ABSTRACT
The Varicella-zoster virus (VZV), classified as a neurotropic member of the Herpesviridae family, exhibits a characteristic pathogenicity, predominantly inducing varicella, commonly known as chickenpox, during the initial infectious phase, and triggering the reactivation of herpes zoster, more commonly recognized as shingles, following its emergence from a latent state. The pathogenesis of VZV-associated neuroinflammation involves a complex interplay between viral replication within sensory ganglia and immune-mediated responses that contribute to tissue damage and dysfunction. Upon primary infection, VZV gains access to sensory ganglia, establishing latent infection within neurons. During reactivation, the virus can spread along sensory nerves, triggering a cascade of inflammatory mediators, chemokines, and immune cell infiltration in the affected neural tissues. The role of both adaptive and innate immune reactions, including the contributions of T and B cells, macrophages, and dendritic cells, in orchestrating the immune-mediated damage in the central nervous system is elucidated. Furthermore, the aberrant activation of the natural defence mechanism, characterised by the dysregulated production of immunomodulatory proteins and chemokines, has been implicated in the pathogenesis of VZV-induced neurological disorders, such as encephalitis, myelitis, and vasculopathy. The intricate balance between protective and detrimental immune responses in the context of VZV infection emphasises the necessity for an exhaustive comprehension of the immunopathogenic mechanisms propelling neuroinflammatory processes. Despite the availability of vaccines and antiviral therapies, VZV-related neurological complications remain a significant concern, particularly in immunocompromised individuals and the elderly. Elucidating these mechanisms might facilitate the emergence of innovative immunomodulatory strategies and targeted therapies aimed at mitigating VZV-induced neuroinflammatory damage and improving clinical outcomes. This comprehensive understanding enhances our grasp of viral pathogenesis and holds promise for pioneering therapeutic strategies designed to mitigate the neurological ramifications of VZV infections.
Subject(s)
Herpesvirus 3, Human , Humans , Herpesvirus 3, Human/immunology , Herpesvirus 3, Human/physiology , Herpesvirus 3, Human/pathogenicity , Herpes Zoster/virology , Herpes Zoster/immunology , Varicella Zoster Virus Infection/immunology , Varicella Zoster Virus Infection/virology , Nervous System Diseases/virology , Nervous System Diseases/immunology , Nervous System Diseases/etiology , Animals , Chickenpox/virology , Chickenpox/immunology , Neuroinflammatory Diseases/immunology , Neuroinflammatory Diseases/virologyABSTRACT
Diabetes affects people of all ages, regardless of gender and background. To date, there is no evidence for the effect of sakuranetin against the streptozotocin (STZ)-induced diabetes paradigm. The research was directed to evaluate the antidiabetic activity of sakuranetin in the STZ model invoking the diabetes-induced disease paradigm. STZ (I.P. 60 mg/kg) is directed to induce type 2 diabetes in experimental rats. Recent research pursued to regulate the anti-diabetic ability of sakuranetin at both 10 and 20 mg/kg in STZ-induced rats. Furthermore, molecular docking research was implemented to evaluate sakuranetin requisite attraction to inflammatory indicators. Various anti-diabetic [(glucose, hemoglobin A1c (HbA1c), and insulin)], lipid profile [triglycerides (TG), total cholesterol (TC), and high-density lipoproteins (HDL)], hematological parameters [Hemoglobin (HGB), packed cell volume (PCV), red blood cells (RBC), mean corpuscular volume (MCV), platelet (PLT), and white blood cells (WBC), pro-inflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6)], antioxidant level [catalase (CAT), superoxide dismutase (SOD), glutathione (GSH)], lipid oxidation, and caspase-3 were evaluated. Furthermore, molecular docking and dynamics were performed for TNF-α (2AZ5), IL-6 (1ALU), IL-1ß (6Y8M), Caspase-3 (1NME) and serum insulin (4IBM) target ligands. Sakuranetin treatment at both doses restored the biochemical parameters i.e. blood glucose, insulin, HbA1c, lipid profile, hematological parameters, pro-inflammatory markers, antioxidant levels, lipid oxidation, and caspase-3 in the context of diabetic rats. It also showed favorable binding affinity on inflammatory markers. Sakuranetin binds to proteins 2AZ5, 1ALU, 6Y8M, 1NME, and 4IBM at -7.489, -6.381, -6.742, -7.202, and -8.166 Kcal/mol, respectively. All of the findings from the molecular dynamics simulations points toward a considerable change in the conformational dynamics of protein upon binding with sakuranetin. The potential use of sakuranetin as an alternative diabetes medication will aid future research as a potent anti-diabetic agent.Communicated by Ramaswamy H. Sarma.
ABSTRACT
One of the viral diseases that affect millions of people around the world, particularly in developing countries, is Japanese encephalitis (JE). In this study, the conserved protein of this virus, that is, non-structural protein 5 (NS5), was used as a target protein for this study, and a compound library of 749 antiviral molecules was screened against NS5. The current study employed machine learning-based virtual screening combined with molecular docking. Here, three hits (24360, 123519051 and 213039) had lower binding energies (< -8 kcal/mol) than the control, S-Adenosyl-L-homocysteine (SAH). All the compounds showed significant H-bond interactions with functional residues, which were also observed by the control. Molecular dynamics simulation, MM/GBSA for binding free energy analysis, principal component analysis and free energy landscape were also performed to study the stability of the complex formation. All three compounds had similar root mean square deviation trends, which were comparable to the control, SAH. Post-MD, the 123519051-receptor complex had the highest number of H-bonds (4 to 5) after the control, out of which three exhibited the highest percentage occupancy (50%, 24% and 79%). Both docking and MD, 123519051 showed an H-bond with the residue Gly111, which was also found for the control-protein complex. 123519051 showed the lowest binding free energy with ΔGbind of -89 kJ/mol. Steered molecular dynamics depicted that 123519051 had the maximum magnitude of dissociation (1436.43 kJ/mol/nm), which was more than the control, validating its stable complex formation. This study concluded that 123519051 is a binder and could inhibit the protein NS5 of JE.Communicated by Ramaswamy H. Sarma.
ABSTRACT
Programmed cell death ligand 1 (PD-L1) is a crucial target for cancer therapy. Here, an in silico study investigates PD-L1 to inhibit its interaction with PD1, thereby promoting an immune response to eliminate cancer cells. The study employed machine learning (ML) -based QSAR to detect PDL1 inhibitors. Morgan's fingerprint with docking score showed a 0.83 correlation with the experimental IC50, enabling the screening of 3200 natural compounds. The top three compounds, considered 2819, 2821 and 3188, were selected from the ML-based QSAR and subjected to molecular docking and simulation. The binding scores for 2819, 2821 and 3188 were -7.0, -9.0 and -8.9 kcal/mol, respectively. The stability of the ligands during a 100 ns simulation was assessed using RMSD, showing that 2819 and 2821 maintained stable patterns comparable to the control inhibitor. Notably, 2819 exhibited a consistent stable pattern throughout the simulation, while 2821 showed stability in the last 40 ns. The control compound showed the highest number of hydrogen bonds with proteins, whereas compounds 2819 and 2821 formed continuous H-bonds. 3188 was separated from the protein in later phases and is not regarded as a potential PD-L1-binding molecule. MMGBSA binding free energy for complexes was computed. Control had the lowest binding free energy, while 2819 and 2821 also had lower binding energies. In contrast, 3188 showed poor binding free energy, causing protein separation. Principal component analysis showed a loss of entropy and reduced protein conformational variation. Overall, 2819 and 2821 are potential binders for PD-L1 inhibition and immune response triggering.Communicated by Ramaswamy H. Sarma.
ABSTRACT
Breast cancer persists as a major problem for the world's healthcare, thus it is essential to fully understand the complex molecular processes that cause its growth and development. ncRNAs had been discovered to serve critical roles in a variety of cellular functions, including the regulation of signalling pathways. Within different pathways, the AKT/PI3K/mTOR signalling cascade has received a lot of interest because of its role in cancer. A complex interaction between ncRNAs, notably miRNAs, lncRNAs, and circRNAs, and the AKT/PI3K/mTOR signalling pathway exerts both oncogenic and tumor-suppressive activities by targeting critical components of the pathway directly or indirectly. Through miRNA-mediated post-transcriptional regulation, lncRNA-guided chromatin remodelling, and circRNA sequestration, ncRNAs modulate the activity of PI3K, AKT, and mTOR, influencing cell proliferation, survival, and metastasis. Furthermore, ncRNAs can serve as promising biomarkers for breast cancer prognosis, diagnosis, and treatment response, as their dysregulation is commonly observed in breast cancer patients. Harnessing the potential of ncRNAs as therapeutic targets or tools for restoring pathway homeostasis holds promise for innovative treatment strategies in breast cancer. Understanding the intricate regulatory networks orchestrated by ncRNAs in this context may pave the way for novel diagnostic approaches, therapeutic interventions, and a deeper comprehension of breast cancer's molecular landscape, ultimately improving patient outcomes. This abstract underscores the emerging significance of ncRNAs in the AKT/PI3K/mTOR signaling pathway in breast cancer.
Subject(s)
Breast Neoplasms , MicroRNAs , RNA, Long Noncoding , Female , Humans , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , MicroRNAs/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , RNA, Untranslated/genetics , Signal Transduction , TOR Serine-Threonine Kinases/metabolismABSTRACT
Plastic pollution has emerged as a global challenge necessitating collective efforts to mitigate its adverse environmental consequences. International negotiations are currently underway to establish a global plastic treaty. Emphasizing the need for solution-orientated research, rather than focusing on further defining the problems of widespread environmental occurrence and ecological impacts, this paper extracts insights and draws key patterns that are relevant for these international negotiations. The analysis reveals that (i) environmental rather than human health concerns have been the predominant driving force behind previous regulations targeting pollutants, and (ii) the decision to ban or discontinue the use of harmful pollutants is primarily affected by the availability of viable substitutes. These two key findings are relevant to the discussions of the ongoing Intergovernmental Negotiating Committee (INC) on the global plastic treaty and underscore the recognition of environmental consequences associated with plastic pollution while emphasizing the need to enhance the knowledge base of potential human health risks. Leveraging the availability of substitutes can significantly contribute to the development and implementation of effective strategies aimed at reducing plastic usage and corresponding pollution.
Subject(s)
Environmental Pollutants , Environmental Pollution , Humans , Environment , Environmental Pollutants/toxicity , International Cooperation , PlasticsABSTRACT
The genomic era has brought about a transformative shift in our comprehension of cancer, unveiling the intricate molecular landscape underlying disease development. Eye cancers (ECs), encompassing diverse malignancies affecting ocular tissues, pose distinctive challenges in diagnosis and management. Long non-coding RNAs (lncRNAs), an emerging category of non-coding RNAs, are pivotal actors in the genomic intricacies of eye cancers. LncRNAs have garnered recognition for their multifaceted roles in gene expression regulation and influence on many cellular processes. Many studies support that the lncRNAs have a role in developing various cancers. Recent investigations have pinpointed specific lncRNAs associated with ECs, including retinoblastoma and uveal melanoma. These lncRNAs exert control over critical pathways governing tumor initiation, progression, and metastasis, endowing them with the ability to function as evaluation, predictive, and therapeutic indicators. The article aims to synthesize the existing information concerning the functions of lncRNAs in ECs, elucidating their regulatory mechanisms and clinical significance. By delving into the lncRNAs' expanding relevance in the modulation of oncogenic and tumor-suppressive networks, we gain a deeper understanding of the molecular complexities intrinsic to these diseases. In our exploration of the genomic intricacies of ECs, lncRNAs introduce a fresh perspective, providing an opportunity to function as clinical and therapeutic indicators, and they also have therapeutic benefits that show promise for advancing the treatment of ECs. This comprehensive review bridges the intricate relationship between lncRNAs and ECs within the context of the genomic era.
Subject(s)
RNA, Long Noncoding , Retinal Neoplasms , Retinoblastoma , Humans , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Gene Expression RegulationABSTRACT
In the present study, the formation of a heterodimer involving both epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) has been explored as a potential therapeutic mechanism to inhibit the progression of breast cancer. Virtual screening using molecular docking resulted in the three hit compounds (ZINC08382411, ZINC08382438, and ZINC08382292) with minimum binding scores and commonly binding to both receptors. Further, MD simulation analysis of these complexes illustrated the high stability of these compounds with EGFR and HER2. RMSD showed that ZINC08382411 displayed the most stable RMSD of 2 - 3 Å when bound to both receptors, suggesting to have strong compatibility with the active site of the receptor. Hydrogen bond analysis showed that ZINC08382411 forms the maximum number of H-bonds (2 to 3) in both EGFR and HER2 bound complexes, with the highest occupancy of 62% and 79%, respectively. Binding free energy calculation showed that ZINC08382411 possesses maximum affinity towards both the receptors with ΔGbind = -129.628 and -164.063 kJ/mol, respectively. This approach recognizes the significance of EGFR and HER2 in breast cancer development and aims to disrupt their collaborative signaling, which is known to promote the antagonistic behavior of cancer cells. By focusing on this EGFR/HER2 heterodimer, the study offers a promising avenue for identifying a potential candidate (ZINC08382411) that may inhibit breast cancer cell growth and potentially improve patient outcomes. The study's findings may contribute to the ongoing efforts to advance breast cancer treatment strategies.Communicated by Ramaswamy H. Sarma.
ABSTRACT
The long non-coding RNA (lncRNA) HOTAIR occupies a central position in the complex domain of cancer biology, particularly concerning its intricate interplay with the Wnt/ß-catenin signaling pathway. This comprehensive review explores the multifaceted interactions between HOTAIR and the Wnt/ß-catenin cascade, elucidating their profound function in cancer growth, progression, and therapeutic strategies. The study commences by underscoring the pivotal role of the Wnt/ß-catenin cascade in governing essential cellular activities, emphasizing its dysregulation as a linchpin in cancer initiation and advancement. It introduces HOTAIR as a crucial regulatory entity, influencing gene expression in both healthy and diseased. The core of this review plunges into the intricacies of HOTAIR's engagement with Wnt/ß-catenin signaling. It unravels how HOTAIR, through epigenetic modifications and transcriptional control, exerts its influence over key pathway constituents, including ß-catenin, Wnt ligands, and target genes. This influence drives unchecked cancer cell growth, invasion, and metastasis. Furthermore, the review underscores the clinical significance of the HOTAIR-Wnt/ß-catenin interplay, elucidating its associations with diverse cancer subtypes, patient prognoses, and prospects as a therapy. It provides insights into ongoing research endeavors to develop HOTAIR-targeted treatments and initiatives to facilitate aberrant Wnt/ß-catenin activation. Concluding on a forward-looking note, the article accentuates the broader implications of HOTAIR's involvement in cancer biology, including its contributions to therapy resistance and metastatic dissemination. It underscores the importance of delving deeper into these intricate molecular relationships to pave the way for groundbreaking cancer treatment.
Subject(s)
Neoplasms , RNA, Long Noncoding , Humans , beta Catenin/genetics , beta Catenin/metabolism , Cell Line, Tumor , Cell Proliferation/genetics , Gene Expression Regulation , Gene Expression Regulation, Neoplastic , Neoplasms/genetics , Neoplastic Processes , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Wnt Signaling Pathway/geneticsABSTRACT
Cancer is a complicated illness that spreads indefinitely owing to epigenetic, genetic, and genomic alterations. Cancer cell multidrug susceptibility represents a severe barrier in cancer therapy. As a result, creating effective therapies requires a better knowledge of the mechanisms driving cancer development, progress, and resistance to medications. The human genome is predominantly made up of long non coding RNAs (lncRNAs), which are currently identified as critical moderators in a variety of biological functions. Recent research has found that changes in lncRNAs are closely related to cancer biology. The vascular endothelial growth factor (VEGF) signalling system is necessary for angiogenesis and vascular growth and has been related to an array of health illnesses, such as cancer. LncRNAs have been identified to alter a variety of cancer-related processes, notably the division of cells, movement, angiogenesis, and treatment sensitivity. Furthermore, lncRNAs may modulate immune suppression and are being investigated as possible indicators for early identification of cancer. Various lncRNAs have been associated with cancer development and advancement, serving as cancer-causing or suppressing genes. Several lncRNAs have been demonstrated through research to impact the VEGF cascade, resulting in changes in angiogenesis and tumor severity. For example, the lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) has been shown to foster the formation of oral squamous cell carcinoma and the epithelial-mesenchymal transition by stimulating the VEGF-A and Notch systems. Plasmacytoma variant translocation 1 (PVT1) promotes angiogenesis in non-small-cell lung cancer by affecting miR-29c and boosting the VEGF cascade. Furthermore, lncRNAs regulate VEGF production and angiogenesis by interacting with multiple downstream signalling networks, including Wnt, p53, and AKT systems. Identifying how lncRNAs engage with the VEGF cascade in cancer gives beneficial insights into tumor biology and possible treatment strategies. Exploring the complicated interaction between lncRNAs and the VEGF pathway certainly paves avenues for novel ways to detect better accurately, prognosis, and cure cancers. Future studies in this area could open avenues toward the creation of innovative cancer therapy regimens that enhance the lives of patients.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Carcinoma, Squamous Cell , Lung Neoplasms , Mouth Neoplasms , RNA, Long Noncoding , Humans , Carcinoma, Non-Small-Cell Lung/genetics , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Lung Neoplasms/pathology , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor A/metabolism , Carcinoma, Squamous Cell/genetics , Mouth Neoplasms/genetics , Gene Expression Regulation, NeoplasticABSTRACT
The lncRNA PVT1 has emerged as a pivotal component in the intricate landscape of cancer pathogenesis, particularly in lung cancer. PVT1, situated in the 8q24 chromosomal region, has garnered attention for its aberrant expression patterns in lung cancer, correlating with tumor progression, metastasis, and poor prognosis. Numerous studies have unveiled the diverse mechanisms PVT1 contributes to lung cancer pathogenesis. It modulates critical pathways, such as cell proliferation, apoptosis evasion, angiogenesis, and epithelial-mesenchymal transition. PVT1's interactions with other molecules, including microRNAs and proteins, amplify its oncogenic influence. Recent advancements in genomic and epigenetic analyses have also illuminated the intricate regulatory networks that govern PVT1 expression. Understanding PVT1's complex involvement in lung cancer holds substantial clinical implications. Targeting PVT1 presents a promising avenue for developing novel diagnostic biomarkers and therapeutic interventions. This abstract encapsulates the expanding knowledge regarding the oncogenic role of PVT1 in lung cancer, underscoring the significance of further research to unravel its complete mechanistic landscape and exploit its potential for improved patient outcomes.
Subject(s)
Lung Neoplasms , MicroRNAs , RNA, Long Noncoding , Humans , Lung Neoplasms/pathology , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Cell Line, Tumor , Carcinogenesis/genetics , MicroRNAs/genetics , Cell Transformation, Neoplastic/genetics , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic/geneticsABSTRACT
Parkinson's disease is the second most common neurodegenerative condition with its prevalence projected to 8.9 million individuals globally in the year 2019. Parkinson's disease affects both motor and certain non-motor functions of an individual. Numerous research has focused on the neuroprotective effect of the glial cell line-derived neurotrophic factor (GDNF) in Parkinson's disease. Discovered in 1993, GDNF is a neurotrophic factor identified from the glial cells which was found to have selective effects on promoting survival and regeneration of certain populations of neurons including the dopaminergic nigrostriatal pathway. Given this property, recent studies have focused on the exogenous administration of GDNF for relieving Parkinson's disease-related symptoms both at a pre-clinical and a clinical level. This review will focus on enumerating the molecular connection between Parkinson's disease and GDNF and shed light on all the available drug delivery approaches to facilitate the selective delivery of GDNF into the brain paving the way as a potential therapeutic candidate for Parkinson's disease in the future.
Subject(s)
Neurodegenerative Diseases , Parkinson Disease , Humans , Parkinson Disease/drug therapy , Parkinson Disease/metabolism , Glial Cell Line-Derived Neurotrophic Factor/therapeutic use , Glial Cell Line-Derived Neurotrophic Factor/metabolism , Glial Cell Line-Derived Neurotrophic Factor/pharmacology , Neurons/metabolism , Neurodegenerative Diseases/metabolism , NeurogliaABSTRACT
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ABSTRACT
With unrelenting SARS-CoV-2 variants, additional COVID-19 mitigation strategies are needed. Oral and nasal saline irrigation (SI) is a traditional approach for respiratory infections/diseases. As a multidisciplinary network with expertise/experience with saline, we conducted a narrative review to examine mechanisms of action and clinical outcomes associated with nasal SI, gargling, spray, or nebulization in COVID-19. SI was found to reduce SARS-CoV-2 nasopharyngeal loads and hasten viral clearance. Other mechanisms may involve inhibition of viral replication, bioaerosol reduction, improved mucociliary clearance, modulation of ENaC, and neutrophil responses. Prophylaxis was documented adjunctive to personal protective equipment. COVID-19 patients experienced significant symptom relief, while overall data suggest lower hospitalization risk. We found no harm and hence recommend SI use, as safe, inexpensive, and easy-to-use hygiene measure, complementary to hand washing or mask-wearing. In view of mainly small studies, large well-controlled or surveillance studies can help to further validate the outcomes and to implement its use.
Subject(s)
COVID-19 , Humans , SARS-CoV-2 , Viral Load , Nasal LavageABSTRACT
The ingestion of nanoplastics (NPs) by fish has led to concerns regarding fish health and food chain transfer, but analytical constraints have hindered quantitative data collection on their uptake and depuration. We used palladium-doped polystyrene nanoplastics (PS-Pd NPs, ~200 nm) to track particle fate in rainbow trout (Oncorhynchus mykiss) during a week-long dietary exposure and subsequent 7-day depuration period on a control diet (no added PS-Pd NPs). At Day 3 and 7 of the exposure, and after depuration, the mid intestine, hind intestine, liver, gallbladder, kidney, gill and carcass were sampled. All organs and the carcass were analysed for total Pd content by inductively couple plasma mass spectrometry. After 3 days of exposure, the mid (32.5 ± 8.3 ng g-1) and hind (42.3 ± 8.2 ng g-1) intestine had significantly higher total Pd concentrations compared to the liver and carcass (1.3 ± 0.4 and 3.4 ± 1.1 ng g-1, respectively). At Day 7, there was no time-related difference in any organ (or the carcass) total Pd concentrations compared to Day 3. When the total Pd content was expressed as a body distribution based on mass of tissue, the carcass contained the highest fraction with 72.5 ± 5.2 % at Day 7, which could raise concerns over transfer to higher trophic levels. The total number of particles that entered the fish over the 7 days was 94.5 ± 13.5 × 106 particles, representing 0.07 ± 0.01 % of the Pd the fish had been fed. Following depuration, there was no detectable Pd in any organ or the carcass, indicating clearance from the fish. These data indicate that these NPs are taken into the internal organs and carcass of fish, yet removal of the exposure results in substantial excretion to below the limit of detection.
Subject(s)
Oncorhynchus mykiss , Water Pollutants, Chemical , Animals , Microplastics , Palladium , Polystyrenes , Dietary Exposure , DietABSTRACT
The purpose of the present review was to examine success, survival and failure following intentional replantation of endodontically treated teeth with existing periapical pathosis and to determine the factors that might affect the outcome of replantation. Clinical trials, longitudinal studies, case series with >10 cases and at least 1-year follow-up were included. The average rate of success following intentional replantation was 77.23%. Meta-analysis revealed the mean weighted survival to be 85.9% (95% CI: 79.6-91.2) Common complications include inflammatory root resorption (0%-27%) and ankylosis (0%-25%). Variables influencing successful outcome include extra alveolar dry time <15 min; root-end resection (2-3 mm) and cavity preparation (3 mm); manipulation of the tooth using the crown only; and use of an appropriate storage media. The review concludes that intentional replantation is a viable treatment option with acceptable survival rates for endodontically treated teeth with periapical pathosis.
Subject(s)
Root Resorption , Tooth Ankylosis , Tooth, Nonvital , Humans , Tooth Ankylosis/complications , Tooth Replantation/adverse effects , Tooth, Nonvital/surgery , Apicoectomy/adverse effects , Treatment OutcomeABSTRACT
BACKGROUND: SARS-CoV-2 emerged in late 2019 and caused COVID-19. Patients treated with Zyesami were found to have a 3-fold decrease in respiratory failure and improved clinical outcomes. It was reported that Zyesami inhibits RNA replication of SARS-CoV-2, including several non-structural proteins essential in viral RNA replication. SARS-CoV-2 is a distinctive virus that requires nsp10 and nsp16 for its methyltransferases activity which is crucial for RNA stability and protein synthesis. OBJECTIVE: We aimed the in silico determination of inhibitory consequences of Zyesami on the SARS-CoV-2 nsp10/nsp16 complex. Targeting SARS-CoV-2 nsp10/ nsp16 protein complex may be used to develop a drug against COVID-19. METHODS: I-TASSER was used for secondary structure prediction of Zyesami. CABS-dock was used to model Zyesami with SARS-CoV-2 nsp16 interaction. The docked complex was visualized using PyMol. The quality of the docking model was checked by using ProQdock. RESULTS: The 3D structure of SARS-CoV 2, nsp10/nsp16 showed that essential interactions exist between nsp10 and nsp16. Significant contact areas of Zyesami exist across amino acid residues of nsp10; Asn40-Thr47, Val57-Pro59, Gly69-Ser72, Cys77-Pro84, Lys93-Tyr96. In addition, polar contacts between nsp16 and Zyesami are Asn299-Ser440, Val297-Asn443, Gly149-Tyr437, Gln159-Lys430, Asn178- Arg429, Ser146-Arg429, Ser146-Arg429, Lys147-Arg429, Asr221-Thr422, Lys183-Asp423, Lys183-Asp423, and Gln219-Asp423 the residues are shown of nsp16 and Zyesami respectively. CONCLUSION: The structural bioinformatics analyses have indicated the potential binding specificity of Zyesami and nsp16. Data predict how the initial binding of Zyesami with nsp10 and nsp16 may occur. Moreover, this binding could significantly inhibit the 2 -O-MTase activity of the SARSCoV nsp10/16 complex.
Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Phentolamine , Drug CombinationsABSTRACT
Microplastics (MPs) pollution in the marine environment has been one of the biggest challenge in developing countries due to a lack of proper solid waste management strategies. This study reports the distribution and types of MPs in beach and seabed zones of the Dar es Salaam and Zanzibar coasts. A total of 641 MPs were identified across all sites, of which 84 % and 16 % originated from beach and seabed sediments, respectively. Fragment and fibers were the most common types in both seabed and beach zone confirming the secondary sources of the MPs. Attenuated Total Reflection Fourier Transform Infrared (ATR-FTIR), revealed four types of polymers with polyethylene (PE) (56%) and polyester (PS) (24 %) being the most common. Microplastics were more abundant on beaches than in seabed zone. A larger abundance of PE and PS reveals a wide range of MPs entering the Ocean.
Subject(s)
Microplastics , Water Pollutants, Chemical , Plastics , Tanzania , Geologic Sediments , Environmental Monitoring , Water Pollutants, Chemical/analysis , PolyethyleneABSTRACT
Limited information exists on the occurrence of microplastics (MPs) in East African coastal waters. A 300 µm manta net was used to collect surface water from 8 sites in the regions Dar es Salaam (DES) and Zanzibar (ZZ) during low and high tides. DES had a higher (p < 0.05) abundance of MPs than ZZ. Fragments and fibers were the dominant MP types at all sites. The number of fibers was significantly higher (p = 0.002) in DES than in ZZ. MPs were more prevalent during high tide in both DES and ZZ. The MPs within the 2-5 mm size range were identified most often. White and blue MPs were the most common in study sites comprising 45% and 18% of the total MPs respectively. Three polymers polypropylene (PP) high-density polyethylene (HDPE) and low-density polyethylene (LDPE) were identified. The occurrence of MPs in nearshore waters of DES and ZZ is probably due to their proximity to industrial areas, poor solid waste management, and high population pressure.