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1.
Artículo en Inglés | MEDLINE | ID: mdl-39299771

RESUMEN

OBJECTIVES: Hospice family caregivers (CGs) may experience poor emotional health and diminished quality of life (QOL) secondary to stressors that accompany home-based end-of-life caregiving. Innovative flexible strategies are needed to support hospice CGs in their homes. Being outdoors in nature enhances well-being but is often not accessible to home-based CGs. The purpose was to evaluate the feasibility/acceptability, and preliminary emotional health and QOL outcomes of a 5-day nature-based virtual reality (VR) intervention. METHODS: A pre-post design was used. Hospice CGs engaged in self-selected 10 min nature experiences via VR headset over 5 days. Preintervention surveys included demographics and the PROMIS-29 QOL measure (physical/social function, anxiety/depressive symptoms, fatigue, sleep and pain). Postintervention surveys included acceptability/feasibility surveys, PROMIS-29 and a VR-related symptom checklist. Data analysis included descriptives and paired t-tests. RESULTS: 15 CGs (mean 61.13±12.47 years; 12 females) completed the study. Findings demonstrated high acceptability (14.46±1.77; range 0-16); feasibility (13.93±2.43;range 0-16). Adverse VR symptoms were minimal. PROMIS-29 overall scores were significantly improved following the 5-day intervention (pre: 66.33±8.47; post: 61.07±7.83,p=0.01). Paired t-tests showed significant pre-post changes in anxiety (t=2.206, p<0.05) and favourable trends on other QOL dimensions. CONCLUSIONS: Feasibility/acceptability and QOL data support further testing of VR nature immersive experiences in the home environment with larger more diverse representative samples.

2.
Molecules ; 29(15)2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-39124887

RESUMEN

This article presents a new method for preparing multifunctional composite biomaterials with applications in advanced biomedical fields. The biomaterials consist of dicalcium phosphate (DCPD) and bioactive silicate glasses (SiO2/Na2O and SiO2/K2O), containing the antibiotic streptomycin sulfate. Materials were deeply characterized by X-ray diffraction and attenuated total reflectance Fourier transform infrared spectroscopy, and zeta potential analysis, UV-visible spectrophotometry, and ion-exchange measurement were applied in a simulating body fluid (SBF) solution. The main results include an in situ chemical transformation of dicalcium phosphate into an apatitic phase under the influence of silicate solutions and the incorporation of the antibiotic. The zeta potential showed a decrease in surface charge from ζ = -24.6 mV to ζ = -16.5 mV. In addition, a controlled and prolonged release of antibiotics was observed over a period of 37 days, with a released concentration of up to 755 ppm. Toxicity tests in mice demonstrated good tolerance of the biomaterials, with no significant adverse effects. Moreover, these biomaterials have shown potent antibacterial activity against various bacterial strains, including Listeria monocytogenes, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa, suggesting their potential use in tissue engineering, drug delivery, and orthopedic and dental implants. By integrating the antibiotic into the biomaterial composites, we achieved controlled release and prolonged antibacterial efficacy. This research contributes to advancing biomaterials by exploring innovative synthetic routes and showcasing their promise in regenerative medicine and controlled drug delivery.


Asunto(s)
Antibacterianos , Materiales Biocompatibles , Medicina Regenerativa , Materiales Biocompatibles/química , Materiales Biocompatibles/síntesis química , Medicina Regenerativa/métodos , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Animales , Ratones , Sistemas de Liberación de Medicamentos , Difracción de Rayos X , Pruebas de Sensibilidad Microbiana , Preparaciones de Acción Retardada/farmacología , Espectroscopía Infrarroja por Transformada de Fourier , Fosfatos de Calcio/química , Fosfatos de Calcio/síntesis química , Liberación de Fármacos , Estreptomicina/farmacología , Dióxido de Silicio/química
3.
Pharmaceuticals (Basel) ; 17(7)2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-39065690

RESUMEN

In an effort to develop improved and effective targeted tyrosine kinase inhibitors (TKIs), a series of twelve novel compounds with the structural motif "(E)-4-(((1H-benzo[d]imidazol-2-yl)methyl)amino)-N'-(halogenated)benzylidenebenzohydrazide" were successfully synthesized in three steps, yielding high product yields (53-97%). Among this new class of compounds, 6c and 6h-j exhibited excellent cytotoxic effects against four different cancer cell lines, with half-maximal inhibitory concentration (IC50) values ranging from 7.82 to 21.48 µM. Notably, compounds 6h and 6i emerged as the most potent inhibitors, demonstrating significant activity against key kinases such as EGFR, HER2, and CDK2. Furthermore, compound 6h displayed potent inhibitory activity against AURKC, while 6i showed potent inhibitory effects against the mTOR enzyme, with excellent IC50 values comparable with well-established TKIs. The mechanistic study of lead compound 6i revealed its ability to induce cell cycle arrest and apoptosis in HepG2 liver cancer cells. This was accompanied by upregulation of pro-apoptotic caspase-3 and Bax and downregulation of anti-apoptotic Bcl-2. Additionally, molecular docking studies indicated that the binding interactions of compounds 6h and 6i with the target enzymes give multiple interactions. These results underscore the ability of compound 6i as a compelling lead candidate warranting further optimization and development as a potent multi-targeted kinase inhibitor, which could have significant implications for the treatment of various cancers. The detailed structural optimization, mechanism of action, and in vivo evaluation of this class of compounds warrant further investigation to assess their therapeutic potential.

4.
Molecules ; 29(14)2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39064901

RESUMEN

As a corrosion inhibitor for mild steel in a molar hydrochloric acid medium, we investigated the potential of Eucalyptus globulus essential oil (EuEO). Through electrochemical impedance spectroscopy (EIS), potentiodynamic polarization curves, and theoretical methods, including DFT/B3LYP 6-31G (d, p) and Monte Carlo simulations, the interactions between the EuEO components and the steel surface were analyzed. D-Allose, Betulinaldehyde, and Uvaol were identified as the major active compounds in the GC-MS analysis. The experimental results showed that EuEO reached an inhibitory efficiency as high as 97% at a 1 g/L concentration. The findings suggest that EuEO operates as a mixed-type inhibitor, reducing both cathodic and anodic reactions, as well as building up a protective coating on the steel surface. Simulations also confirmed that EuEO molecules function as electron donors and acceptors, enhancing corrosion resistance.

5.
Molecules ; 29(14)2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39064944

RESUMEN

This work describes the synthesis, characterization, and in vitro and in silico evaluation of the biological activity of new functionalized isoxazole derivatives. The structures of all new compounds were analyzed by IR and NMR spectroscopy. The structures of 4c and 4f were further confirmed by single crystal X-ray and their compositions unambiguously determined by mass spectrometry (MS). The antibacterial effect of the isoxazoles was assessed in vitro against Escherichia coli, Bacillus subtilis, and Staphylococcusaureus bacterial strains. Isoxazole 4a showed significant activity against E. coli and B. subtilis compared to the reference antibiotic drugs while 4d and 4f also exhibited some antibacterial effects. The molecular docking results indicate that the synthesized compounds exhibit strong interactions with the target proteins. Specifically, 4a displayed a better affinity for E. coli, S. aureus, and B. subtilis in comparison to the reference drugs. The molecular dynamics simulations performed on 4a strongly support the stability of the ligand-receptor complex when interacting with the active sites of proteins from E. coli, S. aureus, and B. subtilis. Lastly, the results of the Absorption, Distribution, Metabolism, Excretion and Toxicity Analysis (ADME-Tox) reveal that the molecules have promising pharmacokinetic properties, suggesting favorable druglike properties and potential therapeutic agents.


Asunto(s)
Antibacterianos , Isoxazoles , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Isoxazoles/química , Isoxazoles/farmacología , Bacillus subtilis/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Escherichia coli/efectos de los fármacos , Estructura Molecular , Staphylococcus aureus/efectos de los fármacos , Relación Estructura-Actividad
6.
Chem Biodivers ; : e202400682, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38941178

RESUMEN

Delayed healing of chronic wounds results in amputation and mortality rates in serious cases. The present study examines the merged wound-restorative efficacy of injectable bone marrow-derived mesenchymal stem cells (BMMSCs) and topical Callyspongia sp. extract in immunocompromised rats. HR-LC-MS analysis of Callyspongia sp. extract tentatively identified twenty-nine compounds (1-29) and highlighted its richness in fatty acids and terpenoids, known for their wound regenerating efficacies. The wound closure was greatly prominent in the BMMSCs/Callyspongia sp. group in contrast to the control group (p<0.001). The RT-PCR gene expression emphasized these results by attenuating the oxidative, inflammatory, and immunity markers, further confirmed by histopathological findings. Additionally, in silico modeling was particularly targeting matrix metalloproteinase-9 (MMP9), a key player in wound healing processes. Computational analysis revealed that compounds 18 and 19 potentially modulate MMP9 activity. The combination of BMMSCs and topical Callyspongia sp. extract holds a promise for regenerative therapy constituting a drastic advance in the wound cure of immunocompromised patients, eventually further safety assessments and clinical trials are required.

7.
Molecules ; 29(12)2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38930959

RESUMEN

We report the synthesis of two novel halogenated nitro-arylhimachalene derivatives: 2-bromo-3,5,5,9-tetramethyl-1-nitro-6,7,8,9-tetrahydro-5H-benzo[7]annulene (bromo-nitro-arylhimachalene) and 2-chloro-3,5,5,9-tetramethyl-1,4-dinitro-6,7,8,9-tetrahydro-5H-benzo[7]annulene (chloro-dinitro-arylhimachalene). These compounds were derived from arylhimachalene, an important sesquiterpene component of Atlas cedar essential oil, via a two-step halogenation and nitration process. Characterization was performed using 1H and 13C NMR spectrometry, complemented by X-ray structural analysis. Quantum chemical calculations employing density functional theory (DFT) with the Becke3-Lee-Yang-parr (B3LYP) functional and a 6-31++G(d,p) basis set were conducted. The optimized geometries of the synthesized compounds were consistent with X-ray structure data. Frontier molecular orbitals and molecular electrostatic potential (MEP) profiles were identified and discussed. DFT reactivity indices provided insights into the compounds' behaviors. Moreover, Hirshfeld surface and 2D fingerprint analyses revealed significant intermolecular interactions within the crystal structures, predominantly H-H and H-O contacts. Molecular docking studies demonstrate strong binding affinities of the synthesized compounds to the active site of protein 7B2W, suggesting potential therapeutic applications against various isolated smooth muscles and neurotransmitters.

8.
Molecules ; 29(11)2024 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-38893386

RESUMEN

Novel isoxazole-triazole conjugates have been efficiently synthesized using 3-formylchromone as starting material according to a multi-step synthetic approach. The structures of the target conjugates and intermediate products were characterized by standard spectroscopic techniques (1H NMR and 13C NMR) and confirmed by mass spectrometry (MS). The all-synthesized compounds were screened for their antibacterial activity against three ATCC reference strains, namely Staphylococcus aureus ATCC 25923, Staphylococcus aureus ATCC BAA-44, and Escherichia coli ATCC 25922 as well as one strain isolated from the hospital environment Pseudomonas aeruginosa. The findings indicate that conjugate 7b exhibits a stronger antibacterial response against the tested Escherichia coli ATCC 25922 and Pseudomonas aeruginosa pathogenic strains compared to the standard antibiotics. Furthermore, hybrid compound 7b proved to have a bactericidal action on the Escherichia coli ATCC 25922 strain, as evidenced by the results of the MBC determination. Moreover, the ADMET pharmacokinetic characteristics revealed a favorable profile for the examined compound, as well as a good level of oral bioavailability. Molecular docking and molecular dynamics simulations were performed to explore the inhibition mechanism and binding energies of conjugate 7b with the proteins of Escherichia coli and Pseudomonas aeruginosa bacterial strains. The in silico results corroborated the data observed in the in vitro evaluation for compound 7b.


Asunto(s)
Antibacterianos , Escherichia coli , Isoxazoles , Pruebas de Sensibilidad Microbiana , Simulación del Acoplamiento Molecular , Pseudomonas aeruginosa , Triazoles , Antibacterianos/farmacología , Antibacterianos/síntesis química , Antibacterianos/química , Triazoles/química , Triazoles/farmacología , Triazoles/síntesis química , Pseudomonas aeruginosa/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Isoxazoles/química , Isoxazoles/farmacología , Isoxazoles/síntesis química , Staphylococcus aureus/efectos de los fármacos , Diseño de Fármacos , Simulación de Dinámica Molecular , Estructura Molecular , Relación Estructura-Actividad , Simulación por Computador
9.
Res Aging ; : 1640275241256990, 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38898773

RESUMEN

This study aimed to examine the consequences of COVID-19 socialization restrictions on familial and social support systems of older Middle Eastern/Arab immigrants in Michigan, home to the largest, most visible concentration of Middle Eastern/Arab Americans in the United States. Six focus group (N = 45) interviews were conducted with Middle Eastern/Arab American immigrants aged 60 and older to assess difficulties faced during the pandemic as it related to familial, social, and medical care. Inductive analysis identified two major themes to advance meanings of intergenerational relations among older immigrants (a) the breakdown of family relations, which describes a shift in both the experience and expectations of intergenerational relations in Middle Eastern/Arab families; and (b) cultural sources of increased stress, illustrating how the pandemic interfered with valued family interactions to affect well-being. These findings indicated social and cultural sources of heightened stress linked to shifts in intergenerational relations among Middle Eastern/Arab American older immigrants.

10.
Chem Biodivers ; : e202400865, 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38867399

RESUMEN

Chamaerops humilis L. is clumping palm of the family Arecaceae with promising health-promoting effects. Parts of this species are utilized as food and employed in folk medicine to treat several disorders. This study investigated the phytochemical constituents of C. humilis leaves and their antioxidant and xanthine oxidase (XO) inhibitory activities in vitro and in vivo in acetaminophen (APAP)-induced hepatotoxicity in rats. The chemical structure of the isolated phytochemicals was determined using data obtained from UV, MS, IR, and 1H-, 13C-NMR spectroscopic tools as well as comparison with authentic markers. Eleven compounds, including tricin 7-O-ß-rutinoside, vicenin, tricin, astragalin, borassoside D, pregnane-3,5,6,16-tetrol, oleanolic acid, ß-sitosterol and campesterol were isolated from C. humilis ethanolic extract (CHEE). CHEE and the butanol, n-hexane, and dichloromethane fractions exhibited in vitro radical scavenging and XO inhibitory efficacies. The computational findings revealed the tendency of the isolated compounds towards the active site of XO. In vivo, CHEE ameliorated liver function markers and prevented tissue injury induced by APAP in rats. CHEE suppressed hepatic XO, decreased serum uric acid and liver malondialdehyde (MDA), and enhanced reduced glutathione (GSH), superoxide dismutase (SOD), and catalase in APAP-treated rats. CHEE ameliorated serum tumor necrosis factor alpha (TNF-α) and interleukin (IL)-1ß in APAP-treated rats. Thus, C. humilis is rich in beneficial phytochemicals that possess binding affinity towards XO. C. humilis exhibited potent in vitro antioxidant and XO inhibitory activities, and prevented APAP hepatotoxicity by attenuating tissue injury, oxidative stress and inflammation.

11.
Infect Drug Resist ; 17: 2227-2236, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38854778

RESUMEN

Background: Earlier reports suggested high rates of antibiotic utilization among COVID-19 patients despite the lack of direct evidence of their activity against viral pathogens. Different trends in antibiotic consumption during 2020 compared to 2019 have been reported. Purpose: The objective of this study is to assess the impact of COVID-19 pandemic on antibiotic consumption in the presence of active Antibiotic Stewardship Program. Methods: This study represented a five years assessment of the consumption of the commonly prescribed antibiotics measured as DDDs/100-Bed Days. We analyzed the data by using nonparametric Friedman and Friedman tests to compare the antibiotic consumption before and during the three subsequent waves of COVID-19. Results: Antibiotic consumption through the DDDs/100-BD has shown reduction in the median of antibiotics consumption of most antibiotics during the period of COVID-19 as compared to the pre-COVID-19 period, which was significant for meropenem and ciprofloxacin, except colomycin that slightly increased. Significant reduction in the consumption of imipenem and meropenem during the second and third waves as compared to the pre-COVID period. Throughout the years, significant reductions were observed between 2018 and 2019 (p=<.001), 2018 and 2020 (p=0.008), and 2018 and 2022 (p=0.002). Conclusion: The reduction in antibiotic consumption is attributed to the strong influence if the ASP and the reluctance of people to visit hospitals during the COVID-19 pandemic. Other related COVID-19 precautions such as physical distance, good hand hygiene, facemasks, that resulted in the prevention of secondary bacterial infections have contributed to the reduction in antibiotic utilization during the pandemic.

12.
Pak J Biol Sci ; 27(4): 168-181, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38812108

RESUMEN

<b>Background and Objective:</b> Prenatal ionizing radiation exposure may hinder fetal and embryonic growth depending on the dose and gestational age. The current study's objective was to discover how bone marrow transplants affected the spleens of pregnant rats that had been subjected to γ (Gamma) radiation. <b>Materials and Methods:</b> Sixty rats that were pregnant were separated into five different groups, each with 6 females. The pregnant rats in the second Group were exposed to 2Gy of γ-rays. Group III; pregnant rats subjected to 2Gy of γ-rays, followed by an intraperitoneal injection of newly prepared bone marrow transplantation (BMT). The fifth Group were exposed to 2Gy γ-rays and received 1 dosage of BMT an hour later. Spleen samples from the pregnant rats as well as their fetuses were taken for histological and histochemical analyses. <b>Results:</b> Gamma rays damaged the splenic tissue of women and their fetuses on days 7 or 14 of pregnancy in a variety of histological and histochemical ways, although bone marrow transplantation significantly reduced the damage. Treated mothers with bone marrow post-radiation showed a noticeable recovery in spleen of their fetuses. Improved spleen architecture was accompanied by appearance of normal content of collagen, polysaccharides and total protein in the fetal spleen tissue especially on day 7 of gestation. <b>Conclusion:</b> Bone marrow transplantation can lessen the damage caused by gamma radiation.


Asunto(s)
Trasplante de Médula Ósea , Feto , Rayos gamma , Bazo , Animales , Femenino , Embarazo , Bazo/efectos de la radiación , Bazo/metabolismo , Ratas , Feto/efectos de la radiación
13.
Saudi Pharm J ; 32(6): 102093, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38737807

RESUMEN

Carbohydrate analogs are an important, well-established class of clinically useful medicinal agents that exhibit potent antimicrobial activity. Thus, we explored the various therapeutic potential of methyl α-D-mannopyranoside (MαDM) analogs, including their ability to synthesize and assess their antibacterial, antifungal, and anticancer properties; additionally, molecular docking, molecular dynamics simulation, and ADMET analysis were performed. The structure of the synthesized MαDM analogs was ascertained by spectroscopic techniques and physicochemical and elemental analysis. In vitro antimicrobial activity was assessed and revealed significant inhibitory effects, particularly against gram-negative bacteria along with the prediction of activity spectra for substances (PASS). Concurrently, MαDM analogs showed good results against antifungal pathogens and exhibited promising anticancer effects in vitro, demonstrating dose-dependent cytotoxicity against Ehrlich ascites carcinoma (EAC) cancer cells while sparing normal cells from compound 5, with an IC50 of 4511.65 µg/mL according to the MTT colorimetric assay. A structure-activity relationship (SAR) study revealed that hexose combined with the acyl chains of decanoyl (C-10) and benzenesulfonyl (C6H5SO2-) had synergistic effects on the bacteria and fungi that were examined. Molecular docking was performed against the Escherichia coli (6KZV) and Candida albicans (1EAG) proteins to acquire insights into the molecular interactions underlying the observed biological activities. The docking results were further supported by 100 ns molecular dynamics simulations, which provided a dynamic view of the stability and flexibility of complexes involving MαDM and its targets. In addition, ADMET analysis was used to evaluate the toxicological and pharmacokinetic profiles. Owing to their promising drug-like properties, these MαDM analogs exhibit potential as prospective therapeutic candidates for future development.

14.
J Pharm Bioallied Sci ; 16(Suppl 1): S530-S533, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38595625

RESUMEN

Aim: The aim of the present study was to determine the prevalence of paraplegia-related fear in spinal anesthesia among the general population in the central region of Saudi Arabia. Materials and Methods: A total of 371 participants were given a pretested, precoded, questionnaire was used to collect data to assess the prevalence of fear of paraplegia in spinal anesthesia. The questionnaire contained questions to assess variables like the extent of fear, causes, gender preponderance, any false information about paraplegia in spinal anesthesia, and complications experienced after receiving spinal anesthesia. Results: It was noted that 80.1% of the respondents were familiar with the term spinal/regional/epidural anesthesia. Forty one point eight percent of the respondents their reference of knowledge about regional anesthesia was family of friends. Thirteen point nine percent of the responses were paralysis, 8.2% of the responses were feeling of pain during the operation, and 7.9% of the responses were nausea or vomiting. Conclusion: The present study revealed that the participants exhibited a certain degree of apprehension stemming from their inadequate understanding and awareness regarding spinal anesthesia.

16.
PLoS One ; 19(4): e0300543, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38573954

RESUMEN

Wound healing, one of the most intricate and dynamic processes of the body, maintains skin integrity following trauma. One of the main issues that still exists is impaired wound healing, particularly for immunosuppressed patients. Recently, natural products from marine environments have been employed in wound-repairing activities. This work investigates the mesenchymal stem cells in the combined capacity of the bone marrow (BMMSC) for wound healing and Cystoseira sp. Algae extract in immunosuppressed rats. High-resolution liquid chromatography / MS investigation of Cystoseira extract revealed the prevalence of fatty acids that have wound-soothing potential. From constructed PPI network for wound healing and further analysis through molecular docking and molecular dynamics (MD) simulation experiments suggested that cystalgerone metabolite may be responsible for the wound healing-promoting effect of Cystoseira extract. According to the CD marker characterization of the BMMSC, 98.21% of them expressed CD90, and 97.1% expressed CD105. Sixteen d after immunity suppression (by 40 mg/kg hydrocortisone daily), an incision was made in the dorsal skin of the rat. The treatments were applied for 16 d and samples were taken from the tested groups on the 8th, 14th, and 16th days. The BMMSCs / Cystoseira group showed significantly improved wound closure, thickness, density of new layers, and skin elasticity than the control group (p < 0.001). The BMMSCs / Cystoseira combination significantly reduced the oxidative indicators, pro-inflammatory cytokines, and immune markers, according to the RT-PCR gene expression study. In order to delve deeper into the complex interconnections among wound healing-related biological targets and pinpoint key factors in this complex process, we engaged in network pharmacology and computational research. Subsequently, we conducted a comprehensive computational analysis, including reverse docking, free energy (ΔG) computation, and molecular dynamics simulations, on the molecular structures of the annotated compounds. The purpose of this investigation was to identify potential new targets for these chemicals as well as any potential interactions they may have with different signaling pathways related to the wound healing process. Our research indicates that the primary compounds of Cystoseira holds potential wound healing therapeutic activity. Although more safety testing and clinical studies are required, the combination has great potential for regenerative medicine and could be a revolutionary advance in the healing of the wounds of immunosuppressed patients.


Asunto(s)
Células Madre Mesenquimatosas , Phaeophyceae , Humanos , Ratas , Animales , Simulación del Acoplamiento Molecular , Cicatrización de Heridas , Células Madre Mesenquimatosas/metabolismo , Piel/lesiones
17.
Future Med Chem ; 16(4): 335-348, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38314616

RESUMEN

Aim: Recently, thiadiazole-containing drugs have gained greater clinical relevance and are being explored for the development of new antidiabetic, antiurease and antimicrobial agents that target drug resistance. Methods & results: The authors disclose the synthesis of N-(5-[4-(trifluoromethyl)phenyl]-1,3,4-thiadiazol-2-yl)methanimine derivatives starting from 4-(trifluoromethyl)benzoic acid. All of the synthesized derivatives were evaluated for their biological potential in order to investigate the inhibitory activity against antidiabetic, antiurease and antibacterial profiles. Compounds 1, 2 and 9 showed excellent inhibitory activities due to the hydrogen bonding presence of -OH, -F and -CF3 substitutions attached with the phenyl ring. Conclusion: The present study provides potent antidiabetic, antiurease and antimicrobial agents that can be further optimized to discover novel antidiabetic, antiurease drugs.


Asunto(s)
Antiinfecciosos , Tiadiazoles , Simulación del Acoplamiento Molecular , Relación Estructura-Actividad , Bases de Schiff/farmacología , Tiadiazoles/farmacología , Antiinfecciosos/farmacología , Hipoglucemiantes/farmacología , Estructura Molecular
18.
Cureus ; 16(1): e52508, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38371106

RESUMEN

Background The most frequent gynecologic cancer in women is cervical cancer. The majority of incidents take place in less developed nations without access to reliable screening tools. Human papillomavirus (HPV) exposure, smoking, and immune system dysfunction are risk factors. As a result of effective screening, its incidence and death have significantly decreased in many nations. Hence, this study aims to assess the level of knowledge and awareness among parents regarding HPV, including its associated health risks and the benefits of vaccination. Methodology A descriptive cross-sectional study was carried out in the Riyadh region of Saudi Arabia from September to November 2023. The main tool used for gathering data was an online, self-administered survey via Google Forms. Collected data was analysed using SPSS v. 24 (IBM Corp., Armonk, NY), where all applicable statistical tests were used. Results Females exhibited higher levels of confidence and agreement with COVID-19 and HPV vaccination recommendations compared to males. A substantial percentage of males expressed strong disagreement and reduced confidence in HPV vaccination, contributing to the gender-based divergence. Individuals with higher education levels, such as university degree graduates, showed greater support for compulsory vaccines and a preference for natural immunity development in their children. Marital status played a role in vaccine-related decisions, with variations in vaccine refusal rates and difficulty discussing the HPV vaccine noted among individuals based on their marital status. Conclusion The study highlights the value of medical experts and specifically created training programs to close knowledge gaps and boost HPV vaccination rates. Demographic factors have an impact on attitudes, which highlights the need for targeted interventions.

19.
Saudi Pharm J ; 32(2): 101932, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38261946

RESUMEN

Methicillin-resistant Staphylococcus aureus (MRSA) is a significant concern in both healthcare and community settings, as it causes numerous infections worldwide with high morbidity and mortality rates. One promising strategy is to target the quorum sensing (QS) system of MRSA using a dendrimer loaded with kinase inhibitor peptide. The present investigation has formulated a poly-amidoamine dendrimer (PAMAM) G5 dendrimer that is loaded with Quorum Quencher (QQ) peptide, which functions as a histidine kinase inhibitor. The particle average size of the formulated G5-QQ3 complex was determined to be 276 nm, and polydispersity index values of 0.33. The MIC50 for the formulated nanoparticles was 18 µM as demonstrated by a growth assay. Furthermore, the G5-QQ3 complex was able to inhibit the hemolysis activity of the MRSA with a concentration of 10 µM, and for Staphylococcus aureus was 3 µM. The G5-QQ3 complex possesses the ability to inhibit, penetrate, and eradicate biofilm in MRSA, Staphylococcus aureus, and different agr mutants with inhibition percentages ranging from 60 to 72%. Furthermore, live/dead viability assay confirmed the ability of the formulated nanoparticles to effectively kill all strains within the biofilm structure as evidenced by a confocal microscope, and the cytotoxicity of the G5-QQ3 complex was dose-dependent (p < 0.05). against RAW 264.7 cells. In general, the study confirmed that encapsulating QQ3 peptide within PAMAM G5 dendrimer results in a potent anti-virulence and anti-bacterial action and suggests a synergistic effect. The findings of this study have significant implications for the development of new treatments for MRSA infections, which are a major public health concern.

20.
Int J Nanomedicine ; 19: 609-631, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38264736

RESUMEN

Introduction: The emergence of Neisseria gonorrhoeae-resistant strains represents one of the most urgent global threats. In this regard, C7-3 peptide is one of the anti-virulence therapies that has demonstrated promising anti-gonococcal activity. Accordingly, this research aimed to formulate C7-3 peptide and its derivatives in chitosan nanoparticles. Methods: The peptide loaded chitosan nanoparticles were prepared using ion gelation method, and their physicochemical characteristics were investigated. The anti-gonococcal and antibiofilm activity of prepared NPs was assessed, and their cytotoxicity in human ovarian cells was evaluated. Results: All prepared NPs were optimized for the smallest particle size of 136.9 to 168.3 nm. The EE% of C7-3, C7-3m1, and C7-3m2 CNPs reached 90.2, 92.5, and 91.8%, respectively. An in vitro release study demonstrated a continuous sustained-release pattern of C7-3 peptide from NPs. The SDS-PAGE assay confirmed the integrity of C7-3 peptide after the fabrication process. When comparing each peptide alone, the generated NPs demonstrated higher anti-gonococcal and anti-biofilm effectiveness against standard and resistant bacterial strains under anaerobic conditions. The cytotoxicity experiments revealed the cytocompatibility of NPs in HeLa cell lines. Given the advantages of enhanced anti-gonococcal activity of the C7-3 peptide and its derivatives when loaded with CNPs, as well as the antimicrobial properties of chitosan NPs, the reported NPs have great potential in the treatment of gonococcal infection.


Asunto(s)
Quitosano , Nanopartículas , Humanos , Neisseria gonorrhoeae , Células HeLa , Biopelículas
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