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1.
Artigo em Inglês | MEDLINE | ID: mdl-33813698

RESUMO

Bacterial community structure is one of the essential components of aquaculture dynamics and plays an important role in maintaining wetland health. The present work is an effort to study the structure of bacterial communities in the world's largest sewage-fed fish farms, the East Kolkata Wetlands (EKWs), along with their predicted functional metabolic pathways and correlation with environmental variables. Sequencing data analysis revealed the abundance of genera such as Arcobacter (0-50%), Pseudomonas (0-15%), Sulfurospirillum (0-9%), Cloacibacterium (0-6%), hgcI clade (7-29%), C39 (0-9%), V6 (3-36%), Fluiivicola (1-6%) and Cyanobium (3-8%) in the EKWs. Further, water quality analysis of three treatment groups, i.e. Sewage, Sewage F-1 and Sewage F-2, revealed that dissolved oxygen (DO), biochemical oxygen demand (BOD) and chemical oxygen demand (COD) differed significantly and violated the standard prescribed norms (Central Pollution Control Board, CPCB, New Delhi) for fishery propagation and irrigation in India. Further, the correlation matrix analysis between the abundance of bacterial genera and environmental variables indicated that DO, BOD and COD were mainly responsible for bacterial community structure and their proliferation in the EKWs. Our results indicated that the abundance of genera such as Arcobacter, Pseudomonas, Sulfurospirillum and Cloacibacterium has an inverse relationship with BOD and COD. Our observations based on the bacterial community structure and deteriorated water quality indicate the ineffective functioning and poor management of this man-made constructed wetland.

2.
Pharmaceuticals (Basel) ; 14(3)2021 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-33801030

RESUMO

The mammalian target of rapamycin (mTOR) is a serine/threonine kinase portraying a quintessential role in cellular proliferation and survival. Aberrations in the mTOR signaling pathway have been reported in numerous cancers including thyroid, lung, gastric and ovarian cancer, thus making it a therapeutic target. To attain this objective, an in silico investigation was designed, employing a pharmacophore modeling approach. A structure-based pharmacophore (SBP) model exploiting the key features of a selective mTOR inhibitor, Torkinib directed at the ATP-binding pocket was generated. A Marine Natural Products (MNP) library was screened using SBP model as a query. The retrieved compounds after consequent drug-likeness filtration were subjected to molecular docking with mTOR, thus revealing four MNPs with better scores than Torkinib. Successive refinement via molecular dynamics simulations demonstrated that the hits formed crucial interactions with key residues of the pocket. Furthermore, the four identified hits exhibited good binding free energy scores through MM-PBSA calculations and the subsequent in silico toxicity assessments displayed three hits deemed essentially non-carcinogenic and non-mutagenic. The hits presented in this investigation could act as potent ATP-competitive mTOR inhibitors, representing a platform for the future discovery of drugs from marine natural origin.

3.
ACS Infect Dis ; 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33890759

RESUMO

This study aims to push the frontier of the engineering of human cathelicidin LL-37, a critical antimicrobial innate immune peptide that wards off invading pathogens. By sequential truncation of the smallest antibacterial peptide (KR12) of LL-37 and conjugation with fatty acids, with varying chain lengths, a library of lipopeptides is generated. These peptides are subjected to antibacterial activity and hemolytic assays. Candidates (including both forms made of l- and d-amino acids) with the optimal cell selectivity are subsequently fed to the second layer of in vitro filters, including salts, pH, serum, and media. These practices lead to the identification of a miniature LL-37 like peptide (d-form) with selectivity, stability, and robust antimicrobial activity in vitro against both Gram-positive and negative bacteria. Proteomic studies reveal far fewer serum proteins that bind to the d-form than the l-form peptide. C10-KR8d targets bacterial membranes to become helical, making it difficult for bacteria to develop resistance in a multiple passage experiment. In vivo, C10-KR8d is able to reduce bacterial burden of methicillin-resistant Staphylococcus aureus (MRSA) USA300 LAC in neutropenic mice. In addition, this designer peptide prevents bacterial biofilm formation in a catheter-associated mouse model. Meanwhile, C10-KR8d also recruits cytokines to the vicinity of catheters to clear infection. Thus, based on the antimicrobial region of LL-37, this study succeeds in identifying the smallest anti-infective peptide C10-KR8d with both robust antimicrobial, antibiofilm, and immune modulation activities.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33821466

RESUMO

The outbreak of diseases leading to substantial loss is a major bottleneck in aquaculture. Over the last decades, the concept of using feed probiotics was more in focus to address the growth and health of cultivable aquatic organisms. The objective of this review is to provide an overview of the distinct functionality of archaea from conventional probiotics in nutrient utilization, specific caloric contribution, evading immune response and processing thermal resistance. The prime limitation of conventional probiotics is the viability of desired microbes under harsh feed processing conditions. To overcome the constraints of commercial probiotics pertaining to incompatibility towards industrial processing procedure, a super microbe, archaea, appears to be a potential alternative approach in aquaculture. The peculiarity of the archaeal cell wall provides them with heat stability and rigidity under industrial processing conditions. Besides, archaea being one of the gut microbial communities participates in various health-oriented biological functions in animals. Thus, the current review devoted that administration of archaea in aquafeed could be a promising strategy in aquaculture. Archaea may be used as a potential probiotic with the possible modes of functions and advantages over conventional probiotics in aquafeed preparation. The present review also provides the challenges associated with the use of archaea for aquaculture and a brief outline of the patents on archaea to highlight the various use of archaea in different sectors.

5.
Sci Adv ; 7(14)2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33789892

RESUMO

Xinjiang is a key region in northwestern China, connecting East and West Eurasian populations and cultures for thousands of years. To understand the genetic history of Xinjiang, we sequenced 237 complete ancient human mitochondrial genomes from the Bronze Age through Historical Era (41 archaeological sites). Overall, the Bronze Age Xinjiang populations show high diversity and regional genetic affinities with Steppe and northeastern Asian populations along with a deep ancient Siberian connection for the Tarim Basin Xiaohe individuals. In the Iron Age, in general, Steppe-related and northeastern Asian admixture intensified, with North and East Xinjiang populations showing more affinity with northeastern Asians and South Xinjiang populations showing more affinity with Central Asians. The genetic structure observed in the Historical Era of Xinjiang is similar to that in the Iron Age, demonstrating genetic continuity since the Iron Age with some additional genetic admixture with populations surrounding the Xinjiang region.

6.
Molecules ; 26(8)2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33917039

RESUMO

Non-small cell lung cancer (NSCLC) is a lethal non-immunogenic malignancy and proto-oncogene ROS-1 tyrosine kinase is one of its clinically relevant oncogenic markers. The ROS-1 inhibitor, crizotinib, demonstrated resistance due to the Gly2032Arg mutation. To curtail this resistance, researchers developed lorlatinib against the mutated kinase. In the present study, a receptor-ligand pharmacophore model exploiting the key features of lorlatinib binding with ROS-1 was exploited to identify inhibitors against the wild-type (WT) and the mutant (MT) kinase domain. The developed model was utilized to virtually screen the TimTec flavonoids database and the retrieved drug-like hits were subjected for docking with the WT and MT ROS-1 kinase. A total of 10 flavonoids displayed higher docking scores than lorlatinib. Subsequent molecular dynamics simulations of the acquired flavonoids with WT and MT ROS-1 revealed no steric clashes with the Arg2032 (MT ROS-1). The binding free energy calculations computed via molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) demonstrated one flavonoid (Hit) with better energy than lorlatinib in binding with WT and MT ROS-1. The Hit compound was observed to bind in the ROS-1 selectivity pocket comprised of residues from the ß-3 sheet and DFG-motif. The identified Hit from this investigation could act as a potent WT and MT ROS-1 inhibitor.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33924408

RESUMO

The use of dental hand pieces endanger dentists to vibration exposure as they are subjected to very high amplitude and vibration frequency. This paper has envisaged a comparative analysis of vibration amplitudes and transmissibility during idling and drilling with micro motor (MM) and air-turbine (AT) hand pieces. The study aims to identify the mean difference in vibration amplitudes during idling, explore different grasp forces while drilling with irrigant injection by the dentist, and various vibration transmission of these hand pieces. The study utilized 22 separate frequency resonances on two new and eight used MMs and two new and eight used ATs of different brands by observing the investigator at 16 different dentist clinics. The study adopted a descriptive research design with non-probability sampling techniques for selecting dentists and hand pieces. Statistical methods like Levene Test of Homogeneity, Welch ANOVA, independent t-test, and Games-Howell test were utilized with SPSS version 22 and MS-Excel. The results reveal that vibration amplitudes and vibration transmissibility when measured at position 2 are higher than in another position 1. Vibrations during idling for used MMs are more than AT hand pieces, and the used MM (MUD) and used AT (AUA) hand pieces differ due to their obsolescence and over-usage. Vibration amplitudes increase every time with the tightening of grasping of the hand piece. Vibration amplitudes for each grasping style of MM hand piece differ from all other grasping styles of AT hand pieces. Routine exposure to consistent vibrations has ill physical, mental, and psychological effects on dentists. The used hand pieces more hazardous as compared to newer ones. The study suggests that these hand pieces must be replaced periodically, sufficient to break between two operations, especially after every hand piece usage. Hence, the present research work can be further extended by creating some control groups among dentists and then studying the vibration amplitude exposure of various dental hand pieces and subsequent transmissibility to their body parts.

8.
J Pharm Sci ; 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33684397

RESUMO

The novel coronavirus (SARS-CoV-2) outbreak has started taking away the millions of lives worldwide. Identification of known and approved drugs against novel coronavirus disease (COVID-19) seems to be an urgent need for the repurposing of the existing drugs. So, here we examined a safe strategy of using approved drugs of SuperDRUG2 database against modeled membrane protein (M-protein) of SARS-CoV-2 which is essential for virus assembly by using molecular docking-based virtual screening. A total of 3639 drugs from SuperDRUG2 database and additionally 14 potential drugs reported against COVID-19 proteins were selected. Molecular docking analyses revealed that nine drugs can bind the active site of M-protein with desirable molecular interactions. We therefore applied molecular dynamics simulations and binding free energy calculation using MM-PBSA to analyze the stability of the compounds. The complexes of M-protein with the selected drugs were simulated for 50 ns and ranked according to their binding free energies. The binding mode of the drugs with M-protein was analyzed and it was observed that Colchicine, Remdesivir, Bafilomycin A1 from COVID-19 suggested drugs and Temozolomide from SuperDRUG2 database displayed desirable molecular interactions and higher binding affinity towards M-protein. Interestingly, Colchicine was found as the top most binder among tested drugs against M-protein. We therefore additionally identified four Colchicine derivatives which can bind efficiently with M-protein and have better pharmacokinetic properties. We recommend that these drugs can be tested further through in vitro studies against SARS-CoV-2 M-protein.

9.
Semin Cancer Biol ; 2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33766649

RESUMO

Any alteration at the genetic or epigenetic level, may result in multiplex of diseases including tumorigenesis which ultimately results in the cancer development. Restoration of the normal epigenome by reversing the epigenetic alterations have been reported in tumors paving the way for development of an effective epigenetic treatment in cancer. However, delineating various epigenetic events has been a challenging task so far despite substantial progress in understanding DNA methylation and histone modifications during transcription of genes. Many inhibitors in the form of epigenetic drugs mostly targeting chromatin and histone modifying enzymes including DNA methyltransferase (DNMT) enzyme inhibitors and a histone deacetylases (HDACs) inhibitor, have been in use subsequent to the approval by FDA for cancer treatment. Similarly, other inhibitory drugs, such as FK228, suberoylanilide hydroxamic acid (SAHA) and MS-275, have been successfully tested in clinical studies. Despite all these advancements, still we see a hazy view as far as a promising epigenetic anticancer therapy is concerned. The challenges are to have more specific and effective inhibitors with negligible side effects. Moreover, the alterations seen in tumors are not well understood for which one has to gain deeper insight into the tumor pathology as well. Current review focusses on such epigenetic alterations occurring in cancer and the effective strategies to utilize such alterations for potential therapeutic use and treatment in cancer.

10.
Biomed Pharmacother ; 137: 111298, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33761590

RESUMO

The objective of this study was to evaluate the anticancer effects of Melstoma malabathricum L. (MM) MDA-MB-231 human breast cancer and in vivo mammary tumor model and decipher the potential mechanism. The phyto-constituents in the extract have been identified by liquid chromatography-mass spectrometry (LC-MS). The anti-cancer activity of MM extract was tested on MDA-MB-231 human breast cancer cells. Chemical carcinogen 7,12-dimethylbenz(a)anthracene (DMBA) was used for the induction of breast cancer in rodents. Burden, volume, tumor incidence, pro-inflammatory cytokines, antioxidant parameters and mitochondrial parameters were estimated. Histological analysis was determined in mammary gland, vagina, uterus, heart, liver, lung and renal tissues. LC-MS showed the 21 phyto-constituents present in the extract of MM. MM extract showed the potent cytotoxicity against MDA-MB-231 cells and exhibited the IC50 value (14.6 µM). MM extract significantly decreased the body weight and altered the organ weight such as ovary, uterus, liver, spleen, lungs, renal, adrenal and brain tissue. MM extract significantly down-regulated the tumor incidence, tumor burden and average tumor weight at dose dependently manner. MM extract significantly altered the antioxidants activity in term of augmented the level of superoxide dismutase (SOD), catalase (CAT) and suppressed the level of malonaldehyde (MDA); pro-inflammatory cytokines levels such as reduced the level of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6) in the serum, hepatic and mammary gland tissue in DMBA induced mammary gland tumor rats. MM extract significantly (P < 0.001) enhanced the activity of mitochondrial parameters include Isocitrate dehydrogenase (ICDH), succinate dehydrogenase (SDH), Malate dehydrogenase (MDH) and alpha-keto glutaraldehyde dehydrogenase (α-KGDH). The histopathological finding exhibited that MM extract has a marked reduced effect on mammary glands, mammary gland, vagina, uterus, heart, liver, lung and renal.These data provide the scientific evidence that MM extract might be used as a traditional medicine to cure the breast cancer.

11.
Zootaxa ; 4941(2): zootaxa.4941.2.2, 2021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33756938

RESUMO

Oneilliella shivii sp.n. (Panchaetothripinae) is described from India as the second species in this genus. Trachynotothrips brevispinis and T. striatus (Thripinae) are newly recorded from India, and the first description provided of the female of T. brevispinis. Partial sequence data of mitochondrial cytochrome c oxidase (mtCOI) of these species were generated.


Assuntos
Tisanópteros , Animais , Feminino , Índia , Mitocôndrias
12.
Environ Res ; 196: 110941, 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33647302

RESUMO

This study was aimed at reconstructing the exposure to bisphenol (BPA) of 60 pregnant women from the EXHES-Spain cohort. A biomonitoring study was conducted by determining BPA levels in urine samples over the three trimesters of pregnancy. Moreover, the correlations between BPA levels and the role of different potential exposure sources, with special emphasis on the dietary intake, were also studied. Urine samples were subjected to dispersive liquid-liquid microextraction and the subsequent analysis via gas chromatography-mass spectrometry. BPA was detected in 76% of the urine samples. A significant decrease of urinary BPA levels was observed along pregnancy, as mean concentrations of creatinine-adjusted BPA were 4.64, 4.84 and 2.51 µg/g in the first, second and third trimester, respectively. This decrease was essentially associated with changes in the dietary habits of the pregnant women, including a lower intake of canned food and drinks. However, the potential role of other pregnancy-related biochemical or physiological factors should not be disregarded. Very interestingly, significant differences in urine BPA levels were found according to the fruit consumption pattern, as women who ate more citrus fruits showed lower BPA concentrations in urine. The reconstructed exposure to BPA was estimated in 0.072, 0.069 and 0.038 µg BPA/kg of body weight/day in the first, second and third trimesters, respectively. These values are far below the temporary tolerable daily intake (t-TDI) established by the EFSA.

13.
Spectrochim Acta A Mol Biomol Spectrosc ; 254: 119622, 2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-33743304

RESUMO

Ultraviolet resonance Raman scattering (UVRR) has been frequently used for studying peptide and protein structure and dynamics, while applications in supramolecular chemistry are quite rare. Since UVRR offers the additional advantages of chromophore selectivity and high sensitivity compared with conventional non-resonant Raman scattering, it is ideally suited for label-free probing of relatively small artificial/supramolecular ligands exhibiting electronic resonances in the UV. In this perspective article, we first summarize results of UVRR spectroscopy in supramolecular chemistry in the context of peptide/protein recognition. We focus on selected artificial ligands which were rationally designed as selective carboxylate binders (guanidiniocarbonyl pyrrole, GCP, and guanidiniocarbonyl indole, GCI) and selective lysine binder (molecular tweezer, CLR01), respectively, via a combination of non-covalent interactions involving electrostatics, hydrogen bonding, and hydrophobic effects/van der Waals forces. Current limitations of applying UVRR as a universally applicable method for label-free and site-specific probing of molecular recognition between supramolecular ligands and proteins are highlighted. We then propose solutions to overcome these limitations for transforming UVRR spectroscopy into a generic tool in supramolecular chemistry on proteins, with an emphasis on mono- and multivalent GCP- and GCI-based ligands. Finally, we outline specific cases of supramolecular ligands such as molecular tweezers where alternative approaches such as laser-based mid-IR spectroscopy are required since UVRR can intrinsically not provide the required molecular information.

14.
Comp Biochem Physiol B Biochem Mol Biol ; 255: 110589, 2021 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-33657457

RESUMO

Replacement of fishmeal as the major protein source in feeds is critical for continued growth and sustainability of the aquaculture industry. However, numerous studies have shown suboptimal fish growth performance and reduced protein retention efficiency when carnivorous fish species are fed low fishmeal-high plant protein feeds. A study was conducted using a commercial strain and a genetically improved strain of rainbow trout selected for improved performance when fed an all plant protein diet to identify physiological differences associated with growth performance in the selected trout strain. Fifty individuals per strain (average weight ~ 580 g) were force-fed a plant-protein blend with and without amino acid supplementation (lysine, methionine and threonine) at 0.5% body weight and sampled at intervals over 24 h. Samples from intestine and liver were analyzed for specific gene expression analysis related to amino acid transporters, digestive process control, protein degradation and amino acid metabolism. The results showed that expression levels of various intestinal amino acid transporters (SLC1A1, SLC7A9, SLC15A, SLC1A5 SLC6A19 and SLC36A1) were affected by strain, diet and time. Moreover, significant interactions were found regarding the temporal expression levels of cholecystokinin (CCK-L), Krüppel-like factor 15 (KLF15) and aspartate aminotransferase (GOT) transcripts in the examined tissues. The results provide evidence that improved growth and protein retention of the selected strain fed an all-plant protein diet is a result of nutritional adaptation and an overall change in physiological homeostatic control.

15.
J Card Surg ; 36(4): 1370-1375, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33567115

RESUMO

BACKGROUND AND AIM OF THE STUDY: The morphological heterogeneity of anomalous pulmonary venous drainage in mixed type total anomalous pulmonary venous connection (TAPVC) has important implications in preoperative diagnosis and surgical repair resulting in high mortality in these patients. METHODS: A retrospective review of 14 patients with mixed type TAPVC undergoing biventricular repair between January 2012 and December 2019 was conducted. A descriptive analysis was done, highlighting the anatomic variation, diagnostic and surgical approach, and surgical outcomes in these patients. RESULTS: The most common anatomic pattern was "3 by 1" (79%) followed by "2 by 2" (21%). The correct diagnosis by transthoracic echocardiography was made in 10 (71%) of the 14 patients. In contrast, preoperative computed tomographic (CT) angiography was performed in 10 patients and correct diagnosis was obtained in 8 (80%) of them. Pulmonary venous obstruction was seen in one patient before surgery. The in-hospital mortality was 14% (2/14). Four patients had pulmonary hypertensive crisis in the postoperative period. The average follow-up was 54 ± 27 months (range: 17-98 months) after surgical repair, and all surviving patients were asymptomatic. There was no late death. No clinically apparent sequelae were seen in six patients in whom isolated left superior pulmonary vein drainage was left uncorrected. CONCLUSION: An accurate diagnosis of anatomic pattern in mixed type TAPVC can be difficult to establish in all the patients before surgery. Detailed intraoperative assessment, individualized surgical approach, and aggressive perioperative management may reduce surgical mortality. Operative survivors have good midterm outcome.

16.
NPJ Syst Biol Appl ; 7(1): 11, 2021 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-33589646

RESUMO

Advancements in systems biology have resulted in the development of network pharmacology, leading to a paradigm shift from "one-target, one-drug" to "target-network, multi-component therapeutics". We employ a chimeric approach involving in-vivo assays, gene expression analysis, cheminformatics, and network biology to deduce the regulatory actions of a multi-constituent Ayurvedic concoction, Amalaki Rasayana (AR) in animal models for its effect in pressure-overload cardiac hypertrophy. The proteomics analysis of in-vivo assays for Aorta Constricted and Biologically Aged rat models identify proteins expressed under each condition. Network analysis mapping protein-protein interactions and synergistic actions of AR using multi-component networks reveal drug targets such as ACADM, COX4I1, COX6B1, HBB, MYH14, and SLC25A4, as potential pharmacological co-targets for cardiac hypertrophy. Further, five out of eighteen AR constituents potentially target these proteins. We propose a distinct prospective strategy for the discovery of network pharmacological therapies and repositioning of existing drug molecules for treating pressure-overload cardiac hypertrophy.

17.
Biomed Pharmacother ; 137: 111356, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33561649

RESUMO

All the plants and their secondary metabolites used in the present study were obtained from Ayurveda, with historical roots in the Indian subcontinent. The selected secondary metabolites have been experimentally validated and reported as potent antiviral agents against genetically-close human viruses. The plants have also been used as a folk medicine to treat cold, cough, asthma, bronchitis, and severe acute respiratory syndrome in India and across the globe since time immemorial. The present study aimed to assess the repurposing possibility of potent antiviral compounds with SARS-CoV-2 target proteins and also with host-specific receptor and activator protease that facilitates the viral entry into the host body. Molecular docking (MDc) was performed to study molecular affinities of antiviral compounds with aforesaid target proteins. The top-scoring conformations identified through docking analysis were further validated by 100 ns molecular dynamic (MD) simulation run. The stability of the conformation was studied in detail by investigating the binding free energy using MM-PBSA method. Finally, the binding affinities of all the compounds were also compared with a reference ligand, remdesivir, against the target protein RdRp. Additionally, pharmacophore features, 3D structure alignment of potent compounds and Bayesian machine learning model were also used to support the MDc and MD simulation. Overall, the study emphasized that curcumin possesses a strong binding ability with host-specific receptors, furin and ACE2. In contrast, gingerol has shown strong interactions with spike protein, and RdRp and quercetin with main protease (Mpro) of SARS-CoV-2. In fact, all these target proteins play an essential role in mediating viral replication, and therefore, compounds targeting aforesaid target proteins are expected to block the viral replication and transcription. Overall, gingerol, curcumin and quercetin own multitarget binding ability that can be used alone or in combination to enhance therapeutic efficacy against COVID-19. The obtained results encourage further in vitro and in vivo investigations and also support the traditional use of antiviral plants preventively.


Assuntos
Catecóis/farmacologia , Curcumina/farmacologia , Álcoois Graxos/farmacologia , Medicina Ayurvédica/métodos , Quercetina/farmacologia , Antivirais/farmacologia , Reposicionamento de Medicamentos/métodos , Humanos , Simulação de Acoplamento Molecular , /fisiologia , Proteínas Virais/antagonistas & inibidores
18.
Artigo em Inglês | MEDLINE | ID: mdl-33567765

RESUMO

Seafood, one of the most important food commodities consumed worldwide, is considered a high-quality, healthy, and safe food option. However, marine ecosystems are the ultimate destination for a large group of chemicals, including contaminants of emerging concern, and seafood consumption is a major pathway of human exposure. With growing awareness of food safety and food quality, and increased demand for information on the risk of contaminants of emerging concern, there is a need to assess food safety issues related to harmful contaminants in seafood and ensure the safety of marine food resources. In this study, the risks of emerging compounds (endocrine disruptors, brominated flame retardants, pharmaceuticals and personal care products, and toxic elements) in fish and seafood were analyzed according to their PBT (persistence, bioaccumulation, toxicity) properties as well as in terms of their concentration levels in seafood. A hazard index (HI) was estimated for each compound by applying an artificial neural network (ANN) approach known as Self-Organizing-Maps. Subsequently, an integrated risk rank (IRI) was developed considering the values of HI and the concentrations of emerging compounds in seafood species gathered from the scientific literature. Current results identified HHCB, MeHg, NP, AHTN and PBDE209 as the top five highest ranked compounds present in seafood, according to the 50th percentile (mean) of the IRI. However, this ranking slightly changed when taking into account the 99th percentile of the IRI, showing toxic elements, methylmercury and inorganic arsenic, as having the highest risk. The outcome of this study identified the priority contaminants and should help in regulatory decision-making and scientific panels to design screening programs as well as to take the appropriate safety measures.


Assuntos
Alimentos Marinhos , Poluentes Químicos da Água , Animais , Ecossistema , Europa (Continente) , Contaminação de Alimentos/análise , Humanos , Redes Neurais de Computação , Alimentos Marinhos/análise , Poluentes Químicos da Água/análise
19.
Artigo em Inglês | MEDLINE | ID: mdl-33607333

RESUMO

BACKGROUND: We propose a new clinical assessment tool constructed using machine learning, called the Shoulder Arthroplasty Smart (SAS) score to quantify outcomes following total shoulder arthroplasty (TSA). METHODS: Clinical data from 3667 TSA patients with 8104 postoperative follow-up reports were used to quantify the psychometric properties of validity, responsiveness, and clinical interpretability for the proposed SAS score and each of the Simple Shoulder Test (SST), Constant, American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES), University of California Los Angeles (UCLA), and Shoulder Pain and Disability Index (SPADI) scores. RESULTS: Convergent construct validity was demonstrated, with all 6 outcome measures being moderately to highly correlated preoperatively and highly correlated postoperatively when quantifying TSA outcomes. The SAS score was most correlated with the UCLA score and least correlated with the SST. No clinical outcome score exhibited significant floor effects preoperatively or postoperatively or significant ceiling effects preoperatively; however, significant ceiling effects occurred postoperatively for each of the SST (44.3%), UCLA (13.9%), ASES (18.7%), and SPADI (19.3%) measures. Ceiling effects were more pronounced for anatomic than reverse TSA, and generally, men, younger patients, and whites who received TSA were more likely to experience a ceiling effect than TSA patients who were female, older, and of non-white race or ethnicity. The SAS score had the least number of patients with floor and ceiling effects and also exhibited no response bias in any patient characteristic analyzed in this study. Regarding clinical interpretability, patient satisfaction anchor-based thresholds for minimal clinically importance difference and substantial clinical benefit were quantified for all 6 outcome measures; the SAS score thresholds were most similar in magnitude to the Constant score. Regarding responsiveness, all 6 outcome measures detected a large effect, with the UCLA exhibiting the most responsiveness and the SST exhibiting the least. Finally, each of the SAS, ASES, Constant, and SPADI scores had similarly large standardized response mean and effect size responsiveness. DISCUSSION: The 6-question SAS score is an efficient TSA-specific outcome measure with equivalent or better validity, responsiveness, and clinical interpretability as 5 other historical assessment tools. The SAS score has an appropriate response range without floor or ceiling effects and without bias in any target patient characteristic, unlike the age, gender, or race/ethnicity bias observed in the ceiling scores with the other outcome measures. Because of these substantial benefits, we recommend the use of the new SAS score for quantifying TSA outcomes.

20.
Curr Pharm Des ; 2021 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-33550966

RESUMO

The spike (S) glycoprotein of SARS coronavirus (SARS-CoV-2) and human Angiotensin-converting enzyme 2 (ACE2), are both considered the key factors for the initiation of virus infection. The present work is an effort for a computational target to block the spike proteins (S) and ACE2 receptor proteins with Macrolide antibiotics like Azithromycin, (AZM), Clarithromycin (CLAM) and Erythromycin (ERY) along with RNA-dependent RNA polymerase (RdRp). These compounds were able to block the residues (Arg553, Arg555, and Ala558) surrounding the deep grove catalytic site (Val557) of RdRp and thus plays an important role in tight blocking of enzyme active site. Reference drug Remdesivir was used to compare the docking score of antibiotics with RdRp. Docking value exhibited good binding energy (-7.7 up to -8.2 kcal/mol) with RdRp, indicating their potential as a potent RdRp inhibitor. Interaction of CLAM and ERY presented low binding energy (-6.8 and -6.6) with the ACE2 receptor. At the same time, CLAM exhibited a good binding affinity of -6.4 kcal/mol, making it an excellent tool to block the attachment of spike protein to ACE2 receptors. Macrolides not only affected the attachment to ACE2 but also blocked the spike proteins further, consequently inhibiting the internalization in the host cell. Three Alkyl bonds between Arg555, Ala558, and Met542 by CLAM and two Alkyl bonds of Arg624 and Lys621 by ERY plays an important role for RdRp inactivation that can prevent the rise of newly budded progeny virus. These macrolides interacted with the main protease protein in the pocket responsible for the dimerization and catalytic function of this protein. The interaction occurred with residue Glu166, along with the catalytic residues (Tyr343, and His235) of Endoribonuclease (NSP15) protein. The present study gives three-way options either by blocking S proteins or ACE2 receptor proteins or inhibiting RdRp to counter any effect of COVID-19 by macrolide and could be useful in the treatment of COVID-19 till some better option available.

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