Exploring the theranostic potentials of miRNA and epigenetic networks in autoimmune diseases: A comprehensive review.

BACKGROUND: Autoimmune diseases (AD) are severe pathophysiological ailments that are stimulated by an exaggerated immunogenic response towards self-antigens, which can cause systemic or site-specific organ damage. An array of complex genetic and epigenetic facets majorly contributes to the progression of AD, thus providing significant insight into the regulatory mechanism of microRNA (miRNA). miRNAs are short, non-coding RNAs that have been identified as essential contributors to the post-transcriptional regulation of host genome expression and as crucial regulators of a myriad of biological processes such as immune homeostasis, T helper cell differentiation, central and peripheral tolerance, and immune cell development. AIMS: This article tends to deliberate and conceptualize the brief pathogenesis and pertinent epigenetic regulatory mechanism as well as miRNA networks majorly affecting five different ADs namely rheumatoid arthritis (RA), type 1 diabetes, multiple sclerosis (MS), systemic lupus erythematosus (SLE) and inflammatory bowel disorder (IBD) thereby providing novel miRNA-based theranostic interventions. RESULTS & DISCUSSION: Pertaining to the differential expression of miRNA attributed in target tissues and cellular bodies of innate and adaptive immunity, a paradigm of scientific expeditions suggests an optimistic correlation between immunogenic dysfunction and miRNA alterations. CONCLUSION: Therefore, it is not astonishing that dysregulations in miRNA expression patterns are now recognized in a wide spectrum of disorders, establishing themselves as potential biomarkers and therapeutic targets. Owing to its theranostic potencies, miRNA targets have been widely utilized in the development of biosensors and other therapeutic molecules originating from the same.

Virulence traits and novel drug delivery strategies for mucormycosis post-COVID-19: a comprehensive review.

The outbreak of a fatal black fungus infection after the resurgence of the cadaverous COVID-19 has exhorted scientists worldwide to develop a nutshell by repurposing or designing new formulations to address the crisis. Patients expressing COVID-19 are more susceptible to Mucormycosis (MCR) and thus fall easy prey to decease accounting for this global threat. Their mortality rates range around 32-70% depending on the organs affected and grow even higher despite the treatment. The many contemporary recommendations strongly advise using liposomal amphotericin B and surgery as first-line therapy whenever practicable. MCR is a dangerous infection that requires an antifungal drug administration on appropriate prescription, typically one of the following: Amphotericin B, Posaconazole, or Isavuconazole since the fungi that cause MCR are resistant to other medications like fluconazole, voriconazole, and echinocandins. Amphotericin B and Posaconazole are administered through veins (intravenously), and isavuconazole by mouth (orally). From last several years so many compounds are developed against invasive fungal disease but only few of them are able to induce effective treatment against the micorals. Adjuvant medicines, more particularly, are difficult to assess without prospective randomized controlled investigations, which are challenging to conduct given the lower incidence and higher mortality from Mucormycosis. The present analysis provides insight into pathogenesis, epidemiology, clinical manifestations, underlying fungal virulence, and growth mechanisms. In addition, current therapy for MCR in Post Covid-19 individuals includes conventional and novel nano-based advanced management systems for procuring against deadly fungal infection. The study urges involving nanomedicine to prevent fungal growth at the commencement of infection, delay the progression, and mitigate fatality risk.

Myocarditis manifestations in dengue cases: A systematic review and meta-analysis.

BACKGROUND: Dengue fever is a zoonotic viral infection that raises a global alarm in the tropics and subtropics, with the potentially escalating into newer geographical regions. Severe dengue may be associated with fatal complications such as myocarditis. There is a paucity of available data on the prevalence of dengue-associated myocarditis. The objective of this systematic review and meta-analysis was to estimate the global prevalence of dengue-associated myocarditis. METHODS: A systematic search was conducted utilizing the Cochrane library, PubMed, Scopus, ProQuest, Web of Science, and Preprint servers such as arXiv, medRxiv, bioRxiv, BioRN, ChiRN, ChiRxiv, and SSRN as of November 25, 2022. All primary studies (case series, cross-sectional, retrospective, and prospective) that reported confirmed cases of dengue myocarditis were included. The I2 statistic test assessed the heterogenic characteristics and publication bias was evaluated using Doi plot and Egger regression tests. RESULTS: A total of 12 studies conducted between 2007 and 2022 with 2795 laboratory-confirmed dengue patients were included. Of the included cases, 502 were positive for myocarditis, with a prevalence of 2.4-78%. The pooled prevalence of dengue-induced myocarditis in the studied population was 21.0% (95% CI, 9 - 38%). The prediction interval was estimated to be 0.00 - 0.81. CONCLUSION: Myocarditis in dengue patients is a significant and understudied complication in many aspects. To prevent dengue-associated myocarditis, appropriate measures such as early detection of cases and signs, symptoms-based diagnosis via electrocardiography and echocardiography, as well as relevant vector control policies must be implemented.

Emergence of Marburg virus: a global perspective on fatal outbreaks and clinical challenges.

The Marburg virus (MV), identified in 1967, has caused deadly outbreaks worldwide, the mortality rate of Marburg virus disease (MVD) varies depending on the outbreak and virus strain, but the average case fatality rate is around 50%. However, case fatality rates have varied from 24 to 88% in past outbreaks depending on virus strain and case management. Designated a priority pathogen by the National Institute of Allergy and Infectious Diseases (NIAID), MV induces hemorrhagic fever, organ failure, and coagulation issues in both humans and non-human primates. This review presents an extensive exploration of MVD outbreak evolution, virus structure, and genome, as well as the sources and transmission routes of MV, including human-to-human spread and involvement of natural hosts such as the Egyptian fruit bat (Rousettus aegyptiacus) and other Chiroptera species. The disease progression involves early viral replication impacting immune cells like monocytes, macrophages, and dendritic cells, followed by damage to the spleen, liver, and secondary lymphoid organs. Subsequent spread occurs to hepatocytes, endothelial cells, fibroblasts, and epithelial cells. MV can evade host immune response by inhibiting interferon type I (IFN-1) synthesis. This comprehensive investigation aims to enhance understanding of pathophysiology, cellular tropism, and injury sites in the host, aiding insights into MVD causes. Clinical data and treatments are discussed, albeit current methods to halt MVD outbreaks remain elusive. By elucidating MV infection's history and mechanisms, this review seeks to advance MV disease treatment, drug development, and vaccine creation. The World Health Organization (WHO) considers MV a high-concern filovirus causing severe and fatal hemorrhagic fever, with a death rate ranging from 24 to 88%. The virus often spreads through contact with infected individuals, originating from animals. Visitors to bat habitats like caves or mines face higher risk. We tailored this search strategy for four databases: Scopus, Web of Science, Google Scholar, and PubMed. we primarily utilized search terms such as "Marburg virus," "Epidemiology," "Vaccine," "Outbreak," and "Transmission." To enhance comprehension of the virus and associated disease, this summary offers a comprehensive overview of MV outbreaks, pathophysiology, and management strategies. Continued research and learning hold promise for preventing and controlling future MVD outbreaks. GRAPHICAL ABSTRACT.

COVID-19 vaccines and their underbelly: Are we going the right way?

Background: Historically, a critical aetiological agent of health concern stays till eternity after its discovery, so shall it be with the COVID-19 outbreak. It has transformed human life to a 'new normal' with huge tolls on the social, psychological, intellectual and financial spheres. Aim: This perspective aimed to collate numerous reported COVID-19 vaccine-associated adverse events and the predisposing factors. It focussed on the efficacy of mix-n-match (cocktail) vaccines to effectively counter COVID-19 infection to facilitate future research and possible interventions. Material and Methods: Databases like Scopus, Pubmed and the Web-of-science were searched for published literature on 'adverse events associated with COVID-19 vaccine'. The reports and updates from health agencies like the WHO and CDC were also considered for the purpose. The details with respect to the adverse events associated with COVID-19 vaccination and the predisposing factors were compiled to obtain insights and suggest possible future directions in vaccine research. Results: India stood strong to manage its health resources in time and turned into a dominant global vaccine supplier at a time when healthcare infrastructure of many countries was still significantly challenged. Developing indigenous vaccines and the vaccination drive in India were its major achievements during the second and the subsequent COVID-19 waves. The fully indigenous Covaxin vaccine, primarily as an emergency intervention, was successfully rapidly launched. Similar such vaccines for emergency use were developed elsewhere as well. However, all of these reached the marketplace with a 'emergency use only' tag, without formal clinical trials and other associated formalities to validate and verify them as these would require much longer incubation time before they are available for human use. Discussion: Many adverse events associated with either the first or the second/booster vaccination doses were reported. Evidently, these associated adverse events were considered as 'usually rare' or were often underreported. Without the additional financial or ethical burden on the vaccine companies, fortunately, the Phase IV (human) clinical trials of their manufactured vaccines are occurring by default as the human population receives these under the tag 'emergency use'. Thus, focused and collaborative strategies to unveil the molecular mechanisms in vaccine-related adverse events in a time-bound manner are suggested. Conclusion: Reliable data particularly on the safety of children is lacking as majority of the current over-the-counter COVID-19 vaccines were for emergency use. Many of these were still in their Phase III and Phase IV trials. The need for a mutant-proof, next-gen COVID-19 vaccine in the face of vaccine-associated adverse events is opined.

Socio-demographic determinants of Monkeypox virus preventive behavior: A cross-sectional study in Pakistan.

BACKGROUND: Monkeypox (mpox), re-emerging zoonotic infectious disease, is striking the world with serious public health concerns, especially in non-endemic countries. The public's knowledge and attitude towards the monkeypox virus (MPXV) influence their adherence to preventive strategies. Therefore, we aimed to assess the public's knowledge, attitudes, and perceptions (KAP) of MPXV in Pakistan. METHODS: We collected data for this cross-sectional study from 1040 participants via online self-reported questionnaire from July 5th, 2022, to August 1st, 2022. The questionnaire consisted of a total of 29 items in four sections, assessing socio-demographics, knowledge, attitudes, and practices regarding MPXV. The data were analyzed using IBM SPSS V.25, and factors associated with MPXV knowledge, attitude, and practices were identified by using logistic regression analyses. RESULTS: A total of 1040 participants were included. 61.4% were male, and 57.2% had graduation level education. Only 34.4% had good knowledge about MPXV, and 30% knew the effectiveness of the smallpox vaccine against MPXV. 41.7% had a positive attitude, 48.6% agreed that it is a fatal disease, and 44.6% were in favour of banning travel from endemic to non-endemic regions. 57.7% had good practices, and 69.9% would use protective measures if MPXV became an epidemic. Binary logistic regression analysis revealed that gender and education significantly impacted knowledge (p<0.05). While monthly income status had a significant impact on attitudes (p<0.05). The practices were positively correlated with gender and education (p<0.05). CONCLUSION: The majority of study participants had inadequate levels of knowledge, and attitudes regarding MPXV. To prevent the emergence and spread of MPXV in Pakistan, a comprehensive strategic framework for public health education must be established and implemented.

A proposed management classification for spinal brucellosis from India.

INTRODUCTION: The myriad presentation of osteoarticular brucellosis make the patient seek the help of general practitioners, orthopaedic and rheumatology specialists. Moreover, the lack of disease-specific symptomatology is the leading cause of the delay in diagnosing osteoarticular brucellosis. Given the increasing number of spinal brucellosis cases across the country, no literature is presented on the systematic management of spinal brucellosis. However, with our experience, we formulated a classification for managing spinal brucellosis. METHODS: A single-centred prospective observational study was conducted with 25 confirmed cases of spinal brucellosis. Patients were analysed and graded clinically, serologically, and radiologically and were managed with antibiotics for 10-12 weeks, and if necessary, stabilisation and fusion were done based on the treatment classification devised. All patients were followed up to ensure disease clearance at serial follow-up with relevant investigations. RESULTS: The mean age of the study participants was 52.16 ± 12.53 years. According to spondylodiscitis severity code (SSC) grading, four patients belong to grades 1, 12 to grade 2 and 9 to grade 3 at presentation. Erythrocyte sedimentation rate (p = 0.02), c-reactive protein (p < 0.001), Brucella agglutination titers (p < 0.001), and radiological outcomes improved statistically by six months. The treatment duration was individualised according to the patient's response to the treatment, with a mean time of 11.42 ± 2.66 weeks. The mean follow-up period was 14.42 ± 8 months. CONCLUSION: High index of suspicion of patients from endemic regions, proper clinical assessment, serological evaluation, radiological assessment, appropriate decision-making (medical/surgical) in treatment, and regular follow-up were the key to successful comprehensive management of spinal brucellosis.

Unravelling COVID-19 vaccination attributes worldwide: an extensive review regarding uptake, hesitancy, and future implication.

Since the declaration of the coronavirus disease 2019 pandemic, all efforts were directed towards limiting the transfer of the disease and preventing severe disease forms from occurring. In this regard, numerous vaccines were quickly developed to limit the associated morbidity and mortality of the disease and to reduce the burden on healthcare systems worldwide. However, to date, vaccine hesitancy remains a major limitation to vaccine distribution, with varying degrees in different countries. Therefore, the authors conducted this literature review to highlight the magnitude of this issue throughout the globe and summarize some of its major causes (i.e. governmental, healthcare system-related, population-related, and vaccine-related) and contributing factors (i.e. knowledge/awareness, social media, etc.). In addition, the authors highlighted some of the main motivating factors that can minimize the burden of vaccine hesitancy at the population, governmental, and worldwide levels. These include structural (i.e. government, country), extrinsic (i.e. family, friends), intrinsic (i.e. self-perception), and other factors (financial and nonfinancial). Finally, the authors proposed some implications for future research to ease the vaccination process and hopefully, put an end to this problem.

System Biology Approach to Identify the Hub Genes and Pathways Associated with Human H5N1 Infection.

INTRODUCTION: H5N1 is a highly pathogenic avian influenza virus that can infect humans and has an estimated fatality rate of 53%. As shown by the current situation of the COVID-19 pandemic, emerging and re-emerging viruses such as H5N1 have the potential to cause another pandemic. Thus, this study outlined the hub genes and pathways associated with H5N1 infection in humans. METHODS: The genes associated with H5N1 infection in humans were retrieved from the NCBI Gene database using "H5N1 virus infection" as the keyword. The genes obtained were investigated for protein-protein interaction (PPI) using STRING version 11.5 and studied for functional enrichment analysis using DAVID 2021. Further, the PPI network was visualised and analysed using Cytoscape 3.7.2, and the hub genes were obtained using the local topological analysis method of the cytoHubba plugin. RESULTS: A total of 39 genes associated with H5N1 infection in humans significantly interacted with each other, forming a PPI network with 38 nodes and 149 edges modulating 74 KEGG pathways, 76 biological processes, 13 cellular components, and 22 molecular functions. Further, the PPI network analysis revealed that 33 nodes interacted, forming 1056 shortest paths at 0.282 network density, along with a 1.947 characteristic path length. The local topological analysis predicted IFNA1, IRF3, CXCL8, CXCL10, IFNB1, and CHUK as the critical hub genes in human H5N1 infection. CONCLUSION: The hub genes associated with the H5N1 infection and their pathways could serve as diagnostic, prognostic, and therapeutic targets for H5N1 infection among humans.

Vaccine Derived Poliovirus (VDPV).

Poliomyelitis is caused by Poliovirus, a member of a large group of enteroviruses. Vaccine-derived polioviruses (VDPVs) stem from mutated live poliovirus, which is contained in the Oral Polio Virus vaccine (OPV). In addition, the emergence of VDPV is one of the global challenges for the eradication of poliomyelitis. VDPVs continue to affect different parts of the world; 1081 cases occurred in 2020 and 682 cases in 2021. There are several reasons that may have caused the increase in circulating vaccine-derived poliovirus (cVDPV) after the "switch" from the trivalent to the bivalent oral polio vaccine. One reason is the low vaccination rate among the targeted population, which has been further aggravated by the COVID-19 pandemic. Several strategies could control the spread of VDPV including the use of the monovalent OPV (mOPV-2). The risk of VDPV can be minimized through increased immunization rates and the use of safer vaccine alternatives. The global effort to eradicate polio has made significant progress over the years, but continued vigilance and investment in immunization programs are needed to achieve the ultimate goal of a polio-free world.

Knowledge of mpox and its determinants among the healthcare personnel in Arabic regions: A multi-country cross-sectional study.

Background & aim: The monkeypox virus (MPXV), an Orthopoxvirus family member, is the zoonotic agent that causes mpox (formerly known as monkeypox). The ongoing mpox pandemic has caused cases across continents involving 110 countries. This study aimed to assess mpox knowledge and its determinants among healthcare personnel. Methods: This cross-sectional study was conducted from June 6 to June 25, 2022, among 17 Arab countries. The self-administered questionnaire consists of 53 questions assessing the knowledge about the monkeypox virus. Results: In total, 5874 medical students and clinical doctors from 17 Arab countries participated in this study. Only 13.8% (n = 812) of respondents have ever received information about mpox during their studies in medicine. The mean knowledge score was 13.84, and the median score was 15 (range 1-34). More than half (51.3%, n = 3012) have heard about mpox before. A low proportion of the participants had a good level of knowledge on mpox. Only 11.7% of respondents had correctly identified the natural host and the incubation period of mpox. More than half (58.9%) were aware of the signs and symptoms of mpox. Few respondents (28%) believed that mpox and smallpox have similar signs and symptoms. Specialist doctors had higher knowledge of mpox (AOR = 2.96, 95% CI = 2.24-3.92, p < 0.001) than other cadres. Conclusion: Mpox awareness among Arabic medical students and practitioners is low; hence immediate action in creating awareness among arab healthcare professionals is the need of the hour. This is crucial in the mpox early detection and prevention of its spread.

The Global Monkeypox (Mpox) Outbreak: A Comprehensive Review.

Monkeypox (Mpox) is a contagious illness that is caused by the monkeypox virus, which is part of the same family of viruses as variola, vaccinia, and cowpox. It was first detected in the Democratic Republic of the Congo in 1970 and has since caused sporadic cases and outbreaks in a few countries in West and Central Africa. In July 2022, the World Health Organization (WHO) declared a public-health emergency of international concern due to the unprecedented global spread of the disease. Despite breakthroughs in medical treatments, vaccines, and diagnostics, diseases like monkeypox still cause death and suffering around the world and have a heavy economic impact. The 85,189 reported cases of Mpox as of 29 January 2023 have raised alarm bells. Vaccines for the vaccinia virus can protect against monkeypox, but these immunizations were stopped after smallpox was eradicated. There are, however, treatments available once the illness has taken hold. During the 2022 outbreak, most cases occurred among men who had sex with men, and there was a range of 7-10 days between exposure and the onset of symptoms. Three vaccines are currently used against the Monkeypox virus. Two of these vaccines were initially developed for smallpox, and the third is specifically designed for biological-terrorism protection. The first vaccine is an attenuated, nonreplicating smallpox vaccine that can also be used for immunocompromised individuals, marketed under different names in different regions. The second vaccine, ACAM2000, is a recombinant second-generation vaccine initially developed for smallpox. It is recommended for use in preventing monkeypox infection but is not recommended for individuals with certain health conditions or during pregnancy. The third vaccine, LC16m8, is a licensed attenuated smallpox vaccine designed to lack the B5R envelope-protein gene to reduce neurotoxicity. It generates neutralizing antibodies to multiple poxviruses and broad T-cell responses. The immune response takes 14 days after the second dose of the first two vaccines and 4 weeks after the ACAM2000 dose for maximal immunity development. The efficacy of these vaccines in the current outbreak of monkeypox is uncertain. Adverse events have been reported, and a next generation of safer and specific vaccines is needed. Although some experts claim that developing vaccines with a large spectrum of specificity can be advantageous, epitope-focused immunogens are often more effective in enhancing neutralization.