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1.
J Pharm Sci ; 113(4): 906-917, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38042341

RESUMO

The West Nile virus (WNV) is the causative agent of West Nile disease (WND), which poses a potential risk of meningitis or encephalitis. The aim of the study was to design an epitope-based vaccine for WNV by utilizing computational analyses. The epitope-based vaccine design process encompassed WNV sequence collection, phylogenetic tree construction, and sequence alignment. Computational models identified B-cell and T-cell epitopes, followed by immunological property analysis. Epitopes were then modeled and docked with B-cell receptors, MHC I, and MHC II. Molecular dynamics simulations further explored dynamic interactions between epitopes and receptors. The findings indicated that the B-cell epitope QINHHWHKSGSSIG, along with three T-cell epitopes (FLVHREWFM for MHC I, NPFVSVATANAKVLI for MHC II, and NAYYVMTVGTKTFLV for MHC II), successfully passed the immunological evaluations. These four epitopes were further subjected to docking and molecular dynamics simulation studies. Although each demonstrated favorable affinities with their respective receptors, only NAYYVMTVGTKTFLV displayed a stable interaction with MHC II during MDS analysis, hence emerging as a potential candidate for a WNV epitope-based vaccine. This study demonstrates a comprehensive approach to epitope vaccine design, combining computational analyses, molecular modeling, and simulation techniques to identify potential vaccine candidates for WNV.


Assuntos
Vírus do Nilo Ocidental , Epitopos de Linfócito T , Imunoinformática , Filogenia , Epitopos de Linfócito B , Simulação de Acoplamento Molecular , Biologia Computacional/métodos , Vacinas de Subunidades Antigênicas
2.
Curr Oncol ; 30(2): 1954-1976, 2023 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-36826113

RESUMO

Gene editing, especially with clustered regularly interspaced short palindromic repeats associated protein 9 (CRISPR-Cas9), has advanced gene function science. Gene editing's rapid advancement has increased its medical/clinical value. Due to its great specificity and efficiency, CRISPR/Cas9 can accurately and swiftly screen the whole genome. This simplifies disease-specific gene therapy. To study tumor origins, development, and metastasis, CRISPR/Cas9 can change genomes. In recent years, tumor treatment research has increasingly employed this method. CRISPR/Cas9 can treat cancer by removing genes or correcting mutations. Numerous preliminary tumor treatment studies have been conducted in relevant fields. CRISPR/Cas9 may treat gene-level tumors. CRISPR/Cas9-based personalized and targeted medicines may shape tumor treatment. This review examines CRISPR/Cas9 for tumor therapy research, which will be helpful in providing references for future studies on the pathogenesis of malignancy and its treatment.


Assuntos
Sistemas CRISPR-Cas , Neoplasias , Humanos , Edição de Genes/métodos , Terapia Genética/métodos , Fenótipo
3.
Microorganisms ; 11(2)2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36838306

RESUMO

The scale at which the SARS-CoV-2/COVID-19 pandemic has spread remains enormous. Provided the genetic makeup of the virus and humans is readily available, the quest for knowing the mechanism and epidemiology continues to prevail across the entire scientific community. Several aspects, including immunology, molecular biology, and host-pathogen interaction, are continuously being dug into for preparing the human race for future pandemics. The exact reasons for vast differences in symptoms, pathophysiological implications of COVID-infections, and mortality differences remain elusive. Hence, researchers are also looking beyond traditional genomics, proteomics, and transcriptomics approach, especially entrusting the environmental regulation of the genetic landscape of COVID-human interactions. In line with these questions lies a critical process called epigenetics. The epigenetic perturbations in both host and parasites are a matter of great interest to unravel the disparities in COVID-19 mortalities and pathology. This review provides a deeper insight into current research on the epigenetic landscape of SARS-CoV-2 infection in humans and potential targets for augmenting the ongoing investigation. It also explores the potential targets, pathways, and networks associated with the epigenetic regulation of processes involved in SARS-CoV-2 pathology.

4.
Molecules ; 27(24)2022 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-36557793

RESUMO

Conventional anticancer treatments, such as radiotherapy and chemotherapy, have significantly improved cancer therapy. Nevertheless, the existing traditional anticancer treatments have been reported to cause serious side effects and resistance to cancer and even to severely affect the quality of life of cancer survivors, which indicates the utmost urgency to develop effective and safe anticancer treatments. As the primary focus of cancer nanotheranostics, nanomaterials with unique surface chemistry and shape have been investigated for integrating cancer diagnostics with treatment techniques, including guiding a prompt diagnosis, precise imaging, treatment with an effective dose, and real-time supervision of therapeutic efficacy. Several theranostic nanosystems have been explored for cancer diagnosis and treatment in the past decade. However, metal-based nanotheranostics continue to be the most common types of nonentities. Consequently, the present review covers the physical characteristics of effective metallic, functionalized, and hybrid nanotheranostic systems. The scope of coverage also includes the clinical advantages and limitations of cancer nanotheranostics. In light of these viewpoints, future research directions exploring the robustness and clinical viability of cancer nanotheranostics through various strategies to enhance the biocompatibility of theranostic nanoparticles are summarised.


Assuntos
Nanopartículas Multifuncionais , Nanopartículas , Nanoestruturas , Neoplasias , Humanos , Medicina de Precisão , Qualidade de Vida , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Nanoestruturas/uso terapêutico , Nanopartículas/uso terapêutico , Nanomedicina Teranóstica/métodos
5.
Cancers (Basel) ; 14(22)2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36428686

RESUMO

As medical science and technology progress towards the era of "big data", a multi-dimensional dataset pertaining to medical diagnosis and treatment is becoming accessible for mathematical modelling. However, these datasets are frequently inconsistent, noisy, and often characterized by a significant degree of redundancy. Thus, extensive data processing is widely advised to clean the dataset before feeding it into the mathematical model. In this context, Artificial intelligence (AI) techniques, including machine learning (ML) and deep learning (DL) algorithms based on artificial neural networks (ANNs) and their types, are being used to produce a precise and cross-sectional illustration of clinical data. For prostate cancer patients, datasets derived from the prostate-specific antigen (PSA), MRI-guided biopsies, genetic biomarkers, and the Gleason grading are primarily used for diagnosis, risk stratification, and patient monitoring. However, recording diagnoses and further stratifying risks based on such diagnostic data frequently involves much subjectivity. Thus, implementing an AI algorithm on a PC's diagnostic data can reduce the subjectivity of the process and assist in decision making. In addition, AI is used to cut down the processing time and help with early detection, which provides a superior outcome in critical cases of prostate cancer. Furthermore, this also facilitates offering the service at a lower cost by reducing the amount of human labor. Herein, the prime objective of this review is to provide a deep analysis encompassing the existing AI algorithms that are being deployed in the field of prostate cancer (PC) for diagnosis and treatment. Based on the available literature, AI-powered technology has the potential for extensive growth and penetration in PC diagnosis and treatment to ease and expedite the existing medical process.

6.
Vaccines (Basel) ; 10(7)2022 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-35891149

RESUMO

COVID-19, caused by SARS-CoV-2, is one of the longest viral pandemics in the history of mankind, which have caused millions of deaths globally and induced severe deformities in the survivals. For instance, fibrosis and cavities in the infected lungs of COVID-19 are some of the complications observed in infected patients post COVID-19 recovery. These health abnormalities, including is multiple organ failure-the most striking pathological features of COVID-19-have been linked with diverse distribution of ACE2 receptor. Additionally, several health complications reports were reported after administration of COVID-19 vaccines in healthy individuals, but clinical or molecular pathways causing such complications are not yet studied in detail. Thus, the present systematic review established the comparison of health complication noted in vaccinated and non-vaccinated individuals (COVID-19 infected patients) to identify the association between vaccination and the multiorgan failure based on the data obtained from case studies, research articles, clinical trials/Cohort based studies and review articles published between 2020-2022. This review also includes the biological rationale behind the COVID-19 infection and its subsequent symptoms and effects including multiorgan failure. In addition, multisystem inflammatory syndrome (MIS) has been informed in individuals post vaccination that resulted in multiorgan failure but, no direct correlation of vaccination with MIS has been established. Similarly, hemophagocytic lymphohistiocytosis (HLH) also noted to cause multiorgan failure in some individuals following full vaccination. Furthermore, severe complications were recorded in elderly patients (+40 years of age), indicates that older age individuals are higher risk by COVID-19 and post vaccination, but available literature is not sufficient to comply with any conclusive statements on relationship between vaccination and multiorgan failure.

7.
Medicina (Kaunas) ; 58(7)2022 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-35888623

RESUMO

Background and Objective: Bacterial infections are among the major complications of many viral respiratory tract illnesses, such as influenza and coronavirus disease-2019 (COVID-19). These bacterial co-infections are associated with an increase in morbidity and mortality rates. The current observational study was conducted at a tertiary care hospital in Lahore, Pakistan among COVID-19 patients with the status of oxygen dependency to see the prevalence of bacterial co-infections and their antibiotic susceptibility patterns. Materials and Methods: A total of 1251 clinical samples were collected from already diagnosed COVID-19 patients and tested for bacterial identification (cultures) and susceptibility testing (disk diffusion and minimum inhibitory concentration) using gold standard diagnostic methods. Results: From the total collected samples, 234 were found positive for different bacterial isolates. The most common isolated bacteria were Escherichia coli (E. coli) (n = 62) and Acinetobacter baumannii (A. baumannii) (n = 47). The E. coli isolates have shown the highest resistance to amoxicillin and ampicillin, while in the case of A. baumannii, the highest resistance was noted against tetracycline. The prevalence of methicillin resistant Staphylococcus aureus (MRSA) was 14.9%, carbapenem resistant Enterobacteriaceae (CRE) was 4.5%, and vancomycin resistant Enterococcus (VRE) was 3.96%. Conclusions: The results of the current study conclude that empiric antimicrobial treatment in critically ill COVID-19 patients may be considered if properly managed within institutional or national level antibiotic stewardship programs, because it may play a protective role in the case of bacterial co-infections, especially when a patient has other AMR risk factors, such as hospital admission within the previous six months.


Assuntos
Acinetobacter baumannii , COVID-19 , Coinfecção , Staphylococcus aureus Resistente à Meticilina , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Coinfecção/tratamento farmacológico , Coinfecção/epidemiologia , Resistência Microbiana a Medicamentos , Escherichia coli , Humanos , Paquistão/epidemiologia
8.
Antibiotics (Basel) ; 11(6)2022 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-35740190

RESUMO

Artificial intelligence (AI) is a branch of science and engineering that focuses on the computational understanding of intelligent behavior. Many human professions, including clinical diagnosis and prognosis, are greatly useful from AI. Antimicrobial resistance (AMR) is among the most critical challenges facing Pakistan and the rest of the world. The rising incidence of AMR has become a significant issue, and authorities must take measures to combat the overuse and incorrect use of antibiotics in order to combat rising resistance rates. The widespread use of antibiotics in clinical practice has not only resulted in drug resistance but has also increased the threat of super-resistant bacteria emergence. As AMR rises, clinicians find it more difficult to treat many bacterial infections in a timely manner, and therapy becomes prohibitively costly for patients. To combat the rise in AMR rates, it is critical to implement an institutional antibiotic stewardship program that monitors correct antibiotic use, controls antibiotics, and generates antibiograms. Furthermore, these types of tools may aid in the treatment of patients in the event of a medical emergency in which a physician is unable to wait for bacterial culture results. AI's applications in healthcare might be unlimited, reducing the time it takes to discover new antimicrobial drugs, improving diagnostic and treatment accuracy, and lowering expenses at the same time. The majority of suggested AI solutions for AMR are meant to supplement rather than replace a doctor's prescription or opinion, but rather to serve as a valuable tool for making their work easier. When it comes to infectious diseases, AI has the potential to be a game-changer in the battle against antibiotic resistance. Finally, when selecting antibiotic therapy for infections, data from local antibiotic stewardship programs are critical to ensuring that these bacteria are treated quickly and effectively. Furthermore, organizations such as the World Health Organization (WHO) have underlined the necessity of selecting the appropriate antibiotic and treating for the shortest time feasible to minimize the spread of resistant and invasive resistant bacterial strains.

9.
Vaccines (Basel) ; 10(6)2022 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-35746477

RESUMO

Human Parainfluenza Virus (HPIV) Type-1, which is an anti-sense ribonucleic acid (RNA) virus belonging to the paramyxoviridae family, induces upper and lower respiratory tract infections. The infections caused by the HPIV Type-1 virus are usually confined to northwestern regions of America. HPIV-1 causes infections through the virulence of the hemagglutinin-neuraminidase (HN) protein, which plays a key role in the attachment of the viral particle with the host's receptor cells. To the best of our knowledge, there is no effective antiviral drugs or vaccines being developed to combat the infection caused by HPIV-1. In the current study, a multiple epitope-based vaccine was designed against HPIV-1 by taking the viral HN protein as a probable vaccine candidate. The multiple epitopes were selected in accordance with their allergenicity, antigenicity and toxicity scoring. The determined epitopes of the HN protein were connected simultaneously using specific conjugates along with an adjuvant to construct the subunit vaccine, with an antigenicity score of 0.6406. The constructed vaccine model was docked with various Toll-like Receptors (TLRs) and was computationally cloned in a pET28a (+) vector to analyze the expression of vaccine sequence in the biological system. Immune stimulations carried out by the C-ImmSim Server showed an excellent result of the body's defense system against the constructed vaccine model. The AllerTop tool predicted that the construct was non-allergen with and without the adjuvant sequence, and the VaxiJen 2.0 with 0.4 threshold predicted that the construct was antigenic, while the Toxinpred predicted that the construct was non-toxic. Protparam results showed that the selected protein was stable with 36.48 instability index (II) scores. The Grand average of Hydropathicity or GRAVY score indicated that the constructed protein was hydrophilic in nature. Aliphatic index values (93.53) confirmed that the construct was thermostable. This integrated computational approach shows that the constructed vaccine model has a potential to combat laryngotracheobronchitis infections caused by HPIV-I.

10.
Molecules ; 27(10)2022 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-35630660

RESUMO

In the present study, chitosan-decorated multiple nanoemulsion (MNE) was formulated using a two-step emulsification process. The formulated multiple nanoemuslion was evaluated physiochemically for its size and zeta potential, surface morphology, creaming and cracking, viscosity and pH. A Franz diffusion cell apparatus was used to carry out in vitro drug-release and permeation studies. The formulated nanoemulsion showed uniform droplet size and zeta potential. The pH and viscosity of the formulated emulsion were in the range of and suitable for topical delivery. The drug contents of the simple nanoemulsion (SNE), the chitosan-decorated nanoemulsion (CNE) and the MNE were 71 ± 2%, 82 ± 2% and 90 ± 2%, respectively. The formulated MNE showed controlled release of itraconazole as compared with that of the SNE and CNE. This was attributed to the chitosan decoration as well as to formulating multiple emulsions. The significant permeation and skin drug retention profile of the MNE were attributed to using the surfactants tween 80 and span 20 and the co-surfactant PEG 400. ATR-FTIR analysis confirmed that the MNE mainly affects the lipids and proteins of the skin, particularly the stratum corneum, which results in significantly higher permeation and retention of the drug. It was concluded that the proposed MNE formulation delivers drug to the target site of the skin and can be therapeutically used for various cutaneous fungal infections.


Assuntos
Quitosana , Administração Cutânea , Quitosana/química , Emulsões/química , Pele/metabolismo , Absorção Cutânea , Tensoativos/metabolismo
11.
Genes (Basel) ; 13(4)2022 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-35456478

RESUMO

Human DNA contains several variations, which can affect the structure and normal functioning of a protein. These variations could be single nucleotide polymorphisms (SNPs) or insertion-deletions (InDels). SNPs, as opposed to InDels, are more commonly present in DNA and may cause genetic disorders. In the current study, several bioinformatic tools were used to prioritize the pathogenic variants in the SLITRK1 gene. Out of all of the variants, 16 were commonly predicted to be pathogenic by these tools. All the variants had very low frequency, i.e., <0.0001 in the global population. The secondary structure of all filtered variants was predicted, but no structural change was observed at the site of variation in any variant. Protein stability analysis of these variants was then performed, which determined a decrease in protein stability of 10 of the variants. Amino acid conservation analysis revealed that all the amino acids were highly conserved, indicating their structural and functional importance. Protein 3D structure of wildtype SLITRK1 and all of its variants was predicted using I-TASSER, and the effect of variation on 3D structure of the protein was observed using the Missense3D tool, which presented the probable structural loss in three variants, i.e., Asn529Lys, Leu496Pro and Leu94Phe. The wildtype SLITRK1 protein and these three variants were independently docked with their close interactor protein PTPRD, and remarkable differences were observed in the docking sites of normal and variants, which will ultimately affect the functional activity of the SLITRK1 protein. Previous studies have shown that mutations in SLITRK1 are involved in Tourette syndrome. The present study may assist a molecular geneticist in interpreting the variant pathogenicity in research as well as diagnostic setup.


Assuntos
Polimorfismo de Nucleotídeo Único , Síndrome de Tourette , Biologia Computacional , Humanos , Proteínas de Membrana/genética , Mutação , Proteínas do Tecido Nervoso/genética , Polimorfismo de Nucleotídeo Único/genética , Estabilidade Proteica , Síndrome de Tourette/genética
12.
Genes (Basel) ; 13(4)2022 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-35456504

RESUMO

The L-2-hydroxyglutarate dehydrogenase (L2HGDH) gene encodes an important mitochondrial enzyme. However, its altered activity results in excessive levels of L-2-hydroxyglutarate, which results in diverse psychiatric features of intellectual disability. In the current study, we executed an in-silico analysis of all reported L2HGDH missense and nonsense variants in order to investigate their biological significance. Among the superimposed 3D models, the highest similarity index for a wild-type structure was shown by the mutant Glu336Lys (87.26%), while the lowest similarity index value was shown by Arg70* (10.00%). Three large active site pockets were determined using protein active site prediction, in which the 2nd largest pocket was shown to encompass the substrate L-2-hydroxyglutarate (L2HG) binding residues, i.e., 89Gln, 195Tyr, 402Ala, 403Gly and 404Val. Moreover, interactions of wild-type and mutant L2HGDH variants with the close functional interactor D2HGDH protein resulted in alterations in the position, number and nature of networking residues. We observed that the binding of L2HG with the L2HGDH enzyme is affected by the nature of the amino acid substitution, as well as the number and nature of bonds between the substrate and protein molecule, which are able to affect its biological activity.


Assuntos
Oxirredutases do Álcool , Deficiência Intelectual , Oxirredutases do Álcool/genética , Oxirredutases do Álcool/metabolismo , Humanos , Mutação
13.
Cancers (Basel) ; 14(8)2022 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-35454766

RESUMO

The role of tumor-associated macrophages (TAMs) in the pathogenesis of hepatocellular carcinoma (HCC) is poorly understood. Most studies rely on platforms that remove intrahepatic macrophages from the microenvironment prior to evaluation. Cell isolation causes activation and phenotypic changes that may not represent their actual biology and function in situ. State-of-the-art methods provides new strategies to study TAMs without losing the context of tissue architecture and spatial relationship with neighboring cells. These technologies, such as multispectral imaging (e.g., Vectra Polaris), mass cytometry by time-of-flight (e.g., Fluidigm CyTOF), cycling of fluorochromes (e.g., Akoya Biosciences CODEX/PhenoCycler-Fusion, Bruker Canopy, Lunaphore Comet, and CyCIF) and digital spatial profiling or transcriptomics (e.g., GeoMx or Visium, Vizgen Merscope) are being utilized to accurately assess the complex cellular network within the tissue microenvironment. In cancer research, these platforms enable characterization of immune cell phenotypes and expression of potential therapeutic targets, such as PDL-1 and CTLA-4. Newer spatial profiling platforms allow for detection of numerous protein targets, in combination with whole transcriptome analysis, in a single liver biopsy tissue section. Macrophages can also be specifically targeted and analyzed, enabling quantification of both protein and gene expression within specific cell phenotypes, including TAMs. This review describes the workflow of each platform, summarizes recent research using these approaches, and explains the advantages and limitations of each.

14.
Polymers (Basel) ; 14(7)2022 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-35406184

RESUMO

This study attempted to develop and evaluate controlled-release matrix-type transdermal patches with different ratios of hydrophilic polymers (sodium carboxymethylcellulose and hydroxypropyl methylcellulose) for the local delivery of methotrexate. Transdermal patches were formulated by employing a solvent casting technique using blends of sodium carboxymethylcellulose (CMC-Na) and hydroxypropylmethylcellulose (HPMC) polymers as rate-controlling agents. The F1 formulated patch served as the control formulation with a 1:1 polymer concentration. The F9 formulation served as our optimized formulation due to suitable physicochemical properties yielded through the combination of CMC-Na and HPMC (5:1). Drug excipient compatibilities (ATR-FTIR) were performed as a preformulation study. The ATR-FTIR study depicted great compatibility between the drug and the polymers. Physicochemical parameters, kinetic modeling, in vitro drug release, ex vivo drug permeation, skin drug retention, and in vivo studies were also carried out for the formulated patches. The formulated patches exhibited a clear, smooth, elastic nature with good weight uniformity, % moisture uptake, drug content, and thickness. Physicochemical characterization revealed folding endurance ranging from 62 ± 2.21 to 78 ± 1.54, tensile strength from 9.42 ± 0.52 to 12.32 ± 0.72, % swelling index from 37.16 ± 0.17 to 76.24 ± 1.37, and % drug content from 93.57 ± 5.34 to 98.19 ± 1.56. An increase in the concentration of the CMC-Na polymer (F9) resulted in increased drug release from the formulated transdermal patches. Similarly, drug permeation and retention were found to be higher in the F9 formulation compared to the other formulations (F1-F8). A drug retention analysis revealed that the F9 formulation exhibited 13.43% drug retention in the deep layers of the skin compared to other formulations (F1-F8). The stability study indicated that, during the study period of 60 days, no significant changes in the drug content and physical characteristics were found. ATR-FTIR analysis of rabbit skin samples treated with the formulated transdermal patches revealed that hydrophilic polymers mainly affect the skin proteins (ceramide and keratins). A pharmacokinetic profile revealed Cmax was 1.77.38 ng/mL, Tmax was 12 h, and t1/2 was 17.3 ± 2.21. In vivo studies showed that the skin drug retention of F9 was higher compared to the drug solution. These findings reinforce that methotrexate-based patches can possibly be used for the management of psoriasis. This study can reasonably conclude that methotrexate transdermal matrix-type patches with CMC-Na and HPMC polymers at different concentrations effectively sustain drug release with prime permeation profiles and better bioavailability. Therefore, these formulated patches can be employed for the potential management of topical diseases, such as psoriasis.

15.
Gels ; 8(2)2022 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-35200510

RESUMO

The currently available topical formulations of tacrolimus have minimal and variable absorption, elevated mean disposition half-life, and skin irritation effects resulting in patient noncompliance. In our study, we fabricated tacrolimus-loaded solid lipid nanoparticles (SLNs) that were converted into a gel for improved topical applications. The SLNs were prepared using a solvent evaporation method and characterized for their physicochemical properties. The particle size of the SLNs was in the range of 439 nm to 669 nm with a PDI of ≤0.4, indicating a monodispersed system. The Zeta potential of uncoated SLNs (F1-F5) ranged from -25.80 to -15.40 mV. Those values reverted to positive values for chitosan-decorated formulation (F6). The drug content and entrapment efficiency ranged between 0.86 ± 0.03 and 0.91 ± 0.03 mg/mL and 68.95 ± 0.03 and 83.68 ± 0.04%, respectively. The pH values of 5.45 to 5.53 depict their compatibility for skin application. The surface tension of the SLNs decreased with increasing surfactant concentration that could increase the adherence of the SLNs to the skin. The release of drug from gel formulations was significantly retarded in comparison to their corresponding SLN counterparts (p ≤ 0.05). Both SLNs and their corresponding gel achieved the same level of drug permeation, but the retention of the drug was significantly improved with the conversion of SLNs into their corresponding gel formulation (p ≤ 0.05) due to its higher bioadhesive properties.

16.
Int J Mol Sci ; 23(2)2022 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-35054816

RESUMO

The efficiency of the RNA-guided AsCas12a nuclease of Acidaminococcus sp. was compared with SpCas9 from Streptococcus pyogenes, for functional genomics in Schistosoma mansoni. We deployed optimized conditions for the ratio of guide RNAs to the nuclease, donor templates, and electroporation parameters, to target a key schistosome enzyme termed omega-1. Programmed cleavages catalyzed by Cas12a and Cas9 resulted in staggered- and blunt-ended strand breaks, respectively. AsCas12a was more efficient than SpCas9 for gene knockout, as determined by TIDE analysis. CRISPResso2 analysis confirmed that most mutations were deletions. Knockout efficiency of both nucleases markedly increased in the presence of single-stranded oligodeoxynucleotide (ssODN) template. With AsCas12a, ssODNs representative of both the non-CRISPR target (NT) and target (T) strands were tested, resulting in KO efficiencies of 15.67, 28.71, and 21.43% in the SpCas9 plus ssODN, AsCas12a plus NT-ssODN, and AsCas12a plus T-ssODN groups, respectively. Trans-cleavage against the ssODNs by activated AsCas12a was not apparent in vitro. SpCas9 catalyzed more precise transgene insertion, with knock-in efficiencies of 17.07% for the KI_Cas9 group, 14.58% for KI_Cas12a-NT-ssODN, and 12.37% for KI_Cas12a-T-ssODN. Although AsCas12a induced fewer mutations per genome than SpCas9, the phenotypic impact on transcription and expression of omega-1 was similar for both nucleases.


Assuntos
Técnicas de Inativação de Genes , Genes de Protozoários , Loci Gênicos , RNA Guia de Cinetoplastídeos/metabolismo , Reparo de DNA por Recombinação , Ribonucleases/genética , Schistosoma mansoni/genética , Animais , Sequência de Bases , Sistemas CRISPR-Cas/genética , Catálise , Feminino , Dosagem de Genes , Humanos , Mutação/genética , Oligonucleotídeos/metabolismo , Reparo de DNA por Recombinação/genética , Padrões de Referência , Transcrição Gênica , Transgenes
17.
Polymers (Basel) ; 14(1)2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-35012201

RESUMO

Polypropylene (PP) is a semi-crystalline polymer that is brittle under severe conditions. To meet industry needs, and to increase the applications of polypropylene, its mechanical properties should be improved. In this research, the mechanical properties of polypropylene, such as tensile strength at break, tensile strength at yield, % elongation, and Young's modulus, were improved using two types of additives. Additives used were calcium carbonate master batch filler composed of 80% calcium carbonate and 20% polyethylene, and a mixture of linear low-density polyethylene (LLDPE)/low density polyethylene (LDPE). Results showed that both tensile strength at break, and tensile strength at yield, decrease with increasing the amount of both additives. Percentage elongation of PP increased using both additives. The modulus of elasticity of PP increases by increasing the amount of both additives, until a value of 20 wt%. Analysis of variance (ANOVA test) or (F-test) shows significant differences between the effect of different weights of LLDPE/LDPE mixture and calcium carbonate filler on the four mechanical properties of polypropylene studied at a level of 0.05. T-tests are applied to compare between the effect of both calcium carbonate master batch filler and the mixture LLDPE/LDPE on the four mechanical properties of polypropylene studied. T-tests show no significant differences between the effect of both calcium carbonate master batch filler and the mixture LLDPE/LDPE on all mechanical properties of polypropylene studied at a level of 0.05.

18.
Khirurgiia (Mosk) ; (6. Vyp. 2): 59-64, 2021.
Artigo em Russo | MEDLINE | ID: mdl-34032790

RESUMO

OBJECTIVE: To determine the criteria for choosing a surgical approach and compare an effectiveness of carotid endarterectomy (CEAE) via 3 approaches. MATERIAL AND METHODS: The study included 120 patients who underwent CEAE via 3 different approaches. Intraoperative skin marking included lower jaw angle, skin fold closest to common carotid artery bifurcation. Carotid artery bifurcation and borders of atherosclerotic plaque were visualized using ultrasound. An effectiveness of each access was evaluated in accordance with the following criteria: neurological complications, cosmetic effect and quality of life after 1 and 12 months. The patients were divided into 2 groups. Group I - 80 patients with CEAE with access through the natural skin fold (NSF); group II - 40 patients with CEAE using the classical longitudinal access. The 1st group was divided into 2 subgroups. Subgroup I A - 39 patients with CEAE using mini-access via NSF; subgroup I B - 41 patients with CEAE using extended access via NSF. RESULTS: There were no strokes and transient ischemic attacks in a month after surgery in both groups. After 12 months, stroke occurred in 2 (%) patients of group II, cranial neuropathy - 8 (21%) patients in the same group. The best cosmic effect was achieved in subgroup I A after 1 and 12 months (37.1±6.7 scores). Mean score of physical health was 51.59±5.9 scores in subgroup I A, 46.03±7.53 scores - in subgroup I B, 38.84±5.28 scores - in group II. Index of mental health was 49.63±6.69, 45.68±5.6, and 48.59±7.29 scores, respectively. CONCLUSION: Considering these data, we developed a personalized computer program ensuring fast choice of optimal surgical approach.


Assuntos
Estenose das Carótidas , Endarterectomia das Carótidas , Acidente Vascular Cerebral , Artérias Carótidas , Artéria Carótida Primitiva , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/cirurgia , Endarterectomia das Carótidas/efeitos adversos , Humanos , Qualidade de Vida , Resultado do Tratamento
19.
Nanomaterials (Basel) ; 12(1)2021 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-35010069

RESUMO

The demand for supercapacitors has been high during the integration of renewable energy devices into the electrical grid. Although activated carbon materials have been widely utilized as supercapacitor electrodes, the need for economic and sustainable processes to extract and activate carbon nanomaterials is still crucial. In this work, the biomass waste of date palm fronds is converted to a hierarchical porous nanostructure of activated carbon using simple ball-milling and sonication methods. Chemical and physical activation agents of NaOH and CO2, receptively, were applied on two samples separately. Compared with the specific surface area of 603.5 m2/g for the CO2-activated carbon, the NaOH-activated carbon shows a higher specific surface area of 1011 m2/g with a finer nanostructure. Their structural and electrochemical properties are functionalized to enhance electrode-electrolyte contact, ion diffusion, charge accumulation, and redox reactions. Consequently, when used as electrodes in an H2SO4 electrolyte for supercapacitors, the NaOH-activated carbon exhibits an almost two-fold higher specific capacitance (125.9 vs. 56.8 F/g) than that of the CO2-activated carbon at the same current density of 1 A/g. Moreover, using carbon cloth as a current collector provides mechanical flexibility to our electrodes. Our practical approach produces cost-effective, eco-friendly, and flexible activated carbon electrodes with a hierarchical porous nanostructure for supercapacitor applications.

20.
J Appl Microbiol ; 130(4): 1181-1191, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32813930

RESUMO

AIMS: The major aims of this study are to determine the capability of sulphur oxidizing bacterium (SOB-1) to desulphurize dibenzothiophene (DBT) and crude oil, detection of the reaction kinetics and identify the proposed pathway of DBT desulphurization. METHODS AND RESULTS: The isolate was genetically identified based on 16S rRNA gene sequencing as Klebsiella oxytoca and deposited in the Genebank database under the accession number: MT355440. The HPLC analysis of the remaining DBT concentration revealed that, SOB-1 could desulphurize 90% of DBT (0·25 mmol l-1 ) within 96 h. The maximum production of sulphate ions from the desulphurization of DBT (0·36 mmol l-1 ) and crude oil (0·4 mmol l-1 ) could be quantitatively detected after 48 h of incubation at 30°C. The high values of correlation coefficient (R2 ) obtained at all studied concentrations; suggested that biodesulfurization kinetics of DBT follows the first-order reaction model. The kinetics studies showed that, DBT may have an inhibitory effect on SOB-1 when the initial concentration exceeded 0·75 mmol l-1 . The GC-MS analysis exhibited four main metabolites rather than DBT. The most important ones are 2-hydroxybiphenyl (2-HBP) and methoxybiphenyl n(2-MBP). CONCLUSIONS: Klebsiella oxytoca SOB-1 catalyzes the desulphurization of DBT through 4S pathway and forms four main metabolic products. The release of sulphate ion and formation of 2-HBP indicating the elimination of sulphur group without altering the carbon skeleton of DBT. The bacterial strain could also catalyzes desulphurization of crude oil. The desulphurization kinetics follows the first-order reaction model. SIGNIFICANCE AND IMPACT OF THE STUDY: Klebsiella oxytoca SOB-1 could be used as a promising industrial and environmental biodesulfurizing agent as it is not affecting carbon skeleton of thiophenic compounds and forming less toxic metabolic product (2-MBP).


Assuntos
Poluentes Ambientais/metabolismo , Klebsiella oxytoca/metabolismo , Enxofre/metabolismo , Tiofenos/metabolismo , Biodegradação Ambiental , Cinética , Klebsiella oxytoca/classificação , Klebsiella oxytoca/genética , Klebsiella oxytoca/isolamento & purificação , Redes e Vias Metabólicas , Petróleo/metabolismo , RNA Ribossômico 16S/genética , Sulfatos/metabolismo
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