Anti-inflammatory activities of flavonoid derivates.

Background and purpose: Flavonoids are a group of phytochemicals found abundantly in various plants. Scientific evidence has revealed that flavonoids display potential biological activities, including their ability to alleviate inflammation. This activity is closely related to their action in blocking the inflammatory cascade and inhibiting the production of pro-inflammatory factors. However, as flavonoids typically have poor bioavailability and pharmacokinetic profile, it is quite challenging to establish these compounds as a drug. Nevertheless, progressive advancements in drug delivery systems, particularly in nanotechnology, have shown promising approaches to overcome such challenges. Review approach: This narrative review provides an overview of scientific knowledge about the mechanism of action of flavonoids in the mitigation of inflammatory reaction prior to delivering a comprehensive discussion about the opportunity of the nanotechnology-based delivery system in the preparation of the flavonoid-based drug. Key results: Various studies conducted in silico, in vitro, in vivo, and clinical trials have deciphered that the anti-inflammatory activities of flavonoids are closely linked to their ability to modulate various biochemical mediators, enzymes, and signalling pathways involved in the inflammatory processes. This compound could be encapsulated in nanotechnology platforms to increase the solubility, bioavailability, and pharmacological activity of flavonoids as well as reduce the toxic effects of these compounds. Conclusion: In Summary, we conclude that flavonoids and their derivates have given promising results in their development as new anti-inflammatory drug candidates, especially if they formulate in nanoparticles.

Natural products targeting inflammation-related metabolic disorders: A comprehensive review.

Currently, the incidence of metabolic disorders is increasing, setting a challenge to global health. With major advancement in the diagnostic tools and clinical procedures, much has been known in the etiology of metabolic disorders and their corresponding pathophysiologies. In addition, the use of in vitro and in vivo experimental models prior to clinical studies has promoted numerous biomedical breakthroughs, including in the discovery and development of drug candidates to treat metabolic disorders. Indeed, chemicals isolated from natural products have been extensively studied as prospective drug candidates to manage diabetes, obesity, heart-related diseases, and cancer, partly due to their antioxidant and anti-inflammatory properties. Continuous efforts have been made in parallel to improve their bioactivity and bioavailability using selected drug delivery approaches. Here, we provide insights on recent progress in the role of inflammatory-mediated responses on the initiation of metabolic disorders, with particular reference to diabetes mellitus, obesity, heart-related diseases, and cancer. In addition, we discussed the prospective role of natural products in the management of diabetes, obesity, heart-related diseases, and cancers and provide lists of potential biological targets for high throughput screening in drug discovery and development. Lastly, we discussed findings observed in the preclinical and clinical studies prior to identifying suitable approaches on the phytochemical drug delivery systems that are potential to be used in the treatment of metabolic disorders.

Inflammation-Mediated Responses in the Development of Neurodegenerative Diseases.

Since its first description over a century ago, neurodegenerative diseases (NDDs) have impaired the lives of millions of people worldwide. As one of the major threats to human health, NDDs are characterized by progressive loss of neuronal structure and function, leading to the impaired function of the CNS. While the precise mechanisms underlying the emergence of NDDs remains elusive, association of neuroinflammation with the emergence of NDDs has been suggested. The immune system is tightly controlled to maintain homeostatic milieu and failure in doing so has been shown catastrophic. Here, we review current concepts on the cellular and molecular drivers responsible in the induction of neuroinflammation and how such event further promotes neuronal damage leading to neurodegeneration. Experimental data generated from cell culture and animal studies, gross and molecular pathologies of human CNS samples, and genome-wide association study are discussed to provide deeper insights into the mechanistic details of neuroinflammation and its roles in the emergence of NDDs.

Global emerging Omicron variant of SARS-CoV-2: Impacts, challenges and strategies.

Newly emerging variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are continuously posing high global public health concerns and panic resulting in waves of coronavirus disease 2019 (COVID-19) pandemic. Depending on the extent of genomic variations, mutations and adaptation, few of the variants gain the ability to spread quickly across many countries, acquire higher virulency and ability to cause severe disease, morbidity and mortality. These variants have been implicated in lessening the efficacy of the current COVID-19 vaccines and immunotherapies resulting in break-through viral infections in vaccinated individuals and recovered patients. Altogether, these could hinder the protective herd immunity to be achieved through the ongoing progressive COVID-19 vaccination. Currently, the only variant of interest of SARS-CoV-2 is Omicron that was first identified in South Africa. In this review, we present the overview on the emerging SARS-CoV-2 variants with a special focus on the Omicron variant, its lineages and hybrid variants. We discuss the hypotheses of the origin, genetic change and underlying molecular mechanism behind higher transmissibility and immune escape of Omicron variant. Major concerns related to Omicron including the efficacy of the current available immunotherapeutics and vaccines, transmissibility, disease severity, and mortality are discussed. In the last part, challenges and strategies to counter Omicron variant, its lineages and hybrid variants amid the ongoing COVID-19 pandemic are presented.

Marine Macrolides to Tackle Antimicrobial Resistance of Mycobacterium tuberculosis.

Tuberculosis has become a major health problem globally. This is worsened by the emergence of resistant strains of Mycobacterium tuberculosis showing ability to evade the effectiveness of the current antimycobacterial therapies. Therefore, the efforts carried out to explore new entities from many sources, including marine, are critical. This review summarizes several marine-derived macrolides that show promising activity against M. tuberculosis. We also provide information regarding the biosynthetic processes of marine macrolides, including the challenges that are usually experienced in this process. As most of the studies reporting the antimycobacterial activities of the listed marine macrolides are based on in vitro studies, the future direction should consider expanding the trials to in vivo and clinical trials. In addition, in silico studies should also be explored for a quick screening on marine macrolides with potent activities against mycobacterial infection. To sum up, macrolides derived from marine organisms might become therapeutical options for tackling antimycobacterial resistance of M. tuberculosis.

Monkeypox: A Comprehensive Review.

The 2022 multi-country monkeypox outbreak in humans has brought new public health adversity on top of the ongoing coronavirus disease 2019 (COVID-19) pandemic. The disease has spread to 104 countries throughout six continents of the world, with the highest burden in North America and Europe. The etiologic agent, monkeypox virus (MPXV), has been known since 1959 after isolation from infected monkeys, and virulence among humans has been reported since the 1970s, mainly in endemic countries in West and Central Africa. However, the disease has re-emerged in 2022 at an unprecedented pace, with particular concern on its human-to-human transmissibility and community spread in non-endemic regions. As a mitigation effort, healthcare workers, public health policymakers, and the general public worldwide need to be well-informed on this relatively neglected viral disease. Here, we provide a comprehensive and up-to-date overview of monkeypox, including the following aspects: epidemiology, etiology, pathogenesis, clinical features, diagnosis, and management. In addition, the current review discusses the preventive and control measures, the latest vaccine developments, and the future research areas in this re-emerging viral disease that was declared as a public health emergency of international concern.

Cruciferous vegetables as a treasure of functional foods bioactive compounds: Targeting p53 family in gastrointestinal tract and associated cancers.

In the past few years, phytochemicals from natural products have gotten the boundless praise in treating cancer. The promising role of cruciferous vegetables and active components contained in these vegetables, such as isothiocyanates, indole-3-carbinol, and isothiocyanates, has been widely researched in experimental in vitro and in vivo carcinogenesis models. The chemopreventive agents produced from the cruciferous vegetables were recurrently proven to affect carcinogenesis throughout the onset and developmental phases of cancer formation. Likewise, findings from clinical investigations and epidemiological research supported this statement. The anticancer activities of these functional foods bioactive compounds are closely related to their ability to upregulate p53 and its related target genes, e.g., p21. As the "guardian of the genome," the p53 family (p53, p63, and p73) plays a pivotal role in preventing the cancer progression associated with DNA damage. This review discusses the functional foods bioactive compounds derived from several cruciferous vegetables and their use in altering the tumor-suppressive effect of p53 proteins. The association between the mutation of p53 and the incidence of gastrointestinal malignancies (gastric, small intestine, colon, liver, and pancreatic cancers) is also discussed. This review contains crucial information about the use of cruciferous vegetables in the treatment of gastrointestinal tract malignancies.

Acute severe hepatitis of unknown etiology in children: A mini-review.

The emergence of acute, severe non hepA-E hepatitis of unknown etiology (ASHUE) has attracted global concern owing to the very young age of the patients and its unknown etiology. Although this condition has been linked to several possible causes, including viral infection, drugs and/or toxin exposure, the exact cause remains unknown; this makes treatment recommendation very difficult. In this review, we summarize recent updates on the clinical manifestations, complemented with laboratory results, case numbers with the global distribution and other epidemiological characteristics, and the possible etiologies. We also provide the proposed actions that could be undertaken to control and prevent further spread of this hepatitis. Since many etiological and pathological aspects of the acute non hepA-E hepatitis remain unclear, further research is needed to minimize the severe impact of this disease.

The role of single nucleotide polymorphisms of IL-1A -889C>T (rs1800587), TNF-A -238G>A (rs361525), and VDR TaqI (rs731236) on susceptibility to herniated nucleus pulposus: a systematic review and meta-analysis.

Background: The objective of this study was to determine the role of single nucleotide polymorphisms (SNPs) in interleukin 1 alpha ( IL-1A), tumor necrosis factor-alpha ( TNF-A), and vitamin D receptor ( VDR) genes on the susceptibility to herniated nucleus pulposus (HNP). Methods: Four databases (PubMed, Embase, Cochrane, and Web of Science) were searched as of April 1 st, 2021. Authors, publication year, targeted genes, genotype and allele frequency in each case and control groups were collected. Newcastle-Ottawa scale was used to evaluate the publication quality. The pooled estimates of association of IL-1A -889C>T (rs1800587), TNF-A -238G>A (rs361525), and VDR TaqI (rs731236) and susceptibility to HNP were assessed using Z test and presented as odd ratio (OR) and 95% confidence intervals (95%CI). Results: We screened 3,067 unique studies for eligibility and three, two and nine studies on IL-1A -889C>T, TNF-A -238G>A, and VDR TaqI were included, respectively, in our meta-analysis. The studies consisting 369 HNP cases and 433 controls for IL-1A -889C>T, 252 cases and 259 controls for TNF-A -238G>A and 1130 cases and 2096 controls for VDR TaqI. Our pooled estimates indicated that there was no significant association of those SNPs with the susceptibility to HNP in any genotype, dominant model, recessive model, or allele comparations. Conclusion: Although individual studies suggested the important role of gene expression dysregulation associated with SNPs in IL-1A, TNF-A, and VDR, our data indicated that IL-1A -889C>T, TNF-A -238G>A, and VDR TaqI had weak association with HNP susceptibility in both genotypes and allele distributions. However, since heterogeneity was identified among studies included in this meta-analysis, further meta-analysis with a larger population and subgroup analysis on specific population are warranted to support this finding.

Global prevalence of prolonged gastrointestinal symptoms in COVID-19 survivors and potential pathogenesis: A systematic review and meta-analysis.

Background: This study aimed to determine the cumulative prevalence of prolonged gastrointestinal (GI) symptoms, including nausea, vomiting, diarrhea, lack of appetite, abdominal pain, and dysgeusia, in survivors of both mild and severe COVID-19 worldwide and to discuss the potential pathogenesis.   Methods: Three databases (PubMed, Scopus, and Web of Science) were searched for relevant articles up to January 30, 2021. Data on study characteristics, clinical characteristics during follow-up, the number of patients with prolonged GI symptoms, and total number of COVID-19 survivors were retrieved according to PRISMA guidelines. The quality of eligible studies was assessed using the Newcastle-Ottawa scale. The pooled prevalence of specific prolonged GI symptoms was calculated and the association between COVID-19 severity and the occurrence of prolonged GI symptoms was assessed if appropriate.   Results: The global prevalence of prolonged nausea was 3.23% (95% CI: 0.54%-16.53%) among 527 COVID-19 survivors. Vomiting persisted in 93 of 2,238 COVID-19 survivors (3.19%, 95% CI: 1.62%-6.17%) and prolonged diarrhea was found in 34 of 1,073 survivors (4.12%, 95% CI: 1.07%-14.64%). A total of 156 patients among 2,238 COVID-19 survivors (4.41%, 95% CI: 1.91%-9.94%) complained of persistent decreased or loss of appetite. The cumulative prevalence of prolonged abdominal pain was 1.68% (95% CI: 0.84%-3.32%), whereas persistent dysgeusia was identified in 130 cases among 1,887 COVID-19 survivors (7.04%, 95% CI: 5.96%-8.30%). Data was insufficient to assess the relationship between COVID-19 severity and the occurrence of all prolonged GI symptoms.   Conclusion: Persistent GI symptoms among COVID-19 survivors after discharge or recovery raises a concern regarding the long-term impact of the COVID-19 infection on the quality of life of the survivors. Despite several potential explanations proposed, studies that aim to follow patients after recovery from COVID-19 and determine the pathogenesis of the prolonged symptoms of COVID-19 survivors are warranted.   PROSPERO registration: CRD42021239187.

Anosmia and dysgeusia in SARS-CoV-2 infection: incidence and effects on COVID-19 severity and mortality, and the possible pathobiology mechanisms - a systematic review and meta-analysis.

Background: The present study aimed to determine the global prevalence of anosmia and dysgeusia in coronavirus disease 2019 (COVID-19) patients and to assess their association with severity and mortality of COVID-19. Moreover, this study aimed to discuss the possible pathobiological mechanisms of anosmia and dysgeusia in COVID-19. Methods: Available articles from PubMed, Scopus, Web of Science, and preprint databases (MedRxiv, BioRxiv, and Researchsquare) were searched on November 10th, 2020. Data on the characteristics of the study (anosmia, dysgeusia, and COVID-19) were extracted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Newcastle-Ottawa scale was used to assess research quality. Moreover, the pooled prevalence of anosmia and dysgeusia were calculated, and the association between anosmia and dysgeusia in presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was assessed using the Z test. Results: Out of 32,142 COVID-19 patients from 107 studies, anosmia was reported in 12,038 patients with a prevalence of 38.2% (95% CI: 36.5%, 47.2%); whereas, dysgeusia was reported in 11,337 patients out of 30,901 COVID-19 patients from 101 studies, with prevalence of 36.6% (95% CI: 35.2%, 45.2%), worldwide. Furthermore, the prevalence of anosmia was 10.2-fold higher (OR: 10.21; 95% CI: 6.53, 15.96, p < 0.001) and that of dysgeusia was 8.6-fold higher (OR: 8.61; 95% CI: 5.26, 14.11, p < 0.001) in COVID-19 patients compared to those with other respiratory infections or COVID-19 like illness. To date, no study has assessed the association of anosmia and dysgeusia with severity and mortality of COVID-19. Conclusion: Anosmia and dysgeusia are prevalent in COVID-19 patients compared to those with the other non-COVID-19 respiratory infections. Several possible mechanisms have been hypothesized; however, future studies are warranted to elucidate the definitive mechanisms of anosmia and dysgeusia in COVID-19. Protocol registration: PROSPERO CRD42020223204.

Hemorrhagic and ischemic stroke in patients with coronavirus disease 2019: incidence, risk factors, and pathogenesis - a systematic review and meta-analysis.

Background: In this study, we aimed to determine the global prevalence, chronological order of symptom appearance, and mortality rates with regard to hemorrhagic and ischemic stroke in patients with coronavirus disease 2019 (COVID-19) and to discuss possible pathogeneses of hemorrhagic and ischemic stroke in individuals with the disease. Methods: We searched the PubMed, Scopus, and Web of Science databases for relevant articles published up to November 8, 2020. Data regarding study characteristics, hemorrhagic stroke, ischemic stroke, and COVID-19 were retrieved in accordance with the PRISMA guidelines. The Newcastle-Ottawa scale was used to assess the quality of the eligible studies. The pooled prevalence and mortality rate of hemorrhagic and ischemic stroke were calculated. Results: The pooled estimate of prevalence of hemorrhagic stroke was 0.46% (95% CI 0.40%-0.53%; I 2 =89.81%) among 67,155 COVID-19 patients and that of ischemic stroke was 1.11% (95% CI 1.03%-1.22%; I 2 =94.07%) among 58,104 COVID-19 patients. Ischemic stroke was more predominant (incidence: 71.58%) than hemorrhagic stroke (incidence: 28.42%) in COVID-19 patients who experienced a stroke. In COVID-19 patients who experienced a stroke, hospital admission with respiratory symptoms was more commonly reported than that with neurological symptoms (20.83% for hemorrhagic stroke and 5.51% for ischemic stroke versus 6.94% for hemorrhagic stroke and 5.33% for ischemic stroke, respectively). The pooled mortality rate of COVID-19 patients who experienced a hemorrhagic and ischemic stroke was 44.72% (95% CI 36.73%-52.98%) and 36.23% (95% CI 30.63%-42.24%), respectively. Conclusions: Although the occurrence of hemorrhagic and ischemic stroke is low, the mortality rates of both stroke types in patients with COVID-19 are concerning, and therefore, despite several potential pathogeneses that have been proposed, studies aimed at definitively elucidating the mechanisms of hemorrhagic and ischemic stroke in individuals with COVID-19 are warranted. PROSPERO registration: CRD42020224470 (04/12/20).

Global prevalence of persistent neuromuscular symptoms and the possible pathomechanisms in COVID-19 recovered individuals: A systematic review and meta-analysis.

This study was conducted to determine the prevalence of prolonged neuromuscular symptoms, including fatigue, anosmia, headache, myalgia, and joint pain in COVID-19 survivors hospitalized with mild, moderate, or severe infections worldwide. The search was conducted up to January 30th, 2021 using three databases (PubMed, Scopus, and Web of Science) to identify potentially eligible studies. Data on study characteristics, follow-up characteristics, and severity of COVID-19 during hospitalization were collected in accordance with PRISMA guidelines. The Newcastle-Ottawa scale was used to assess the quality of relevant articles. The estimated prevalence of specific prolonged neuromuscular symptoms and the association between COVID-19 severity and occurrence of prolonged neuromuscular symptoms was analyzed wherever appropriate. Database search yielded 4,050 articles and 22 articles were included for meta-analysis. The estimated prevalence of prolonged fatigue was recorded in 21.2% (95%CI: 11.9%- 34.8%) of 3,730 COVID-19 survivors. Persistent anosmia was recorded in 239 of 2,600 COVID-19 survivors (9.7%, 95%CI: 6.1%-15.2%). In 84 out of 2,412 COVID-19 survivors (8.9%, 95%CI: 3.2%-22.6%), prolonged headache was observed. A total of 53 out of 1,125 COVID-19 patients (5.6%, 95%CI: 2.1%-14.2%) complained of persistent myalgia even after being discharged from the hospital. The prevalence of prolonged joint pain was in 15.4% (95%CI: 8.2%-27.2%) of subjects. Due to data scarcity on COVID-19 severity and prolonged neuromuscular symptoms, association analysis could not be conducted. Widespread concern regarding long-term impacts of COVID-19 was raised after several studies reported prolonged symptoms in COVID-19 survivors. Numerous theories have been proposed to address this concern; however, as the research on this pandemic is still ongoing, no explanation is definitive yet. Therefore, follow-up studies in COVID-19 survivors after recovery from COVID-19 are warranted to determine the pathogenesis of prolonged symptoms. PROSPERO registration: CRD42021242332.

Global prevalence and pathogenesis of headache in COVID-19: A systematic review and meta-analysis.

Background: This study was conducted to determine the prevalence of headache in coronavirus disease 2019 (COVID-19) and to assess its association as a predictor for COVID-19. This study also aimed to discuss the possible pathogenesis of headache in COVID-19. Methods: Available articles from PubMed, Scopus, and Web of Science were searched as of September 2 nd, 2020. Data on characteristics of the study, headache and COVID-19 were extracted following the PRISMA guidelines. Biases were assessed using the Newcastle-Ottawa scale. The cumulative prevalence of headache was calculated for the general population (i.e. adults and children). The pooled odd ratio (OR) with 95% confidence intervals (95%CI) was calculated using the Z test to assess the association between headache and the presence of COVID-19 cases. Results: We included 104,751 COVID-19 cases from 78 eligible studies to calculate the global prevalence of headache in COVID-19 and 17 studies were included to calculate the association of headache and COVID-19. The cumulative prevalence of headache in COVID-19 was 25.2% (26,464 out of 104,751 cases). Headache was found to be more prevalent, approximately by two-fold, in COVID-19 patients than in non-COVID-19 patients with symptoms of other respiratory viral infections, OR: 1.73; 95% CI: 1.94, 2.5 with p=0.04. Conclusion: Headache is common among COVID-19 patients and seems to be more common in COVID-19 patients compared to those with the non-COVID-19 viral infection. No definitive mechanisms on how headache  emerges in COVID-19 patients but several possible hypotheses have been proposed. However, extensive studies are warranted to elucidate the mechanisms. PROSPERO registration: CRD42020210332 (28/09/2020).