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1.
Chemistry ; : e202402696, 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39190899

RESUMO

Electrochemical transformations are considered a green alternative to classical redox chemistry as it eliminates the necessity for toxic and waste producing redox reagents. Typical electrochemical reactions require the addition of a so-called supporting electrolyte - a salt bridge - and other additives, such as hexafluorisopropanol, to enhance conductivity and reaction outcomes, respectively. However, this is often accompanied by an increase in the amount of produced waste. Here, we report an "in-situ electrolyte" concept for facile, transition-metal-free, additive-free one-pot electrochemical preparation of isoxazol(in)es, important scaffolds for biologically active natural and synthetic molecules, from the respective aldehydes. The protocol utilizes no halogenated solvents and no external oxidants, while salt side-products provide the ionic conductivity necessary for the electrosynthesis. The electrolysis is performed in an undivided cell, using the state-of-the-art electrodes for the chlor-alkali industry dimensionally stable and scalable mixed metal oxide anode and platinized titanium anode of high durability. The cascade transformation comprises the condensation of aldehyde to oxime followed by its anodic oxidation and subsequent intra- and/or intermolecular [3+2] cycloadditions with an appropriate dipolarophile. Chemical yields up to 97%, and good Faradaic efficiency, scalability, and stability are observed for most substrates in a broad scope.

2.
Chemphyschem ; 25(18): e202400273, 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-38819992

RESUMO

Photocatalysis using transition-metal complexes is widely considered the future of effective and affordable clean-air technology. In particular, redox-stable, easily accessible ligands are decisive. Here, we report a straightforward and facile synthesis of a new highly stable 2,6-bis(triazolyl)pyridine ligand, containing a nitrile moiety as a masked anchoring group, using copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) click reaction. The reported structure mimics the binding motif of uneasy to synthesize ligands. Pulse radiolysis under oxidizing and reducing conditions provided evidence for the high stability of the formed radical cation and radical anion 2,6-di(1,2,3-triazol-1-yl)-pyridine compound, thus indicating the feasibility of utilizing this as a ligand for redox active metal complexes and the sensitization of metal-oxide semiconductors (e. g., TiO2 nanoparticles or nanotubes).

3.
BMC Med Res Methodol ; 24(1): 82, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38580928

RESUMO

BACKGROUND: This retrospective analysis aimed to comprehensively review the design and regulatory aspects of bioequivalence trials submitted to the Saudi Food and Drug Authority (SFDA) since 2017. METHODS: This was a retrospective, comprehensive analysis study. The Data extracted from the SFDA bioequivalence assessment reports were analyzed for reviewing the overall design and regulatory aspects of the successful bioequivalence trials, exploring the impact of the coefficient of variation of within-subject variability (CVw) on some design aspects, and providing an in-depth assessment of bioequivalence trial submissions that were deemed insufficient in demonstrating bioequivalence. RESULTS: A total of 590 bioequivalence trials were included of which 521 demonstrated bioequivalence (440 single active pharmaceutical ingredients [APIs] and 81 fixed combinations). Most of the successful trials were for cardiovascular drugs (84 out of 521 [16.1%]), and the 2 × 2 crossover design was used in 455 (87.3%) trials. The sample size tended to increase with the increase in the CVw in trials of single APIs. Biopharmaceutics Classification System Class II and IV drugs accounted for the majority of highly variable drugs (58 out of 82 [70.7%]) in the study. Most of the 51 rejected trials were rejected due to concerns related to the study center (n = 21 [41.2%]). CONCLUSION: This comprehensive analysis provides valuable insights into the regulatory and design aspects of bioequivalence trials and can inform future research and assist in identifying opportunities for improvement in conducting bioequivalence trials in Saudi Arabia.


Assuntos
Medicamentos Genéricos , Humanos , Equivalência Terapêutica , Medicamentos Genéricos/uso terapêutico , Arábia Saudita , Estudos Retrospectivos , Tamanho da Amostra
4.
Phys Chem Chem Phys ; 26(18): 13955-13964, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38668770

RESUMO

The search for low-diffusion barriers and high-capacity anode materials is considered a key step in boosting the efficiency of metal-ion batteries. Herein, we investigate the impact of a series of conducting polymers (CPs), namely, polyacetylene (PA), polypyrrole (PP), poly-p-phenylene (PPPh), and polythiophene (PT), on enhancing the material design and anodic performance of boron nitride nanosheet (BNNS)-based Li-ion and Na-ion batteries. For this purpose, first principle DFT simulations, utilizing both clustered and periodic models, are systematically performed to assess the stability of such nanostructures and their electronic behavior as potential anodic materials. It is revealed that frontier molecular orbitals calculated for BNNSs are stabilized upon association with the series of CPs, resulting in a reduction in the energy gaps of CP-BNNSs by nearly 50%, which in turn improves the charge transfer properties and cell reaction kinetics. A remarkable improvement in the cell voltage is predicted for PP and PT functionalized BNNSs, reaching approximately 3.5 V for Li+ and 3.0 V for Na+ ions. The outcome of the study emphasizes the influence of the size of metal ions, whether mono- or di-valent, and the nature of adsorbed conducting polymers. Manipulating the electronic features of boron nitride nanostructured surfaces through non-covalent functionalization with conducting polymers could pave the way for the design of highly efficient energy storage anodic CP-BNNS-based systems.

5.
Biometals ; 37(4): 905-921, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38361146

RESUMO

Palladium and platinum complexes, especially those that include cisplatin, can be useful chemotherapeutic drugs. Alternatives that have less adverse effects and require lower dosages of treatment could be provided by complexes containing pyridine bases. The complexes [Pd(SCN)2(4-Acpy)2] (1), [Pd(N3)2(4-Acpy)2] (2) [Pd(paOH)2].2Cl (3) and [Pt(SCN)2(paO)2] (4) were prepared by self-assembly method at ambient temperature; (4-Acpy = 4-acetylpyridine and paOH = pyridine-2-carbaldehyde-oxime). The structure of complexes 1-4 was confirmed using spectroscopic and X-ray crystallography methods. Complexes 1-4 have similar features in isomerism that include the trans coordination geometry of pyridine ligands with Pd or Pt ion. The 3D network structure of complexes 1-4 was constructed by an infinite number of discrete mononuclear molecules extending via H-bonds. The Pd and Pt complexes 1-4 with pyridine ligands were assessed on MCF-7, T47D breast cancer cells and HCT116 colon cancer cells. The study evaluated cell death through apoptosis and cell cycle phases in MCF-7 cells treated with palladium or platinum conjugated with pyridine base. Upon treatment of MCF-7 with these complexes, the expression of apoptotic signals (Bcl2, p53, Bax and c-Myc) and cell cycle signals (p16, CDK1A, CDK1B) were evaluated. Compared to other complexes and cisplatin, IC50 of complex 1 was lowest in MCF-7 cells and complex 2 in T47D cells. Complex 4 has the highest effectiveness on HCT116. The selective index (SI) of complexes 1-4 has a value of more than two for all cancer cell lines, indicating that the complexes were less toxic to normal cells when given the same dose. MCF-7 cells treated with complex 2 and platinum complex 4 exhibited the highest level of early apoptosis. p16 may be signal arrest cells in Sub G, which was observed in cells treated with palladium complexes that suppress excessive cell proliferation. High c-Myc expression of treated cells with four complexes 1-4 and cisplatin could induce p53. All complexes 1-4 elevated the expression of Bax and triggered by the tumor suppressor gene p53. p53 was downregulating the expression of Bcl2.


Assuntos
Antineoplásicos , Apoptose , Complexos de Coordenação , Paládio , Piridinas , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Paládio/química , Paládio/farmacologia , Piridinas/química , Piridinas/farmacologia , Apoptose/efeitos dos fármacos , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Transdução de Sinais/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Platina/química , Platina/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Linhagem Celular Tumoral , Compostos Organoplatínicos/farmacologia , Compostos Organoplatínicos/química , Compostos Organoplatínicos/síntese química , Cristalografia por Raios X , Estrutura Molecular , Relação Dose-Resposta a Droga
6.
Cell Biochem Funct ; 42(7): e4113, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39223765

RESUMO

Due to their exceptional physicochemical features, green synthesized silver nanoparticles (AgNPs) have been of considerable interest in cancer treatment. In the present study, for the first time, we aimed to green synthesize AgNPs from Euphorbia retusa and explore their anticancer potential on human breast cancer (MCF-7) cells. First, the green synthesized AgNPs (EU-AgNPs) were well characterized by UV-visible spectroscopy, Fourier transmission infrared (FTIR) spectrum, XRD, scanning and transmission electron microscopy (SEM and TEM), and EDX techniques. The characterization data exhibited that EU-AgNPs were spherical in shape and crystalline in nature with an average size of 17.8 nm. FTIR results established the presence of active metabolites in EU-AgNPs. Second, the anticancer effect of EU-AgNPs was evaluated against MCF-7 cells by MTT and neutral red uptake (NRU) assays. Moreover, morphological changes, ROS production, MMP, and apoptotic marker genes were also studied upon exposure to cytotoxic doses of EU-AgNPs. Our results showed that EU-AgNPs induce cytotoxicity in a concentration-dependent manner, with an IC50 value of 40 µg/mL. Morphological changes in MCF-7 cells exposed to EU-AgNPs also confirm their cytotoxic effects. Increased ROS and decreased MMP levels revealed that EU-AgNPs induced oxidative stress and mitochondrial membrane dysfunction. Moreover, ROS-mediated apoptosis was confirmed by elevated levels of proapoptotic marker genes (p53, Bax, caspase-3, and caspase-9) and reduced levels of an antiapoptotic gene (Bcl-2). Altogether, these findings suggested that EU-AgNPs could induce potential anticancer effects through ROS-mediated apoptosis in MCF-7 cells.


Assuntos
Antineoplásicos , Neoplasias da Mama , Euphorbia , Nanopartículas Metálicas , Extratos Vegetais , Prata , Células MCF-7 , Euphorbia/química , Prata/química , Prata/farmacologia , Nanopartículas Metálicas/química , Nanopartículas Metálicas/ultraestrutura , Espécies Reativas de Oxigênio , Análise Espectral , Extratos Vegetais/farmacologia , Neoplasias da Mama/tratamento farmacológico , Espectroscopia de Infravermelho com Transformada de Fourier , Microscopia Eletrônica , Ácido Ascórbico/farmacologia , Membranas Mitocondriais/efeitos dos fármacos , Membranas Mitocondriais/fisiologia , Apoptose , Reação em Cadeia da Polimerase em Tempo Real , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia
7.
BMC Public Health ; 24(1): 605, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38408947

RESUMO

BACKGROUND: A considerable body of research has demonstrated that reducing sitting time benefits health. Therefore, the current study aimed to explore the prevalence of sedentary behavior (SB) and its patterns. METHODS: A total of 6975 university students (49.1% female) were chosen randomly to participate in a face-to-face interview. The original English version of the sedentary behavior questionnaire (SBQ) was previously translated into Arabic. Then, the validated Arabic version of the SBQ was used to assess SB. The Arabic SBQ included 9 types of SB (watching television, playing computer/video games, sitting while listening to music, sitting and talking on the phone, doing paperwork or office work, sitting and reading, playing a musical instrument, doing arts and crafts, and sitting and driving/riding in a car, bus or train) on weekdays and weekends. RESULTS: SBQ indicated that the total time of SB was considerably high (478.75 ± 256.60 and 535.86 ± 316.53 (min/day) during weekdays and weekends, respectively). On average, participants spent the most time during the day doing office/paperwork (item number 4) during weekdays (112.47 ± 111.11 min/day) and weekends (122.05 ± 113.49 min/day), followed by sitting time in transportation (item number 9) during weekdays (78.95 ± 83.25 min/day) and weekends (92.84 ± 100.19 min/day). The average total sitting time of the SBQ was 495.09 ± 247.38 (min/day) and 58.4% of the participants reported a high amount of sitting time (≥ 7 hours/day). Independent t-test showed significant differences (P ≤ 0.05) between males and females in all types of SB except with doing office/paperwork (item number 4). The results also showed that male students have a longer daily sitting time (521.73 ± 236.53 min/day) than females (467.38 ± 255.28 min/day). Finally, 64.1% of the males reported a high amount of sitting time (≥ 7 hours/day) compared to females (52.3%). CONCLUSION: In conclusion, the total mean length of SB in minutes per day for male and female university students was considerably high. About 58% of the population appeared to spend ≥7 h/day sedentary. Male university students are likelier to sit longer than female students. Our findings also indicated that SB and physical activity interventions are needed to raise awareness of the importance of adopting an active lifestyle and reducing sitting time.


Assuntos
Comportamento Sedentário , Estudantes , Humanos , Masculino , Feminino , Prevalência , Arábia Saudita/epidemiologia , Universidades
8.
Brain Inj ; 38(7): 569-573, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38481094

RESUMO

INTRODUCTION: Concussion is a common brain injury that has significant effects on multiple functional domains in children. However, limited research exists on the relationship between concussion severity and functional performance in this population. This study aimed to examine the relationship between the severity of concussion symptoms and children's balance and functional performance. METHODS: This cross-sectional study recruited 23 children (9 males and 14 females; mean age 13.9 ± 2.2 years) with clinically diagnosed concussions from a tertiary balance center in 2016. Participants underwent clinical and functional evaluations by specialized physical therapists. Symptom severity was assessed using the Post-Concussion Symptom Scale (PCSS), while functional performance was measured using the Functional Gait Assessment (FGA). RESULTS: There was a trend suggesting a negative correlation between symptom severity (PCSS) and functional performance (FGA), indicating potentially better performance in individuals with milder symptoms. However, this trend was not significant (rs (21) = -.072, p = 0.744). Furthermore, no significant correlation was found between FGA scores and the severity of individual symptoms. CONCLUSION: The findings suggest that concussion symptom severity may not be directly related to functional performance in children. Therefore, it is crucial to incorporate functional performance measures alongside symptom assessment for comprehensive concussion management.


Assuntos
Concussão Encefálica , Humanos , Feminino , Masculino , Concussão Encefálica/fisiopatologia , Concussão Encefálica/diagnóstico , Concussão Encefálica/complicações , Criança , Estudos Transversais , Adolescente , Índice de Gravidade de Doença , Equilíbrio Postural/fisiologia , Testes Neuropsicológicos , Desempenho Físico Funcional , Síndrome Pós-Concussão/diagnóstico , Síndrome Pós-Concussão/fisiopatologia
9.
Artigo em Inglês | MEDLINE | ID: mdl-39044061

RESUMO

PURPOSE: Septal perforations (SPs) present a distinct challenge. There are many described surgical approaches with variable success rates. The goal of this study is to describe a new technique in repairing SP. METHODS: A case series of eighteen patients with anterior septal perforation who underwent endoscopic repair with the "tunnel technique" based on anterior ethmoid artery flap (AEA) were analyzed. Demographic data, etiology, size of perforation, and success rate were collected. RESULTS: Eighteen cases with male predominance (67%) were enrolled from 2019 to 2022. The average perforation size was 1.5 cm (0.5- 3.6 cm). The success rate of complete SP closure was 94% (n = 17/18) with no complications after surgery. The patients were followed up for 7 ± 5.2 months. CONCLUSIONS: AEA flap reconstruction with the tunnel technique is associated with favorable outcomes in SP closure. The tunnel technique provides a useful flap bolster and minimizes the use of other supportive measures. This technique offers an addition to other techniques for septal perforation repair. LEVEL OF EVIDENCE: Level 4.

10.
Int J Mol Sci ; 25(8)2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38674156

RESUMO

This study investigated the association between apolipoprotein E (APOE) gene polymorphisms (rs429358 and rs7412) and primary angle-closure glaucoma (PACG) and pseudoexfoliation glaucoma (PXG) in a Saudi cohort. Genotyping of 437 DNA samples (251 controls, 92 PACG, 94 PXG) was conducted using PCR-based Sanger sequencing. The results showed no significant differences in the allele and genotype frequencies of rs429358 and rs7412 between the PACG/PXG cases and controls. Haplotype analysis revealed ε3 as predominant, followed by ε4 and ε2 alleles, with no significant variance in PACG/PXG. However, APOE genotype analysis indicated a significant association between ε2-carriers and PACG (odds ratio = 4.82, 95% CI 1.52-15.26, p = 0.007), whereas no notable association was observed with PXG. Logistic regression confirmed ε2-carriers as a significant predictor for PACG (p = 0.008), while age emerged as significant for PXG (p < 0.001). These findings suggest a potential role of ε2-carriers in PACG risk within the Saudi cohort. Further validation and larger-scale investigations are essential to elucidate the precise role of APOE in PACG pathogenesis and progression.


Assuntos
Apolipoproteína E2 , Predisposição Genética para Doença , Glaucoma de Ângulo Fechado , Polimorfismo de Nucleotídeo Único , Feminino , Humanos , Masculino , Alelos , Apolipoproteína E2/genética , Estudos de Casos e Controles , Frequência do Gene , Genótipo , Glaucoma de Ângulo Fechado/genética , Haplótipos , Heterozigoto , Fatores de Risco , Arábia Saudita/epidemiologia
11.
J Stroke Cerebrovasc Dis ; 33(6): 107676, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38492657

RESUMO

INTRODUCTION: Posterior circulation stroke (PCS) may be less prevalent than its anterior counterpart but contributes to substantial morbidity and mortality. The aim was to characterize PCS's demographics, clinical presentation, management, and outcomes between younger and older adults in Saudi Arabia. METHODS: This retrospective cohort study was conducted at two tertiary medical centers in Saudi Arabia between March 2016 and December 2020. All patients who presented with symptoms of posterior circulation stroke and had positive brain imaging were included. RESULTS: The study involved 160 posterior circulation stroke patients, stratified into two age groups: 71 patients aged 18-59 years and 89 patients aged 60 years and above. The mean age of the entire cohort was 60.9 years, and 77 % were males. Hypertension was more prevalent in the older age group (88 % vs. 69 %, p=0.005), and smoking was significantly higher among younger patients (38 % vs. 15 %; p=0.0009). Only 22.4 % received thrombolysis and/or thrombectomy. Most strokes involved the posterior cerebral artery (45.6 %). Large artery atherosclerosis was the most common subtype. At discharge, younger patients had higher NIHSS compared to older patients. CONCLUSION: Our investigation of 160 PCS patients in Saudi Arabia uncovers notable trends: a mere 22.4 % received thrombolysis and/or thrombectomy and a significant prevalence of posterior cerebral artery involvement due to large artery atherosclerosis. The study further reveals younger patients disproportionately had severe outcomes. Highlighting the need for improved stroke care and heightened awareness, this research contributes vital data to an underexplored domain, urging further study to optimize care and understand PCS dynamics in Saudi Arabia.


Assuntos
Terapia Trombolítica , Humanos , Masculino , Estudos Retrospectivos , Feminino , Pessoa de Meia-Idade , Arábia Saudita/epidemiologia , Fatores de Risco , Adulto , Adulto Jovem , Adolescente , Fatores Etários , Idoso , Resultado do Tratamento , Prevalência , Medição de Risco , Avaliação da Deficiência , Trombectomia , Fatores de Tempo , Idoso de 80 Anos ou mais , Infarto da Artéria Cerebral Posterior/epidemiologia , Infarto da Artéria Cerebral Posterior/diagnóstico , Infarto da Artéria Cerebral Posterior/fisiopatologia , Infarto da Artéria Cerebral Posterior/diagnóstico por imagem
12.
J Prosthet Dent ; 132(4): 781.e1-781.e7, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38594088

RESUMO

STATEMENT OF PROBLEM: A predictable protocol for accurately scanning implants in a complete edentulous arch has not been established. PURPOSE: The purpose of this clinical study was to investigate the effect of splinting implant scan bodies intraorally on the accuracy and scan time for digital scans of edentulous arches. MATERIAL AND METHODS: This single center, nonrandomized, clinical trial included a total of 19 arches. Definitive casts with scan bodies were fabricated and scanned with a laboratory scanner as the reference (control) scan. Each participant received 2 intraoral scans, the first with unsplinted scan bodies and the second with resin-splinted scan bodies. The scan time was also recorded for each scan. To compare the accuracy of the scans, the standard tessellation language (STL) files of the 2 scans were superimposed on the control scan, and positional and angular deviations were analyzed by using a 3-dimensional (3D) metrology software program. The Mann-Whitney U test was used to compare the distance and angular deviations between the splinted group and the unsplinted group with the control. The ANOVA test was conducted to examine the effect of the scan technique on trueness (distance deviation and angular deviation) and scan time (α=.05 for all tests). RESULTS: Statistically significant differences were found in the overall 3D positional and angular deviations of the unsplinted and splinted digital scans when compared with the reference scans (P<.05). No statistically significant differences in overall 3-dimensional positional deviations (P=.644) and angular deviations (P=.665) were found between the splinted and unsplinted experimental groups. A faster scan time was found with the splinted group in the maxillary arch. CONCLUSIONS: Conventional complete arch implant impressions were more accurate than digital complete arch implant scans. Splinting implant scan bodies did not significantly affect the trueness of complete arch digital scans, but splinting appeared to reduce the scan time. However, fabricating the splint was not considered in the time measurement.


Assuntos
Imageamento Tridimensional , Humanos , Imageamento Tridimensional/métodos , Arco Dental/diagnóstico por imagem , Implantes Dentários , Desenho Assistido por Computador , Arcada Edêntula/diagnóstico por imagem , Contenções , Técnica de Moldagem Odontológica , Planejamento de Prótese Dentária/métodos
13.
Molecules ; 29(15)2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39124881

RESUMO

Classical Hodgkin lymphoma (cHL) is a common B-cell cancer and a significant health concern, especially in Western and Asian countries. Despite the effectiveness of chemotherapy, many relapse cases are being reported, highlighting the need for improved treatments. This study aimed to address this issue by discovering biomarkers through the analysis of gene expression data specific to cHL. Additionally, potential anticancer inhibitors were explored to target the discovered biomarkers. This study proceeded by retrieving microarray gene expression data from cHL patients, which was then analyzed to identify significant differentially expressed genes (DEGs). Functional and network annotation of the upregulated genes revealed the active involvement of matrix metallopeptidase 12 (MMP12) and C-C motif metallopeptidase ligand 22 (CCL22) genes in the progression of cHL. Additionally, the mentioned genes were found to be actively involved in cancer-related pathways, i.e., oxidative phosphorylation, complement pathway, myc_targets_v1 pathway, TNFA signaling via NFKB, etc., and showed strong associations with other genes known to promote cancer progression. MMP12, topping the list with a logFC value of +6.6378, was selected for inhibition using docking and simulation strategies. The known anticancer compounds were docked into the active site of the MMP12 molecular structure, revealing significant binding scores of -7.7 kcal/mol and -7.6 kcal/mol for BDC_24037121 and BDC_27854277, respectively. Simulation studies of the docked complexes further supported the effective binding of the ligands, yielding MMGBSA and MMPBSA scores of -78.08 kcal/mol and -82.05 kcal/mol for MMP12-BDC_24037121 and -48.79 kcal/mol and -49.67 kcal/mol for MMP12-BDC_27854277, respectively. Our findings highlight the active role of MMP12 in the progression of cHL, with known compounds effectively inhibiting its function and potentially halting the advancement of cHL. Further exploration of downregulated genes is warranted, as associated genes may play a role in cHL. Additionally, CCL22 should be considered for further investigation due to its significant role in the progression of cHL.


Assuntos
Regulação Neoplásica da Expressão Gênica , Doença de Hodgkin , Humanos , Doença de Hodgkin/genética , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/metabolismo , Doença de Hodgkin/patologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Perfilação da Expressão Gênica , Simulação de Acoplamento Molecular , Transcriptoma , Antineoplásicos/farmacologia , Antineoplásicos/química , Metaloproteinase 12 da Matriz/genética , Metaloproteinase 12 da Matriz/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Terapia de Alvo Molecular
14.
Molecules ; 29(5)2024 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-38474509

RESUMO

We provide promising computational (in silico) data on phytochemicals (compounds 1-10) from Arabian Peninsula medicinal plants as strong binders, targeting 3-chymotrypsin-like protease (3CLPro) and papain-like proteases (PLPro) of SARS-CoV-2. Compounds 1-10 followed the Lipinski rules of five (RO5) and ADMET analysis, exhibiting drug-like characters. Non-covalent (reversible) docking of compounds 1-10 demonstrated their binding with the catalytic dyad (CYS145 and HIS41) of 3CLPro and catalytic triad (CYS111, HIS272, and ASP286) of PLPro. Moreover, the implementation of the covalent (irreversible) docking protocol revealed that only compounds 7, 8, and 9 possess covalent warheads, which allowed the formation of the covalent bond with the catalytic dyad (CYS145) in 3CLPro and the catalytic triad (CYS111) in PLPro. Root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF), and radius of gyration (Rg) analysis from molecular dynamic (MD) simulations revealed that complexation between ligands (compounds 7, 8, and 9) and 3CLPro and PLPro was stable, and there was less deviation of ligands. Overall, the in silico data on the inherent properties of the above phytochemicals unravel the fact that they can act as reversible inhibitors for 3CLPro and PLPro. Moreover, compounds 7, 8, and 9 also showed their novel properties to inhibit dual targets by irreversible inhibition, indicating their effectiveness for possibly developing future drugs against SARS-CoV-2. Nonetheless, to confirm the theoretical findings here, the effectiveness of the above compounds as inhibitors of 3CLPro and PLPro warrants future investigations using suitable in vitro and in vivo tests.


Assuntos
COVID-19 , Plantas Medicinais , Peptídeo Hidrolases , Simulação de Acoplamento Molecular , SARS-CoV-2 , Papaína , Simulação de Dinâmica Molecular , Compostos Fitoquímicos , Antivirais , Inibidores de Proteases
15.
Molecules ; 29(4)2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38398601

RESUMO

Compounds derived from natural sources continue to serve as chemical scaffolds for designing prophylactic/therapeutic options for human healthcare. In this study, we aimed to systematically unravel the chemical profile and antioxidant and anti-inflammatory activities of myrtle methanolic extract (MMEx) using in vitro, in vivo, and in silico approaches. High levels of TPC (415.85 ± 15.52 mg GAE/g) and TFC (285.80 ± 1.64 mg QE/g) were observed. Mass spectrophotometry (GC-MS) analysis revealed the presence of 1,8-cineole (33.80%), α-pinene (10.06%), linalool (4.83%), p-dimethylaminobenzophenone (4.21%), thunbergol (4%), terpineol (3.60%), cis-geranyl acetate (3.25%), and totarol (3.30%) as major compounds. MMEx induced pronounced dose-dependent inhibition in all assays, and the best antioxidant activity was found with H2O2, with an IC50 of 17.81 ± 3.67 µg.mL-1. MMEx showed a good anti-inflammatory effect in vivo by limiting the development of carrageenan-induced paw edema. The pharmacokinetic profiles of the active molecules were determined using the SwissADME website, followed by virtual screening against anti-inflammatory targets including phospholipase A2 (PLA-2), cyclooxygenase-2 (COX-2), tumor necrosis factor alpha (TNF-α), interleukin-1ß (IL-1ß), and NF-κB. A pharmacokinetic study revealed that the molecules have good absorption, distribution, and metabolism profiles, with negative organ toxicity. Among the compounds identified by GC-MS analysis, pinostrobin chalcone, cinnamyl cinnamate, hedycaryol, totarol, and p-dimethylaminobenzophenone were observed to have good binding scores, thus appreciable anti-inflammatory potential. Our study reveals that MMEx from Algerian Myrtus communis L. can be considered to be a promising candidate for alleviating many health complaints associated with oxidative stress and inflammation.


Assuntos
Abietanos , Antioxidantes , Myrtus , Humanos , Antioxidantes/farmacologia , Myrtus/química , Simulação de Acoplamento Molecular , Peróxido de Hidrogênio , Anti-Inflamatórios/farmacologia , Extratos Vegetais/farmacologia
16.
BMC Oral Health ; 24(1): 271, 2024 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-38402388

RESUMO

BACKGROUND: In recent era, digitalization in the dental sciences has been observed in wide ranges. This cross-sectional study aimed to assess knowledge and practice of additive manufacturing (AM) in dentistry among university teaching faculty in Saudi Arabia. METHODS: A questionnaire was prepared and validated to distribute to the different dental colleges in Saudi Arabia. The questionnaire was divided into three parts: demographic information, knowledge and practices of AM among the dental teaching faculty. After receiving all the responses, descriptive statistics were used for the frequency distribution of all the responses. RESULTS: A total of 367 responses were received from the different faculty members. Most of the participants were male (67.30%), holding assistant professor (52.50%) positions in the field of prosthodontics (23.40%). In terms of knowledge, even though most of the participants were aware of AM (64.30%); however, do not understand the AM techniques (33.50). Moreover, 71.90% of the participants had no experience working with AM and only 13.60% of participants used AM in their respective dental colleges. CONCLUSION: AM techniques are not commonly used in the field of dentistry in Saudi Arabia; therefore, more platforms should have created to enhance the knowledge and practice of AM in the current population.


Assuntos
Odontologia , Docentes , Humanos , Masculino , Feminino , Arábia Saudita , Universidades , Estudos Transversais
17.
Trop Anim Health Prod ; 56(2): 50, 2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38236506

RESUMO

Nowadays, there is a global shortage in feed supply for animal nutrition; however, there are a considerable amount of agro-industrial co- and by-products that may offer a reasonable solution. Flaxseed cake (FSC) is a by-product of flaxseed for oil extraction rich in n-3 α-linolenic acid (ALA). Thus, the dietary inclusion of FSC on laying performance, egg quality, and serum and egg trace elements (Se, Zn, and Fe) was evaluated using Hisex White hens. The hens were distributed to three equal experimental treatments and provided diets including 0%, 5%, or 10% FSC from 48 to 58 weeks of age. Findings clarified that up to 10% FSC in the laying hen diet had no detrimental effect on laying rate, egg mass, and feed utilization. It was found that FSC resulted in a valuable source of protein, energy, macro- (Ca and P), micro- (Se, Zn and Fe) elements, and essential amino acids, with arginine being the highest. Dietary FSC did not negatively influence the egg quality traits, as well as egg sensory attributes. Including 5% or 10% FSC in diet did not significantly affect serum total protein and renal function in terms of creatinine, uric acid, and uric acid-to-creatinine ratio. Different FSC levels did not influence the chemical composition of eggs and trace elements in serum and eggs. It could be concluded that FSC is a valuable feedstuff that can provide a good source of energy, protein, amino acids, and macro- and micro-elements for hens' nutrition. The inclusion of up to 10% of FSC in hens diet did not adversely influence egg laying performance, egg quality of both fresh and stored eggs, sensory attributes, and nutritional composition, as well as Se, Zn, and Fe in serum and eggs due to balanced nutrient profile of FSC.


Assuntos
Linho , Oligoelementos , Animais , Feminino , Galinhas , Creatinina , Ácido Úrico , Óvulo , Dieta/veterinária , Ferro
18.
Medicina (Kaunas) ; 60(4)2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38674234

RESUMO

Background and Objectives: Despite the identified benefits of early implant loading, studies have questioned its advantages compared to delayed loading in edentulous patients. This study aimed to evaluate clinical peri-implant parameters and marginal bone loss around early placed and loaded mandibular implant overdentures with a 60-month follow-up. Materials and Methods: In this prospective cohort study, 43 patients were enrolled to receive 86 early loading sub-crestal dental implants through prosthetic guides. Implant overdentures were supported by two isolated implant locator attachments between two mental foramens. Clinical peri-implant parameters, including plaque index (PI), bleeding index (BI), peri-implant pocket depth (PIPD), and marginal bone loss (MBL) were evaluated using standardized techniques at 1, 12, 24, 36, 48, and 60 months follow-up. At 60 months, complications associated with implant overdentures (IOD's) were noted. The mean comparison of peri-implant clinical parameters was performed through ANOVA test. A p-value of ≤0.05 was taken as significant. Results: Out of the total 43 enrolled patients, 8 patients were lost during follow-up; as a result, 35 patients completed the 5 years follow-up. The mean values of PI, BI, and PIPD increased with no statistical difference (p > 0.05). For marginal bone loss, an increase in the mean values was noted at different time intervals with statistical differences (p < 0.001). The most common complications noted were loosening of the abutment, occlusal adjustment, retentive locator loosening and replacement, and relining of the denture. Conclusions: Early placement of IODs failed to prevent bone loss over time and was associated with complications, predominantly consisting of abutment loosening, occlusal adjustments, broken retentive locator components, relining, and rebasing.


Assuntos
Perda do Osso Alveolar , Revestimento de Dentadura , Mandíbula , Humanos , Feminino , Masculino , Estudos Prospectivos , Perda do Osso Alveolar/etiologia , Pessoa de Meia-Idade , Seguimentos , Mandíbula/cirurgia , Idoso , Prótese Dentária Fixada por Implante/métodos , Prótese Dentária Fixada por Implante/efeitos adversos , Implantes Dentários/efeitos adversos , Estudos de Coortes , Adulto
19.
Medicina (Kaunas) ; 60(3)2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38541227

RESUMO

Background and Objectives: Enterococcus faecalis (E. faecalis) is a primary pathogen responsible for dental abscesses, which cause inflammation and pain when trapped between the crown and soft tissues of an erupted tooth. Therefore, this study aims to use specific phages as an alternative method instead of classical treatments based on antibiotics to destroy multidrug-resistant E. faecalis bacteria for treating dental issues. Materials and Methods: In the current study, twenty-five bacterial isolates were obtained from infected dental specimens; only five had the ability to grow on bile esculin agar, and among these five, only two were described to be extensive multidrug-resistant isolates. Results: Two bacterial isolates, Enterococcus faecalis A.R.A.01 [ON797462.1] and Enterococcus faecalis A.R.A.02, were identified biochemically and through 16S rDNA, which were used as hosts for isolating specific phages. Two isolated phages were characterized through TEM imaging, which indicated that E. faecalis_phage-01 had a long and flexible tail, belonging to the family Siphoviridae, while E. faecalis_phage-02 had a contractile tail, belonging to the family Myoviridae. Genetically, two phages were identified through the PCR amplification and sequencing of the RNA ligase of Enterococcus phage vB_EfaS_HEf13, through which our phages shared 97.2% similarity with Enterococcus phage vB-EfaS-HEf13 based on BLAST analysis. Furthermore, through in silico analysis and annotations of the two phages' genomes, it was determined that a total of 69 open reading frames (ORFs) were found to be involved in various functions related to integration excision, replication recombination, repair, stability, and defense. In phage optimization, the two isolated phages exhibited a high specific host range with Enterococcus faecalis among six different bacterial hosts, where E. faecalis_phage-01 had a latent period of 30 min with 115.76 PFU/mL, while E. faecalis_phage-02 had a latent period of 25 min with 80.6 PFU/mL. They were also characterized with stability at wide ranges of pH (4-11) and temperature (10-60 °C), with a low cytotoxic effect on the oral epithelial cell line at different concentrations (1000-31.25 PFU/mL). Conclusions: The findings highlight the promise of phage therapy in dental medicine, offering a novel approach to combating antibiotic resistance and enhancing patient outcomes. Further research and clinical trials will be essential to fully understand the therapeutic potential and safety profile of these bacteriophages in human populations.


Assuntos
Bacteriófagos , Humanos , Bacteriófagos/genética , Enterococcus faecalis/genética , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Abscesso/terapia , Temperatura
20.
Medicina (Kaunas) ; 60(3)2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38541241

RESUMO

Background and Objectives: Urinary tract infections [UTIs] are considered the third most known risk of infection in human health around the world. There is increasing appreciation for the pathogenicity of Gram-positive and Gram-negative strains in UTIs, aside from fungal infection, as they have numerous virulence factors. Materials and Methods: In this study, fifty urine samples were collected from patients suffering from UTI. Among the isolates of UTI microbes, six isolates were described as MDR isolates after an antibiotic susceptibility test carried out using ten different antibiotics. An alternative treatment for microbial elimination involved the use of biosynthesized silver nanoparticles (AgNPs) derived from Solanum lycopersicum [S. cumin]. Results: The sizes and shapes of AgNPs were characterized through TEM imaging, which showed spherical particles in a size range of 35-80 nm, of which the average size was 53 nm. Additionally, the silver nanoparticles (AgNPs) demonstrated inhibitory activity against Staphylococcus aureus (OR648079), exhibiting a 31 mm zone of inhibition at a minimum inhibitory concentration (MIC) of 4 mg/mL and a minimum bactericidal concentration (MBC) of 8 mg/mL. This was followed by Aspergillus niger (OR648075), which showed a 30 mm inhibition zone at an MIC of 16 mg/mL and a minimum fungicidal concentration (MFC) of 32 mg/mL. Then, Enterococcus faecalis (OR648078), Klebsiella pneumoniae (OR648081), and Acinetobacter baumannii (OR648080) each displayed a 29 mm zone of inhibition at an MIC of 8 mg/mL and an MBC of 16 mg/mL. The least inhibition was observed against Candida auris (OR648076), with a 25 mm inhibition zone at an MIC of 16 mg/mL and an MFC of 32 mg/mL. Furthermore, AgNPs at different concentrations removed DPPH and H2O2 at an IC50 value of 13.54 µg/mL. Also, AgNPs at 3 mg/mL showed remarkable DNA fragmentation in all bacterial strains except Enterococcus faecalis. The phytochemical analysis showed the presence of different active organic components in the plant extract, which concluded that rutin was 88.3 mg/g, garlic acid was 70.4 mg/g, and tannic acid was 23.7 mg/g. Finally, AgNPs concentrations in the range of 3-6 mg/mL showed decreased expression of two of the fundamental genes necessary for biofilm formation within Staphylococcus aureus, fnbA (6 folds), and Cna (12.5 folds) when compared with the RecA gene, which decreased by one-fold when compared with the control sample. These two genes were submitted with NCBI accession numbers [OR682119] and [OR682118], respectively. Conclusions: The findings from this study indicate that biosynthesized AgNPs from Solanum lycopersicum exhibit promising antimicrobial and antioxidant properties against UTI pathogens, including strains resistant to multiple antibiotics. This suggests their potential as an effective alternative treatment for UTIs. Further research is warranted to fully understand the mechanisms of action and to explore the therapeutic applications of these nanoparticles in combating UTIs.


Assuntos
Adesinas Bacterianas , Anti-Infecciosos , Nanopartículas Metálicas , Polifenóis , Solanum lycopersicum , Humanos , Prata/farmacologia , Antioxidantes/farmacologia , Virulência , Nanopartículas Metálicas/uso terapêutico , Peróxido de Hidrogênio/farmacologia , Anti-Infecciosos/farmacologia , Antibacterianos/farmacologia , Staphylococcus aureus , Biofilmes , Anti-Inflamatórios/farmacologia
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