RESUMEN
The pathophysiology of several illnesses, including cancer and autoimmune diseasesdepends on human regulatory T cells (Tregs), and abnormalities in these cells may function as triggers for these conditions. Cancer and autoimmune, and gynecological diseases are associated with the differentiation of the proinflammatory T cell subset TH17 and its balance with the production of Treg. Recently, long non-coding RNAs (lncRNAs) have become important regulatory molecules in a wide range of illnesses. During epigenetic regulation, they can control the expression of important genes at several levels by affecting transcription, post-transcriptional actions, translation, and protein modification. They might connect with different molecules, such as proteins, DNA and RNA, and their structural composition is intricate. Because lncRNAs regulatebiological processes, including cell division, death, and growth, they are linked to severaldiseases. A notable instance of this is the lncRNA NEAT1, which has been the subject of several investigations to ascertain its function in immune cell development. In the context of immune cell development, several additional lncRNAs have been connected to Treg cell differentiation. In this work, we summarize current findings about the diverse functions of lncRNAs in Treg cell differentiation and control of the Th17/Treg homeostasis in autoimmune disorders, cancers, as well as several gynecological diseases where Tregs are key players.
Asunto(s)
Enfermedades Autoinmunes , Diferenciación Celular , ARN Largo no Codificante , Linfocitos T Reguladores , Humanos , ARN Largo no Codificante/genética , ARN Largo no Codificante/inmunología , Linfocitos T Reguladores/inmunología , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/genética , Diferenciación Celular/inmunología , Diferenciación Celular/genética , Animales , Células Th17/inmunología , Neoplasias/inmunología , Neoplasias/genética , Enfermedades del Sistema Inmune/inmunología , Enfermedades del Sistema Inmune/genéticaRESUMEN
Dengue virus (DENV) infection is a worldwide public health concern infecting approximately 400 million individuals and about 40,000 mortalities yearly. Despite this, no licensed or readily available antiviral medication is currently available specifically for DENV infection, and therapy is typically symptomatic. Therefore, the objective of the study is to investigate the antiviral activity of Beta vulgaris L. phytoconstituents against DENV-2 targeting NS3 protein. The antiviral activity of phytochemicals was examined through virtual ligand-based screening, antiviral inhibition assays, dosage response assays, western blotting analysis and MD simulations. We conducted toxicological, and pharmacokinetic analysis to assess plant-based natural compounds' efficacy, safety, and non-toxic doses. Molecular docking and MD simulation results revealed that the nonstructural protein NS3 is the primary target for Betanin and Glycine Betaine against the Dengue virus. Betanin and Glycine betaine were initially studied for their non-toxic doses in HeLa, CHO, and Vero cells via MTT assay. HeLa cells were transiently transfected with cloned vector pcDNA3.1/Zeo(+)/DENV-2 NS3 along with non-toxic doses (80 µM- 10 µM) of selected phytochemicals. The dose-response assay illustrated the downregulated expression of the DENV-2 NS3 gene after the post-treatment of Betanin (IC50 =4.35 µM) and Glycine Betaine (IC50 = 4.49 µM). Betanin (80 µM- 10 µM) was found to inhibit the NS3 protein. These results suggested the down regulated expression of DENV-2 NS3 protein at mRNA level as well as protein level depicting the DENV replication inhibition. Based on our study findings, NS3 protease is depicted as distinctive DENV-2 inhibitor target. We will channel our study further into in vitro characterization employing the mechanistic study to understand the role of host factors in anti-flavi therapeutic.
RESUMEN
A novel series of ethylidenehydrazineylthiazol-4(5H)-ones were synthesized using various eco-friendly one-pot multicomponent synthetic techniques. The anticancer activity of compounds (4a-m) was tested against 11 cancer cell lines. While the IC50 of all compounds was evaluated against the most sensitive cell lines (MDA-MB-468 and FaDu). Our SAR study pinpointed that compound 4a, having a phenyl substituent, exhibited a significant growth inhibition % against all cancer cell lines. The frontier anticancer candidates against the MDA-MB-468 were also examined against the wild EGFR (EGFR-WT) and mutant EGFR (EGFR-T790M) receptors. Most of the synthesized compounds exhibited a higher inhibitory potential against EGFR-T790M than the wild type of EGFR. Remarkably, compound 4k exhibited the highest inhibitory activity against both EGFR-WT and EGFR-T790M with IC50 values (0.051 and 0.021 µM), respectively. The pro-apoptotic protein markers (p53, BAX, caspase 3, caspase 6, caspase 8, and caspase 9) and the anti-apoptotic key marker (BCL-2) were also measured to propose a mechanism of action for the compound 4k as an apoptotic inducer for MDA-MB-468. Investigation of the cell cycle arrest potential of compound 4k was also conducted on MDA-MB-468 cancer cells. We also evaluated the inhibitory activities of compounds (4a-m) against both EGFR-WT and EGFR-T790M using two different molecular docking processes.
Asunto(s)
Antineoplásicos , Neoplasias Pulmonares , Neoplasias de la Mama Triple Negativas , Humanos , Estructura Molecular , Receptores ErbB , Relación Estructura-Actividad , Proliferación Celular , Simulación del Acoplamiento Molecular , Ensayos de Selección de Medicamentos Antitumorales , Inhibidores de Proteínas Quinasas , Mutación , Línea Celular Tumoral , ApoptosisRESUMEN
Herein, we envisioned the design and synthesis of novel pyrazolopyrimidines (confirmed by elemental analysis, 1H and 13C NMR, and mass spectra) as multitarget-directed drug candidates acting as EGFR/TOPO II inhibitors, DNA intercalators, and apoptosis inducers. The target diphenyl-tethered pyrazolopyrimidines were synthesized starting from the reaction of phenyl hydrazine and ethoxymethylenemalononitrile to give aminopyrazole-carbonitrile 2. The latter hydrolysis with NaOH and subsequent reaction with 4-chlorobenzaldhyde afforded the corresponding pyrazolo[3,4-d]pyrimidin-4-ol 4. Chlorination of 4 with POCl3 and sequential reaction with different amines afforded the target compounds in good yields (up to 73 %). The growth inhibition % of the new derivatives (6a-m) was investigated against different cancer and normal cells and the IC50 values of the most promising candidates were estimated for HNO97, MDA-MB-468, FaDu, and HeLa cancer cells. The frontier derivatives (6a, 6i, 6k, 6l, and 6m) were pursued for their EGFR inhibitory activity. Compound 6l decreased EGFR protein concentration by a 6.10-fold change, compared to imatinib as a reference standard. On the other side, compounds (6a, 6i, 6k, 6l, and 6m) underwent topoisomerase II (TOPO II) inhibitory assay. In particular, compounds 6a and 6l exhibited IC50s of 17.89 and 19.39 µM, respectively, surpassing etoposide with IC50 of 20.82 µM. Besides, the DNA fragmentation images described the great potential of both candidates 6a and 6l in inducing DNA degradation at lower concentrations compared to etoposide and doxorubicin. Moreover, compound 6l, with the most promising EGFR/TOPO II inhibition and DNA intercalation, was selected for further investigation for its apoptosis induction ability by measuring caspases 3, 7, 8, and 9, Bax, p53, MMP2, MMP9, and BCL-2 proteins. Additionally, molecular docking was used to explain the SAR results based on the differences in the molecular features of the investigated congeners and the target receptors' topology.
Asunto(s)
Antineoplásicos , Compuestos de Bifenilo , Humanos , Estructura Molecular , Relación Estructura-Actividad , Simulación del Acoplamiento Molecular , Antineoplásicos/química , Etopósido/farmacología , ADN-Topoisomerasas de Tipo II/metabolismo , Proliferación Celular , Inhibidores de Topoisomerasa II , Apoptosis , Receptores ErbB/metabolismo , ADN , Ensayos de Selección de Medicamentos AntitumoralesRESUMEN
Utilizing microwave heating and an aqueous saturated solution of K2CO3 as a catalyst, a rapidone-pot synthesis of oxospiro[chromene-4.3-indoline] derivatives was produced in high yields. The experimental results confirmed that the saturated solution of K2CO3 gives outstanding yield to dangerous metals and strong bases during investigations into high-performance catalysts. The used catalyst is green, affordable, incredibly mild, and widely accessible. However, it generates samples, reduces the amount of byproducts, and is expected to be used in industrial-scale heterocyclic derivatives. New oxospiro[chromene-4.3-indoline] derivatives have been created from various isatin by condensing with various phenols. The biological activities results showed that when compared to erlotinib, the derivatives 3b, 4b, 5b, and 6b were the most effective analogues on A549, MCF-7, HepG-2, and HCT-116 cells, with an IC50 range of 3.32 to 11.88 µM. In A549 cells, compounds 3b, 4b, 5b, and 6b induced apoptosis, as shown by the up-regulation of Bax, the up-regulation of Bcl-2, and the stimulation of caspase-3 and -9. With IC50 value of 0.19 ± 0.09, compound3b was demonstrated to be the most effective against EGFRWT. Compounds 4b and 6b have good antibacterial activity toward Staphylococcus aureus, comparable to ciprofloxacin, and about half as much activity as ampicillin, according to the MIC value. Compound 6b's MIC is about 25% lower than clotrimazole drug. The in silico molecular docking outcomes of compounds 3b, 4b, 5b, and 6b in the EGFR active site depicted their ability to adopt essential binding interactions compared to the reference Erlotinib. Moreover, the investigation of the physicochemical properties of the most promising dual acting antiproliferative and antimicrobial compounds 4b and 6b through the egg-boiled method illustrated acceptable lipophilicity, GIT absorption, and blood-brain barrier penetration characteristics.
RESUMEN
Currently, it has been stated that psychiatric and psychological problems are equally paramount aspects of the clinical modulation and manifestation of both the central nervous and digestive systems, which could be used to restore balance. The present narrative review aims to provide an elaborate description of the bio-psycho-social facets of refractory functional gastrointestinal disorders, psychiatrists' role, specific psychiatric approach, and the latest psychiatric and psychological perspectives on practical therapeutic management. In this respect, "psyche," "psychiatry," "psychology," "psychiatrist," "psychotropic," and "refractory functional gastrointestinal disorders" (as the keywords) were searched in relevant English publications from January 1, 1950, to March 1, 2024, in the PubMed, Web of Science, Scopus, EMBASE, Cochrane Library, and Google Scholar databases. Eventually, the narrative technique was adopted to reach a compelling story with a high level of cohesion through material synthesis. The current literature recognizes the brain-gut axis modulation as a therapeutic target for refractory functional gastrointestinal disorders and the bio-psycho-social model as an integrated framework to explain disease pathogenesis. The results also reveal some evidence to affirm the benefits of psychotropic medications and psychological therapies in refractory functional gastrointestinal disorders, even when psychiatric symptoms were absent. It seems that psychiatrists are required to pay higher levels of attention to both the assessment and treatment of patients with refractory functional gastrointestinal disorders, accompanied by educating and training practitioners who take care of these patients.
RESUMEN
About 70% of cases of breast cancer are compromised by Estrogen-positive breast cancer. Through its regulation of several processes, including cell proliferation, cell cycle progression, and apoptosis, Estrogen signaling plays a pivotal role in the genesis and progression of this particular kind of breast cancer. One of the best treatment strategies for treating Estrogen-positive breast cancer is blocking Estrogen signaling. However, patients' treatment failure is mainly caused by the emergence of resistance and metastases, necessitating the development of novel therapeutic targets. Numerous studies have shown long noncoding RNAs (lncRNAs) to play a role in Estrogen-mediated carcinogenesis. These lncRNAs interact with co-regulators and the Estrogen signaling cascade components, primarily due to Estrogen activation. Vimentin and E-cadherin are examples of epithelial-to-mesenchymal transition markers, and they regulate genes involved in cell cycle progression, such as Cyclins, to affect the growth, proliferation, and metastasis of Estrogen-positive breast cancer. Furthermore, a few of these lncRNAs contribute to developing resistance to chemotherapy, making them more desirable targets for enhancing results. Thus, to shed light on the creation of fresh approaches for treating this cancer, this review attempts to compile recently conducted studies on the relationship between lncRNAs and the advancement of Estrogen-positive breast cancer.
Asunto(s)
Neoplasias de la Mama , ARN Largo no Codificante , Humanos , Femenino , Neoplasias de la Mama/patología , ARN Largo no Codificante/genética , Estrógenos , Proliferación Celular/genética , Receptores de Estrógenos/metabolismo , Regulación Neoplásica de la Expresión GénicaRESUMEN
Findings on the effect of walnut consumption on endothelial function are conflicting. Therefore, the present systematic review and meta-analysis summarized available trials in this regard. A systematic search was performed in online databases including PubMed-Medline, Scopus, and ISI Web of Science up to October 2023. Articles that reported the effect of walnut intake on flow-mediated dilation (FMD), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and stimulus-adjusted response measure (SARM) were included. Random effects models for a weighted mean difference (WMD) or standardized mean difference (SMD) were used to test for the overall effect. Six eligible trials were analyzed (250 participants). Walnut intake significantly increased FMD (WMD: 0.94%, 95% CI: 0.12 to 1.75; p = 0.02). However, meta-analysis could not show any beneficial effect of walnut intake on ICAM-1 (SMD: -0.23, 95% CI: -0.68 to 0.22; p = 0.31), VCAM-1 (SMD: -0.02, 95% CI: -1.38 to 1.34; p = 0.97), and SARM (WMD: 0.01%, 95% CI: -0.01 to 0.04; p = 0.28). In conclusion, the present meta-analysis suggests that walnuts may reduce cardiovascular disease risk by improving FMD. However, further studies should be performed on adults to determine the effect of walnut intake on endothelial function.
Asunto(s)
Juglans , Adulto , Humanos , Molécula 1 de Adhesión Intercelular , Nueces , Ensayos Clínicos Controlados Aleatorios como Asunto , Molécula 1 de Adhesión Celular VascularRESUMEN
Wound healing is a critical process in tissue repair following injury, and traditional herbal therapies have long been utilized to facilitate this process. This review delves into the mechanistic understanding of the significant contribution of pharmacologically demonstrated natural products in wound healing. Natural products, often perceived as complex yet safely consumed compared to synthetic chemicals, play a crucial role in enhancing the wound-healing process. Drawing upon a comprehensive search strategy utilizing databases such as PubMed, Scopus, Web of Science, and Google Scholar, this review synthesizes evidence on the role of natural products in wound healing. While the exact pharmacological mechanisms of secondary metabolites in wound healing remain to be fully elucidated, compounds from alkaloids, phenols, terpenes, and other sources are explored here to delineate their specific roles in wound repair. Each phytochemical group exerts distinct actions in tissue repair, with some displaying multifaceted roles in various pathways, potentially enhancing their therapeutic value, supported by reported safety profiles. Additionally, these compounds exhibit promise in the prevention of keloids and scars. Their potential alongside economic feasibility may propel them towards pharmaceutical product development. Several isolated compounds, from natural sources, are undergoing investigation in clinical trials, with many reaching advanced stages.
RESUMEN
Although various approaches exist for treating cancer, chemotherapy continues to hold a prominent role in the management of this disease. Besides, microtubules serve as a vital component of the cellular skeleton, playing a pivotal role in the process of cell division making it an attractive target for cancer treatment. Hence, the scope of this work was adapted to design and synthesize new anti-tubulin tetrabromophthalimide hybrids (3-17) with colchicine binding site (CBS) inhibitory potential. The conducted in vitro studies showed that compound 16 displayed the lowest IC50 values (11.46 µM) at the FaDu cancer cell lines, whereas compound 17 exhibited the lowest IC50 value (13.62 µM) at the PC3 cancer cell line. However, compound 7b exhibited the lowest IC50 value (11.45 µM) at the MDA-MB-468 cancer cell line. Moreover, compound 17 was observed to be the superior antitumor candidate against all three tested cancer cell lines (MDA-MB-468, PC3, and FaDu) with IC50 values of 17.22, 13.15, and 13.62 µM, respectively. In addition, compound 17 showed a well-established upregulation of apoptotic markers (Caspases 3, 7, 8, and 9, Bax, and P53). Moreover, compound 17 induced downregulation of the antiapoptotic markers (MMP2, MMP9, and BCL-2). Furthermore, the colchicine binding site inhibition assay showed that compounds 15a and 17 exhibited particularly significant inhibitory potentials, with IC50 values of 23.07 and 4.25 µM, respectively, compared to colchicine, which had an IC50 value of 3.89 µM. Additionally, cell cycle analysis was conducted, showing that compound 17 could prompt cell cycle arrest at both the G0-G1 and G2-M phases. On the other hand, a molecular docking approach was applied to investigate the binding interactions of the examined candidates compared to colchicine towards CBS of the ß-tubulin subunit. Thus, the synthesized tetrabromophthalimide hybrids can be regarded as outstanding anticancer candidates with significant apoptotic activity.
Asunto(s)
Antineoplásicos , Apoptosis , Diseño de Fármacos , Ftalimidas , Moduladores de Tubulina , Humanos , Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Simulación del Acoplamiento Molecular , Ftalimidas/síntesis química , Ftalimidas/farmacología , Relación Estructura-Actividad , Tubulina (Proteína)/metabolismo , Moduladores de Tubulina/síntesis química , Moduladores de Tubulina/farmacologíaRESUMEN
Intestinal inflammation is one of the main health challenges affecting the quality of life of millions of people worldwide. Accumulating evidence introduces several flavonoids with multifaceted therapeutic properties in inflammatory diseases including intestinal inflammation. Herein, we examined potential anti-inflammatory properties of 5,4'-dihydroxy-6,8-dimethoxy7-O-rhamnosylflavone (DDR) flavone derived from Indigofera aspalathoides Vahl (I. aspalathoides Vahl) on lipopolysaccharide (LPS)-induced intestinal inflammation and injury in mice. Oral DDR treatment decreased serum levels of pro-inflammatory cytokines including TNF-α, IL-6, and IL-1ß. It reduced oxidative stress through augmenting the activities of catalase (CAT) and superoxide dismutase (SOD) and reducing the level of malondialdehyde (MDA) in the duodenum and colon tissues. Moreover, DDR enhanced the activities of digestive enzymes including trypsin, pancreatic lipase, and amylase, and increased the production of short-chain fatty acids (SCFAs) by colon microbiota. Histopathological investigation of duodenum and colon revealed that DDR inhibited inflammatory infiltration and largely restored mucosal architecture and protected lining integrity. Importantly, DDR suppressed activation of nuclear factor-κB (NF-κB) signaling pathway through reduced expression of Toll-like receptor 4 (TLR4) and expression and phosphorylation of P65. The current study identified DDR as anti-inflammatory flavonoid capable of ameliorating LPS-induced intestinal inflammation through suppression of NF-κB signaling.
RESUMEN
In this study, numerical simulations are conducted with the goal of exploring the impact of the direction of the moving wall, solute and thermal transport, and entropy production on doubly diffusive convection in a chamber occupied by a Casson liquid. Wall movement has a significant impact on convective flow, which, in turn, affects the rate of mass and heat transfer; this sparked our interest in conducting further analysis. The left and right (upright) walls are preserved with constant (but different) thermal and solutal distributions, while the horizontal boundaries are impermeable to mass transfer and insulated from heat transfer. Numerical solutions are acquired using the control volume technique. Outcomes under a variety of Casson fluid parameters, including Ri, Gr, buoyancy ratio, and direction of the moving wall(s), are explored, and the influences of entropy generation are comprehensively investigated. While the flow field consists of a single cell in case I, it is dual-cellular in case III for all values of the considered parameters. Comparing the three cases, the average heat and mass transport presented lower values in case III due to the movement of an isothermal (left) wall against the buoyant force, while these values are enhanced in case I. The obtained results are expected to be useful in thermal engineering, material, food, and chemical processing applications.
RESUMEN
Mephedrone is an illegal drug that is used recreationally. Few studies have been conducted to investigate the mechanisms by which mephedrone is harming cells. In this research, we investigated the effect of mephedrone using toxicology coupled with LC-MS/MS based metabolomics in the two CNS derived cell lines. Methods of assessment such as neutral red (NR) assay, dimethylthiazolyl diphenyltetrazolium bromide (MTT), lactose dehydrogenase (LDH) measurement, and morphology were performed to identify the effect on cell viability and to identify the best concentration to be used in a metabolomics study. A concentration of 100 µM of mephedrone was used in the metabolomic experiment because at this concentration mephedrone had induced several intracellular changes. Although there no clear indicators of cellular damage caused by mephedrone. In astrocytes there was a clear indication that cell membrane function might be impaired by depletion of ether lipids.
RESUMEN
Onosma species (Boraginaceae) are well known as medicinal plants due to their wide range of pharmaceutical potential. The present study aims to investigate the anticancer (in vitro) and chemo-protective (in vivo) efficacies of Onosma mutabilis extract (OME) in the azoxymethane (AOM)-induced aberrant crypt foci (ACF) in rats. The in vitro antiproliferative effects of OME were determined on two human tumor cell lines (Caco-2 and HT-29) via MTT assay. The in vivo chemoprotective effects of OME were investigated by performing various biochemical analyses in serum and tissue homogenates of albino rats, along with determining oxidative stress biomarkers. Inflammatory biomarkers of colon, colonic gross morphology (by methylene blue), ACF formation, and colonic histopathology (H & E stain) were determined. The immunohistochemistry of colonic tissues was also assessed by Bax and Bcl-2 protein expression. The results showed that the antitumor activity of OME against Caco-2 and HT-29 colorectal cancer cells ranged between 22.28-36.55 µg/mL. OME supplementation caused a significant drop in the ACF values and improved the immunohistochemistry of the rats shown by up-regulation of Bax and down-regulation of Bcl-2 protein expressions. These outcomes reveal that O. mutabilis may have chemoprotective efficiency against AOM-induced colon cancer represented by the attenuation of ACF formation possibly through inhibition of free radicals, inflammation, and stimulation of the colon antioxidant armory (SOD, CAT, and GPx) and positive regulation of the Nrf2-Keap1 pathway.
RESUMEN
Blood borne sexually transmitted infections are among the most serious health problems worldwide. Many people possessing these infections do not have symptoms and may remain undiagnosed. The current study aimed to screen premaritally the incidence of blood borne viruses among Saudi nationals. A retrospective longitudinal study was conducted, using a total of 91,000 medical records, in the blood bank from a single center in the Western region of Saudi Arabia. All persons who underwent premarital examination during the period 2016-2021 for the presence of hepatitis B and C viruses as a part of the national screening program in Saudi Arabia were included in the study. Serological tests were used to screen the presence of HBc Ab and HBs Ag. Both anti-HCV antibodies and the presence of virus RNA using real-time reverse transcriptase polymerase chain reaction (RT-PCR) were also performed. The study reported the presence of 378/91000 (0.42%) infections with hepatitis B virus (HBV) as indicated by the presence of HBc Ab and HBs Ag. Meanwhile, 208 (0.23%) cases were found to be exposed to HCV including 49/91000 (0.05%) active HCV cases, positive for the HCV RNA, while 159/91000 (0.17%) persons were found to possess positive HCV antibodies in the absence of detectable HCV RNA. It was concluded that there is a low prevalence of HBV and HBV among Saudi citizens who were subjected to premarital screening.
Asunto(s)
Hepatitis B , Humanos , Estudios Retrospectivos , Arabia Saudita/epidemiología , Estudios Longitudinales , Hepatitis B/diagnóstico , Hepatitis B/epidemiología , Virus de la Hepatitis B/genética , Antígenos de Superficie de la Hepatitis B , ARN Viral/genética , PrevalenciaRESUMEN
Organizations and individuals worldwide are becoming increasingly vulnerable to cyberattacks as phishing continues to grow and the number of phishing websites grows. As a result, improved cyber defense necessitates more effective phishing detection (PD). In this paper, we introduce a novel method for detecting phishing sites with high accuracy. Our approach utilizes a Convolution Neural Network (CNN)-based model for precise classification that effectively distinguishes legitimate websites from phishing websites. We evaluate the performance of our model on the PhishTank dataset, which is a widely used dataset for detecting phishing websites based solely on Uniform Resource Locators (URL) features. Our approach presents a unique contribution to the field of phishing detection by achieving high accuracy rates and outperforming previous state-of-the-art models. Experiment results revealed that our proposed method performs well in terms of accuracy and its false-positive rate. We created a real data set by crawling 10,000 phishing URLs from PhishTank and 10,000 legitimate websites and then ran experiments using standard evaluation metrics on the data sets. This approach is founded on integrated and deep learning (DL). The CNN-based model can distinguish phishing websites from legitimate websites with a high degree of accuracy. When binary-categorical loss and the Adam optimizer are used, the accuracy of the k-nearest neighbors (KNN), Natural Language Processing (NLP), Recurrent Neural Network (RNN), and Random Forest (RF) models is 87%, 97.98%, 97.4% and 94.26%, respectively, in contrast to previous publications. Our model outperformed previous works due to several factors, including the use of more layers and larger training sizes, and the extraction of additional features from the PhishTank dataset. Specifically, our proposed model comprises seven layers, starting with the input layer and progressing to the seventh, which incorporates a layer with pooling, convolutional, linear 1 and 2, and linear six layers as the output layers. These design choices contribute to the high accuracy of our model, which achieved a 98.77% accuracy rate.
RESUMEN
The article presents a Co-planar Waveguide (CPW) fed antenna of a low-profile, simple geometry, and compact size operating at the dual band for ISM and WLAN applications for 5G communication devices. The antenna has a small size of 30 mm × 18 mm × 0.79 mm and is realized using Rogers RT/Duroid 5880 substrate. The proposed dual-band antenna contains a CPW feedline along with the triangular patch. Later on, various stubs are loaded to obtain optimal results. The proposed antenna offers a dual band at 2.4 and 5.4 GHz while covering the impedance bandwidths of 2.25-2.8 GHz for ISM and 5.45-5.65 GHz for WLAN applications, respectively. The proposed antenna design is studied and analyzed using the Electromagnetic (EM) High-Frequency Structure Simulator (HFSSv9) tool, and a hardware prototype is fabricated to verify the simulated results. As the antenna is intended for on-body applications, therefore, Specific Absorption Rate (SAR) analysis is carried out to investigate the Electromagnetic effects of the antenna on the human body. Moreover, a comparison between the proposed dual-band antenna and other relevant works in the literature is presented. The results and comparison of the proposed work with other literary works validate that the proposed dual-band antenna is suitable for future 5G devices working in Industrial, Scientific, Medical (ISM), and Wireless Local Area Network (WLAN) bands.
Asunto(s)
Redes de Área Local , Tecnología Inalámbrica , Humanos , Diseño de Equipo , ComunicaciónRESUMEN
In this manuscript, a compact in size yet geometrically simple Ultra-Wideband (UWB) antenna is demonstrated. The flexible-by-nature substrate ROGERS 5880, having a thickness of 0.254 mm, is utilized to design the proposed work. The antenna configuration is an excerpt of a traditional rectangular monopole antenna resonating at 5 GHz. Initially, a pair of triangular slots are employed to extend the impedance bandwidth of the antenna. In addition, a semi-circular-shaped, short-ended stub is connected at the upper edges of the patch to further increase the operational bandwidth. After optimization, the proposed antenna offers UWB ranging from 2.73-9.68 GHz, covering almost the entire spectrum allocated globally for UWB applications. Further, the antenna offers a compact size of 15 × 20 mm2 that can easily be integrated into small, flexible electronics. The flexibility analysis is done by bending the antenna on both the x and y axes. The antenna offers performance stability in terms of return loss, radiation pattern, and gain for both conformal and non-conformal conditions. Furthermore, the strong comparison between simulated and measured results for both rigid and bent cases of the antenna, along with the performance comparison with the state-of-the-art, makes it a potential candidate for present and future compact-sized flexible devices.
Asunto(s)
Electrónica , Tecnología Inalámbrica , Diseño de Equipo , Impedancia EléctricaRESUMEN
Osteoarthritis (OA) and rheumatoid arthritis (RA) are two common disorders that disrupt the quality of life of millions of people. These two chronic diseases cause damage to the joint cartilage and surrounding tissues of more than 220 million people worldwide. Sex-determining region Y-related (SRY) high-mobility group (HMG) box C, SOXC, is a superfamily of transcription factors that have been recently shown to be involved in various physiological and pathological processes. These include embryonic development, cell differentiation, fate determination, and autoimmune diseases, as well as carcinogenesis and tumor progression. The SOXC superfamily includes SOX4, SOX11, and SOX12, all have a similar DNA-binding domain, i.e., HMG. Herein, we summarize the current knowledge about the role of SOXC transcription factors during arthritis progression and their potential utilization as diagnostic biomarkers and therapeutic targets. The involved mechanistic processes and signaling molecules are discussed. SOX12 appears to have no role in arthritis, however SOX11 is dysregulated and promotes arthritic progression according to some studies but supports joint maintenance and protects cartilage and bone cells according to others. On the other hand, SOX4 upregulation during OA and RA was documented in almost all studies including preclinical and clinical models. Molecular details have indicated that SOX4 can autoregulate its own expression besides regulating the expression of SOX11, a characteristic associated with the transcription factors that protects their abundance and activity. From analyzing the currently available data, SOX4 seems to be a potential diagnostic biomarker and therapeutic target of arthritis.
Asunto(s)
Artritis Reumatoide , Cartílago Articular , Osteoartritis , Humanos , Factores de Transcripción SOXC/metabolismo , Calidad de Vida , Factores de Transcripción/metabolismo , Osteoartritis/metabolismo , Cartílago Articular/metabolismo , BiomarcadoresRESUMEN
Recent research on dipeptidyl peptidase-IV (DPP-IV) inhibitors has made it feasible to treat type 2 diabetes mellitus (T2DM) with minimal side effects. Therefore, in the present investigation, we aimed to discover and develop some coumarin-based sulphonamides as potential DPP-IV inhibitors in light of the fact that molecular hybridization of many bioactive pharmacophores frequently results in synergistic activity. Each of the proposed derivatives was subjected to an in silico virtual screening, and those that met all of the criteria and had a higher binding affinity with the DPP-IV enzyme were then subjected to wet lab synthesis, followed by an in vitro biological evaluation. The results of the pre-ADME and pre-tox predictions indicated that compounds 6e, 6f, 6h, and 6m to 6q were inferior and violated the most drug-like criteria. It was observed that 6a, 6b, 6c, 6d, 6i, 6j, 6r, 6s, and 6t displayed less binding free energy (PDB ID: 5Y7H) than the reference inhibitor and demonstrated drug-likeness properties, hence being selected for wet lab synthesis and the structures being confirmed by spectral analysis. In the in vitro enzyme assay, the standard drug Sitagliptin had an IC50 of 0.018 µM in the experiment which is the most potent. All the tested compounds also displayed significant inhibition of the DPP-IV enzyme, but 6i and 6j demonstrated 10.98 and 10.14 µM IC50 values, respectively, i.e., the most potent among the synthesized compounds. Based on our findings, we concluded that coumarin-based sulphonamide derivatives have significant DPP-IV binding ability and exhibit optimal enzyme inhibition in an in vitro enzyme assay.