subsequent analysis revealed 31 biological pathways shared by all 11pesticides and MPTP that were overrepresented by 46 crucial proteins. Among these, CTNNB1, NDUFS6, and CAV1 were prioritized to show a significant change in gene expression in pesticide-exposed PD which guides toward therapy.

Silver nanoparticles (AgNPs) are the most common nanomaterials in consumer products. Therefore, it has been crucial to control AgNPs toxicological effects to improve their safety and increase the outcome of their applications. This work investigated the possible protective effect of thymoquinone (TQ) against AgNPs-induced hepatic and renal cytotoxicity in rats. Serum markers of liver and kidney functions as well as liver and kidney oxidative stress status, pro-inflammatory cytokines, apoptosis markers, and histopathology were assessed. TQ reversed AgNPs-induced elevation in serum liver and kidney function markers, including aspartate transaminase, alanine transaminase, urea, and creatinine. Moreover, TQ co-administration with AgNPs alleviates hepatic and renal oxidative insults by decreasing MDA and NO levels with a significant increase in the activity of antioxidant enzymes (superoxide dismutase, catalase, and glutathione recycling enzymes peroxidase and reductase) compared to AgNPs-treated rats. Besides, TQ upregulated hepatic and renal Nrf2 gene expression in AgNPs-intoxicated rats. Furthermore, TQ co-administration decreased the hepatic and renal pro-inflammatory mediators represented by IL-1β, TNF-α, TGF-β, and NF-κB levels. Besides, TQ co-administration decreased apoptotic protein (Bax) levels and increased the anti-apoptotic protein (Bcl-2) levels. These findings were confirmed by the histopathological examination of hepatic and renal tissues. Our data affirmed the protective effect of TQ against AgNPs cytotoxicity and proposed a possible mechanism of TQ antioxidant, anti-inflammatory, and anti-apoptotic effects. Consequently, we could conclude that using TQ might control AgNPs toxicological effects, improve their safety, and increase the outcome of their applications., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: The aim of this study is to assess the efficacy of hand and ultrasonic scaling and to evaluate the surface roughness on the root surface of periodontally involved teeth using a scanning electron microscope., Patients and Methods: A sample of 90 single-rooted teeth with a hopeless prognosis was selected for the study and divided into three separate groups. Group I consist of no treatment. In Group II, hand scaling was done using Gracey curettes, and in Group III, ultrasonic scaling was done. The teeth were then extracted and fixed in 10% formaldehyde solution for 24-48 hours and subjected to scanning electron microscopic (SEM) evaluation., Results: The SEM analysis revealed that the remaining calculus index was found to be similar in the ultrasonic group and the hand scaling group, whereas the surface roughness was found to be the least in the ultrasonic group., Conclusions: Hand instrumentation has resulted in more surface roughness as compared to ultrasonic instruments.

Rheumatoid arthritis (RA) is an inflammatory condition that primarily affects the joints and progress to affect other vital organs. Variety of drugs are being recommended to control the disease progression that benefits patients to perform day-to-day activities. Few of these RA drugs have noticeable side effects; therefore, it's crucial to choose the appropriate drug for treating RA with an understanding of the disease's pathophysiology. Herein, we investigated the RA genes from GWAS data to construct protein-protein interaction (PPI) network and to define appropriate drug targets for RA. The predicted drug targets were screened with the known RA drugs based on molecular docking. Further, the molecular dynamics simulations were performed to comprehend the conformational changes and stability of the targets upon binding of the selected top ranked RA drug. As a result, our constructed protein network from GWAS data revealed, STAT3 and IL2 could be potential pharmacogenetics targets that interlink most of the RA genes encoding proteins. These interlinked proteins of both the targets showed involvement in cell signaling, immune response, and TNF signaling pathway. Among the 192 RA drugs investigated, zoledronic acid had the lowest binding energy that inhibit both STAT3 (-6.307 kcal/mol) and IL2 (-6.231 kcal/mol). Additionally, STAT3 and IL2 trajectories on zoledronic acid binding exhibit notable differences in MD simulations as compared to a drug-free environment. Also, the in vitro assessment with the zoledronic acid confirms the outcome of our computational study. Overall, our study identify zoledronic acid could be potential inhibitor against these targets, that will benefits patients with RA. Comparative efficiency assessments between the RA drugs through clinical trials are needed to validate our findings in the treatment of RA., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background & Objectives: During the COVID-19 pandemic, the death rate was reportedly 5-8 fold lower in India which is densely populated as compared to less populated western countries. The aim of this study was to investigate whether dietary habits were associated with the variations in COVID-19 severity and deaths between western and Indian population at the nutrigenomics level., Methods: In this study nutrigenomics approach was applied. Blood transcriptome of severe COVID-19 patients from three western countries (showing high fatality) and two datasets from Indian patients were used. Gene set enrichment analyses were performed for pathways, metabolites, nutrients, etc., and compared for western and Indian samples to identify the food- and nutrient-related factors, which may be associated with COVID-19 severity. Data on the daily consumption of twelve key food components across four countries were collected and a correlation between nutrigenomics analyses and per capita daily dietary intake was investigated., Results: Distinct dietary habits of Indians were observed, which may be associated with low death rate from COVID-19. Increased consumption of red meat, dairy products and processed foods by western populations may increase the severity and death rate by activating cytokine storm-related pathways, intussusceptive angiogenesis, hypercapnia and enhancing blood glucose levels due to high contents of sphingolipids, palmitic acid and byproducts such as CO 2 and lipopolysaccharide (LPS). Palmitic acid also induces ACE2 expression and increases the infection rate. Coffee and alcohol that are highly consumed in western countries may increase the severity and death rates from COVID-19 by deregulating blood iron, zinc and triglyceride levels. The components of Indian diets maintain high iron and zinc concentrations in blood and rich fibre in their foods may prevent CO 2 and LPS-mediated COVID-19 severity. Regular consumption of tea by Indians maintains high high-density lipoprotein (HDL) and low triglyceride in blood as catechins in tea act as natural atorvastatin. Importantly, regular consumption of turmeric in daily food by Indians maintains strong immunity and curcumin in turmeric may prevent pathways and mechanisms associated with SARS-CoV-2 infection and COVID-19 severity and lowered the death rate., Interpretation & Conclusions: Our results suggest that Indian food components suppress cytokine storm and various other severity related pathways of COVID-19 and may have a role in lowering severity and death rates from COVID-19 in India as compared to western populations. However, large multi-centered case-control studies are required to support our current findings.

Beta-tubulin (TUBB) protein is one of the components of the microtubule cytoskeleton that plays a critical role in the central nervous system. Genetic variants of TUBB cause cortical dysplasia, a developmental brain defect implicated in axonal guidance and the neuron migration. In this study, we assess pathogenic variants (Q15K, Y222F, M299V, V353I, and E401K) of TUBB protein and compared with non-pathogenic variant G235S to determine their impact on protein dynamic to cause cortical dysplasia. Among the analyzed variants, Q15K, Y222F, M299V, and E401K were noticed to have deleterious effect. Then, variant structures were modeled and their affinity with their known cofactor Guanosine-5'-triphosphate (GTP) was assessed which showed diverse binding energies ranged between (-7.436 to -6.950 kcal/mol) for the variants compared to wild-type (-7.428 kcal/mol). Finally, the molecular dynamics simulation of each variant was investigated which showed difference in trajectory between the pathogenic and non-pathogenic variant. Our analysis suggests change in amino acid residue of TUBB structure has notably affects the protein flexibility and their interactions with known cofactor. Overall, our findings provide insight on the relationship between TUBB variants and their structural dynamics that may cause diverse effects leading to cortical dysplasia., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

BACKGROUND The chorion membrane has been used for several decades as an allograft in tissue repair and various periodontal regenerative procedures. The present study, conducted at a single center in India, aimed to evaluate and compare the clinical outcomes of 26 gingival recession sites in chronic smokers treated using a pouch and tunnel technique with connective tissue graft (CTG) and lyophilized chorion membrane (LCM). MATERIAL AND METHODS The study included 22 smokers with 26 sites of recession defect, with Miller's class I and class II gingival recession, which were allotted into control and test groups. The control group (13 sites) was treated with CTG, and the test group (13 sites) was treated with LCM. Clinical parameters like recession depth, recession width, relative clinical attachment level (RCAL), relative gingival position, width of attached gingiva, and width of keratinized gingiva were recorded at baseline and 6 months postoperatively. Visual analogue scores for pain and wound-healing index scores were assessed in the first week after surgery. RESULTS All clinical parameters showed significant improvements from baseline to 6 months postoperatively in the control and test groups. Recession width, RCAL, width of attached gingiva, and width of keratinized gingiva demonstrated significant differences, whereas mean root coverage percentage and recession depth did not show any significant differences between the study groups at 6 months postoperatively. CONCLUSIONS This study supports the role of LCM allograft as a scaffold to promote soft tissue regeneration and has demonstrated a favorable role for its use in root coverage procedures in patients who smoke.

The ever-increasing global energy demand has led world towards negative repercussions such as depletion of fossil fuels, pollution, global warming and climate change. Designing microbial cell factories for the sustainable production of biofuels is therefore an active area of research. Different yeast cells have been successfully engineered using synthetic biology and metabolic engineering approaches for the production of various biofuels. In the present article, recent advancements in genetic engineering strategies for production of bioalcohols, isoprenoid-based biofuels and biodiesels in different yeast chassis designs are reviewed, along with challenges that must be overcome for efficient and high titre production of biofuels., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Exposure to lead (Pb) is associated with serious health problems including hepatorenal toxicity. Apigenin is a natural-sourced flavonoid with promising antioxidant and anti-inflammatory effects. In this research, we investigated the potential protective role of apigenin against lead acetate (PbAc)-induced hepatorenal damage. Thus, this experiment studied the exposure of male Wistar Albino rats to apigenin and/or PbAc and their effects in comparison to the control rats. Apigenin administration decreased the levels of Pb and prevented the histopathological deformations in liver and kidney tissues following PbAc exposure. This was confirmed by the normalized levels of liver and kidney function markers. Additionally, apigenin inhibited significantly oxidative reactions through upregulating Nrf2 and HO-1, and activating their downstreamed antioxidants accompanied by a marked depletion of pro-oxidants. Moreover, apigenin decreased the elevated pro-inflammatory cytokines and inhibited cell loss in liver and kidney tissues in response to PbAc intoxication in both tissues. The obtained results demonstrated that apigenin could be used to attenuate the molecular, biochemical, and histological alterations associated with Pb exposure due to its potent antioxidant, anti-inflammatory, and antiapoptotic effects., (© 2022 Wiley Periodicals LLC.)

The COVID-19 pandemic has triggered intensive research and development of drugs and vaccines against SARS-CoV-2 during the last two years. The major success was especially observed with development of vaccines based on viral vectors, nucleic acids and whole viral particles, which have received emergent authorization leading to global mass vaccinations. Although the vaccine programs have made a big impact on COVID-19 spread and severity, emerging novel variants have raised serious concerns about vaccine efficacy. Due to the urgent demand, drug development had originally to rely on repurposing of antiviral drugs developed against other infectious diseases. For both drug and vaccine development the focus has been mainly on SARS-CoV-2 surface proteins and host cell receptors involved in viral attachment and entry. In this review, we expand the spectrum of SARS-CoV-2 targets by investigating the COVID-19 signalome. In addition to the SARS-CoV-2 Spike protein, the envelope, membrane, and nucleoprotein targets have been subjected to research. Moreover, viral proteases have presented the possibility to develop different strategies for the inhibition of SARS-CoV-2 replication and spread. Several signaling pathways involving the renin-angiotensin system, angiotensin-converting enzymes, immune pathways, hypoxia, and calcium signaling have provided attractive alternative targets for more efficient drug development., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Replacement of missing teeth in patients with prolonged edentulism poses a challenge for clinicians. An extended period of edentulism results in severe atrophy of alveolar ridges rendering them unsatisfactory for rehabilitation using an implant-supported prosthesis. To overcome this difficulty, Guided Bone Regeneration (GBR) was introduced and constructed upon the principles of Guided Tissue Regeneration (GTR) procedures. Evidence suggests that GBR has proven to be a predictable treatment modality for treating vertical and horizontal ridge deficiencies., Objective: The present systematic review aimed to evaluate the efficacy of non-resorbable ( N -RES) membranes compared to resorbable (RES) membranes in patients undergoing GBR., Methods: An electronic search of three databases, including PubMed, Web of Science, and Scopus, was conducted for articles published until March 2022. A supplementary manual search of references from these articles was performed to include any articles that may have been overlooked in the electronic search. Articles that evaluated the efficacy of RES membranes and N -RES membranes in GBR were included. Case reports, case series, commentaries, letters to the editor, narrative or systematic reviews were excluded. Articles in languages other than English were also excluded. The articles were assessed against risk of bias 2 tool for Randomized Control Trials (RCTs) and ROBINS-I tool for Non-Randomized Clinical Trials ( N -RCTs). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) assessment was followed based on the Cochrane Handbook for quality assessment. A summary of findings table was used to present the results., Results: One hundred and fifty one articles were identified in an electronic search. Eight articles met the inclusion criteria and were included in the present systematic review. The studies were conducted on partially or completely edentulous patients with alveolar ridge deficiencies undergoing vertical or horizontal bone for subsequent implant placement. The majority of the studies reported similar results for bone gain in both RES and N -RES membrane groups., Conclusion: The available evidence suggests that RES and N -RES membranes are equally effective in GBR. However, the evidence must be interpreted with caution due to its 'low quality' GRADE assessment., Clinical Implications: Further research focusing on human clinical trials with well-matched subjects with homogeneity in the type and method of GBR and method of assessment of new bone formation will derive conclusive results on the efficacy of RES and N -RES membranes in achieving new bone formation., Competing Interests: The authors declare no conflicts of interest. Marcos Roberto Tovani-Palone is one of the section editors of Heliyon, however the article will not be assigned to him or any of his colleagues., (© 2023 Published by Elsevier Ltd.)

Transmission and increase in cases and fatalities of coronavirus disease-2019 (COVID-19) are significantly influenced by the parameters of weather, human activities and population factors. However, study gap on the seasonality of COVID-19 and impact of environmental factors on the pandemic in Saudi Arabia is present. The main aim of the study is to evaluate the impact of environment on the COVID-19 pandemic. Data were analyzed from January 2020 to July 2021. The generalized estimating equation (GEE) was used to determine the effect of environmental variables on longitudinal outcomes. Spearman's rank correlation coefficient ( r s ) was used to analyze the impact of different parameters on the outcome of the pandemic. Multiple sequence alignment was performed by using ClustalW. Vaccination and fatalities ( r s  = -0.85) had the highest association followed by vaccination with cases ( r s  = -0.81) and population density with the fatalities ( r s  = 0.71). The growth rate had the highest correlation with sun hours ( r s  = -0.63). Isolates from variant of concern alpha and beta were detected. Most of the reference sequences in Saudi Arabia were closely related with B.1.427/429 variant. Clade GH (54%) was the most prevalent followed by O (27%), GR (9%), G (6%), and S (4%), respectively. Male to female patient ratio was 1.4:1. About 95% fatality and hospitalization were reported in patients aged >60 years. This study will create a comprehensive insight of the interaction of environmental factors and the pandemic and add knowledge on seasonality of COVID-19 in Saudi Arabia., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Hyper-transmissibility with decreased disease severity is a typical characteristic of the SARS-CoV-2 Omicron variant. To understand this phenomenon, we used various bioinformatics approaches to analyze randomly selected genome sequences (one each) of the Gamma, Delta, and Omicron variants submitted to NCBI from December 15 to 31, 2021. We report that the pathogenicity of SARS-CoV-2 variants decreases in the order of Wuhan > Gamma > Delta > Omicron; however, the antigenic property follows the order of Omicron > Gamma > Wuhan > Delta. The Omicron spike RBD shows lower pathogenicity but higher antigenicity than other variants. The reported decreased disease severity by the Omicron variant may be due to its decreased pro-inflammatory and IL-6 stimulation and increased IFN-γ and IL-4 induction efficacy. The mutations in the N protein are probably associated with this decreased IL-6 induction and human DDX21-mediated increased IL-4 production for Omicron. Due to the mutations, the stability of S, M, N, and E proteins decreases in the order of Omicron > Gamma > Delta > Wuhan. Although a stronger spike RBD-hACE2 binding of Omicron increases its transmissibility, the lowest stability of its spike protein makes spike RBD-hACE2 interaction weak for systemic infection and for causing severe disease. Finally, the highest instability of the Omicron E protein may also be associated with decreased viral maturation and low viral load, leading to less severe disease and faster recovery. Our findings will contribute to the understanding of the dynamics of SARS-CoV-2 variants and the management of emerging variants. This minimal genome-based method may be used for other similar viruses avoiding robust analysis., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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.

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.

Over the last 20 years, granulocyte colony-stimulating factors (G-CSFs) have become the major therapeutic option for the treatment of patients with neutropenia. Most of the current G-CSFs require daily injections, which are inconvenient and expensive for patients. Increased understanding of G-CSFs' structure, expression, and mechanism of clearance has been very instrumental in the development of new generations of long-acting G-CSFs with improved efficacy. Several approaches to reducing G-CSF clearance via conjugation techniques have been investigated. PEGylation, glycosylation, polysialylation, or conjugation with immunoglobulins or albumins have successfully increased G-CSFs' half-lives. Pegfilgrastim (Neulasta) has been successfully approved and marketed for the treatment of patients with neutropenia. The rapidly expanding market for G-CSFs has increased demand for G-CSF biosimilars. Therefore, the importance of this review is to highlight the principle, elimination's route, half-life, clearance, safety, benefits, and limitations of different strategies and techniques used to increase the half-life of biotherapeutic G-CSFs. Understanding these strategies will allow for a new treatment with more competitive manufacturing and lower unit costs compared with that of Neulasta., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Theyab, Alsharif, Alzahrani, Oyouni, Hawsawi, Algahtani, Alghamdi and Alshammary.)