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1.
Int J Biol Macromol ; 275(Pt 1): 133513, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38955292

RESUMO

This research uses a novel TiO2@CSC.Alg composite sponge was created by encasing TiO2 nanoparticles in the natural polymers alginate and chitosan, resulting in a nanocomposite that is both ecologically friendly and biocompatible. Using the generated nanocomposite as a new environmentally friendly adsorbent, As(V) heavy metal ions were effectively removed from aqueous media. The following techniques were used to analyse the physicochemical properties of the obtained materials: pHZPC, FTIR, XRD, BET, SEM, and XPS. Utilizing nitrogen adsorption/desorption isotherms, the TiO2@CSC.Alg composite sponge's textural properties were identified. This revealed a BET surface area of 168.42 m2/g and a total pore volume of 1.18 cc/g, indicating its porous nature and potential for high adsorption capacity. Examine the effects of temperature, pH, dose, and beginning concentration on adsorption. The adsorption characteristics were determined based on equilibrium and adsorption kinetics measurements. The adsorption process was both pseudo-second-order (PSOE) and Langmuir isothermally fit. Chemisorption was the adsorption method since the adsorption energy was 25.45 kJ·mol-1. An endothermic and spontaneous adsorption process was indicated by more metal being absorbed as the temperature increased. The optimal conditions for adsorption were optimized via Box-Behnken design software to be pH of 5 in the solution, a dosage of 0.02 g of the TiO2@CSC.Alg composite sponge per 25 mL, and an arsenate (As(V)) solution the adsorption capacity was 202.27 mg/g are ideal for efficient adsorption. These parameters are critical in achieving the maximum adsorption capacity of the composite sponge for arsenate, which could be beneficial for water purification applications. Utilizing Design-Expert software's response surface methodology (RSM) and Box-Behnken design (BBD), the adsorption process was optimized with the fewest planned tests. After six successive cycles of adsorption and desorption, the adsorbent stability was confirmed by the adsorbent reusability test without any noticeable decrease in removal efficacy. Additionally, it displayed good efficiency, the same XRD and XPS data before and after reuse, and no change in chemical composition.

2.
ACS Omega ; 8(44): 41064-41076, 2023 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-37970001

RESUMO

Heterogeneous growth of photocatalysts on different porous substrates is a solution to avoid secondary pollution caused by composite photocatalysts themselves. However, the heterogeneous growth of composite photocatalysts with nitrogen-doped carbon quantum dots (NCQDs) inclusions-introduced during synthesis-impedes the direct growth on the substrate. To overcome this problem, NCQDs were grown on a Co9S8 (NCQDs-G@Co9S8) layer, decorated on cotton fabric. This optimal coupling mode of NCQDs and Co9S8 showed 54% degradation, compared to 33% dye degradation via NCQDs-doped Co9S8 (NCQDs-D@Co9S8). The change in the crystal structure and its lower loading on fabric results in significantly lower performance of NCQDs-D@Co9S8. Even with the combination of both surface growth and doping (NCQDs-DG@Co9S8), the performance was still limited to 42%. In addition, the optimum growth concentration of NCQDs on Co9S8 was observed for 7.5 w/w %, resulting in 92% photocatalytic activity (PCA) in 80 min. Comparing different surface states formed in NCQDs using different solvents, water-based surface states (oxygen-rich surface) are most suitable for the dye degradation. NCQDs-G@Co9S8 also offers 67% Cr-VI reduction to Cr-III, showing its suitability for both inorganic and organic compounds. Better electrode performance was related to suitable charge separation of the composite, where -OH groups mainly contribute in the photocatalytic dye degradation..

3.
Molecules ; 28(21)2023 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-37959821

RESUMO

In the last decade, the urgent need to explore medicinal plants or drug development has increased enormously around the world to overcome numerous health problems. In the present investigation, HPLC indicated the existence of 18 phenolic and flavonoid compounds in the Cupressus sempervirens extract. Hesperetin represents the greatest concentration (25,579.57 µg/mL), while other compounds, such as pyro catechol, rutin, gallic acid, chlorogenic acid, naringenin, and quercetin, were recognized in concentrations of 2922.53 µg/mL, 1313.26 µg/mL, 1107.26 µg/mL, 389.09 µg/mL, 156.53 µg/mL, and 97.56 µg/mL, respectively. The well diffusion method documented the antibacterial/antifungal activity of C. sempervirens extract against E. faecalis, E. coli, C. albicans, S. typhi, S.aureus, and M. circinelloid with 35, 33, 32, 25, 23, and 21 mm inhibition zones, respectively, more than the standard antibiotic/antifungal agent. Low values ranging from 7.80 to 15.62 µg/mL of MIC and MBC were recorded for E. faecalis, E. coli, and C. albicans. From the 1- diphenyl-2-picryl hydrazyl (DPPH) assay, promising antioxidant activity was recorded for C. sempervirens extract with IC50 of an 8.97 µg/mL. Moreover, ferric reducing antioxidant power (FRAP) and total antioxidant capacity assays (TAC) confirmed the antioxidant activity of the extract, which was expressed as the ascorbic acid equivalent (AAE) of 366.9 ± 0.2 µg/mg and 102 ± 0.2 µg/mg of extracts, respectively. α-amylase and α-glucosidase inhibition % were determined to express the antidiabetic activity of the extract in vitro, with promising IC50 value (27.01 µg/mL) for α-amylase compared to that of acarbose (50.93 µg/mL), while IC50 value of the extract for α-glucosidase was 19.21µg/mL compared to that of acarbose 4.13 µg/mL. Prothrombin time (PT) and activated partial thromboplastin time (APTT) revealed the role of C. sempervirens extract as an anticoagulant agent if compared with the activity of heparin. Binding interactions of hesperetin and gallic acid were examined via the Molecular Operating Environment (MOE) Dock software against E. faecalis (PDB ID: 3CLQ), C. albicans (PDB ID: 7RJC), α-amylase (PDB ID: 4W93), and α-glucosidase (PDB ID: 3TOP). The obtained results shed light on how molecular modeling methods might inhibit the tested compounds, which have the potential to be useful in the treatment of target proteins.


Assuntos
Antioxidantes , Cupressus , Antioxidantes/farmacologia , Antioxidantes/química , Hipoglicemiantes/farmacologia , Hipoglicemiantes/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Acarbose , alfa-Glucosidases/metabolismo , Escherichia coli/metabolismo , Antibacterianos/farmacologia , Antifúngicos/farmacologia , alfa-Amilases
4.
Pharmaceutics ; 15(11)2023 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-38004522

RESUMO

Metabolic syndrome (MetS) is a global issue affecting over a billion people, raising the risk of diabetes, cardiovascular disorders, and other ailments. It is often characterized by hypertension, dyslipidemia and/or obesity, and hyperglycemia. Chemical investigation of Aeonium arboreum (L.) Webb & Berthel led to the isolation of six compounds, viz. ß-sitosterol, ß-sitosterol glucoside, myricetin galactoside, quercetin rhamnoside, kaempferol rhamnoside, and myricetin glucoside. Interestingly, A. arboreum's dichloromethane (DCM), 100 and 50% MeOH Diaion fractions and the isolated compound (quercetin-3-rhamnoside) revealed potent α-glucosidase inhibitory activity, especially 50% Diaion fraction. In addition, they also showed very potent antioxidant potential, especially the polar fractions, using DPPH, ABTS, FRAP, ORAC, and metal chelation assays. Notably, the 50% Diaion fraction had the highest antioxidant potential using DPPH and ORAC assays, while the 100% Diaion fraction and quercetin-3-rhamnoside showed the highest activity using ABTS, FRAP, and metal chelation assays. Also, quercetin-3-rhamnoside showed a good docking score of -5.82 kcal/mol in comparison to acarbose. In addition, molecular dynamic stimulation studies illustrated high stability of compound binding to pocket of protein. Such potent activities present A. arboreum as a complementary safe approach for the management of diabetes mellitus as well as MetS.

5.
iScience ; 26(10): 107964, 2023 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-37810219

RESUMO

The Polycomb group protein SCML2 and the transcriptional cofactor YAP1 regulate diverse cellular biology, including stem cell maintenance, developmental processes, and gene regulation in mammals and flies. However, their molecular and functional interactions are unknown. Here, we show that SCML2 interacts with YAP1, as revealed by immunological assays and mass spectroscopy. We have demonstrated that the steroid hormone androgen regulates the interaction of SCML2 with YAP1 in human tumor cell models. Our proximity ligation assay and GST pulldown showed that SCML2 and YAP1 physically interacted with each other. Silencing SCML2 by RNAi changed the growth behaviors of cells in response to androgen signaling. Mechanistically, this phenomenon is attributed to the interplay between distinct chromatin modifications and transcriptional programs, likely coordinated by the opposing SCML2 and YAP1 activity. These findings suggest that YAP1 and SCML2 cooperate to regulate cell growth, cell survival, and tumor biology downstream of steroid hormones.

6.
Molecules ; 28(1)2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36615605

RESUMO

Hazardous dyes in industrial wastewater are an internationally recognized issue for community health. Nanoparticles synthesized through green protocols are a fascinating research field with numerous applications. The current study mainly aimed to investigate the degradation of Congo red (CR) dye under UV light in the presence of H2O2 and the photocatalytic activity of copper oxide nanoparticles (CuONPs). For CuONP formation, Citrus maxima extract contains a high number of phytochemical constituents. The size of CuONPs ranges between 25 and 90 nm. The photocatalytic activity of CuONPs with the addition of H2O2 was observed and analyzed under UV light to eliminate CR dye. The UV light caused the decomposition of H2O2, which produced ·OH radicals. The results revealed a significant increment in dye degradation during the presence of H2O2. The effect of concentration on the degradation of the CR dye was also studied. The degradation pathway of organic pollutants was reputable from the hydroxy radical medicated degradation of CR. Advanced Oxidation Treatment depends on the in situ production of reactive ·OH species and is presented as the most effective procedure for decontamination. The biological activity of CuONPs was evaluated against Escherichia coli Bacillus subtillis, Staphylococcus aureus, Shigella flexenari, Acinetobacter Klebsiella pneumonia, Salmonella typhi and Micrococcus luteus. The newly synthesised nanomaterials showed strong inhibition activity against Escherichia coli (45%), Bacillus subtilis (42%) and Acinetobacter species (25%). The activity of CuONPs was also investigated against different fungus species such as: Aspergillus flavus, A. niger, Candida glabrata, T. longifusus, M. Canis, C. glabrata and showed a good inhibition zone against Candida glabrata 75%, Aspergillus flavus 68%, T. longifusus 60%. The materials showed good activity against C. glaberata, A. flavus and T. longifusus. Furthermore, CuONPs were tested for antioxidant properties using 2, 2 diphenyl-1-picrylhydrazyl) (DPPH).


Assuntos
Vermelho Congo , Nanopartículas Metálicas , Peróxido de Hidrogênio/farmacologia , Raios Ultravioleta , Nanopartículas Metálicas/química , Corantes/química , Escherichia coli , Antibacterianos/farmacologia
7.
AME Case Rep ; 6: 36, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36339910

RESUMO

Background: Meningiomas are usually associated with neurofibromatosis type 2 (NF-2), while gliomas are usually associated with neurofibromatosis type 1 (NF-1). NF-1 is an autosomal dominant genetic disorder associated with skin manifestations, bone conditions, and different types of benign and malignant tumors. Grade 3 anaplastic meningiomas are rare tumors with a poor prognosis. Systemic treatments in grade 3 meningiomas are experimental, with some reports suggestive of minimal clinical benefits. They are used occasionally for recurrent cases with no surgical or radiotherapy roles. In our case, we will focus the discussion on grade 3 anaplastic meningioma in a patient with NF-1, using chemotherapy for this aggressive, recurrent tumor. To our knowledge, this is the first case of NF-1 associated with malignant anaplastic meningioma in English literature. Case Description: In this case report, we present a 25-year-old left-handed female patient who fits the diagnostic criteria for NF-1. She presented with focal seizure and was diagnosed with grade 3 anaplastic meningioma, a highly aggressive tumor. She experienced a rapid recurrence after her initial surgery and eventually received multiple lines of treatments, including radiation and chemotherapy [temozolomide (TMZ)]. Conclusions: Systemic therapy in grade 3 meningiomas is still experimental and may have a slight clinical benefit. As a result, further prospective, multicentric studies are needed to ascertain these outcomes. Patients should be included in prospective trials because of the poor prognosis and aggressive nature of grade 3 meningiomas. In addition, discovering specific molecular biomarkers will allow us to suggest an individualized treatment. This case suggests that the differential diagnosis of a mass in a patient with NF-1 should include tumors known to be associated with the syndrome as well as sporadic, unrelated neoplasms.

8.
Molecules ; 27(15)2022 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-35956775

RESUMO

Multiple biological functions of Mentha pulegium extract were evaluated in the current work. Phytochemical components of the M. pulegium extract were detected by Gas Chromatography-Mass Spectrometry (GC-MS) and High-performance liquid chromatography (HPLC). Moreover, M. pulegium extract was estimated for antioxidant potential by 2,2-Diphenyl-1-picryl-hydrazyl-hydrate (DPPH) free radical scavenging, antimicrobial activity by well diffusion, and anticoagulant activity via prothrombin time (PT) and activated partial thromboplastin time (APTT). GC-MS analysis detected compounds including cholesterol margarate, stigmast-5-en-3-ol, 19-nor-4-androstenediol, androstan-17-one, pulegone-1,2-epoxide, isochiapin B, dotriacontane, hexadecanoic acid and neophytadiene. Chrysoeriol (15.36 µg/mL) was followed by kaempferol (11.14 µg/mL) and 7-OH flavone (10.14 µg/mL), catechin (4.11 µg/mL), hisperdin (3.05 µg/mL), and luteolin (2.36 µg/mL) were detected by HPLC as flavonoids, in addition to ferulic (13.19 µg/mL), cinnamic (12.69 µg/mL), caffeic (11.45 µg/mL), pyrogallol (9.36 µg/mL), p-coumaric (5.06 µg/mL) and salicylic (4.17 µg/mL) as phenolics. Antioxidant activity was detected with IC50 18 µg/mL, hemolysis inhibition was recorded as 79.8% at 1000 µg/mL, and PT and APTT were at 21.5 s and 49.5 s, respectively, at 50 µg/mL of M. pulegium extract. The acute toxicity of M. pulegium extract was recorded against PC3 (IC50 97.99 µg/mL) and MCF7 (IC50 80.21 µg/mL). Antimicrobial activity of M. pulegium extract was documented against Bacillus subtilis, Escherichia coli, Pseudomonasaureus, Candida albicans, Pseudomonas aeruginosa, but not against black fungus Mucor circinelloides. Molecular docking was applied using MOE (Molecular Operating Environment) to explain the biological activity of neophytadiene, luteolin, chrysoeriol and kaempferol. These compounds could be suitable for the development of novel pharmacological agents for treatment of cancer and bacterial infections.


Assuntos
Anti-Infecciosos , Mentha pulegium , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Antioxidantes/química , Hemólise , Hemolíticos , Quempferóis , Luteolina , Mentha pulegium/química , Simulação de Acoplamento Molecular , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia
9.
Int J Pharm ; 625: 122039, 2022 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-35902059

RESUMO

Hepatospecific delivery by ligand based receptor targeting is an established strategy to augment therapy associated with liver diseases and disorders. Previously, we have investigated the effect of ligand headgroup on cellular uptake mediated by the asialoglycoprotein receptor by in silico and in vitro approach. In this paper, we report the design of agarose based liposomes for delivery to liver cancer cells and provide a proof of concept of the targeting efficiency against galactose liposomes using an in vivo approach. Sorafenib Tosylate loaded targeting liposomes were developed and optimized using factorial design. Comparative evaluation including cell cytotoxicity, pharmacokinetics and biodistribution and hepatospecific uptake was performed for both the liposomal systems. The formulations possessed a particle size of 150 - 180 nm and a zeta potential of 30 - 60 mV depending on the amount of ligand and drug loading, with more than 90% entrapment efficiency. A two-fold increase in cytotoxicity was observed with agarose-based liposomes as compared to galactose based liposomes. In vivo PK evaluation indicated a reduction in half life of drug when loaded in agarose ligand loaded system, probably due to greater uptake in the liver as evidenced in biodistribution study. Intrahepatic disposition revealed a higher PC/NPC uptake ratio with the targeted systems as compared to conventional liposomes, although the agarose-based system resulted in highest uptake ratio. A biocompatible platform for specific delivery of drugs to hepatocytes was established validating a rational approach to design liver targeting systems.


Assuntos
Galactose , Lipossomos , Sistemas de Liberação de Medicamentos , Ligantes , Lipossomos/farmacocinética , Fígado/metabolismo , Monossacarídeos/metabolismo , Monossacarídeos/farmacologia , Tamanho da Partícula , Polissacarídeos/farmacologia , Sefarose/metabolismo , Sefarose/farmacologia , Sorafenibe/farmacologia , Distribuição Tecidual
10.
Sci Rep ; 12(1): 5914, 2022 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-35396383

RESUMO

Secondary plant metabolites remain one of the key sources of therapeutic agents despite the development of new approaches for the discovery of medicinal drugs. In the current study, chemical analysis, and biological activities of Kei apple (Dovyalis caffra) methanolic extract were evaluated. Chemical analysis was performed using HPLC and GC-MS. Antiviral and anticancer effect were assessed using the crystal violet technique and activity against human liver cells (HepG2), respectively. Antibacterial activity was tested with the disc diffusion method. The obtained results showed that chlorogenic acid (2107.96 ± 0.07 µg/g), catechin (168 ± 0.58 µg/g), and gallic acid (15.66 ± 0.02 µg/g) were the main bioactive compounds identified by HPLC techniques. While, compounds containing furan moieties, as well as levoglucosenone, isochiapin B, dotriacontane, 7-nonynoic acid and tert-hexadecanethiol, with different biological activities were identified by GC-MS. Additionally, inhibition of 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) scavenging was 79.25% at 2000 µg/mL, indicating its antioxidant activity with IC50 of 728.20 ± 1.04 µg/mL. The tested extract exhibited potential anticancer activity (58.90% toxicity) against HepG2 cells at 1000 µg/mL. Potential bacterial inhibition was observed mainly against Escherichia coli and Proteus vulgaris, followed by Staphylococcus aureus and Bacillus subtilis with a diameter of growth inhibition ranging from 13 to 24 mm. While weak activities were recorded for fungi Candida albicans (10 mm). The extract showed mild antiviral activity against human coronavirus 229E with a selective index (SI) of 10.4, but not against human H3N2 (SI of 0.67). The molecular docking study's energy ratings were in good promise with the experiment documents of antibacterial and antiviral activities. The findings suggest that D. caffra juice extract is a potential candidate for further experiments to assess its use as potential alternative therapeutic agent.


Assuntos
Antioxidantes , Salicaceae , Antibacterianos/análise , Antibacterianos/farmacologia , Antioxidantes/química , Antivirais/análise , Antivirais/farmacologia , Frutas/química , Humanos , Vírus da Influenza A Subtipo H3N2 , Simulação de Acoplamento Molecular , Extratos Vegetais/química
11.
Infection ; 50(5): 1121-1129, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35247163

RESUMO

BACKGROUND: The COVID-19 infection has impacted pregnancy outcomes; however, few studies have assessed the association between haematological parameters and virus-related pregnancy and neonatal outcomes. We hypothesised differences in routine haematology indices in pregnant and non-pregnant COVID-19 patients as well as COVID-19-negative pregnant subjects and observed neonatal outcomes in all pregnant populations. Further, we tested if pattern identification in the COVID-19 pregnant population would facilitate prediction of neonates with a poor Apgar score. METHODS: We tested our hypothesis in 327 patients (111 COVID-19-positive pregnant females, 169 COVID-19-negative pregnant females and 47 COVID-19-positive non-pregnant females) in whom standard routine laboratory indices were collected on admission. RESULTS: Pregnant COVID-19-positive patients exhibited higher WBC, neutrophil, monocyte counts as well as neutrophil/lymphocyte and neutrophil/eosinophil ratio compared to non-pregnant COVID-19-positive patients (p = 0.00001, p = 0.0023, p = 0.00002, p = 0.0402, p = 0.0161, p = 0.0352, respectively). Preterm delivery was more prevalent in COVID-19-positive pregnant patients accompanied with a significantly lower birth weight (2894.37 (± 67.50) g compared with 3194.16 (± 50.61) g, p = 0.02) in COVID-19-negative pregnant patients. The COVID-19-Induced Immunity Response (CIIR) was defined as (WBC × neutrophil) / eosinophil; Apgar scores were significantly and inversely correlated with the CIIR index (r =-0.162). INTERPRETATION: Pregnancy appears to give rise to an increased immune response to COVID-19 which appears to protect the mother, however may give rise to complications during labour as well as neonatal concerns. CIIR is a simple metric that predicts neonatal distress to aid clinicians in determining the prognosis of COVID-19 and help provide early intensive intervention to reduce complications.


Assuntos
COVID-19 , Complicações Infecciosas na Gravidez , Nascimento Prematuro , Índice de Apgar , COVID-19/diagnóstico , Feminino , Humanos , Recém-Nascido , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/epidemiologia , Resultado da Gravidez/epidemiologia , Nascimento Prematuro/epidemiologia , Prognóstico , SARS-CoV-2
12.
BMC Oral Health ; 22(1): 53, 2022 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-35241051

RESUMO

BACKGROUND: Caries prevalence has declined significantly since the introduction of fluoridated toothpaste. There have been several developments regarding specific active fluoride ingredients but not enough evidence to support one over the other. The purpose of this double-blind randomized controlled trial was to compare salivary fluoride concentrations of different fluoride formulations in the form of toothpaste with and without post-brushing water rinsing in adults. METHODS: The study included 120 participants who were randomly assigned to one of 12 groups (10 participants/group). The toothpaste formulas investigated included (1) fluoride-free (0 ppmF); (2) sodium fluoride (1450 ppmF); (3) sodium monofluorophosphate (1450 ppmF); (4) sodium fluoride and monofluorophosphate combined (1450 ppmF); (5) stannous fluoride and sodium fluoride combined (1450 ppmF); and (6) amine fluoride (1400 ppmF). Block randomisation was used to assign each participant to one of the 12 groups. Participants brushed with 1.0 g of one of the six different toothpaste formulations either with or without post-brushing water rinsing. Saliva was collected at six different times (baseline and at 1, 15, 30, 60, and 90 min/s post-brushing). Samples were analysed using a fluoride ion-specific sensitive electrode connected to an ion analyser. RESULTS: The demographic characteristics of the participants were not significantly different among the groups (P > 0.05). Time, toothpaste formulation, and post-brushing rinsing routines had significant effects on saliva fluoride retention (P < 0.05). Amine fluoride-containing toothpaste was the only formula that showed statistically significantly higher concentrations of salivary fluoride at 90 min in both the rinsing and non-rinsing groups. Sodium monofluorophosphate toothpaste did not result in a significant difference compared to the control group at any time point, in both rinsing and non-rinsing groups. CONCLUSIONS: Based on the results from this study, no rinsing after toothbrushing in adults can be recommended when sodium monofluorophosphate containing toothpaste formula is used. It also concludes that amine fluoride resulted in a significantly higher saliva fluoride concentration at 90 min in both the rinsing and non-rinsing groups compared to other fluoride toothpaste formulations. Registry: Protocol Registration and Results System (ClinicalTrials.gov). CLINICAL TRIAL REGISTRATION NUMBER: NCT02740803 (15/04/2016).


Assuntos
Fluoretos , Escovação Dentária , Adulto , Cariostáticos/análise , Cariostáticos/uso terapêutico , Fluoretos/análise , Fluoretos/uso terapêutico , Humanos , Saliva/química , Fluoreto de Sódio/uso terapêutico , Cremes Dentais/uso terapêutico
13.
Sci Rep ; 12(1): 3840, 2022 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-35264657

RESUMO

The EPHA3 protein tyrosine kinase, a member of the ephrin receptor family, regulates cell fate, cell motility, and cell-cell interaction. These cellular events are critical for tissue development, immunological responses, and the processes of tumorigenesis. Earlier studies revealed that signaling via the STK4-encoded MST1 serine-threonine protein kinase, a core component of the Hippo pathway, attenuated EPHA3 expression. Here, we investigated the mechanism by which MST1 regulates EPHA3. Our findings have revealed that the transcriptional regulators YAP1 and TEAD1 are crucial activators of EPHA3 transcription. Silencing YAP1 and TEAD1 suppressed the EPHA3 protein and mRNA levels. In addition, we identified putative TEAD enhancers in the distal EPHA3 promoter, where YAP1 and TEAD1 bind and promote EPHA3 expression. Furthermore, EPHA3 knockout by CRISPR/Cas9 technology reduced cell-cell interaction and cell motility. These findings demonstrate that EPHA3 is transcriptionally regulated by YAP1/TEAD1 of the Hippo pathway, suggesting that it is sensitive to cell contact-dependent interactions.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Proteínas de Sinalização YAP , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Serina-Treonina Quinases/genética , Receptor EphA3/genética , Receptor EphA3/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
14.
J Leukoc Biol ; 112(4): 617-628, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35213745

RESUMO

Tumor-infiltrating monocytes can mature into Macrophages that support tumor survival or that display antitumor properties. To explore mechanisms steering Macrophage maturation, we assessed the effects of supernatants from squamous cell carcinoma cell lines (FaDu and SCC) on monocyte-derived Macrophage maturation. Purified monocytes were incubated in medium or medium supplemented with supernatants from FaDu and SCC9 or the leukemia monocytic cell line, THP-1. Macrophages were examined for markers of maturation (CD14, CD68), activation (HLA-DR, CD86, IL15R), scavenger receptor (CD36), toll-like receptor (TLR4), M2 marker (CD206), immune checkpoint (PD-L1), and intracellular chemokine expression (IP-10). Compared to other conditions, cells incubated with FaDu or SCC9 supernatants displayed enhanced survival, down-regulation of cell surface HLA-DR, CD86, IL-15R, CD36, and intracellular IP-10 expression, and increased cell surface PD-L1, CD14, and CD206 expression. Despite expressing TLR4 and CD14, Macrophages matured in tumor supernatants failed to respond to stimulation with the canonical TLR4 agonist, LPS. These changes were accompanied by a decrease in intracellular phospho-p38 expression in tumor supernatant conditioned Macrophages. Depletion of fatty acids from tumor supernatants or treatment of cell cultures with an inhibitor of fatty acid oxidation, Etomoxir, reversed a number of these phenotypic changes induced by tumor supernatants. Additionally, Macrophages incubated with either palmitic acid or oleic acid developed similar phenotypes as cells incubated in tumor supernatants. Together, these data suggest that fatty acids derived from tumor cells can mediate the maturation of Macrophages into a cell type with limited pro-inflammatory characteristics.


Assuntos
Antígeno B7-H1 , Neoplasias de Cabeça e Pescoço , Antígeno B7-H1/metabolismo , Quimiocina CXCL10/metabolismo , Ácidos Graxos/metabolismo , Antígenos HLA-DR/metabolismo , Humanos , Lipopolissacarídeos/farmacologia , Macrófagos/metabolismo , Ácidos Oleicos/metabolismo , Ácidos Oleicos/farmacologia , Ácidos Palmíticos/metabolismo , Ácidos Palmíticos/farmacologia , Receptor 4 Toll-Like/metabolismo
15.
Cureus ; 14(12): e32607, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36654576

RESUMO

An intracranial solitary fibrous tumor (SFT) is a rare and aggressive tumor with a high propensity for locoregional recurrence and distant metastasis. The formerly used collective term for this tumor, "solitary fibrous tumor/hemangiopericytoma", has recently fallen out of use and is now commonly replaced with the term "solitary fibrous tumor". We describe a rare case of intracranial SFT with simultaneous metastasis to the spine, the right humerus, and the lungs four years after resection and radiotherapy of the primary tumor.

16.
Risk Manag Healthc Policy ; 14: 3541-3550, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34466043

RESUMO

PURPOSE: This study compared the most used sources of information by caregivers for scheduled childhood vaccination in Saudi Arabia before and during the COVID-19 pandemic and examined the effect of this decision-making. METHODS: An electronic survey was administered to 577 caregivers of children aged ≤2 years residing in Saudi Arabia during the COVID-19 pandemic curfew. The sources of information on childhood vaccination considered by the caregivers and their influence on the caregivers' decision to delay scheduled vaccination were assessed and statistically analyzed. RESULTS: Most participants (90.8%) were mothers aged 32.6 ± 5.7 years. Before the pandemic, most caregivers sought information about children's vaccinations personally from the healthcare workers, or trustworthy sources, including the Ministry of Health (MOH), MOH call center 937, and MOH Sehha app. However, during the pandemic, there was a noticeable decrease in the searches for health information through professional consultations (in person and health websites) and a significant increase in the use of social media platforms. Twitter was the most used platform (29.9%) and the use of Snapchat was significantly higher during the lockdown period compared to its use before the pandemic (21.9% vs 17.2%, P < 0.001). The use of social media not only increased the level of fear among the caregivers but also had a negative effect on their decisions about children's vaccinations. Searches on YouTube and Facebook particularly increased the odds of delaying vaccinations by 2.63 times (P = 0.008) and 3.66 times (P = 0.025), respectively. CONCLUSION: During the pandemic, caregivers' health-information seeking behavior was directed towards social media networking. In Saudi Arabia, YouTube and Facebook, in particular, played an important role in the caregivers' decision-making about childhood vaccinations. The results of this survey provide valuable information on how to reach the Saudi population and launch an effective awareness campaign using the most commonly accessed and influential sources of information.

17.
Curr Opin Biotechnol ; 71: 164-174, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34416662

RESUMO

Cell therapies represent a new era of treatment modalities for cancer. Through agile bioprocessing and bioengineering, patient-derived T-cells can be directed toward cancer biomarkers to impart a more robust and targeted immune response. In order to avoid delays in critical treatment timeframes, new bioanalytical tools are needed to accelerate, streamline, and maximize the throughput of T-cell bioprocessing. This review offers a survey of recent biotechnological advances supporting enhanced and expedited biomanufacturing workflows for autologous and allogeneic cell therapies, ranging from novel genetic engineering techniques and cell sorting platforms to stem cells and tumor organoid models. Collectively, these methods can increase the clinical impact of cancer therapeutics by improving the specificity, efficacy, and timely delivery of cell-based products.


Assuntos
Bioengenharia , Terapia Baseada em Transplante de Células e Tecidos , Biotecnologia , Humanos , Células-Tronco , Fluxo de Trabalho
18.
Front Pediatr ; 9: 692877, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34222155

RESUMO

Background: Routine childhood immunization is the most cost-effective method to prevent infection and decrease childhood morbidity and mortality. The COVID-19 pandemic has affected access to health care in Saudi Arabia, including mandatory vaccinations for young children. We aimed to assess the prevalence of intentionally delayed vaccinations in children aged ≤ 2 years during the COVID-19 pandemic curfew in Saudi Arabia, its relation to the caregivers' fear of infection, and identifying factors affecting the caregivers' decision. Methods: We conducted a cross-sectional study using a self-administered survey that targeted primary caregivers of children aged ≤ 2 years residing in Saudi Arabia during the COVID-19 pandemic curfew (March 4-July 6, 2020). Results: We received responses from 577 caregivers, of whom 90.8% were mothers. The prevalence of intentional vaccination delay was 37%. Upon adjusting the potential confounders, the odds of delaying scheduled childhood vaccination because of COVID-19 pandemic fears were greater among caregivers with higher levels of fear (OR 1.10, 95% CI 1.02-1.11). Common reasons for delaying vaccinations were COVID-19 infection and prevention of exposure to COVID-19 cases. Conclusion: Intentional vaccination delay leaves young children vulnerable to preventable infectious diseases. Identifying these children and offering catch-up vaccinations reduces this risk. Campaigns to increase awareness about the dangers of delaying vaccine-preventable diseases must be promoted to caregivers in addition to the promotion of home vaccination services. In preparation for future pandemics, we recommend countries consider interventions to control the level of fear and anxiety provoked by the pandemics and media, and interventions for improved access to vaccinations.

19.
Phys Chem Chem Phys ; 23(15): 9259-9269, 2021 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-33885072

RESUMO

Many chemical and biological reactions, including ligand exchange processes, require thermal energy for the reactants to overcome a transition barrier and reach the product state. Temperature-jump (T-jump) spectroscopy uses a near-infrared (NIR) pulse to rapidly heat a sample, offering an approach for triggering these processes and directly accessing thermally-activated pathways. However, thermal activation inherently increases the disorder of the system under study and, as a consequence, can make quantitative interpretations of structural changes challenging. In this Article, we optimise a deep neural network (DNN) for the instantaneous prediction of Co K-edge X-ray absorption near-edge structure (XANES) spectra. We apply our DNN to analyse T-jump pump/X-ray probe data pertaining to the ligand exchange processes and solvation dynamics of Co2+ in chlorinated aqueous solution. Our analysis is greatly facilitated by machine learning, as our DNN is able to predict quickly and cost-effectively the XANES spectra of thousands of geometric configurations sampled from ab initio molecular dynamics (MD) using nothing more than the local geometric environment around the X-ray absorption site. We identify directly the structural changes following the T-jump, which are dominated by sample heating and a commensurate increase in the Debye-Waller factor.

20.
Biomed J ; 44(1): 86-93, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33602634

RESUMO

Coronavirus disease 2019 (COVID-19) outbreak is proving to be an unprecedented disaster that lays its dark shadow on global health, economics and personal freedom. Severe acute respiratory syndrome (SARS) and middle east respiratory syndrome (MERS) epidemics provide scientific data that is useful in better understanding and resolution of COVID-19. Similarities among SARS-CoV, MERS-CoV and SARS-CoV-2 have been investigated in the light of available data. SARS-CoV, MERS-CoV and SARS-CoV-2 evolved in bats and have positive-sense RNA genomes of 27.9 kb, 30.1 kb and 29.9 kb, respectively. Molecular and serological tools used for diagnosis of SARS and MERS patients resemble COVID-19 diagnostic tools. Stability and longevity data of SARS and MERS epidemics contribute in the current pandemic precaution policies. Trials to produce vaccines for SARS-CoV and MERS-CoV failed, therefore different strategies were employed for SARS-CoV2 vaccines production and during the past period antiviral agents, Convalescent plasma and monoclonal antibodies provide potential treatments for sever patients. The mortality rate caused by the SARS-CoV and MERS-CoV reached 15% and 37%, respectively. The first declarations about mortality rate of SARS-CoV-2 was around 2-4% but now this rate differed globally and reached more than 13% in some countries. A realistic COVID-19 outbreak scenario suggest that the pandemic might last for three years with fluctuation in the number of infected cases, unless vaccination process goes faster and/or antiviral drug is discovered.


Assuntos
COVID-19/epidemiologia , Infecções por Coronavirus/epidemiologia , SARS-CoV-2 , Síndrome Respiratória Aguda Grave/epidemiologia , Adulto , Fatores Etários , Idoso , COVID-19/mortalidade , COVID-19/terapia , Comorbidade , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome Respiratória Aguda Grave/mortalidade , Síndrome Respiratória Aguda Grave/terapia , Caracteres Sexuais
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