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2.
J Biomol Struct Dyn ; : 1-18, 2024 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-38459941

RESUMO

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.

3.
J Biomol Struct Dyn ; : 1-18, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38407246

RESUMO

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.

4.
Sci Rep ; 14(1): 2750, 2024 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-38302652

RESUMO

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.


Assuntos
Poluentes Ambientais , Poluição Ambiental , Humanos , Meio Ambiente , Poluentes Ambientais/toxicidade , Cooperação Internacional , Plásticos
5.
Pathol Res Pract ; 255: 155180, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38330621

RESUMO

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.


Assuntos
Neoplasias da Mama , MicroRNAs , RNA Longo não Codificante , Feminino , Humanos , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , MicroRNAs/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA não Traduzido/genética , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo
6.
J Biomol Struct Dyn ; : 1-21, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38385444

RESUMO

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.

7.
J Biomol Struct Dyn ; : 1-12, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38234016

RESUMO

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.

8.
Pathol Res Pract ; 254: 155081, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38211388

RESUMO

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.


Assuntos
RNA Longo não Codificante , Neoplasias da Retina , Retinoblastoma , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Regulação da Expressão Gênica
9.
Pathol Res Pract ; 253: 155019, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38091883

RESUMO

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.


Assuntos
Neoplasias Pulmonares , MicroRNAs , RNA Longo não Codificante , Humanos , Neoplasias Pulmonares/patologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Linhagem Celular Tumoral , Carcinogênese/genética , MicroRNAs/genética , Transformação Celular Neoplásica/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica/genética
10.
Neurol Sci ; 45(4): 1409-1418, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38082050

RESUMO

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.


Assuntos
Doenças Neurodegenerativas , Doença de Parkinson , Humanos , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Fator Neurotrófico Derivado de Linhagem de Célula Glial/uso terapêutico , Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo , Fator Neurotrófico Derivado de Linhagem de Célula Glial/farmacologia , Neurônios/metabolismo , Doenças Neurodegenerativas/metabolismo , Neuroglia
11.
Pathol Res Pract ; 253: 154998, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38056133

RESUMO

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.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Neoplasias Bucais , RNA Longo não Codificante , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Neoplasias Pulmonares/patologia , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Carcinoma de Células Escamosas/genética , Neoplasias Bucais/genética , Regulação Neoplásica da Expressão Gênica
12.
Pathol Res Pract ; 253: 154957, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38000201

RESUMO

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.


Assuntos
Neoplasias , RNA Longo não Codificante , Humanos , beta Catenina/genética , beta Catenina/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Neoplasias/genética , Processos Neoplásicos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Via de Sinalização Wnt/genética
13.
14.
Front Public Health ; 11: 1161881, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37397736

RESUMO

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.


Assuntos
COVID-19 , Humanos , SARS-CoV-2 , Carga Viral , Lavagem Nasal
15.
Aust Endod J ; 49 Suppl 1: 494-507, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36354086

RESUMO

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.


Assuntos
Reabsorção da Raiz , Anquilose Dental , Dente não Vital , Humanos , Anquilose Dental/complicações , Reimplante Dentário/efeitos adversos , Dente não Vital/cirurgia , Apicectomia/efeitos adversos , Resultado do Tratamento
16.
Comb Chem High Throughput Screen ; 26(6): 1196-1203, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35975856

RESUMO

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.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Fentolamina , Combinação de Medicamentos
17.
Sci Total Environ ; 854: 158765, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36113800

RESUMO

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.


Assuntos
Oncorhynchus mykiss , Poluentes Químicos da Água , Animais , Microplásticos , Paládio , Poliestirenos , Exposição Dietética , Dieta
18.
Mar Pollut Bull ; 185(Pt A): 114305, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36343543

RESUMO

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.


Assuntos
Microplásticos , Poluentes Químicos da Água , Plásticos , Tanzânia , Sedimentos Geológicos , Monitoramento Ambiental , Poluentes Químicos da Água/análise , Polietileno
19.
Clin Exp Dent Res ; 8(6): 1523-1532, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36177666

RESUMO

BACKGROUND: Early childhood caries poses a significant health issue in children under 6 years old. It is determined that Streptococcus mutans is a primary etiological agent, likely to be transferred through maternal contact. OBJECTIVES: To determine the association of maternal S. mutans counts with S. mutans counts in their children between 6 and 30 months of age, and to determine the maternal and child DMFT (decayed, missing, and filled teeth) indices. MATERIAL AND METHODS: A community-based cross-sectional study was conducted in Karachi, Pakistan. A sample of 193 dyads of mother-children (6-30 months of age) was selected via purposive sampling. Saliva samples of the dyads were collected to assess S. mutans count. Caries assessment was performed for both using the DMFT index. A pretested questionnaire was used. The association of bottle-feeding, oral hygiene measures, and other factors with S. mutans counts in children were also explored. Zero-inflated negative binomial regression model at a 5% level of significance was applied using STATA version 12.0. RESULTS: Out of 193 children, 109 (56.47%) were males and 84 (43.52%) were females. The mean age of mothers and children was 29.4 ± 6.2 years and 19.54 ± 6.8 months, respectively. Maternal S. mutans counts were not statistically associated with child's S. mutans counts (Mean child's S. mutans count ratio: 1; 95% confidence interval [CI]: 1, 1.01; p = .882). Compared with children who were breastfed, S. mutans counts were higher in children who were bottle-fed (mean S. mutans count ratio= 4.85 [95% CI: 1.53, 15.41], p = .007). Age of mother and present caries status of mothers was significantly associated with the child's S. mutans count. CONCLUSION: No association between maternal S. mutans and child S. mutans was observed. However, maternal age, children who were breastfed, children who did not use pacifiers, and children with mothers who did not have caries, exhibited low S. mutans counts in their saliva.


Assuntos
Cárie Dentária , Streptococcus mutans , Masculino , Feminino , Humanos , Pré-Escolar , Adulto Jovem , Adulto , Lactente , Saliva , Cárie Dentária/epidemiologia , Índice CPO , Mães , Estudos Transversais , Paquistão/epidemiologia , Contagem de Colônia Microbiana
20.
Bull Environ Contam Toxicol ; 109(6): 1037-1042, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36121466

RESUMO

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.


Assuntos
Microplásticos , Poluentes Químicos da Água , Plásticos , Tanzânia , Poluentes Químicos da Água/análise , Polietileno , Monitoramento Ambiental
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