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1.
Ann Plast Surg ; 93(4): 425-429, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-38984731

RESUMEN

BACKGROUND: Breast reconstruction following mastectomy can be performed through various surgical techniques that prioritize the patient's safety and quality of life. Plastic surgeons are trained to choose the most appropriate surgical approach based on the individual patient's needs and medical history. The safety of the patient is always the primary concern, followed by considerations such as aesthetic outcomes and long-term health implications. OBJECTIVES: The aim of this study was to assess and document patients' satisfaction and quality of life after breast reconstruction across Saudi Arabia. METHODS: This is a cross-sectional multicenter study among female patients who underwent mastectomy with or without breast reconstruction between 2015 and 2022. Two hundred eighty patients participated in this study through a call-based Arabic version of the BREAST-Q questionnaire to analyze the quality of their lives and satisfaction. RESULTS: Our results showed that patients who underwent delayed reconstruction had lower satisfaction than those who underwent immediate reconstruction. The average BREAST-Q score was lower in patients who used tissue expanders than those with implant-based reconstruction, autologous reconstruction, or combined approaches. Patients who underwent simple mastectomy had lower satisfaction (M = 66.1) than those who had a skin-sparing mastectomy (M = 71.1) and/or nipple-sparing mastectomy (M = 72.6). CONCLUSIONS: This retrospective multicenter study observed a significant association between the time of the reconstructive surgery and patient's satisfaction; patients who underwent immediate reconstruction had higher satisfaction rate. Lower satisfaction rate was associated with tissue expander breast reconstruction. There is a significant association between satisfaction rate and smoking history.


Asunto(s)
Neoplasias de la Mama , Mamoplastia , Mastectomía , Satisfacción del Paciente , Calidad de Vida , Humanos , Estudios Transversales , Femenino , Mamoplastia/psicología , Mamoplastia/métodos , Satisfacción del Paciente/estadística & datos numéricos , Adulto , Persona de Mediana Edad , Arabia Saudita , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/psicología , Mastectomía/psicología , Encuestas y Cuestionarios , Resultado del Tratamiento , Estudios Retrospectivos , Factores de Tiempo
2.
Acta Trop ; 257: 107312, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38972561

RESUMEN

This research aimed to produce and analyze zinc oxide nanoparticles (ZNPs) loaded with linalool (LZNPs), and to evaluate their in vitro and in vivo efficacy through targeting the inflammation and oxidative stress. LZNPs were synthesized using an ethanolic solution of polyvinyl alcohol. The Malstat technique was used to evaluate the effectiveness of LZNPs against both sensitive and resistant strains of Plasmosium falciparum. In vivo effects of ZNPs and LZNPs on parasite growth suppression, survival rate, oxidative stress markers, antioxidant genes, and gene and protein levels of inflammatory cytokines were evaluated by Real-time PCR and Western blot techniques. The results indicated that LZNPs demonstrated noteworthy (P < 0.001) antiplasmodial activity against both susceptible and resistant strains of P. falciparum. P. berghei NK65 strain-infected mice treated with the ZNPs and LZNPs at doses of 5-15 mg/kg notably (p < 0.001) increased the survival rates and parasite growth suppression. LZNPs at 5-15 mg/kg demonstrated a significant (p < 0.001) decrease in oxidative stress markers, increased the expression level of antioxidant genes, and reduced the gene and protein expression level of inflammatory cytokines. The current experimental study demonstrated the potent in vitro antiplasmodial activity of LZNPs against chloroquine-resistant and sensitive strains of P. falciparum compared to ZNPs alone. Additionally, the study identified the potential benefits of this nanocomposite in suppressing the parasite and extending the survival rate in mice infected with P. berghei by targeting inflammation and oxidative stress. It also showed minimal toxicity in liver and kidney function in healthy mice. Nevertheless, further research is essential to elucidate the comprehensive mechanisms and practical effectiveness of LZNPs.


Asunto(s)
Monoterpenos Acíclicos , Antimaláricos , Monoterpenos , Nanopartículas , Estrés Oxidativo , Plasmodium berghei , Plasmodium falciparum , Óxido de Zinc , Animales , Monoterpenos Acíclicos/farmacología , Óxido de Zinc/farmacología , Óxido de Zinc/administración & dosificación , Óxido de Zinc/química , Ratones , Plasmodium berghei/efectos de los fármacos , Antimaláricos/farmacología , Antimaláricos/administración & dosificación , Nanopartículas/química , Estrés Oxidativo/efectos de los fármacos , Plasmodium falciparum/efectos de los fármacos , Monoterpenos/farmacología , Monoterpenos/administración & dosificación , Monoterpenos/química , Malaria/tratamiento farmacológico , Citocinas/metabolismo , Modelos Animales de Enfermedad , Masculino , Antioxidantes/farmacología , Antioxidantes/administración & dosificación , Portadores de Fármacos/química
3.
Open Vet J ; 14(6): 1417-1425, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-39055761

RESUMEN

Background: Escherichia coli is one of the serious pathogens causing various infections in the animal field, such as neonatal calf diarrhea, which is responsible for mortality associated with diarrhea during the first days of life. Aim: Current work is aimed at designing an effective and safe multiepitope vaccine candidate against E. coli infection in calves based on the fimbrial protein K99 of Enterotoxigenic E. coli (ETEC) and Immuno-informatics. Methods: A conserved sequence of K99 protein was generated, and then highly antigenic, nonallergic, and overlapped epitopes were used to construct a multiepitope vaccine. Five THL, six MHC II, and four beta cell epitopes were targeted to create the candidate. The candidate vaccine was produced utilizing 15 epitopes and three types of linkers, two types of untranslated region (UTR) human hemoglobin subunit beta (HBB), UTR beta-globin (Rabb), and RpfE protein as an immunomodulation adjuvant. Results: Immuno-informatics analysis of the constructed protein showed that the protein was antigenic (antigenic score of 0.8841), stable, nonallergen, and soluble. Furthermore, the Immuno-informatics and physiochemical analysis of the constructed protein showed a stable, nonallergic, soluble, hydrophilic, and acidic PI (isoelectric point). of 9.34. Docking of the candidate vaccine with the toll-like receptor TLR3 was performed, and results showed a strong interaction between the immune receptor and the vaccine. Finally, the expression efficiency of the construct in E. coli was estimated via computational cloning of the vaccine sequence into Pet28a. Conclusion: Results of immunoinformatics and in silico approaches reveal that the designed vaccine is antigenic, stable, and able to bind to the immune cell receptors. Our results interpret the proposed multiepitope mRNA vaccine as a good preventive option against E. coli infection in calves.


Asunto(s)
Enfermedades de los Bovinos , Biología Computacional , Escherichia coli Enterotoxigénica , Infecciones por Escherichia coli , Vacunas contra Escherichia coli , Animales , Bovinos , Escherichia coli Enterotoxigénica/inmunología , Infecciones por Escherichia coli/veterinaria , Infecciones por Escherichia coli/prevención & control , Infecciones por Escherichia coli/inmunología , Vacunas contra Escherichia coli/inmunología , Enfermedades de los Bovinos/prevención & control , Enfermedades de los Bovinos/inmunología , Enfermedades de los Bovinos/microbiología , Epítopos/inmunología , ARN Mensajero/genética , ARN Mensajero/metabolismo , Modelos Moleculares , Inmunoinformática
4.
Environ Pollut ; 359: 124595, 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-39053804

RESUMEN

Ultrafine particles (UFPs; PM0.1) possess intensified health risk due to their smaller size and unique spatial variability. One of major emission sources for UFPs is vehicle exhaust, which varies based on the traffic composition in each type of roadside sector. The current challenge of epidemiological UFPs study is limited characterization ability due to expensive instruments. This study assessed the UFPs particle number concentrations (UFPs PNC) exposure dose for typical healthy adults and children at three different roadside sectors, including industrial roadside (IN), residential roadside (RS), and urban background (UB). Furthermore, this study also developed and utilized machine learning (ML) algorithms that could accurately characterize the UFPs exposure dose and explain the covariates effects on the model outputs, representing the intra-urban variability of UFPs between sectors. It was found that the average inhaled UFPs dose for healthy adults and children during off-peak season (warm period) were 1.71 ± 0.19 × 1010; 1.28 ± 0.22 × 1010; 1.09 ± 0.18 × 1010 #/hour and 1.33 ± 0.15 × 1010; 0.99 ± 0.17 × 1010; 0.86 ± 0.14 × 1010 #/hour at IN, RS, UB. Inhaled UFPs were mainly deposited in tracheobronchial (TB) respiratory fraction for adults (67.7%) and in alveoli (ALV) fraction for children (67.5%). Among three ML algorithms implemented in this study, XGBoost possessed the highest UFPs PNC exposure dose estimation performances with R2 = 0.965; 0.959; 0.929 & RMSE = 0.79 × 108; 0.54 × 108; 0.15 × 105 #/hour at IN, RS, and UB which then followed by multiple linear regression (MLR), and random forest (RF). Furthermore, SHAP analysis from the XGBoost model has successfully pointed out the spatial variability of each roadside sector by quantifying the approximated contributions of covariates to the model's output. Findings in this study highlighted the potential use of ML models as an alternative for preliminary particle exposure source apportionment.


Asunto(s)
Contaminantes Atmosféricos , Monitoreo del Ambiente , Aprendizaje Automático , Tamaño de la Partícula , Material Particulado , Emisiones de Vehículos , Material Particulado/análisis , Humanos , Contaminantes Atmosféricos/análisis , Emisiones de Vehículos/análisis , Monitoreo del Ambiente/métodos , Niño , Adulto , Exposición a Riesgos Ambientales/estadística & datos numéricos , Exposición por Inhalación/estadística & datos numéricos , Contaminación del Aire/estadística & datos numéricos
5.
Int J Mol Sci ; 25(12)2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38928021

RESUMEN

Drug repurposing, rebranding an existing drug for a new therapeutic indication, is deemed a beneficial approach for a quick and cost-effective drug discovery process by skipping preclinical, Phase 1 trials and pharmacokinetic studies. Several psychotropic drugs, including selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs), were studied for their potential application in different diseases, especially in cancer therapy. Fluoxetine (FLX) is one of the most prescribed psychotropic agents from the SSRIs class for the treatment of several neuropsychiatric disorders with a favorable safety profile. FLX exhibited different oncolytic effects via mechanisms distinct from its main serotonergic activity. Taking advantage of its ability to rapidly penetrate the blood-brain barrier, FLX could be particularly useful in brain tumors. This was proved by different in vitro and in vivo experiments using FLX as a monotherapy or combination with temozolomide (TMZ) or radiotherapy. In this review of the literature, we summarize the potential pleiotropic oncolytic roles of FLX against different cancers, highlighting the multifaceted activities of FLX and its ability to interrupt cancer proliferation via several molecular mechanisms and even surmount multidrug resistance (MDR). We elaborated on the successful synergistic combinations such as FXR/temozolomide and FXR/raloxifene for the treatment of glioblastoma and breast cancer, respectively. We showcased beneficial pharmaceutical trials to load FLX onto carriers to enhance its safety and efficacy on cancer cells. This is the first review article extensively summarizing all previous FLX repurposing studies for the management of cancer.


Asunto(s)
Reposicionamiento de Medicamentos , Fluoxetina , Humanos , Reposicionamiento de Medicamentos/métodos , Fluoxetina/uso terapéutico , Fluoxetina/farmacología , Animales , Neoplasias/tratamiento farmacológico , Antineoplásicos/uso terapéutico , Antineoplásicos/farmacología , Psicotrópicos/uso terapéutico , Psicotrópicos/farmacología , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Inhibidores Selectivos de la Recaptación de Serotonina/farmacología
6.
Int Immunopharmacol ; 135: 112249, 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-38772297

RESUMEN

Interleukin-35 (IL-35) is a novel anti-inflammatory component, and its role in protecting against acute kidney disease (AKD) has not been explored. Thymoquinone (TQ) has been widely used for many therapeutic targets. Inflammation/oxidative signaling plays essential roles in the pathogenesis of diverse disorders, such as AKD, cancer, cardiac disease, aging, and metabolic and neurodegenerative disorders. The objective of the investigation was to evaluate how IL-35 prevents inflammation and oxidative stress indicators in the kidneys of rats caused by lipopolysaccharide (LPS). The experimental rats were allocated into six groups: control (0.5 mL saline); TQ (0.5 mg/kg, b.w. IP), IL-35 (100 µg of IL-35 /kg, b.w. IP), LPS (500 µg/kg b.w. IP), LPS + IL-35, and LPS + TQ. Results indicate that the hematological and blood biochemical parameters were substantially restored by TQ or IL-35 therapy. The elevation of kidney function (uric acid, creatinine, and cystatin C) and oxidative related biomarkers (MDA, PC, and MYO) in rat kidneys was significantly restored by the TQ and IL-35 therapies after LPS administration (P < 0.05). Serum immunological variables IgM and IgG were significantly restored by TQ and IL-35 in LPS-treated rats. Both IL-35 and TQ markedly mitigated the decrease antioxidant related biomarkers (SOD, GSH, CAT and TAC) triggered by LPS. The IL-35 and TQ treatments significantly diminished serum levels of inflammatory responses such as TNF-α, NF-κB, IL-6 and IFN-γ, and significantly increased IL-10 in LPS-treated rats. Additionally, serum levels of MCP, Caspase-3, andBcl-2 were significantly diminished by TQ or IL-35 therapy. The histopathology and immunohistochemistry for NF-kB, PCNA and TNF-α cytokines revealedremodeling when treated with TQ and IL-35. In summary, administration of IL-35 or TQ can attenuateLPS-induced renal damage by extenuatingoxidative stress, tissue impairment, apoptosis, and inflammation, implicating IL-35 as a promising therapeutic agent in acute-related renal injury.


Asunto(s)
Lesión Renal Aguda , Antiinflamatorios , Benzoquinonas , Interleucinas , Riñón , Lipopolisacáridos , Nanopartículas , Estrés Oxidativo , Animales , Benzoquinonas/farmacología , Benzoquinonas/uso terapéutico , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/tratamiento farmacológico , Lesión Renal Aguda/patología , Lesión Renal Aguda/inmunología , Ratas , Masculino , Interleucinas/metabolismo , Interleucinas/sangre , Riñón/efectos de los fármacos , Riñón/patología , Riñón/metabolismo , Antiinflamatorios/uso terapéutico , Antiinflamatorios/farmacología , Estrés Oxidativo/efectos de los fármacos , Ratas Wistar , Citocinas/metabolismo , Citocinas/sangre
7.
Acta Parasitol ; 69(2): 1201-1211, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38634986

RESUMEN

The present experimental survey designed to green synthesis, characterization, as well as in vitro and in vivo anti-Toxplasma gondii activity of silver nanoparticles (SLN) green synthesized by Lupinus arcticus extract. SLN were green synthesized based on the reducing by L. arcticus extract through the precipitation technique. In vitro lethal effects of SLN on T. gondii tachyzoites, infectivity rate, parasites inside of the human macrophage cells (THP-1 cells), nitric oxide (NO) triggering, and iNOS and interferon gamma (IFN-γ) expression genes were evaluated. In vivo, after establishment of toxoplasmosis in BALB/c mice via T. gondii ME49 strain, mice received SLN at 10 and 20 mg/kg/day alone and combined to pyrimethamine at 5 mg/kg for 14 days. SLN exhibited a spherical form with a size ranging from 25 to 90 nm. The 50% inhibitory concentration (IC50) value of SLN and pyrimethamine against tachyzoites was 29.1 and 25.7 µg/mL, respectively. While, the 50% cytotoxic concentration (CC50) value of SLN and pyrimethamine against THP-1 cells was 412.3 µg/mL and 269.5 µg/mL, respectively. SLN in combined with pyrimethamine obviously (p < 0.05) decreased the number and size of the T. gondii cysts in the infected mice. The level of NO, iNOS and IFN-γ genes was obviously (p < 0.001) upregulated. SLN obviously (p < 0.05) decreased the liver level of oxidative stress and increased the level of antioxidant factors. The findings displayed the promising beneficial effects of SLN mainly in combination with current synthetic drugs against latent T. gondii infection in mice. But we need more experiments to approve these findings, clarifying all possible mechanisms, and its efficiency in clinical phases.


Asunto(s)
Antiinflamatorios , Antioxidantes , Nanopartículas del Metal , Ratones Endogámicos BALB C , Plata , Toxoplasma , Animales , Plata/farmacología , Plata/química , Nanopartículas del Metal/química , Toxoplasma/efectos de los fármacos , Ratones , Antioxidantes/farmacología , Humanos , Antiinflamatorios/farmacología , Antiinflamatorios/química , Toxoplasmosis/tratamiento farmacológico , Toxoplasmosis/parasitología , Factores Inmunológicos/farmacología , Factores Inmunológicos/administración & dosificación , Extractos Vegetales/farmacología , Extractos Vegetales/química , Células THP-1 , Femenino , Agentes Inmunomoduladores/farmacología , Agentes Inmunomoduladores/química , Antiprotozoarios/farmacología , Antiprotozoarios/química , Óxido Nítrico/metabolismo , Pirimetamina/farmacología , Pirimetamina/uso terapéutico , Tecnología Química Verde
8.
Ann Med Surg (Lond) ; 86(2): 666-677, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38333327

RESUMEN

Background: Few studies have been conducted on unintended pregnancies and peripartum depression in Saudi Arabia. This study aimed to evaluate the relationship between unplanned pregnancies and peripartum depression among pregnant women in Jeddah, Saudi Arabia. Methods: This prospective cohort study included pregnant women attending an antenatal care clinic in 2021. The London Measure of Unplanned Pregnancy was used to assess the prevalence of unplanned pregnancy, and the Edinburgh Postnatal Depression Scale (EPDS) was used to assess antenatal and postnatal depression. Results: A total of 236 participants were included, of which 25.8% had unplanned pregnancies, 36.0% had ambivalent pregnancies, and 38.1% had planned pregnancies. EPDS results revealed that 77.5% and 73.35% of the females were negative for antenatal and postnatal depression, respectively. A history of stressful events (P=0.001), husband (P=0.020), and family support (P=0.007) was significantly associated with antenatal EPDS score, whereas age (P=0.005), type of delivery (P=0.019), and family support (P=0.031) were significantly associated with the postnatal score. Conclusion: Unplanned pregnancies may affect the perinatal mental health of women. We demonstrated the importance of family or husbands' support for women with perinatal depression. In addition, our research showed that pregnancy at an early age is a risk factor for postnatal depression. Therefore, these women should be closely monitored not only during their pregnancy but also during the first postpartum year.

9.
Cureus ; 16(1): e52341, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38361697

RESUMEN

Infantile hemangioma is a common benign vascular tumor in children, but it is very unusual to be found intracranially. Our literature review identified 44 reported cases. Presentation can vary from asymptomatic to a life-threatening presentation that necessitates urgent surgical removal. There is no general consensus on management of these rare lesions and until recently, treatment was limited to surgery or pharmacological management with steroids, propranolol or interferon. We present a case of a four-week-old male infant with history of vomiting and increase in head circumference since birth. MRI of the brain revealed a large complex cyst occupying the right frontoparietal region, with round soft tissue component that is isointense on T1 and hyperintense on T2 weighted images. Complete surgical resection with evacuation of the cyst was achieved. Histopathology of the mass showed infantile hemangioma with positive CD31 on immunohistochemistry. The patient achieved an excellent outcome following surgical resection.

10.
Int J Mol Sci ; 25(2)2024 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-38256214

RESUMEN

Lung squamous cell carcinoma (LUSC) is one of the most common malignancies. There is growing evidence that glycolysis-related genes play a critical role in tumor development, maintenance, and therapeutic response by altering tumor metabolism and thereby influencing the tumor immune microenvironment. However, the overall impact of glycolysis-related genes on the prognostic significance, tumor microenvironment characteristics, and treatment outcome of patients with LUSC has not been fully elucidated. We used The Cancer Genome Atlas (TCGA) dataset to screen glycolysis-related genes with prognostic effects in LUSC and constructed signature and nomogram models using Lasso and Cox regression, respectively. In addition, we analyzed the immune infiltration and tumor mutation load of the genes in the models. We finally obtained a total of glycolysis-associated DEGs. The signature model and nomogram model had good prognostic power for LUSC. Gene expression in the models was highly correlated with multiple immune cells in LUSC. Through this analysis, we have identified and validated for the first time that glycolysis-related genes are highly associated with the development of LUSC. In addition, we constructed the signature model and nomogram model for clinical decision-making.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Humanos , Pronóstico , Carcinoma de Células Escamosas/genética , Glucólisis/genética , Neoplasias Pulmonares/genética , Pulmón , Microambiente Tumoral/genética
11.
Pharmaceuticals (Basel) ; 16(11)2023 Nov 07.
Artículo en Inglés | MEDLINE | ID: mdl-38004439

RESUMEN

BACKGROUND: Nowadays, interest in the use of nanotechnology for medical purposes is increasing. The current experimental investigation is planned for the green synthesis, characterization, and efficacy of copper nanoparticles (CLN) against chronic Toxoplasma gondii infection. METHODS: Green synthesis of CNP was performed using the Lupinus arcticus extract via the precipitation method. The effects of CNP on tachyzoites, infectivity rate, parasites inside THP-1 cells, nitric oxide (NO) triggering, iNOS, and IFN-γ expression genes were evaluated. Following toxoplasmosis in BALB/c mice via the T. gondii ME49 strain, mice received CNP at 5 and 10 mg/kg/day alone and combined with pyrimethamine (PYM) at 5 mg/kg for two weeks. CNP's in vivo effects were evaluated by analyzing the load and size of cysts, oxidant/antioxidant enzymes, and bradyzoite surface antigen 1 (BAG1) expression gene levels. RESULTS: CNP displayed a circular shape ranging from 10 to 85 nm. The IC50 value of CNP and PYM against tachyzoites was 37.2 and 25.7 µg/mL, respectively, whereas the CC50 value of CNP and pyrimethamine against THP-1 cells was 491.4 µg/mL and 269.5 µg/mL, respectively. The rate of infectivity and parasite load among THP-1 cells exposed to CNP was obviously reduced (p < 0.05). CNP at the doses of 5 and 10 mg/kg predominantly along with PYM evidently (p < 0.05) reduced the number and size of the T. gondii cysts in the infected mice. The levels of NO, iNOS, and IFN-γ genes were remarkably (p < 0.001) boosted compared with the cells without treatment. CNP at the doses of 10 and 20 mg/kg drastically (p < 0.05) reduced the oxidative stress markers in the infected mice, whereas CNP significantly elevated the level of antioxidant factors. CNP also revealed no toxicity in the liver and kidney at the tested doses in healthy mice. CONCLUSIONS: Our experimental study reported the beneficial effects of CNP principally along with existing chemical drugs against latent toxoplasmosis in mice, whereas the possible action mechanisms of CNP are controlling oxidative stress, refining antioxidant enzymes, and increasing the production of immunomodulatory cytokines with no toxicity to the function of vital organs. But, additional trials are required to confirm these results, as well as to clarify the accurate mechanisms and their toxicity.

12.
Biomolecules ; 13(10)2023 09 28.
Artículo en Inglés | MEDLINE | ID: mdl-37892147

RESUMEN

Nuclear receptors (NRs) constitute a superfamily of ligand-activated transcription factors with a paramount role in ubiquitous physiological functions such as metabolism, growth, and reproduction. Owing to their physiological role and druggability, NRs are deemed attractive and valid targets for medicinal chemists. Pentacyclic triterpenes (PTs) represent one of the most important phytochemical classes present in higher plants, where oleanolic acid (OA) is the most studied PTs representative owing to its multitude of biological activities against cancer, inflammation, diabetes, and liver injury. PTs possess a lipophilic skeleton that imitates the NRs endogenous ligands. Herein, we report a literature overview on the modulation of metabolic NRs by OA and its semi-synthetic derivatives, highlighting their health benefits and potential therapeutic applications. Indeed, OA exhibited varying pharmacological effects on FXR, PPAR, LXR, RXR, PXR, and ROR in a tissue-specific manner. Owing to these NRs modulation, OA showed prominent hepatoprotective properties comparable to ursodeoxycholic acid (UDCA) in a bile duct ligation mice model and antiatherosclerosis effect as simvastatin in a model of New Zealand white (NZW) rabbits. It also demonstrated a great promise in alleviating non-alcoholic steatohepatitis (NASH) and liver fibrosis, attenuated alpha-naphthol isothiocyanate (ANIT)-induced cholestatic liver injury, and controlled blood glucose levels, making it a key player in the therapy of metabolic diseases. We also compiled OA semi-synthetic derivatives and explored their synthetic pathways and pharmacological effects on NRs, showcasing their structure-activity relationship (SAR). To the best of our knowledge, this is the first review article to highlight OA activity in terms of NRs modulation.


Asunto(s)
Colestasis , Ácido Oleanólico , Ratones , Animales , Conejos , Ácido Oleanólico/farmacología , Receptores Citoplasmáticos y Nucleares/metabolismo , Hígado/metabolismo , Factores de Transcripción/metabolismo , Colestasis/metabolismo
13.
Biomedicines ; 11(10)2023 Oct 19.
Artículo en Inglés | MEDLINE | ID: mdl-37893218

RESUMEN

Nuclear receptors (NRs) form a family of druggable transcription factors that are regulated by ligand binding to orchestrate multifaceted physiological functions, including reproduction, immunity, metabolism, and growth. NRs represent attractive and valid targets for the management and treatment of a vast array of ailments. Pentacyclic triterpenes (PTs) are ubiquitously distributed natural products in medicinal and aromatic plants, of which ursolic acid (UA) is an extensively studied member, due to its diverse bio-pertinent activities against different cancers, inflammation, aging, obesity, diabetes, dyslipidemia, and liver injury. In fact, PTs share a common lipophilic structure that resembles NRs' endogenous ligands. Herein, we present a review of the literature on UA's effect on NRs, showcasing the resulting health benefits and potential therapeutic outcomes. De facto, UA exhibited numerous pharmacodynamic effects on PPAR, LXR, FXR, and PXR, resulting in remarkable anti-inflammatory, anti-hyperlipidemic, and hepatoprotective properties, by lowering lipid accumulation in hepatocytes and mitigating non-alcoholic steatohepatitis (NASH) and its subsequent liver fibrosis. Furthermore, UA reversed valproate and rifampicin-induced hepatic lipid accumulation. Additionally, UA showed great promise for the treatment of autoimmune inflammatory diseases such as multiple sclerosis and autoimmune arthritis by antagonizing RORγ. UA exhibited antiproliferative effects against skin, prostate, and breast cancers, partially via PPARα and RORγ pathways. Herein, for the first time, we explore and provide insights into UA bioactivity with respect to NR modulation.

14.
Trop Med Infect Dis ; 8(7)2023 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-37505651

RESUMEN

The present study aimed to evaluate the in vitro, in vivo, and safety of Stachys lavandulifolia Vahl. methanolic extract (SLME) against acute toxoplasmosis caused by Toxoplasma gondii RH strain in mice. METHODS: MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was used to evaluate the in vitro effect of the SLME on T. gondii tachyzoites. Totally, 72 male BALB/c mice (40 mice for in vivo evaluation of SLME and 32 mice for its toxicity effects on liver and kidney serum enzymes) were used for the present investigation. At first, 40 mice were orally pre-treated with the SLME at doses of 25, 50, and 75 mg/kg/day for two weeks. Mice were checked daily, and the rate of survival and the mean number of tachyzoites were recorded. Liver lipid peroxidation (LPO) and nitric oxide (NO) levels, the effects on kidney and liver function, as well as the expression level of the proinflammatory cytokines such as interleukin-1ß (IL-1ß) and interferon-γ (IFN-γ), were studied by the quantitative real-time PCR. Flow cytometry analysis was performed on the effects of SLME on the detection of apoptotic and necrotic cells in T. gondii tachyzoites. RESULTS: The SLME at the concentrations 75 and 150 µg/mL completely killed the tachyzoites after 2 hr of incubation. SLME at 25, 50, and 75 mg/kg/day increased the survival rate of infected mice by the sixth, seventh, and eighth days, respectively. SLME also significantly (p < 0.05) decreased the LPO and NO levels and upregulated the IL-1ß and IFN-γ mRNA gene expression levels, whereas no considerable change was observed in the serum level of kidney and liver enzymes. Flow cytometry analysis revealed the prompted early and late apoptosis after exposure to T. gondii tachyzoites with various concentrations of SLME. CONCLUSION: We found the relevant in vitro anti-Toxoplasma effects of SLME against T. gondii. Moreover, the results confirmed the promising in vivo prophylactic effects of SLME. SLME provokes the innate immune system, induces apoptosis, modulates the proinflammatory cytokines, and inhibits hepatic injury in infected mice. With all these descriptions, further surveys are required to support these findings and elucidate this plant's possible mechanisms of action.

15.
Cureus ; 15(4): e37391, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37182053

RESUMEN

Background  Artificial intelligence (AI) is a broad spectrum of computer-executed operations that mimics the human intellect. It is expected to improve healthcare practice in general and radiology in particular by enhancing image acquisition, image analysis, and processing speed. Despite the rapid development of AI systems, successful application in radiology requires analysis of social factors such as the public's perspectives toward the technology. Objectives The current study aims to investigate the general population's perspectives on AI implementation in radiology in the Western region of Saudi Arabia. Methods A cross-sectional study was conducted from November 2022 and July 2023 utilizing a self-administrative online survey distributed via social media platforms. A convenience sampling technique was used to recruit the study participants. After obtaining Institutional Review Board approval, data were collected from citizens and residents of the western region of Saudi Arabia aged 18 years or older. Results A total of 1,024 participants were included in the present study, with the mean age of respondents being 29.6 ± 11.3. Of them, 49.9% (511) were men, and 50.1% (513) were women. The comprehensive mean score of the first four domains among our participants was 3.93 out of 5.00. Higher mean scores suggest being more negative regarding AI in radiology, except for the fifth domain. Respondents had less trust in AI utilization in radiology, as evidenced by their overall distrust and accountability domain mean score of 3.52 out of 5. The majority of respondents agreed that it is essential to understand every step of the diagnostic process, and the mean score for the procedural knowledge domain was 4.34 out of 5. The mean score for the personal interaction domain was 4.31 out of 5, indicating that the participants agreed on the value of direct communication between the patient and the radiologist for discussing test results and asking questions. Our data show that people think AI is more effective than human doctors in making accurate diagnoses and decreasing patient wait times, with an overall mean score of the efficiency domain of 3.56 out of 5. Finally, the fifth domain, "being informed," had a mean score of 3.91 out of 5. Conclusion The application of AI in radiologic assessment and interpretation is generally viewed negatively. Even though people think AI is more efficient and accurate at diagnosing than humans, they still think that computers will never be able to match a specialist doctor's years of training.

16.
Cureus ; 15(2): e34816, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36915846

RESUMEN

Background Foreign body aspiration (FBA) is a life-threatening event and one of the most common causes of mortality in children. As it has different clinical presentations, parental knowledge is essential for early management to prevent complications. Objectives This study was designed to assess the knowledge and practices relating to FBA in children among parents living in Makkah city, Saudi Arabia. Methods An online questionnaire was designed using Google Forms (Google LLC, Mountain View, California, United States) and distributed in October 2022 among parents living in Makkah city. After data collection, an appropriate statistical analysis was conducted. Results A total of 1087 parents enrolled in this study; 63.9% were women and the majority were married 93%. Additionally, 52% of the parents had at least three children. Moreover, 17.6% had an experience of a child having aspirated a foreign body once. The Internet was the most popular source of information on FBA (43.5%). Furthermore, the parents had poor levels of knowledge and practices related to FBA (65.4% and 78.6%, respectively). Conclusion This study reported that parental levels of knowledge of FBA and FBA practices were inadequate. There is a need to increase awareness, which will lead to better outcomes.

17.
Cureus ; 15(2): e34531, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36874299

RESUMEN

Background While magnetic resonance imaging (MRI) is one of the most efficient diagnostic methods used today, some patients may find an MRI examination to be a frightening experience. The proximity to the machine during screening and being in a confined space can cause a feeling of claustrophobia. Severe anxiety during MRI screening can cause the patient to move, which lowers the quality of the imaging and diagnostic test, and can result in the early termination of the MRI examination and the patient declining further testing. Objectives The objective of this study is to evaluate MRI examination-associated anxiety among Saudi Arabia's general population in the western region of the country. Methods Altogether, 465 participants who had undergone an MRI examination in the western region of Saudi Arabia were recruited for this cross-sectional study. We used the Magnetic Resonance Imaging-Anxiety Questionnaire (MRI-AQ) to collect data. Results Regarding anxiety symptoms, 82.8% of the participants believed that they had control over the event, 80.2% were concerned beforehand, 74% required more specific information, just 48% had difficulty breathing, and 51% were panicked. On the other hand, 57.4% felt safe, 56.8% were calm, and 49.2% were relaxed. The majority of the participants (55.9%, 260) reported moderate MRI-related anxiety. Conclusion More than half of our respondents had mild to moderate MRI-related anxiety. The majority needed more detailed information, panicked, and had breathing problems. Statistically, females showed a significantly higher level of anxiety compared with male participants.

18.
Molecules ; 28(4)2023 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-36838959

RESUMEN

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common form of liver cancer that occurs in hepatocytes. Although many chemical drugs, e.g., cisplatin, methotrexate, taxis, and doxorubicin are used to treat HCC, there have been numerous reports related to the side effects of these drugs (e.g., emerging drug resistance, bone marrow failure, and gastrointestinal disorders). These issues led scientists to search for the novel anti-cancer drugs, mainly in natural products with greater efficiency and less toxicity. The current survey was intended to assess the anti-cancer effects of queen bee acid (10-Hydroxy-2-Decenoic Acid, 10-HDA) and its cellular mechanisms against the human hepatoma cell line HepG2. MATERIALS AND METHODS: The MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay was used to evaluate the effect of 10-HDA on the viability of HepG2 cells. The initial and late apoptosis in the HepG2 cells treated with 10-HDA were assessed by the Annexin-V (AV) assay. The level of the gene and protein expression of some apoptosis genes (e.g., caspase-3, Bcl-2-associated X protein (BAX), and B-cell lymphoma protein 2 (Bcl-2)), Poly (ADP-ribose) polymerases (PARP), and miRNA-34a (miR-34a), were measured by real-time PCR and Western blot. RESULTS: The obtained findings revealed that HepG2 cell viability was markedly reduced (p < 0.01) following exposure to 10-HDA in a dose-dependent matter. The calculated half maximal cytotoxic concentration (CC50) value of 10-HDA was 59.6 µg/mL for HepG2 cells, while this value for normal THLE-3 cells was 106.4 µg/mL. We found that 10-HDA markedly elevated (p < 0.01) the percentage of necrotic and apoptotic cells from 0.94 to 9.7 and 27.6%, respectively. The real-time PCR results showed that the expression levels of the caspase-3, Bax, and miR-34a genes were significantly (p < 0.001) elevated. Contrary to these results, a significant (p < 0.01) reduction in the expression level of the Bcl2 gene was observed. The levels of protein expression of Caspase-3, PARP, and Bax were markedly elevated following exposure of HepG2 cells to 10-HDA at » CC50, ½ CC50, and CC50. The level of protein expression of Bcl-2 was markedly reduced following exposure of HepG2 cells to 10-HDA at » CC50, ½ CC50, and CC50 (p < 0.01). CONCLUSION: The current results confirmed the potent in vitro cytotoxic effects of 10-HDA on HepG2 cells with no significant cytotoxic effects on normal cells. Although its mechanisms of action have not been fully studied, the induction of apoptosis via different pathways was determined as one of the principle mechanisms of action of 10-HDA against HepG2 cells. Nevertheless, additional surveys must be performed to clearly understand the mechanisms of action and safety of this fatty acid.


Asunto(s)
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroARNs , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Proteína X Asociada a bcl-2/genética , Caspasa 3/metabolismo , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Apoptosis , Proteínas Proto-Oncogénicas c-bcl-2/genética , Antineoplásicos/farmacología , Células Hep G2 , MicroARNs/uso terapéutico
19.
Environ Res ; 218: 115061, 2023 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-36525995

RESUMEN

The problem of ultrafine particles (UFPs; PM0.1) has been prevalent since the past decades. In addition to become easily inhaled by human respiratory system due to their ultrafine diameter (<100 nm), ambient UFPs possess various physicochemical properties which make it more toxic. These properties vary based on the emission source profile. The current development of UFPs studies is hindered by the problem of expensive instruments and the inexistence of standardized measurement method. This review provides detailed insights on ambient UFPs sources, physicochemical properties, measurements, and estimation models development. Implications on health impacts due to short-term and long-term exposure of ambient UFPs are also presented alongside the development progress of potentially low-cost UFPs sensors which can be used for future UFPs studies references. Current challenge and future outlook of ambient UFPs research are also discussed in this review. Based on the review results, ambient UFPs may originate from primary and secondary sources which include anthropogenic and natural activities. In addition to that, it is confirmed from various chemical content analysis that UFPs carry heavy metals, PAHs, BCs which are toxic in its nature. Measurement of ambient UFPs may be performed through stationary and mobile methods for environmental profiling and exposure assessment purposes. UFPs PNC estimation model (LUR) developed from measurement data could be deployed to support future epidemiological study of ambient UFPs. Low-cost sensors such as bipolar ion and ionization sensor from common smoke detector device may be further developed as affordable instrument to monitor ambient UFPs. Recent studies indicate that short-term exposure of UFPs can be associated with HRV change and increased cardiopulmonary effects. On the other hand, long-term UFPs exposure have positive association with COPD, CVD, CHF, pre-term birth, asthma, and also acute myocardial infarction cases.


Asunto(s)
Contaminantes Atmosféricos , Asma , Humanos , Material Particulado/toxicidad , Material Particulado/análisis , Contaminantes Atmosféricos/toxicidad , Contaminantes Atmosféricos/análisis , Humo/análisis , Estudios Epidemiológicos , Tamaño de la Partícula
20.
Comb Chem High Throughput Screen ; 26(6): 1196-1203, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-35975856

RESUMEN

BACKGROUND: SARS-CoV-2 emerged in late 2019 and caused COVID-19. Patients treated with Zyesami were found to have a 3-fold decrease in respiratory failure and improved clinical outcomes. It was reported that Zyesami inhibits RNA replication of SARS-CoV-2, including several non-structural proteins essential in viral RNA replication. SARS-CoV-2 is a distinctive virus that requires nsp10 and nsp16 for its methyltransferases activity which is crucial for RNA stability and protein synthesis. OBJECTIVE: We aimed the in silico determination of inhibitory consequences of Zyesami on the SARS-CoV-2 nsp10/nsp16 complex. Targeting SARS-CoV-2 nsp10/ nsp16 protein complex may be used to develop a drug against COVID-19. METHODS: I-TASSER was used for secondary structure prediction of Zyesami. CABS-dock was used to model Zyesami with SARS-CoV-2 nsp16 interaction. The docked complex was visualized using PyMol. The quality of the docking model was checked by using ProQdock. RESULTS: The 3D structure of SARS-CoV 2, nsp10/nsp16 showed that essential interactions exist between nsp10 and nsp16. Significant contact areas of Zyesami exist across amino acid residues of nsp10; Asn40-Thr47, Val57-Pro59, Gly69-Ser72, Cys77-Pro84, Lys93-Tyr96. In addition, polar contacts between nsp16 and Zyesami are Asn299-Ser440, Val297-Asn443, Gly149-Tyr437, Gln159-Lys430, Asn178- Arg429, Ser146-Arg429, Ser146-Arg429, Lys147-Arg429, Asr221-Thr422, Lys183-Asp423, Lys183-Asp423, and Gln219-Asp423 the residues are shown of nsp16 and Zyesami respectively. CONCLUSION: The structural bioinformatics analyses have indicated the potential binding specificity of Zyesami and nsp16. Data predict how the initial binding of Zyesami with nsp10 and nsp16 may occur. Moreover, this binding could significantly inhibit the 2 -O-MTase activity of the SARSCoV nsp10/16 complex.


Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , Fentolamina , Combinación de Medicamentos
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