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1.
FASEB J ; 38(11): e23734, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38847486

RESUMEN

The cell cycle is tightly regulated to ensure controlled cell proliferation. Dysregulation of the cell cycle machinery is a hallmark of cancer that leads to unchecked growth. This review comprehensively analyzes key molecular regulators of the cell cycle and how they contribute to carcinogenesis when mutated or overexpressed. It focuses on cyclins, cyclin-dependent kinases (CDKs), CDK inhibitors, checkpoint kinases, and mitotic regulators as therapeutic targets. Promising strategies include CDK4/6 inhibitors like palbociclib, ribociclib, and abemaciclib for breast cancer treatment. Other possible targets include the anaphase-promoting complex/cyclosome (APC/C), Skp2, p21, and aurora kinase inhibitors. However, challenges with resistance have limited clinical successes so far. Future efforts should focus on combinatorial therapies, next-generation inhibitors, and biomarkers for patient selection. Targeting the cell cycle holds promise but further optimization is necessary to fully exploit it as an anti-cancer strategy across diverse malignancies.


Asunto(s)
Ciclo Celular , Neoplasias , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Neoplasias/patología , Antineoplásicos/uso terapéutico , Antineoplásicos/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/farmacología , Animales , Terapia Molecular Dirigida/métodos
2.
FASEB J ; 38(13): e23813, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38976162

RESUMEN

Beta-blockers are commonly used medications that antagonize ß-adrenoceptors, reducing sympathetic nervous system activity. Emerging evidence suggests that beta-blockers may also have anticancer effects and help overcome drug resistance in cancer treatment. This review summarizes the contribution of different isoforms of beta-adrenoceptors in cancer progression, the current preclinical and clinical data on associations between beta-blockers use and cancer outcomes, as well as their ability to enhance responses to chemotherapy and other standard therapies. We discuss proposed mechanisms, including effects on angiogenesis, metastasis, cancer stem cells, and apoptotic pathways. Overall, results from epidemiological studies and small clinical trials largely indicate the beneficial effects of beta-blockers on cancer progression and drug resistance. However, larger randomized controlled trials are needed to firmly establish their clinical efficacy and optimal utilization as adjuvant agents in cancer therapy.


Asunto(s)
Antagonistas Adrenérgicos beta , Resistencia a Antineoplásicos , Neoplasias , Humanos , Antagonistas Adrenérgicos beta/uso terapéutico , Antagonistas Adrenérgicos beta/farmacología , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Animales , Enfermedades Cardiovasculares/tratamiento farmacológico , Progresión de la Enfermedad , Receptores Adrenérgicos beta/metabolismo , Antineoplásicos/uso terapéutico , Antineoplásicos/farmacología
3.
FASEB J ; 38(4): e23480, 2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38354025

RESUMEN

Accumulating evidence suggests that dysregulation of FOXO3a plays a significant role in the progression of various malignancies, including hepatocellular carcinoma (HCC). FOXO3a inactivation, driven by oncogenic stimuli, can lead to abnormal cell growth, suppression of apoptosis, and resistance to anticancer drugs. Therefore, FOXO3a emerges as a potential molecular target for the development of innovative treatments in the era of oncology. Linagliptin (LNGTN), a DPP-4 inhibitor known for its safe profile, has exhibited noteworthy anti-inflammatory and anti-oxidative properties in previous in vivo studies. Several potential molecular mechanisms have been proposed to explain these effects. However, the capacity of LNGTN to activate FOXO3a through AMPK activation has not been investigated. In our investigation, we examined the potential repurposing of LNGTN as a hepatoprotective agent against diethylnitrosamine (DENA) intoxication. Additionally, we assessed LNGTN's impact on apoptosis and autophagy. Following a 10-week administration of DENA, the liver underwent damage marked by inflammation and early neoplastic alterations. Our study presents the first experimental evidence demonstrating that LNGTN can reinstate the aberrantly regulated FOXO3a activity by elevating the nuclear fraction of FOXO3a in comparison to the cytosolic fraction, subsequent to AMPK activation. Moreover, noteworthy inactivation of NFκB induced by LNGTN was observed. These effects culminated in the initiation of apoptosis, the activation of autophagy, and the manifestation of anti-inflammatory, antiproliferative, and antiangiogenic outcomes. These effects were concomitant with improved liver function and microstructure. In conclusion, our findings open new avenues for the development of novel therapeutic strategies targeting the AMPK/FOXO3a signaling pathway in the management of chronic liver damage.


Asunto(s)
Carcinoma Hepatocelular , Inhibidores de la Dipeptidil-Peptidasa IV , Neoplasias Hepáticas , Animales , Ratas , Linagliptina/farmacología , Proteínas Quinasas Activadas por AMP , Dietilnitrosamina/toxicidad , Carcinoma Hepatocelular/inducido químicamente , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/inducido químicamente , Neoplasias Hepáticas/tratamiento farmacológico , Hipoglucemiantes , Inhibidores de Proteasas , Antivirales , Antiinflamatorios
4.
J Infect Dis ; 2024 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-38408366

RESUMEN

Chronic viral hepatitis is caused by hepatitis B virus, hepatitis C virus or hepatitis D virus (HBV, HCV, and HDV). Despite different replication strategies, all these viruses rely on secretion through the host endoplasmic reticulum-Golgi pathway, providing potential host targets for antiviral therapy. Knockdown of transmembrane 6 superfamily member 2 (TM6SF2) in virus cell culture models reduced secretion of infectious HCV virions, HDV virions and HBV subviral particles. Moreover, in a cohort of people with hepatitis B a TM6SF2 polymorphism (rs58542926 CT/TT, which causes protein misfolding and reduced TM6SF2 in the liver) correlated with lower concentrations of subviral particles in blood, complementing our previous work showing decreased HCV viral load in people with this polymorphism. In conclusion, the host protein TM6SF2 plays a key role in secretion of HBV, HCV and HDV, providing the potential for novel pan-viral agents to treat people with chronic viral hepatitis.

5.
Lancet Oncol ; 25(3): 400-410, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38423052

RESUMEN

BACKGROUND: The extended acquisition times required for MRI limit its availability in resource-constrained settings. Consequently, accelerating MRI by undersampling k-space data, which is necessary to reconstruct an image, has been a long-standing but important challenge. We aimed to develop a deep convolutional neural network (dCNN) optimisation method for MRI reconstruction and to reduce scan times and evaluate its effect on image quality and accuracy of oncological imaging biomarkers. METHODS: In this multicentre, retrospective, cohort study, MRI data from patients with glioblastoma treated at Heidelberg University Hospital (775 patients and 775 examinations) and from the phase 2 CORE trial (260 patients, 1083 examinations, and 58 institutions) and the phase 3 CENTRIC trial (505 patients, 3147 examinations, and 139 institutions) were used to develop, train, and test dCNN for reconstructing MRI from highly undersampled single-coil k-space data with various acceleration rates (R=2, 4, 6, 8, 10, and 15). Independent testing was performed with MRIs from the phase 2/3 EORTC-26101 trial (528 patients with glioblastoma, 1974 examinations, and 32 institutions). The similarity between undersampled dCNN-reconstructed and original MRIs was quantified with various image quality metrics, including structural similarity index measure (SSIM) and the accuracy of undersampled dCNN-reconstructed MRI on downstream radiological assessment of imaging biomarkers in oncology (automated artificial intelligence-based quantification of tumour burden and treatment response) was performed in the EORTC-26101 test dataset. The public NYU Langone Health fastMRI brain test dataset (558 patients and 558 examinations) was used to validate the generalisability and robustness of the dCNN for reconstructing MRIs from available multi-coil (parallel imaging) k-space data. FINDINGS: In the EORTC-26101 test dataset, the median SSIM of undersampled dCNN-reconstructed MRI ranged from 0·88 to 0·99 across different acceleration rates, with 0·92 (95% CI 0·92-0·93) for 10-times acceleration (R=10). The 10-times undersampled dCNN-reconstructed MRI yielded excellent agreement with original MRI when assessing volumes of contrast-enhancing tumour (median DICE for spatial agreement of 0·89 [95% CI 0·88 to 0·89]; median volume difference of 0·01 cm3 [95% CI 0·00 to 0·03] equalling 0·21%; p=0·0036 for equivalence) or non-enhancing tumour or oedema (median DICE of 0·94 [95% CI 0·94 to 0·95]; median volume difference of -0·79 cm3 [95% CI -0·87 to -0·72] equalling -1·77%; p=0·023 for equivalence) in the EORTC-26101 test dataset. Automated volumetric tumour response assessment in the EORTC-26101 test dataset yielded an identical median time to progression of 4·27 months (95% CI 4·14 to 4·57) when using 10-times-undersampled dCNN-reconstructed or original MRI (log-rank p=0·80) and agreement in the time to progression in 374 (95·2%) of 393 patients with data. The dCNN generalised well to the fastMRI brain dataset, with significant improvements in the median SSIM when using multi-coil compared with single-coil k-space data (p<0·0001). INTERPRETATION: Deep-learning-based reconstruction of undersampled MRI allows for a substantial reduction of scan times, with a 10-times acceleration demonstrating excellent image quality while preserving the accuracy of derived imaging biomarkers for the assessment of oncological treatment response. Our developments are available as open source software and hold considerable promise for increasing the accessibility to MRI, pending further prospective validation. FUNDING: Deutsche Forschungsgemeinschaft (German Research Foundation) and an Else Kröner Clinician Scientist Endowed Professorship by the Else Kröner Fresenius Foundation.


Asunto(s)
Aprendizaje Profundo , Glioblastoma , Humanos , Inteligencia Artificial , Biomarcadores , Estudios de Cohortes , Glioblastoma/diagnóstico por imagen , Imagen por Resonancia Magnética , Estudios Retrospectivos
6.
Toxicol Appl Pharmacol ; 486: 116943, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38677600

RESUMEN

Ulcerative colitis (UC) is an inflammatory condition that affects the colon's lining and increases the risk of colon cancer. Despite ongoing research, there is no identified cure for UC. The recognition of NLRP3 inflammasome activation in the pathogenesis of UC has gained widespread acceptance. Notably, the ketone body ß-hydroxybutyrate inhibits NLRP3 demonstrating its anti-inflammatory properties. Additionally, BD-AcAc 2 is ketone mono ester that increases ß-hydroxybutyrate blood levels. It has the potential to address the constraints associated with exogenous ß-hydroxybutyrate as a therapeutic agent, including issues related to stability and short duration of action. However, the effects of ß-hydroxybutyrate and BD-AcAc 2 on colitis have not been fully investigated. This study found that while both exogenous ß-hydroxybutyrate and BD-AcAc 2 produced the same levels of plasma ß-hydroxybutyrate, BD-AcAc 2 demonstrated superior effectiveness in mitigating dextran sodium sulfate-induced UC in rats. The mechanism of action involves modulating the NF-κB signaling, inhibiting the NLRP3 inflammasome, regulating antioxidant capacity, controlling tight junction protein expression and a potential to inhibit apoptosis and pyroptosis. Certainly, BD-AcAc 2's anti-inflammatory effects require more than just increasing plasma ß-hydroxybutyrate levels and other factors contribute to its efficacy. Local ketone concentrations in the gastrointestinal tract, as well as the combined effect of specific ketone bodies, are likely to have contributed to the stronger protective effect observed with ketone mono ester ingestion in our experiment. As a result, further investigations are necessary to fully understand the mechanisms of BD-AcAc 2 and optimize its use.


Asunto(s)
Ácido 3-Hidroxibutírico , Colitis Ulcerosa , Proteína con Dominio Pirina 3 de la Familia NLR , Animales , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/metabolismo , Colitis Ulcerosa/patología , Ácido 3-Hidroxibutírico/farmacología , Ratas , Masculino , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Ratas Sprague-Dawley , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Inflamasomas/metabolismo , Inflamasomas/efectos de los fármacos , Sulfato de Dextran/toxicidad , Colon/efectos de los fármacos , Colon/patología , Colon/metabolismo , FN-kappa B/metabolismo , Modelos Animales de Enfermedad , Transducción de Señal/efectos de los fármacos , Cetonas/farmacología
7.
Curr Atheroscler Rep ; 26(8): 395-410, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38869707

RESUMEN

PURPOSE OF REVIEW: To eradicate atherosclerotic diseases, novel biomarkers, and future therapy targets must reveal the burden of early atherosclerosis (AS), which occurs before life-threatening unstable plaques form. The chemical and biological features of microRNAs (miRNAs) make them interesting biomarkers for numerous diseases. We summarized the latest research on miRNA regulatory mechanisms in AS progression studies, which may help us use miRNAs as biomarkers and treatments for difficult-to-treat diseases. RECENT FINDINGS: Recent research has demonstrated that miRNAs have a regulatory function in the observed changes in gene and protein expression during atherogenesis, the process that leads to atherosclerosis. Several miRNAs play a role in the development of atherosclerosis, and these miRNAs could potentially serve as non-invasive biomarkers for atherosclerosis in various regions of the body. These miRNAs have the potential to serve as biomarkers and targets for early treatment of atherosclerosis. The start and development of AS require different miRNAs. It reviews new research on miRNAs affecting endothelium, vascular smooth muscle, vascular inflammation, lipid retention, and cholesterol metabolism in AS. A miRNA gene expression profile circulates with AS everywhere. AS therapies include lipid metabolism, inflammation reduction, and oxidative stress inhibition. Clinical use of miRNAs requires tremendous progress. We think tiny miRNAs can enable personalized treatment.


Asunto(s)
Aterosclerosis , Biomarcadores , MicroARNs , Humanos , Aterosclerosis/genética , Aterosclerosis/metabolismo , Aterosclerosis/diagnóstico , Aterosclerosis/terapia , MicroARNs/genética , MicroARNs/metabolismo , Biomarcadores/metabolismo , Pronóstico , Animales
8.
BMC Vet Res ; 20(1): 276, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38926724

RESUMEN

BACKGROUND: Trace elements play a crucial role in fish nutrition, with zinc (Zn) being one of the most important elements. BIO-sourced zinc nanoparticles were synthesized using the green microalga Pediastrum boryanum (BIO-ZnNPs, 29.35 nm). 30 or 60 mg/ kg dry feed of the BIO-ZnNPs (BIO-ZnNPs30 and BIO-ZnNPs60) were mixed with the Nile tilapia (Oreochromis niloticus) basal diet and fed to the fish for 8 weeks to evaluate their impact on fish growth, digestion, intestinal integrity, antioxidative status, and immunity. RESULTS: A significant enhancement was observed in all investigated parameters, except for the serum protein profile. BIO-ZnNPs at 60 mg/kg feed elevated the activities of reduced glutathione (GSH) and catalase (CAT), enzymatic antioxidants, but did not induce oxidative stress as reflected by no change in MDA level. Fish intestinal immunity was improved in a dose-dependent manner, in terms of improved morphometry and a higher count of acid mucin-producing goblet cells. Interleukin-8 (IL-8) was upregulated in BIO-ZnNPs30 compared to BIO-ZnNPs60 and control fish groups, while no significant expressions were noted in tumor necrosis factor-alpha (TNFα), nuclear factor kappa B (NFkB), and Caspase3 genes. CONCLUSION: Overall, BIO-ZnNPs inclusion at 60 mg/kg feed showed the most advantage in different scenarios, compared to BIO-ZnNPs at 30 mg/kg feed. The positive effects on growth and intestinal health suggest that BIO-ZnNPs supplementation of aquafeeds has many benefits for farmed fish.


Asunto(s)
Alimentación Animal , Cíclidos , Dieta , Intestinos , Zinc , Animales , Zinc/farmacología , Zinc/administración & dosificación , Alimentación Animal/análisis , Cíclidos/inmunología , Cíclidos/crecimiento & desarrollo , Intestinos/efectos de los fármacos , Intestinos/inmunología , Dieta/veterinaria , Suplementos Dietéticos , Nanopartículas del Metal , Antioxidantes , Chlorophyta/química , Microalgas
9.
Chem Biodivers ; 21(3): e202400040, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38265183

RESUMEN

Many Vicia species (Fabaceae) were proven to possess bioactive compounds with potential health beneficial properties. The present study was designed to determine the phenolic constituents, antioxidant and enzyme inhibition activities of aerial parts and seed of V. peregrina. Hexane, ethyl acetate and methanol extracts were prepared by maceration and aqueous extract by infusion. The chemical compositions of the extracts were determined using HPLC-MS/MS technology. The antioxidant activities were examined using various assays including free radical scavenging (ABTS and DPPH), reducing ability (CUPRAC and FRAP), metal chelation, and phosphomolybdenum. The enzyme inhibitory effects were investigated against cholinesterase, tyrosinase, amylase and glucosidase. The highest total phenolics and flavonoids contents were recorded in the methanol extracts of the seed (45.42 mg GAE/g) and aerial parts (40.33 mg RE/g) respectively. The aerial parts were characterized by higher accumulation of chlorogenic acid (9893.86 µg g-1 ), isoquercitrin (9400.33 µg g-1 ), delphindin 3,5 diglucoside (9113.28 µg g-1 ), hyperoside (6337.09 µg g-1 ), rutin (3489.83 µg g-1 ) and kaempferol-3-glucoside (2872.84 µg g-1 ). Generally, the methanol and aqueous extracts of the two studied parts exerted the best antioxidant activity with highest anti-DPPH (61.99 mg TE/g), anti-ABTS (101.80 mg TE/g) and Cu++ (16169 mg TE/g) and Fe+++ (172,36 mg TE/g) reducing capacity were recorded from the seed methanol extract. Methanol extract of the seed showed the best anti-tyrosinase activity (75.86 mg KAE/g). These results indicated that V. peregrina is rich with bioactive phenolics suggesting their use in different health promoting applications.


Asunto(s)
Antioxidantes , Vicia , Antioxidantes/farmacología , Antioxidantes/química , Metanol/química , Hipoglucemiantes/farmacología , Espectrometría de Masas en Tándem , Turquía , Cromatografía Líquida con Espectrometría de Masas , Extractos Vegetales/farmacología , Extractos Vegetales/química , Fenoles/química
10.
Chem Biodivers ; 21(2): e202301596, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38126959

RESUMEN

Sorbus torminalis (L.) Crantz has a rich history of versatile applications spanning the fields of medicine and nutrition. It is noteworthy that the decoction obtained from S. torminalis leaves is a traditional treatment method against both diabetes and stomach disorders. Phytochemical profiling determined by HPLC/MS-MS. The effects of the extracts on cell viability were investigated using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) method against MDA-MB-231 cell line (human breast adenocarcinoma).The ethanol/water extract contained more concentration of total phenolic (91.41 mg gallic acid (GAE) equivalent /gr) and flavanoid (29.10 mg rutin (RE) equivalent/gr) in the tested extract (p<0.05). Resulting of HPLC analysis, the chemical constituents varied depending on the solvents and chlorogenic acid, hyperoside, isoquercetin, delphindin-3,5-diglucoside, procyanidin B2, epicatechin, neochlorogenic acid, 3,5-dicaffeoylquinic acid were identified in all extracts. Overall, ethanol, n-hexane and ethyl acetate extracts showed the highest inhibition for the tyrosinase enzyme. The effect of leaf extracts of S. torminalis on antimicrobial, biofilm inhibitory, and anticancer activities was examined. Based on outcomes of our study recognize this plant as a critical source of medically active chemicals for feasible phytopharmaceutical and nutraceutical applications, providing the first scientific insight into the detailed biological and chemical profiles of S. torminalis.


Asunto(s)
Sorbus , Humanos , Antioxidantes/farmacología , Etanol , Flavonoides/farmacología , Fitoquímicos/farmacología , Extractos Vegetales/farmacología , Extractos Vegetales/análisis , Hojas de la Planta/química
11.
Chem Biodivers ; 20(4): e202201181, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36891864

RESUMEN

Arum elongatum (Araceae) is widely used traditionally for the treatment of abdominal pain, arterial hypertension, diabetes mellitus, rheumatism and hemorrhoids. This study investigated the antioxidant properties, individual phenolic compounds, total phenolic and total flavonoid contents (HPLC/MS analysis), reducing power and metal chelating effects of four extracts obtained from A. elongatum (ethyl acetate (EA), methanol (MeOH), methanol/water (MeOH/water) and infusion). The inhibitory activity of the extracts were also determined against acetylcholinesterase, butyrylcholinesterase, tyrosinase, amylase and glucosidase enzymes. The MeOH/water extracts contained the highest amount of phenolic contents (28.85 mg GAE/g) while the highest total flavonoid content was obtained with MeOH extract (36.77 mg RE/g). MeOH/water demonstrated highest antioxidant activity against DPPH⋅ radical at 38.90 mg Trolox equivalent per gram. The infusion extract was the most active against ABTS+ ⋅ (133.08 mg TE/g). MeOH/water extract showed the highest reducing abilities with the CUPRAC value of 102.22 mg TE/g and the FRAP value of 68.50 mg TE/g. A strong metal chelating effect was observed with MeOH/water extract (35.72 mg EDTAE/g). The PBD values of the extracts ranged from 1.01 to 2.17 mmol TE/g. EA extract displayed the highest inhibitory activity against AChE (2.32 mg GALAE/g), BChE (3.80 mg GALAE/g), α-amylase (0.56 mmol ACAE/g) and α-glucosidase (9.16 mmol ACAE/g) enzymes. Infusion extract was the most active against tyrosinase enzyme with a value of 83.33 mg KAE/g. A total of 28 compounds were identified from the different extracts. The compounds present in the highest concentration were chlorogenic acids, 4-hydroxybenzoic acid, caffeic acid, p-coumaric acid, ferulic acid, isoquercitrin, delphindin 3,5-diglucoside, kaempferol-3-glucoside and hyperoside. The biological activities of A. elongatum extracts could be due to the presence of compounds such as gallic acid, chlorogenic acids, ellagic acid, epicatechin, catechin, kaempferol, 4-hydroxybenzoic acid, caffeic acid, p-coumaric acid, ferulic acid, quercetin, isoquercitrin, and hyperoside. Extracts of A. elongatum showed promising biological activities which warrants further investigations in an endeavor to develop biopharmaceuticals.


Asunto(s)
Arum , Inhibidores Enzimáticos , Extractos Vegetales , Acetilcolinesterasa , Antioxidantes/química , Arum/química , Butirilcolinesterasa , Ácidos Cafeicos , Inhibidores Enzimáticos/química , Flavonoides/farmacología , Flavonoides/análisis , Quempferoles , Metanol , Monofenol Monooxigenasa , Parabenos , Extractos Vegetales/farmacología , Extractos Vegetales/química , Solventes , Agua , Ácido Elágico/química , Ácido Elágico/farmacología
12.
Arch Pharm (Weinheim) ; 356(9): e2300263, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37434089

RESUMEN

Six extracts (water, ethanol, ethanol-water, ethyl acetate, dichloromethane, and n-hexane) of Astragalus caraganae were studied for their biological activities and bioactive contents. Based on high-performance liquid chromatography-mass spectrometry (HPLC-MS), the ethanol-water extract yielded the highest total bioactive content (4242.90 µg g-1 ), followed by the ethanol and water extracts (3721.24 and 3661.37 µg g-1 , respectively), while the least total bioactive content was yielded by the hexane extract, followed by the dichloromethane and ethyl acetate extracts (47.44, 274.68, and 688.89 µg g-1 , respectively). Rutin, p-coumaric, chlorogenic, isoquercitrin, and delphindin-3,5-diglucoside were among the major components. Unlike the dichloromethane extracts, all the other extracts showed radical scavenging ability in the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay (8.73-52.11 mg Trolox equivalent [TE]/g), while all extracts displayed scavenging property in the 2,2-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical scavenging assay (16.18-282.74 mg TE/g). The extracts showed antiacetylcholinesterase (1.27-2.73 mg galantamine equivalent [GALAE]/g), antibutyrylcholinesterase (0.20-5.57 mg GALAE/g) and antityrosinase (9.37-63.56 mg kojic acid equivalent [KAE]/g) effects. The molecular mechanism of the H2 O2 -induced oxidative stress pathway was aimed to be elucidated by applying ethanol, ethanol/water and water extracts at 200 µg/mL concentration to human dermal cells (HDFs). A. caraganae in HDF cells had neither a cytotoxic nor genotoxic effect but could have a cytostatic effect in increasing concentrations. The findings have allowed a better insight into the pharmacological potential of the plant, with respect to their chemical entities and bioactive contents, as well as extraction solvents and their polarity.

13.
Int Orthop ; 47(12): 2985-2989, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37610463

RESUMEN

PURPOSE: The use of suction drains in total knee arthroplasty (TKA) remains controversial. The aim of this study is to compare the outcomes of patients who received suction drains versus those who did not, focusing on blood loss, blood transfusion need, and length of hospital stay. METHODS: A retrospective observational cohort study was conducted at a tertiary hospital between January 1, 2015, and December 30, 2019, and included 262 patients who underwent unilateral non-traumatic primary TKA and were over 18 years old. The Institutional Review Board (IRB) approved the study (MRC-02-20-278). RESULTS: A total of 262 patients were included, with an age range of 47 to 91 years. Most of the included patients were females, 74.4% (195). Hypertension was the most frequent risk factor, 67.6%, followed by diabetes. Of 262 patients, 156 (59.5%) received a drain. The drain group had significantly longer hospital stay, 30% longer tourniquet time, greater haemoglobin and haematocrit drops, higher count of transfused packed RBC units, and lower use of anticoagulants. Moreover, tranexamic acid (TXA) use (n = 106) in surgery reduced hospital stays, tourniquet time, drain output, and increased pre- and postoperative haemoglobin and hematocrit levels compared to no TXA group (n = 156) (p < 0.05, z-score reported). CONCLUSIONS: This study found that patients who received a drain had longer hospital stays and greater blood loss and transfusion rates compared to those who did not. The use of TXA in surgery was associated with improved outcomes and reduced overall complications.


Asunto(s)
Antifibrinolíticos , Artroplastia de Reemplazo de Rodilla , Ácido Tranexámico , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Antifibrinolíticos/uso terapéutico , Artroplastia de Reemplazo de Rodilla/efectos adversos , Pérdida de Sangre Quirúrgica/prevención & control , Drenaje/efectos adversos , Hemoglobinas , Estudios Retrospectivos , Ácido Tranexámico/uso terapéutico
14.
Int J Mol Sci ; 24(14)2023 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-37511218

RESUMEN

Water-resistant and environmentally friendly sodium-alginate-based films have been investigated to develop functional materials to extend the food's shelf-life. A water-stable alginate-based film was prepared, employing both the internal and external gelation approach in the presence of CaCl2. To apply this film to food packaging and thus preserve food quality, the aim of this work is to perform a chemical and physical characterization of the proposed materials, evidencing the main features and stability under different work conditions. Water contact angle measurements showed a value of 65°, suggesting an important reduced hydrophilic character of the obtained alginate films due to the novel CaCl2-induced compacted polymer network. The film's stability was thus checked through swelling measurements in water after varying pH, temperature, and ionic strength. The film was stable at high temperatures and not pH-responsive. Only highly concentrated salt-based solutions negatively affected the proposed packaging, causing a large swelling. Furthermore, a water-based polyphenolic extract from grape (Vitis vinifera L.) pomace waste was embedded inside the films in different amounts in order to confer additional properties. The extract's polyphenolic content (evaluated from HPLC/MS-MS measurements) endowed the films' UV-light screening and enhanced antioxidant properties. These important findings suggest the additional potential role of these films in protecting food from light deterioration. The stability of these hybrid films was also checked by observation, as the polyphenols' presence did not largely alter the alginate network that occurred yet was water-resistant under the described work conditions.


Asunto(s)
Alginatos , Vitis , Alginatos/química , Embalaje de Alimentos , Agua , Extractos Vegetales/farmacología , Cloruro de Calcio , Sodio
15.
Molecules ; 28(15)2023 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-37570780

RESUMEN

Strawberries are the most popular berry fruit in the world, due to their distinctive aroma, flavor, and known health properties. Because volatile substances play a large role in strawberry flavor, even little alterations can have a big impact on how the fruit tastes. Strawberries are thought to have a complex aroma. Fresh strawberry fruits contain more than 360 volatile compounds, including esters, furans, terpenes, alcohols, aldehydes, ketones, and sulfur compounds. Despite having far lower concentrations than esters, terpenoids, furanones, and sulfur compounds, all have a considerable impact on how people perceive the aroma of strawberries. With a focus on the active aroma components and the many analytical methods used to identify them, including gas chromatography, electronic nose sensing, and proton-transfer- reaction mass spectrometry, the present review's aim was to provide a summary of the relevant literature. Additionally, strawberry fruits are frequently dried to create a powder in order to increase their shelf life. Consequently, the impact of various drying techniques on strawberries' volatile profile was investigated in the current review. This review can be considered a good reference for research concerning the aroma profile of strawberries. It helps to better understand the complex aroma and flavor of strawberries and provides a guide for the effects of drying processing.


Asunto(s)
Fragaria , Compuestos Orgánicos Volátiles , Humanos , Odorantes/análisis , Fragaria/química , Frutas/química , Cromatografía de Gases y Espectrometría de Masas/métodos , Compuestos Orgánicos Volátiles/análisis , Terpenos/análisis , Ésteres/análisis
16.
Acta Oncol ; 61(10): 1230-1239, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35862646

RESUMEN

PURPOSE: This prospective study aims to assess the diagnostic test characteristics of Na[18F]F PET/CT for the skeletal staging of cancer in morbidly obese patients compared with 99mTc-methylene diphosphonate (MDP), whole-body planar (WBS), SPECT, and SPECT/CT acquisitions. MATERIAL AND METHODS: One hundred seventeen obese patients (BMI 46.5 ± 6.1 kg/m2 and mean age, 59.0 years; range 32-89 years) with BMI > 40 kg/m2 were prospectively enrolled and underwent [99mTc]Tc-MDP WBS, SPECT, SPECT/CT, and Na[18F]F PET/CT within two weeks for the osseous staging of a malignancy. Images were assessed qualitatively using a 3-point scale. Patient and lesion-based diagnostic test characteristics were estimated using an optimistic and pessimistic dichotomization method. RESULTS: Bone metastases were confirmed in 44 patients. Patient-based optimistic diagnostic test characteristics were (sensitivity, specificity, overall accuracy): Na[18F]F PET/CT (95.5%, 95.9%, 95.7%), [99mTc]Tc-MDP WBS (52.3%, 71.2%, 64.1%), SPECT (61.4%, 80.8%, 73.5%) and SPECT/CT (65.9%, 91.8%, 82.1%). Lesion-based optimistic diagnostic test characteristics were: Na[18F]F PET/CT (97.7%, 97.9%, 97.7%), [99mTc]Tc-MDP WBS (39%, 67%, 48.9%), SPECT (52.9%, 93.6%, 67.3%) and SPECT/CT (65.9%, 91.8%, 82.1%). There was no significant difference in the specificity of Na[18F]F and SPECT/CT. All other pairwise comparisons were significant (p<.001). ROC curve analysis showed a high overall accuracy of Na[18F]F with significantly higher AUCs for Na[18F]F PET/CT compared to [99mTc]Tc-MDP WBS, SPECT, and SPECT/CT on both patient and lesion-based analysis (p<.001). Moreover, Na[18F]F PET/CT changed patient management in 38% of patients. CONCLUSIONS: Na[18F]F PET/CT may be the preferred imaging modality for skeletal staging in morbidly obese patients. The technique provides excellent diagnostic test characteristics superior to [99mTc]Tc-MDP bone scan (including SPECT/CT), impacts patient management, has an acceptable radiation exposure profile, and is well-tolerated. Further cost-effectiveness evaluations are warranted.


Asunto(s)
Neoplasias Óseas , Obesidad Mórbida , Humanos , Persona de Mediana Edad , Tomografía Computarizada por Tomografía de Emisión de Positrones , Estudios Prospectivos , Medronato de Tecnecio Tc 99m , Imagen Multimodal/métodos , Tomografía de Emisión de Positrones/métodos , Estadificación de Neoplasias , Obesidad Mórbida/complicaciones , Obesidad Mórbida/diagnóstico por imagen , Tomografía Computarizada de Emisión de Fotón Único , Neoplasias Óseas/diagnóstico por imagen , Neoplasias Óseas/secundario
17.
J Immunoassay Immunochem ; 43(6): 678-694, 2022 Nov 02.
Artículo en Inglés | MEDLINE | ID: mdl-35658838

RESUMEN

We investigated the effects of different concentrations of longevity spinach, Gynura procumbens, on the hematological parameters of acutely stressed Nile tilapia, Oreochromis niloticus, (average weight 461.81 ± 16.60 g and average length 28.71 ± 0.34 cm) and determined the best concentration. The fish were subjected to hormonal stress in this research. We fed the stress control group commercial feed with 0.01% hydrocortisone, a stress hormone (0.01% of fish body weight) without Gynura. All the treatment groups were supplemented with Gynura extracts (0.5 g/kg, 1.0 g/kg, and 1.5 g/kg of feed weight) in combination with hydrocortisone. We evaluated blood glucose, lysozyme activity, phagocytic capacity, hematocrit, spleen somatic index, and hepatosomatic index. During the acute stress period, G. procumbens has been shown to decrease the levels of blood glucose in 1.5 g/kg treatment group (49.60 mg/dl at Day 1; 53.75 mg/dl at Day 3) compared to stress control group (80.00 mg/dl at Day 1; 69.20 mg/dl at Day 3). Higher lysozyme activity observed in 1.5 g/kg Gynura treatment group (11.44 T/min at 540 nm) compared to control (7.85 T/min at 540 nm). The 1.5 g/kg treatment group maintained the homeostatic level of significant physiological parameters including phagocytic capacity, packed cell volume, and hepatosomatic index. These findings are promising for the development of new nutraceuticals for the aquaculture industry.


Asunto(s)
Cíclidos , Enfermedades de los Peces , Tilapia , Alimentación Animal/análisis , Animales , Glucemia , Dieta , Suplementos Dietéticos , Hidrocortisona , Inmunidad , Muramidasa/farmacología , Extractos Vegetales/farmacología , Spinacia oleracea
18.
Chem Biodivers ; 19(7): e202101040, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35638152

RESUMEN

As the safety and effectiveness of synthetic drugs remain in doubt, researchers are trying to develop natural medicines from medicinal plants. Herein, ethyl acetate, methanol and water extracts from the Heracleum humile plant were obtained by an ultrasonic-assisted extraction process and the aim was to evaluate some biological effects of the extracts due to the limited data on the pharmacological properties of Heracleum humile in the literature. Weak antibacterial activity was observed on tested bacterial species. The minimum inhibitory concentration and the minimum bactericidal concentration values ranged from 250 to 500 µg/mL. In addition, cytotoxic activity was determined using the MTT test. The strongest findings were determined for ethyl acetate extract on the MDA-MB-231 cell lines at the 48th  hour (IC50 :97.94 µg/mL), followed by the MCF-7 cell lines at the 24th  hour (IC50 :103.9 µg/mL). All extracts of Heracleum humile contained mainly flavonoids, phenolic acids and their derivatives, i. e., well-known compounds that possess numerous biological activities such as antioxidant, anti-inflammatory, anticancer, antimicrobial etc. The study results could provide important information that Heracleum humile could be a potential candidate as a natural enzyme inhibitor. It can be concluded that these extracts could be useful in the elementary step of improving novel plant-derived multifunctional pharmaceuticals.


Asunto(s)
Heracleum , Magnoliopsida , Antibacterianos/farmacología , Antioxidantes/farmacología , Flavonoides/farmacología , Pruebas de Sensibilidad Microbiana , Extractos Vegetales/farmacología
19.
Chem Biodivers ; 19(4): e202200076, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35263028

RESUMEN

In this study, phytochemical and pharmacological screening of the aerial part and roots extracts from Doronicum orientale Hoffm. (Asteraceae) was carried out. Plant extracts were obtained using solvents of different polarity (hexane, ethyl acetate, ethanol, ethanol/water, water) for selection the most optimal solvent for the extraction of active compounds. For instance, the extracts yielded total phenolic and flavonoid contents in the range of 12.13-45.67 mg GAE/g and 0.75-12.44 mg QE/g, respectively, while the total antioxidant capacity of the extracts determined by the phosphomolybdenum assay ranged from 0.88-2.53 mmol TE/g. HPLC/MS/MS analysis revealed 5-caffeoylquinic acid (2.52-337.05 µg/g) and 3,5-dicaffeoylquinic acid (3.12-299.36 µg/g) to be the major components present in the investigated extracts. Antioxidant activity in terms of radical scavenging ability of the extracts ranged from 0.82-45.56 mg TE/g in DPPH assay and from 5.07-104.58 mg TE/g in ABTS assay. The tested extracts were found to inhibit acetylcholinesterase (aerial part: 0.50-2.33 mg GALAE/g; roots: 0.40-2.43 mg GALAE/g), while with the exception of the water extracts, the other extracts showed butyrylcholinesterase inhibition (aerial part: 2.46-5.02 mg GALAE/g; root: 2.93-4.17 mg GALAE/g). Overall, this study presented an interesting scope of this species in phytomedicine with preliminary data demonstrating some of the tested extracts to possess high bioactive contents, antioxidant potential and enzyme inhibitory activity. Thus, additional investigations are necessary to confirm their safety in herbal drug applications.


Asunto(s)
Antioxidantes , Asteraceae , Acetilcolinesterasa , Antioxidantes/química , Butirilcolinesterasa , Etanol , Flavonoides/análisis , Flavonoides/farmacología , Fitoquímicos/análisis , Extractos Vegetales/química , Extractos Vegetales/farmacología , Espectrometría de Masas en Tándem , Agua
20.
Chem Biodivers ; 19(7): e202200227, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35608187

RESUMEN

Honey is used since ancient time as a food and to cure many diseases. The present study investigated the chemical constituents, antioxidant and enzyme inhibition activities of natural Saudi Sidr (SH) and Talh (TH) honeys. Beside entire honey samples, ethyl acetate, ethanol and water extracts were prepared. The total polyphenolic content of SH, TH and their extracts was in the range of 2.86-7.21 and 3.80-17.33 mg gallic acid equivalents/g, respectively and the total flavonoids content was in the range of 0.05-1.17 and 0.18-2.38 mg rutin equivalents/g, respectively. Out of the 53 standards analyzed by HPLC, 27 compounds were detected with highest number of compounds identified in the ethyl acetate extract of TH (45 %, 24/53) and SH (26 %, 14/53), respectively. Quinic acid was dominant compound identified in all honey samples with the highest content determined in TH ethanol extract (4454 µg/g). The majority of tested samples possessed considerable anti-radicals and reducing ions capacity with the ethyl acetate extract from TH exerted significantly (p<0.05) the highest activity. All honey samples did not show chelating iron metal property. Honey samples revealed variable enzyme inhibition activity with TH (entire and/or ethyl acetate extract) showed significantly (p<0.05) the highest acetylcholinesterase, butyrylcholinesterase, tyrosinase and α-amylase inhibition activity. In conclusion, ethyl acetate is the best solvent for extraction of bioactive molecules from the two honey types. Moreover, the dark-colored TH contained the highest number of molecules and consequently exerted the best antioxidant and enzyme inhibition activities in most assays.


Asunto(s)
Antioxidantes , Miel , Acetilcolinesterasa , Antioxidantes/química , Antioxidantes/farmacología , Butirilcolinesterasa , Etanol , Flavonoides/farmacología , Extractos Vegetales/química , Extractos Vegetales/farmacología , Arabia Saudita
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